Rheumatology manpower in California. Approaches to assessment of quantitative sufficiency. Californian specialists in the treatment of rheumatic diseases were surveyed to determine the spatial distribution of rheumatologic services in the state, the amount of patient care time available for the rhematic diseases in each county, the physicians' capacity to treat all rhemmatic disease patients who seek their care, and their perception of the need for more specialists in their area. The data resulting from the survey are analyzed by four methods to assess the sufficiency of medical manpower resoruces.


Acetylator phenotype in systemic lupus erythematosus. The acetylation rate of sulfamethazine was studied in 25 patients with systemic lupus erythematosus (SLE). Seventeen of 25SLE patients, 68%, were slow acetylators compared to the reported incidence of 52% in the general population. There was no correlation between the acetylator phenotype in SLE patients and the various clinical manifestations or the activity of the disease. Lupus patients who were slow acetylators had a lower lymphocyte response to phytomitogens compared to rapid acetylators.


Quantitation of precipitating antibodies to certain soluble nuclear antigens in SLE. Electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulfate was used to separate and quantitate the components of a washed immune precipitate. Serum was from patients with systemic lupus erythematosus known to have antibodies to soluble nuclear ribonucleoprotein (RNP) or to a soluble nuclear non-nucleic acid protein (Sm). Amounts of antibody that was predominantly IgG ranged from 0.2 to 8 mg/ml of patients' serum, and in some cases accounted for over 20% of the total serum IgG. Results demonstrate that some patients respond to the disease by producing large amounts of a specific antibody, and that these antibodies can contribute significantly to hypergammaglobulinemia.


Decreased lymphocyte reactivity to a suboptimal concentration of phytohemagglutinin in Sjögren's syndrome. Significantly decreased lymphocyte reactivity to a suboptimal concentration of phytohemagglutinin (PHA) was found in patients with Sjögren's syndrome (SS), whereas the response to an optimal concentration was generally normal. Kinetic studies were performed on control lymphocytes. Only suboptimal PHA concentrations stimulated tritiated thymidine (3H-TdR) incorporation in proportion to the number of potentially reactive lymphocytes. Kinetic studies of SS patients suggested that their low reactivity was attributable to fewer functionally reactive lymphocytes rather than to a decreased rate of proliferation.


Central nervous system involvement in SLE. Diagnostic profile and clinical features. The clinical course and diagnostic profile of 13 patients with central nervous system involvement and systemic lupus erythematosus (CNS-SLE) are presented. The diagnostic yield for each procedure was measured as the precent abnormal: CSF total protein was 38%; increased CSF IgG 69%; decreased CSF hemolytic C4 10%; increased CSF anti-DNA 64%; electroencephalogram 80%; flow brain scan 50%; and static brain scan 0%. No single procedure was consistently abnormal, but the battery of tests provided a useful and specific CNS-SLE diagnostic profile.


Chronic polyarthritis associated with hypogammaglobulinemia. A study of two patients. Two adult patients with hypogammaglobulinemia and chronic synovitis were studied. Synovial tissue and fluid were examined by histologic, virologic, and immunologic methods. The synovium lacked characteristic histologic features of rheumatoid arthritis, and B lymphocytes were absent from the synovial tissue, fluid, and peripheral blood. These 2 patients may represent a form of chronic synovitis produced in the absence of any B lymphocyte response.


Phytomitogen-induced, lymphokine-mediated cartilage proteoglycan degradation. The significance of T-cell activation in the immunopathogenesis of articular disease has been studied in an in vitro model to assess the capacity of phytomitogen-induced lymphokines to degrade cartilage matrix proteoglycans. Supernatants derived from T-cell activation of normal human peripheral blood lymphocytes were shown to contain a monocyte-dependent, serum-inhibitable, dialyzable factor or factors capable of inducing significant proteoglycan degradation, as assessed by release of macroprecipitable 35S-labeled proteoglycan from heterologous cartilage substrates.


Disseminated immune deposits in lupus erythematosus. Immunohistologic studies were performed on autopsy tissues of 2 patients with systemic lupus erythematosus. All tissues examined--the kidney, lung, spleen, liver, intestine, peritoneum, and choroid plexus--contained immune deposits. Antinuclear antibody concentration in immunoglobulin G eluted from lung and spleen tissue was higher than in serum immunoglobulin G. These findings support the assumption that in systemic lupus erythematosus the renal as well as the extrarenal lesions can be attributed to vascular deposition of immune complexes.


Localization of proliferating cells in lymphatic tissues triggered by  dextran sulfate. Mice were injected with dextran sulfate in the presence or absence of various amounts of sheep red blood cells. The incorporation of thymidine into the proliferating cells of spleen, lymph nodes and thymus was investigated using autoradiographic and histologic techniques. Dextran sulfate triggered selective proliferation of cells localized in the marginal zone of the white pulp of the spleen. The uptake of colloid carbon particles was also enhanced by dextran sulfate in this area of the spleen. The results are consistent with the suggestion that dextran sulfate triggers proliferation of non-thymus-derived cells probably a sub-population of B-lymphocytes and activates phagocytic cells.


Synthesis and thermal melting behavior of oligomer-polymer complexes containing defined lengths of mismatched dA-dG and dG-dG nucleotides. Model DNA polymers containing heteroduplex regions of defined sequence and size were synthesized using polynucleotide phosphorylase and calf thymus terminal transferase. Heteroduplexes were of the form (dG)n-d(C12AmC-x), where m - 1-6, and (dG)n-d(C10GmC-x), where m = 1 and 3-5. Thermal melting studies of the model DNAs indicated that the heteroduplex regions did not disrupt the cooperative interaction between the flanking regions of dG-dC base pairs. thus, it is possible that the heteroduplex nucleotides are accommodated in a stacked helical structure.


Action of single-strand specific nucleases on model DNA heteroduplexes of defined size and sequence. The sensitivity of the model DNAs containing dA-dG and dtg-dG heteroduplex regions of defined length to S1 and mung bean single-strand specific nucleases was tested by polyacrylamide gel electrophoretic analysis of the distribution of product oligonucleotides. Single-base mismatch heteroduplexes were extremely resistant to these nucleases, although low levels of cleavage at the heteroduplex nucleotide were observed at high nuclease concentrations. The nuclease sensitivity of dA-dtg heteroduplex regions increased gradually as the length of the heteroduplex region increased frome one to six nucleotides. The sensitivity of dG-dG heteroduplexes three to five nucleotides long was considerably greater than that of the single dtg-dG mismatch.


Alterations in electrophysiology of isolated amphibian small intestine produced by removing the muscle layers. Isolated segments of Amphiuma small intestine bathed in chloride or sulfate buffer generate a greater short-circuit current and a larger change in current in response to galactose when the serosal muscle layers are stripped from the mucosa. Intact (unstripped) segments are not apparently anoxic since stripped segments exposed to serosal N2 for 3 h display normal short-circuit currents but a reduced potential response to galactose, while the presence of muscle layers tends to reduce the short-circuit current but does not alter the potential response to galactose. Bullfrog small intestine also generates greater short-circuit current following removal of the muscle layers. The enhancing effect of stripping appears to be related to removal of a resistance to ion flow across the tissue.


On the synthesis of prostaglandins by human gastric mucosa and its modification by drugs. 1. Specific radioimmunoassays for the prostaglandins E2, A2 and F2alpha were used to study the synthesis of prostaglandins by gastroscopically obtained small biopsy specimens of human gastric corpus mucosa. 2. Both prostaglandin E2 and prostaglandin F2alpha were found to be synthesized from arachidonic acid by themicrosomal fraction of human gastric mucosa. The synthesis of prostaglandin E2 exceeded that of prostagladin F2alpha by a factor of about 10. 3. Synthesis of prostaglandin A2 or prostaglandin B2 was not observed under the same incubation conditions. 4. Indometacin effectively inhibited synthesis of both prostaglandin E2 (ID50 4.2 microng/ml) and prostaglandin F2alpha (ID50 1.8 microng/ml) by human gastric mucosa, while paracetamol even in a concentration of 310 microng/ml did not influence prostaglandin synthesis. The anti-ulcer agent carbenoxolone, which has been shown to inhibit prostaglandin inactivation, at the same concentration only slightly inhibited (about 20%) prostaglandin synthesis. 5. The results support the hypothesis that the gastro-intestinal effects or side effects of several drugs are mediated by an influence on the enzymes of prostaglandin synthesis or inactivation.


Some immunological parameters in rheumatoid arthritis from India. The present study describes the immune status of 41 patients with rheumatoid arthritis from India. The results showed a high level of immunoglobulins, normal levels of C3, less proportion of seropositivity (54%) than that reported from the west and 26% having antinuclear antibody in their serum. T lymphocyte proportion in the blood was found to be low in acutely ill patients only. Mantoux and streptokinase-streptodornase skin tests for delayed hypersensitivity were positive only in about 50% of that of controls. However, all the patients could be sensitized to DNCB. For testing the humoral antibody response TAB vaccine was given. The levels of antibody produced against O and H antigens of "Salmonella typhi" were comparable in patients and controls. However, the level of IgM rose significantly in the patients in comparison to that of controls. The cause of this, at least partially, was found to be due to a very significant rise of rheumatoid factor after TAB vaccine in the patients. Also 3 out of 8 patients converted to a seropositive state after TAB vaccination. Controls did not show the development of rheumatoid factor.


Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study. The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.


Sterol content and polyene antibiotic resistance in isolates of Candida krusei, Candida parakrusei, and Candida tropicalis. Three isolates, one from each species of Candida krusei, C. parakrusei, and C. tropicalis, obtained from infected patients, were more tolerant of significantly higher concentrations of polyene antibiotics than the corresponding reference wild types. The resistant strains isolated had the same sterols as their wild-type counterparts but in lower concentrations.


Marker properties of tumor and lymphoid cell lines derived from a patient with squamous cell carcinoma. A squamous cell carcinoma tumor cell line, COLO 227, derived from a metastatic tumor in a Caucasian male, produces both parathyroid hormone and carcinoembryonic antigen. A chromosome mode of 106 predominated and the X and Y chromosomes were retained. Seven marker chromosomes were identified. Cytogenetic analysis revealed an isochromosome 8 marker similar to a HeLa cell line marker and an isochromosome 17 marker described in other cancers. An autochthonous lymphoid cell line, COLO 219, was established and characterized. COLO 219 is a normal lymphoid cell line with B-cell characteristics. This autochthonous system of both cultured tumor cells and cultured lymphocytes is of use in immunological studies.


Adenocarcinoma R-3327 of the Copenhagen rat as a suitable model for immunological studies of prostate cancer. An experimental animal model for the study of host-prostatic tumor cell interactions has been described. R-3327, a line of prostatic adenocarcinoma of the Copenhagen rat, has been proven to be immunogenic to its syngeneic host as evidenced by two different in vitro cell-mediated immune assays. Specificity of the responses has been ascertained on the basis of absence of response: (a) of nonimmune lymphocytes to the R-3327 tumor antigen(s); (b) of R-3327 immune lymphocytes to several normal tissues including normal prostate; (c) of immune lymphocytes to unrelated squamous cell prostatic carcinoma of the Copenhagen rat. Furthermore, the presence of tumor has an effect in several nonspecific aspects of host response, inducing splenomegaly, heightened responses to nonspecific mitogens in lymphocyte transformation assay, and increased levels of killer cell action. Since there are many histological, biochemical, and functional analogies between this tumor line and human prostate carcinomas, this system appears to be suitable for immunological and possible immunotherapeutic studies of this type of neoplasia.


Effect of clofibrate on intravascular coagulation in hyperlipoproteinemia. Intravascular coagulation (IVC) was evaluated in 19 patients with type II and 11 with type IV hyperlipoproteinemia before and after clofibrate therapy by measurements of soluble fibrin complexes (SFC) in plasma; fibrinolysis was estimated by quantitation of fibrin (ogen) degradation products in serum. Untreated type II and type IV patients had increased SFC (P less than 0.01). The former also had activation of the intrinsic coagulation pathway as evidenced by decreased plasma prekallikrein (P less than 0.001), kallikrein inhibitors (P less than 0.001), and factor XII (P less than 0.02). Although clofibrate treatment of the type II patients did not change plasma lipids, it decreased intravascular coagulation, apparently via decreased factor XII activation and stimulation of fibrinolysis. In contrast, treated type IV patients had unchanged SFC and FDP levels, despite decreased plasma triglycerides (P less than 0.01). Clofibrate-induced changes in blood coagulation are independent of lipid-lowering. Clofibrate therapy decreases intravascular coagulation in type II patients and may help to prevent thromboembolic sequelae.


Exercise testing soon after myocardial infarction. Forty-six men under age 70, without clinical congestive heart failure or unstable angina pectoris, performed treadmill tests 3, 5, 7, 9 and 11 weeks after myocardial infarction. Patients were more frequently able to perform moderate exertion (2 mph, 14% grade) at 7 and 11 weeks than at 3 weeks following infarction. Ischemic ST-segment depression, usually unaccompained by angina pectoris, occurred in 45% of patients and was associated with a significantly increased incidence of subsequent coronary events. The presence of exercise-induced ventricular ectopic activity provided little independent prognostic information. No serious complications occurred in 210 tests. Exercise testing soon after myocardial infarction provides objective information concerning the capacity to resume physical activity, including return to work. Two tests, at 3-5 weeks and at 7-11 weeks, appear to provide most of the information contined in five tests performed during this time.


Surgical management of life-threatening ventricular arrhythmias in patients with coronary artery disease. Twenty-one patients with coronary artery disease and severe, symptomatic ventricular arrhythmias underwent cardiac surgery after failure of medical managememt. All had coronary artery disease and either localized areas of severe hypokinesis (three patients), or ventricular aneurysms (18 patients) documented angiographically prior to surgery. Operation within one month after acute infarction resulted in an 80% in-hospital mortality, whereas operation more than one month postinfarction showed a 20% mortality. Operative treatment that included myocardial resection had a significantly lower mortality (P less than 0.05) than that which did not. With an average of 36.5 months of follow-up, 13 of the 21 patients were long-term survivors, despite the persistence of ventricular arrhythmias. Surgical treatment which includes myocardial resection and occurs more than one month after infarction should be considered in patients with symptomatic ventricular arrhythmias and severe, well-localized left ventricular wall motion abnormalities.


Congenital heart block in newborns of mothers with connective tissue disease. Of 22 children with congenital complete heart block (CCHB) available for study, 14 (63.6%) were born to 11 mothers with clinical or laboratory evidence of connective tissue disease, primarily lupus erythematosus (LE). Seven mothers had both clinical and laboratory evidence of disease while four had only positive laboratory studies including fluorescent antinuclear antibody, rheumatoid factor, and depressed complement levels. In adults with systemic LE, pathologic changes in the collagen surrounding the conduction system have led to the fibrosis and death from heart block. Antinuclear antibodies of the IgG class cross the placental barrier and newborn infants have been reported with transient skin lesions of lupus. Placental transmission of such antibodies may affect the fetal cardiac conduction system, surrounding collagen, and myocardium, leading in some cases to CCHB. This is probably one important etiologic factor in CCHB even though the mother is asymptomatic during her pregnancy.


Characterization of human adenoid cells using surface and functional markers for lymphocyte subpopulations. Adenoid lymphocytes from children undergoing adenoidectomy were compared with blood cells from the same children using techniques for identifying T cells and B cells. A high proportion of adenoid lymphocytes were immunoglobulin positive cells. Of these only a minor fraction carried receptors for the Fc part of IgG. Adenoid B lymphocytes respond poorly if at all to polyclonal B-cell activators, such as LPS or PPD, which show a different reactivity compared to human splenic cells. The response to anti B2-microglobulin was also different; blood cells responded better than adenoid cells. Thus distinct subpopulations of B lymphocytes reside in different lymphoid organs. The adenoid lymphocyte reactivity might reflect their function in the defence mechanism against infections.


Antisera against leukaemia-associated antigens on human lymphocytes. Antisera were raised in rabbits against leukaemic lymphosarcoma (LSL) cells which carried surface markers of both thymus-derived T lymphocytes (T cells) and bone marrow-derived B lymphocytes (B cells). After absorption with leucocytes, erythrocytes and serum proteins from normal individuals, the antisera demonstrated significant complement-dependent cytotoxicity against leukaemic cells from patients with acute lymphoblastic leukaemia (ALL) (9/11), LSL (7/9) and chronic lymphocytic leukaemia (CLL) (9/12), with an antibody titre of 1:64 or greater. The antisera did not react with: (a) blood lymphocytes from clinically healthy individuals (0/23), patients with ono-lymphoproliferative disorders (0/8) and normal umbilical cords (0/3), (b) normal lymphocytes stimulated by pokeweed mitogen (0/7), allogeneic lymphocytes (0/3), fetuin (0/1), purified protein derivative (PPD) (0/2), and candida antigen (0/1); (C) normal marrow cells (0/3), (D) normal thymocytes (0/2) and (E) leukaemic cells from patients with acute myeloblastic (AML) (0/10) and chronic granulocytic leukaemia (CGL) (0/3). However, the antisera did react with lymphoblastoid cells from continuous B-cell lines derived from an AML patient and from a non-leukaemic individual and, to a lesser extent, with lymphocytes from patients with infectious mononucleosis. The antisera also reacted with lymphocytes from chronically infected tonsils. Cytotoxicity of the antisera against lymphoblastoid and tonsillar cells was inhibited by ALL and CLL cell-lysates; and, conversely, cytotoxicity against ALL cells was inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal lymphocytes did not inhibit cytotoxicity toward lymphoblastoid, tonsillar or ALL cells. Cytotoxicity of the antisera was neutralized by a goat anti-rabbit IgG (GAR IgG). These results suggest that the antisera contained antibodies reactive with antigens possibly common to neoplastic lymphocytes, tonsillar cells, lymphoblastoid cells and some lymphocytes from patients with infectious mononucleosis.


Immunological findings in immunoblastic lymphadenopathy. A detailed case study. Several immunological parameters were investigated in a patient with immunoblastic lymphadenopathy (IBL). An increased concentration of polyclonal immunoglobulins, the presence of autoantibodies in the serum and an increased level of B lymphocytes with an abnormal DNA synthesis response to LPS in peripheral blood were the most salient features. The findings suggest that in IBL there is a numerical as well as a functional alteration of peripheral blood lymphocytes. We propose that the alteration was due to either an escape of lymphocytes from central lymphatic organs or a defect in maturation of peripheral blood lymphocytes.


T lymphocytes and the transfer of immunity to Trypanosoma musculi in mice. Trypanosoma musculi produces a resolving infection in mice and the immune response is thymus dependent. Spleen cells from immune and from uninfected mice were transferred to T cell-deprived mice and restored their ability to control the infection, the immune cells being effective most rapidly. Treatment of the cells in vitro with anti-theta serum did not impair their ability to restore immunocompetence and it is proposed that, though T-cell dependent, the immune response is effected by theta- cells.


Extracellular release of peroxidase from eosinophils by interaction with immune complexes. Much peroxidase is released from eosinophils that ingest complexes formed of human immunoglobulins with specific rabbit antibody. The complex formed of IgE with rabbit antibody, was particularly effective. The amount and rate of release of peroxidase was closely related to the amounts of complex ingested by the eosinophils, and degree of lysis of the cell granules. It is proposed that eosinophils attracted to an allergic lesion ingest complexes of IgE, show lysis of granules with release of peroxidase, and that the peroxidase reduces the allergic reaction.


Catabolic rate of alpha1-antitrypsin of Pi type M and Z in man. 1. Human alpha1-antitrypsin was isolated from three Pi M and two Pi Z subjects without alteration of its microheterogeneity. The purified proteins were labelled with either 125I or 131I by a lactoperoxidase method. 2. The disappearance rate of two types of alpha1-antitrypsin were studied after simultaneous injection of labelled M-protein and Z-protein into Pi M subjects. 3. The ratio of extravascular to plasma pools of alpha1-antitrypsin ranged between 1-2 and 1-6 with no difference between M- and Z-protein. The mean fractional catabolic rates of M-protein and Z-protein were respectively 0-26 and 0-40 per day. 4. The difference in catabolic rate of Z- and of M-protein is too small to explain why the alpha1-antitrypsin content of the blood in Pi ZZ subjects is only 15% of that normally found in Pi MM subjects. The low alpha1-antitrypsin in Pi ZZ subjects appears mainly to be due to a low rate of biosynthesis.


[Diverticular disease of the colon (author's transl)]. Admission diagnosis of 100 patients with diverticular disease of the colon indicated that the clinical features of the disease is still relatively unknown. The most important cardinal symptoms are abdominal complaints, irregular stools and/or bleeding from the large intestine. These symptoms occur with about equql frequency in patients with diverticular disease, whether or not there was evidence of inflammatory complications. If there is clinically manifest diverticulum formation of the colon, the term "diverticular disease" seems appropriate, since transition between diverticulosis and diverticulitis is fluid. In addition to bleeding and attacks of diverticulitis, fistulae and gut narrowing with or without ileus are other complications. Mechanical small-intestinal ileus with involvement of the small intestine in the inflammatory diverticulitis mass was a feature of several of the authors' cases. Low-residue diet is contra-indicated because such food probably plays an important part in the aetiology and pathogenesis of diverticular disease.


Elevation of plasma corticosterone by swim stress and insulin-induced hypoglycemia in control and fluoxetine-pretreated rats. Fluoxetine, a drug that inhibits serotonin inactivation by reuptake from the synaptic cleft and thereby enhances serotonin nerve function, was used to study the possible role of serotonin neurons in the activation of the pituitary-adrenal system of rats by swim stress or insulin-induced hypoglycemia. Fluoxetine pretreatment enhanced the elevation of plasma corticosterone produced by injection of L-5-hydroxytryptophan but did not significantly alter the elevation of plasma corticosterone by swim stress or by insulin-induced hypoglycemia, even when the stimulus was shown to be submaximal. The results suggest that serotonin neural pathways postulated to stimulate ACTH secretion are not involved in the activation of adrenocortical function by these stimuli.


Massive gastrointestinal hemorrhage into the pancreatic duct - diagnosed by duodenoscopy and ERCP. Case report on two patients with massive hemorrhage from the pancreatic duct as proven by duodenoscopy and retrograde pancreatography. In patients with blood pouring from the orifice of the papilla of Vater retrograde ductography should be performed to prove hemobilia or hemosuccus pancreaticus.


Arteriovenous malformation of the cecum: report of six cases. Patients who have chronic lower gastrointestinal bleeding with negative conventional work-ups should undergo superior mesenteric arteriography to look for arteriovenous malformations. Once the diagnosis is made, treatment is immediate conventional right hemicolectomy. Six patients with arteriovenous malformations described in this report have had no recurrence of rectal bleeding in one to five years.


Endoscopy in bleeding duodenal varices: a rare cause of massive upper G-I-hemorrhage. Endoscopic evidence of bleeding duodenal varices in a patient with portal hypertension and severe upper G-I-hemorrhage is given. Review of our own endoscopic experience and literature suggests that these varices occur more frequently than generally realized. Their diagnosis tends to be overlooked. Possible therapy is discussed.


A new diagnostic aid in traumatic hemobilia. A case report of traumatic hemobilia following suture of superficial laceration of the liver is presented. The diagnosis was confirmed by emergency endoscopy preoperatively. Segmental hepatic resection was successful. Endoscopy is the most convenient as well as harmless procedure in establishing the diagnosis preoperatively. The importance of careful observation of the papilla of Vater in endoscopy to determine the site of upper gastrointestinal hemorrhage is emphasized. In addition, the introduction of serial endoscopy to follow the course of mild hemobilia is suggested.


Surface immunoglobulins of lipopolysaccharide-stimulated spleen cells. The behavior of IgM, IgD and IgG. The nature of Ig receptors carried by lipopolysaccharide (LPS)-stimulated mouse spleen B cells was analyzed by surface iodination, direct antiserum precipitation and polyacrylamide gel electrophoresis. LPS activation led to a rapid decrease of surface IgD to 20 % and 80 % of the original level on days three and five of culture, respectively. Efficiency of iodination of cells doubled after culture but the proportional radioactivity in IgM reace of cells, but only in small amounts (1 % of total surface Ig) and this expression of IgG remained constant during 5 days of culture. We could definitively identify gamma-chains on the surface of cells, but only in small amounts (1% of total surface Ig) and this expression of IgG remained constant during 5 days of culture.


Loss of surface IgD by human B lymphocytes during polyclonal activation. Surface and cytoplasmic immunoglobulins were studied by direct immunofluorescence in pokeweed mitogen-stimulated cultures of human blood lymphocytes. The results compared to those of studies of unstimulated cultures and of fresh normal lymphocytes showed a striking decrease in surface IgD during terminal maturation of B lymphocytes into plasma cells. The number of cells which expressed IgG Fe receptor also decreased, although to a lesser extent.


Down regulation in B lymphocytes: low dose signals. Picogram quantities of dinitrophenylated (DNP) dextran, a thymus-independent antigen or lipopolysaccharide, a B cell mitogen, signal down B lymphocytes to unresponsiveness. Down signals were detected by a decision test in which signaled lymphocytes were allowed one hour to react to an immunogenic pulse of DNP-dextran. Depletion of T cells or macrophages did not interfere with the generation of down signals. The signaling can proceed entirely at 4 degrees C and it its negative effect is transitory. Down signals which could be detected after 15 min at 37 degrees C were reversed by 60 min. It is suggested that down regulation by low dose antigenic signals provides a means of distinguishing background noise from true antigenic stimuli.


Spontaneous release of Fc receptor-like material from human lymphoblastoid cell lines. In the culture medium of some human lymphoblastoid cell lines material is released with the following properties: (a) hemagglutination reaction of IgG-sensitized erythrocytes; (b) enhancement of precipitation of DNA-anti-DNA complexes; (c) inhibition of binding of C1q to immune complexes; (d) inhibition of immune complex binding to lymphocytes; (e) inhibition of antibody-dependent lymphocytotoxicity. The material is not identical with C1q or rheumatoid factor, it is heat resistant (30 min at 56 degrees C); the molecular weight is about 100 000 daltons and it is capable of inhibiting antibody production in vitro. It is suggested that this material consists of Fc receptors spontaneously shed from lymphocyte membranes.


Evaluation of the possible role of B cell receptors in the tendency of B cells to migrate into follicles in mice and chickens. Chicken spleen and bursa cells were examined for the percentage of Fc receptor-bearing cells. Rosette formation was done with chicken 7S antibody-sensitized sheep erythrocytes and was inhibited by heat-aggregated chicken Ig. In the spleen, the percentage was found to increase with age to approximately 26% at 7 to 12 weeks. In contrast, only 3 to 5% of bursa cellss at this age demonstrated Fc receptors. Sleens from bursectomized chickens had 7--10% Fc receptor-bearing cells. In an attempt to determine a possible role of the C3 receptor on migration patterns, the effect of cobra venom factor (CVF) on the localization of transferred lymphoid cells was examined. Pretreatment of recipients with enough CVF to lower mean C3 levels to 11% of controls failed to affect follicular B cell localization in mice at either 24 or 48 h after transfer. Localization of thymus or bursa cells in chickens was similarly unaffected by CVF pretreatment. The possible roles of Fc and C3 receptors on migration of B lymphocytes into follicles and germinal centers were discussed.


Selective antagonism by Mg2+ of amino acid-induced depolarization of spinal neurones. In the isolated frog or rat spinal cord, low concentrations of Mg2+ (0.5-1.00 mM) markedly depress, in a substantially Ca2+-independent manner, ventral root depolarizations produced by dorsal root stimulation and by certain amino acids (e.g. N-methyl-D-aspartate and L-homocysteate) but do not depress depolarizations produced by other excitatory amino acids (e.g. kainate and quisqualate). L-Aspartate-induced depolarizations are more sensitive to Mg2+ then are L-glutamate-induced depolarizations.


[Specificity of the effect of thrombin on the chemoreceptors of the frog carotid labyrinth]. Perfusion of thrombin and trypsin solutions through the frog carotid labyrinth acts on the carotid chemoreceptors and evokes reflex response of the anticoagulating system. The similarity of effects of both these agents seems to be due to similarity of their structures. Other agents acting on the frog vascular chemoreceptors: sodium chloride hypoxia, lobeline,--cause no activation of the reflex anticoagulating system. Thrombin is concluded to be the adequate and specific irritant of the vascular chemoreceptors of the frog anticoagulating system.


Clomipramine (Anafranil) and musculo-skeletal pain in general practice: a pilot, open, non-comparative study of long-standing rheumatic pain. Forty-six patients were admitted to an open general practice study of clomipramine (Anafranil) in the treatment of long-standing rheumatic pain; forty-one patients completed the trial. The duration of the trial was 56 days during which patients received daily doses of either 10 mg or 25 mg of clomipramine. Assessments were made at fortnightly intervals. Patients were assessed for pain using a visual analogue scale, analgesic requirement, joint pain, other pain and morning stiffness. At the completion of the study patients were asked whether the addition of clomipramine to their treatment was better, the same or worse than no additional treatment. Twenty-one patients (57%) felt that it was better, four felt that it was the same and twelve said that it was worse. The doctor also similarly recorded his preference at the end of the trial. In twenty-two cases (60%) the doctor felt it was better, in eight that there was no difference and in seven that it was worse. There was no difference between the 10 mg and the 25 mg regime. It is suggested that better control of rheumatic symptoms can be achieved in some patients by the addition of small daily doses of clomipramine to their standard anti-rheumatic therapy. The author expresses the view that further research in this field is merited.


Pancreatic pseudocyst in a patient with variant von Willebrand's disease. We report a case of pancreatic pseudocyst which occurred in a 32-year-old woman with variant von Willebrand's disease. A curvilinearly calcified shadow incidentally seen in the upper abdomen on radiographic examination was the first sign of the cyst. The abnormality of hemostatic mechanism found in this patient is speculated to be related to the cyst formation.


A bleeding Meckel's diverticulum diagnosed by arteriography. A case of Meckel's bleeding diverticulum diagnosed by emergent arteriography is presented. Arteriography revealed an extravasation of contrast medium into the distal ileum and an abnormal ileal artery which passed to the antimesenteric border of the ileum. The diverticulum was demonstrated by double contrast study of the small intestine. The merits of emergent arteriography and other examinations for diagnosing Meckel's diverticulum are discussed.


[Radioimmunoassay of fibrinopeptide A: double antibody method]. A radioimmunoassay kit was used for measurement of human fibrinopeptide A in plasma. The "charcoal technique" was replaced by the more precise double-antibody method. The possibility of automation allows a shortening of the time for performing the assay and a more general clinical use. Normal values and preliminary results of patients with septic disorders and of a hemophilic patient with antibodies to factor VIII which is substituted by pro-coagulation factors (FEIBA) are reported.


Chronic lung disease in children.

Chronic lung disease in children. Since tuberculosis is still a significant threat, the family physician needs to be familiar with methods of its diagnosis and treatment. Among other entities discussed are atypical mycobacteriosis sarcoidosis, and cystic fibrosis.


Studies on lymph humoral factor. Biological characteristics of a lymphocytopoietic factor in rat thoracic duct lymph. The biological characteristics of a lymphocytopoietic factor obtained from rat thoracic duct lymph (Yamashita, Fukumoto & Miyamoto, 1976) were further investigated. The lymph extract from normal rats failed to stimulate both large pyroninophilic cell-proliferation and mitotic response in the spleen and lymph node of the thymectomized, irradiated and marrow reconstituted rat (B rat). This suggests that target or responsive cells for the factor are not marrow-derived (B) cells, but thymus-derived (T) cells. On the other hand, the lymph extract from the lymphopenic lymph-drained B rats showed similar high lymphopoietic activity to those of normal rats, indicating that the existence of a thymus is not essential for the production or secretion of the factor. The fact that lymphocytotic rats produced by syngeneic lymphocyte transfusion are most sensitive to the lymph extract suggests that liver endogenous level of this factor and the responsiveness of target cells are regulated by the number of circulating T lymphocytes.


Can B-cell tolerance be induced by oligovalent thymus dependent antigens? Spleen cells from adult mice were rendered "tolerant" to TNP by exposing cells in vitro to large concentrations of TNP10BSA. After such treatment the residual response to TNP was measured using TNP-LPS as antigen in vitro or in vivo. The "tolerance" observed in this system was not reversed by treating the cells with trypsin, nor by using non-specific polyclonal activators. Furthermore, responsiveness to TNP-LPS in vitro was not substantially restored when such "tolerant" cells were "parked" in vivo for 7 days. In contrast when TNP-KLH was the antigen used to challenge TNP-BSA treated cells, no unresponsiveness was observed. The results are discussed in terms of the degree of thymus dependence of the challenge antigens; subpopulations of B cells, and current hypotheses of B-cell activation;


Heteroantisera prepared against B lymphocytes at different stages of differentiation. I. Preparation of sera and cytotoxicity to lymphoid cells from different organs. A routine method is described whereby anti-mouse B-cell antisera can be raised in rabbits. As judged by trypan blue dye exclusion these sera have negligible cytotoxicity to murine T lymphocytes but seem to detect differences in non-T lymphocytes in different organs. By sedimentation analysis some of the sera may detect (in addition to mature B cells) earlier precursors of mature B lymphocytes in bone marrow and spleen.


Diminished T cell surveillance function in old mice infected with lymphocyte choriomeningitis virus. The cell-mediated immune response resulting from infection with lymphocytic choriomeningitis virus (LCMV) was compared in old (18--20 month) and young (4--6 month) random-bred ICR mice. Three separate assay systems were used: the level of virus-specific cytotoxic T-cell activity measured in vitro, time of onset of fatal cell-mediated immunopathology in vivo and adoptive transfer of inflammatory process to immunosuppressed, virus-infected recipients. The capacity of old mice to generate virus-immune effector T cells was, by all of these criteria, greatly diminished. It is suggested that the LCMV-specific T-cell response may prove a useful standard system for determining integrity of immunological surveillance function.


Susceptibility of human lymphocyte populations to infection by herpes simplex virus. The antibody response to diphtheria toxoid by cultured tonsil cells was suppressed by herpes simplex virus during its inductive stage. Since only T lymphocytes readily supported virus replication, this immunosuppression may be attributed to a selective effect of the virus on this population of cells.


The humoral immune response of mouse bone marrow lymphocytes in vitro. Mouse bone marrow (BM) small lymphocytes are shown to contain competent precursors for a primary haemolytic plaque forming cell (PFC) response to heterologous red blood cells and TNP in an in vitro culture system. Their response is dependent on T co-operative factors, which can be provided by irradiated spleen cells activated by concanavalin A or the supernatant of an allogeneic culture, added at the beginning or after 24 h of culture. The frequency of PFC precursors for the response to SRBC is found to be equal or higher in BM than spleen cultures. However, BM lymphocyte cultures stimulated by E. coli lipopolysaccharide show an increase of DNA synthesis but contain only few polyclonal PFC, in contrast to spleen.


Enhanced reaginic antibody formation to ovalbumin in mice given repeated injections of concanavalin A. Mice injected with 4 weekly doses of concanavalin A arabinogalactan complex (Con A-AG) give a secondary type of IgE response when they encounter ovalbumin (Ov) for the first time. The IgE-enhancing effect of Con A-AG immunization applies to Ov but not to various other antigens. However, no cross-reaction appears to exist at the humoral level between Con A and Ov. The apparent priming of mice to Ov by Con A can be adoptively transferred to syngeneic irradiated recipients by spleen cells.


Spontaneous 3H-thymidine incorporation by circulating lymphocytes of normal subjects: relative proportion of T and B cells. Peripheral lymphocytes of ten normal, healthy subjects were assayed simultaneously for spontaneous 3H-thymidine flash labelling and erythrocyte, active erythrocyte and erythrocyte antibody complement rosette formation. Spontaneous blastogenesis of T lymphocytes is significantly higher than that of B cells. The majority of T lymphocytes incorporating 3H-thymidine are active E rosette-forming cells.


Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells. The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.


Recovery of Pisum root meristems after mitotic-inhibitory treatments with 3H-thymidine. Inhibition of cell-cycle progression by unincorporated 3H-thymidine. Primary root meristems of Pisum sativum recover form a 3H-thymidine-induced reduction in mitotic activity once the roots are no longer exposed to exogenous 3H-thymidine. Cells arrested in G2 during 3H-thymidine treatment apparently do not divide for at least 16 hours after treatment, whereas cells remaining in G1 and S do divide and thereby account for recovery. Recovery occurs only when meristems are no longer exposed to exogenous (i.e. unincorporated) 3H-thymidine, suggesting that cytoplasmic irradiation from unincorporated 3H-thymidine prevents cellular recovery from 3H-thymidine-induced inhibition of cell progression through the mitotic cycle. Concentrations of 14C-thymidine which result in cytoplasmic irradiation nearly equivalent to that achieved with 3H-thymidine, but much lower levels of nuclear irradiation, also prevent recovery from 3H-thymidine-induced inhibition of mitotic activity, but do not alone produced such inhibition. These results support the contention that cytoplasmic irradiation prevents recovery from the effects of nuclear irradiation. Unincorporated 3H-thymidine also prevents recovery from sucrose deprivation in stationary phase G2 cells which have not incorporated 3H-thymidine into nuclear DNA.


Differences in survival of mouse colon crypts after whole- or partial-body irradiation. The survival of mouse colon crypts after X-irradiation has been studied by the microcolony technique. The Do for crypt survival was 266 rad after whole-body irradiation in air, but when the colon alone was irradiated, the Do was 340 rad. In mice which were breathing 95 per cent oxygen, the Do values were 238 rad for whole-body and 302 rad for colon irradiation. The survival curves were all extrapolated to the same number, and the DQ was also increased with colon irradiation. There was, therefore an enhancement of colon crypt survival of about 27 per cent by local as opposed to whole-body irradiation. These results might be explained by a circulating repair promoter or by the production of a toxin after whole-body irradiation.


The effect of ploidy on the modification of the shoulder region of hypoxic cell-survival curves by the biradical, Ro.03-6061. The biradical nitroxyl, Ro.03-6061, sensitizes two lines of mouse L cell to ionizing radiation when the cells are rendered hypoxic. Although the biradical reduces the Do value of the hypoxic cell-survival curve in each instance, it has no significant effect on the shoulder region. A hybrid line produced from these two strains is more radioresistant than either parent. In this instance, the biradical suppresses the shoulder region of the hypoxic cell-survival curve, but has no effect on the Do value. In a second system, the biradical selectivity sensitizes hypoxic cells of a diploid and a tetraploid clone of Syrian hamster cells (BHK21/C15). The survival-curve characteristics of both clones are similar. The biradical reduces the Do value but does not significantly change the shoulder region of the hypoxic cell-survival curve. An aneuploid line sub-cultured from the tetraploid clone is much more resistant to radiation. In this instance, there is a decrease in the Do value of hypoxic cells in the presence of the biradical, but the extrapolation number is increased to a value similar to that for cells irradiated in air.


Chloride compartments of the frog lens and chloride permeabilities of its isolated surfaces. Total Cl content and exchangeable Cl pools of isolated bull frog lens and Cl permeabilities of its isolated anterior and posterior surfaces were determined. Cl content was 2.81 microEq, corresponding to a cellular concentration of 13.3 mM. After 18 hr. incubation Cl content increased to 3.84 microEq. Three Cl compartments were found: a fast compartment (t1/2 = 130 min.), probably extracellular; a slow compartment (+ 1/2 = 160 min.), probably intracellular; and a bound fraction (24% of the total Cl). 36Cl efflux across anterior and posterior lens surfaces was similar. However, when a correction for the asymmetrical electrical potential difference was made, the permeability of the posterior side, 46.9 x 10(-7) cm./sec., was nearly twice the permeability of the anterior side, 27.6 x 10(-7) cm./sec. The Cl movement and distribution seem to obey passive forces. Iodoaceta increased both total Cl and exhangeable Cl but had little effect on the rate of Cl exchange. Total Cl gain by lenses incubated at 2 degrees C was similar to the control. However, the exchangeable Cl pools and the rate of exchange were significantly diminished.


Cell surface labelling of mononuclear cells with antisera associated to turnip yellow mosaic virus of alphalpha mosaic virus particles. A freeze-etch study. Turnip yellow mosaic virus (TYMV) and alphalpha mosaic virus (AMV) were used as immuno-electron microscopical markers to detect cell surface receptors on mononuclear cells in freeze-etch replicas. TYMV particles were conjugated with vacuum-distilled glutaraldehyde to rabbit IgG anti-mouse immunoglobulins (TYMV-RAMIg conjugate) or to rabbit IgG anti-mouse theta antigen (TYMV-RAMTh conjugate). B-lymphocytes incubated with TYMV-RAMIg conjugate showed either randomly distributed particles or patches of virus particles on the etched surface of the cell membrane. Mouse thymocytes incubated with TYMV-RAMTh conjugate, however, showed only a random distribution of the virus particles. Human mononuclear cells incubated with rabbit IgG anti-AMV and AMV for the demonstration of the receptors for the Fc fragment of IgG showed the oblong shape of the AMV particles on the etched cell membrane, Fc receptors were either randomly distributed or aggregrated into patches. It is concluded that both types of virus particles are useful markers for the demonstration of membrane receptors in freeze-etch replicas of labelled cells.


[Acute isolated vestibular paralysis. A clinical and electronystagmographic follow-up study in 28 patients]. Twenty-eight patients with unilateral acute vestibular paralysis (vestibular neuronitis) were examined after a period of 4-140 months. Seventeen of these patients were examined by electronystagmography with caloric stimuli at 44 degrees, 30 degrees, 17 degrees and 0 degrees C. Most were free of subjective symptoms only one-third had slight unsteadiness after sudden head movement. Subjective symptoms were independent of the presence of permanent canal paralysis or partial recovery of caloric excitability. Spontaneous nystagmus of 3-6,6% intensities was found in 11 of 17 patients. The normal limit for physiological spontaneous nystagmus should therefore be below 3 degrees/s. The most reliable parameter was the maximum velocity of the slow phase, as a mean value of the 4 caloric responses (values corrected for spontaneous nystagmus). The results were: 6 patients with persistent canal paralysis; 4 patients with considerable hypoexcitability; and 7 patients with moderate hypoexcitability. In no patient complete restoration of normal caloric response was found. This is attributed to the described method of caloric testing, which permits exact measurement of small side differences in excitability.


Mucus clearance: in vivo canine tracheal vs. in vitro bullfrog palate studies. Tracheal mucociliary clearance was studied by a radioisotope technique in pentothal-anesthetized beagles in the control, atropinized, or dehydrated state. Mucus collected from a tracheal pouch in each dog was used for in vitro bullfrog (Rana cantesbiana) palate clearance studies and compared to the in vivo clearance rates. In all three experimental states, there was a significant correlation between in vivo and in vitro rates, suggesting that tracheal pouch mucus is a good model for investigating the mucociliary flow properties of intact airway mucus. When compared to matched controls, atropine appeared to cause a slowing of the in vivo clearance rate but not of the in vitro rate. Dehydration had no effect on either. The appropriateness of the frog palate method in the study of human respiratory disease (e.g., chronic bronchitis, cystic fibrosis) as well as its potential as an objective method of assessing the effects of various therapeutic modalities in these diseases is discussed.


Regional ejection fractions in patients with patent and thrombosed grafts after coronary artery vein bypass surgery. Twenty-six patients who had received 43 grafts were studied before and after coronary artery vein bypass surgery. Cine ventriculograms taken in the right anterior oblique projection were analyzed and regional ejection fractions calculated. Single and multiple grafts were considered separately as were thrombosed and patent grafts. Patients were also divided into those with regional ejection fractions below 50% and those with regional ejection fractions above 50%. No statistically significant improvement of the relevant segments was demonstrated in any group. However, those with a regional ejection fraction above 50%, whose grafts had thrombosed, deteriorated from a mean of .66 to .39. There is a significant trend here (p less than .05) and a t test significance at the 7% level.


A study of T and B lymphocytes and chromosomes in breast irradiated mastitis patients. Proportions and absolute numbers of T, B and "Null" lymphocytes, percent of abnormal cells and chromosomal breaks were determined in breast irradiated mastitis patients and control subjects. No significant difference was observed at these values between controls and irradiated patients.


Transport enhancement and reversal: glucose and 3-O-methyl glucose. In chick embryo fibroblast cultures the 15- to 30-fold enhancement of D-glucose uptake observed when cells are starved of glucose for 24 hours is not duplicated for derivatives of glucose that compete effectively for uptake and have generally been considered to use the same carrier. 2-deoxy-D-glucose, D-mannose, D-galactose and D-glucosamine are derepressed progressively less sharply in that order with glucosamine uptake never more than doubled by starvation. D-glucose at a concentration of 5.5 mM in the 24-hour conditioning medium is a strong "repressor" resulting in low "transport" behavior for each of the five sugars cited. D-glucosamine is equally effective at the same concentration. A 10-fold reduction in the concentration of glucosamine (0.55 mM) allows for the escape from repression of mannose, glucose, and deoxyglucose uptake while the others remain repressed. Mannose uptake escapes as well when the glucose concentration in the "conditioning" medium is similarly reduced. Under certain conditions of starvation and cell density dramatic effects of supplemental stimulation by insulin can be achieved. Insulin withdrawal interrupts the supplemental stimulation process. Cycloheximide, actinomycin D and cordycepin block both non-insulin and insulin-induced derepression. Short exposure (15-30 minutes) of 24-hour starved cells to glucose (5.5 mM) reduces glucose sharply but does not affect 3-O-methyl glucose uptake. If the exposure is to 2-deoxyglucose (5.5 mM) further derepression of glucose uptake results.


Conditions controlling the proliferation of haemopoietic stem cells in vitro. A liquid culture system is described whereby proliferation of haemopoietic stem cells (CFU-S), production of granulocyte precursor cells (CFU-C), and extensive granulopoiesis can be maintained in vetro for several months. Such cultures consist of adherent and non-adherent populations of cells. The adherent population contains phagocytic mononuclear cells, "epithelial" cells, and "giant fat" cells. The latter appear to be particularly important for stem cell maintenance and furthermore there is a strong tendency for maturing granulocytes to selectively cluster in and around areas of "giant fat" cell aggregations. By "feeding" the cultures at weekly intervals, between 10 to 15 "population doublings" of functionally normal CFU-S regularly occurs. Increased "population doublings" may be obtained by feeding twice weekly. The cultures show initially extensive granulopoiesis followed, in a majority of cases, by an accumulation of blast cells. Eventually both blast cells and granulocytes decline and the cultures contain predominantly phagocytic mononuclear cells. Culturing at 33 degrees C leads to the development of a more profuse growth of adherent cells and these cultures show better maintenance of stem cells and increased cell density. When tested for colony stimulating activity (CSA) the cultures were uniformly negative. Addition of exogenous CSA caused a rapid decline in stem cells, reduced granulopoiesis and an accumulation of phagocytic mononuclear cells.


Control of proliferation of bovine vascular endothelial cells. The effects of Fibroblast Growth Factor (FGF) and Epidermal Growth Factor (EGF) on the proliferation of bovine vascular endothelial cells has been examined. FGF induces the initiation of DNA synthesis and cell proliferation in cloned endothelial cells of fetal and adult origin at concentrations as low as 1 ng/ml and is saturating at 50 ng/ml. EGF had no effect over the same range of concentrations. The mitogenic effect of FGF is blocked by a crude extract of cartilage. Platelet extract is also mitogenic for vascular endothelial cells although to a lesser extent than the purified FGF. In contrast to vascular endothelial cells, both EGF and FGF are mitogenic for vascular smooth muscle cells although EGF is less mitogenic than FGF at 100 ng/ml. The mitogenic effect of EGF and FGF on vascular smooth muscle is not blocked by the addition of a crude extract of cartilage, thus demonstrating the specificity of the chalone like effect of cartilage crude extract for endothelial cells.


Modulatory effects on immunoglobulin synthesis and secretion by lymphocytes from immunodeficient patients. Incubation of peripheral lymphocytes (PBL) from normal donors with pokeweek mitogen (PWM) induced terminal differentiation by B lymphocytes to immunoglobulin (Ig) synthesizing and secreting plasma cells. B cells from hypogammaglobulinemic patients with different primary immunodeficiencies failed to undergo functional differentiation after similar treatment with PWM. Co-cultures of BL from normal donors and hypogammaglobulinemic patients often resulted in deviations, both positive and negative, from expected levels of PWM-stimulated intracellular Ig biosynthesis. Suppression of B-cell differentiation was manifested by PBL from patients with several different primary immunodeficiencies, including infantile sex-linked agammaglobulinemia. Immunoregulatory activities were noted to vary with the normal donor used in co-culture experiments and with time. Cell populations that were active in influencing B-cell differentiation to functional plasma cells did not have an appreciable modulatory effect on T-lymphocyte responses to mitogens. These observations may provide a functional subclassifications for immunoregulatory cells in man.


Alpha-1-antitrypsin globules in the liver and PiM phenotype. The finding is recorded of typical a1-antitrypsin globules, confirmed by immunofluorescence and immunoperoxidase methods, in the hepatocytes of a patient shown to have a normal serum antitrypsin level and normal phenotype (TiM) for a1-antitrypsin. The identification of such globules can no longer be regarded as conclusive evidence of an abnormal a1-antitrypsin phenotype.


Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.


Cytochemical demonstration of 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase activity. The enzyme 5-formyl tetrahydrofolate cyclodehydrase plays an important role in the conversion of 5-formyl tetrahydrofolate to 5,10-methenyl tetrahydrofolate. A second enzyme, cyclohydrolase, converts 5,10-methenyl tetrahydrofolate to 10-formyl tetrahydrofolate. These folate derivatives play a significant part in the biosynthesis of purines. A method has been devised for the cytochemical demonstration of 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase activity which uses 5-formyl tetrahydrofolate or 5,10-methenyl tetrahydrofolate as substrate respectively, blocking possible interferences by other enzymes, and allows the nonenzymatic reduction of nitro-blue tetrazolium by 5,10-methenyl tetrahydrofolate formed by the action of the cyclodehydrase on the substrate 5-formyl tetrahydrofolate, and by 10-formyl tetrahydrofolate formed by the action of cyclohydrolase on the substrate 5,10-methenyl tetrahydrofolate, thus revealing intracellular sites of enzyme activity. The methods appear to show only intracellular localization of the blue formazan deposits of reduced tetrazolium. The distribution of positivity in cells of human blood and bone marrow is described.


Glucocorticoid receptors in purified subpopulations of human peripheral blood lymphocytes. On the premise that the differential effects of glucocorticoids on various aspects of the immune response may be mediated by differences in the glucocorticoid receptors in the effector cells, subpopulations of human peripheral blood lymphocytes were examined for these receptors as well as for glucocorticoid responsiveness. Purified T and non-T lymphocytes, when studied by a sensitive whole cell assay technique, contained equivalent amounts of specific glucocorticoid receptor, which, by binding affinity and specificity measurements, were indistinguishable from each other. Furthermore, under in vitro incubation conditions, macromolecular synthesis in both of these cell populations was inhibited by glucocorticoid at concentrations which saturated the receptor sites. It is concluded that the putative differential effects of glucocorticoids on T and non-T lymphocyte-associated functions are probably not mediated by differences in the glucocorticoid receptors in these cell populations.


The necessity for T cell help for human tonsil B cell responses to pokeweed mitogens: induction of DNA synthesis, immunoglobulin, and specific antibody production with a T cell helper factor produced with pokeweed mitogen. Human B lymphocytes obtained from tonsils do not proliferate when stimulated with pokeweed mitogen. A soluble factor produced from T cells cultured with pokeweed mitogen stimulates B cells to synthesize DNA and differentiate into immunoglobulin producing cells. This PWM produced supernatant induced a PFC response to SRBC. The T cell supernatant activity is produced within 12 hr of stimulation in the presence of serum and without a requirement for T cell division. Optimal stimulation of B cells occurred at 7 to 9 days of culture. This helper factor activity eluted postalbumin from a column of Sephadex G-200. Insolubilized pokeweed mitogen was not mitogenic for B cells. The continuous presence of the lectin in culture was not required for B cell proliferation or for immunoglobulin synthesis.


Heterologous antiserum to rat lymphohemopoietic precursor cells. Lymphohemopoietic precursor cells in rat bone marrow are members of a subset of lymphocyte-like cells that bears the bone marrow lymphocyte antigen (BMLA) and that lacks antigens present on peripheral B and T cells. This was demonstrated by two experimental approaches. In the first, bone marrow cells with the potential to form hemopoietic colonies in spleen (CFU-S), to repopulate lumphoid tissues and blood, and to rescue lethally irradiated recipients were enriched approximately 10-fold by a fractionation procedure designed to isolate a "null" population of bone marro lymphocytes. In the second approach, the lymphohemopoietic precursor cell activity in bone marrow was completely abrogated by opsonization with rabbit antiserum (ALSBM) raised against this "null" population of bone marrow cells. Precursor cell activity was not affected by treatment with antiserum to T and B cells. Quantitative cross-absorption studies showed that the antigen detected by ALSBM on lymphohemopoietic precursor cells had the same cellular distribution as did the previously described bone marrow lymphocyte antigen. It is likely that this antigen is present both on pluripotent stem cells and on committed progenitors of the myelocytic, erythrocytic and lymphocytic series.


Ag-B-linked analogue of Ia antigens in the rat. The reactions of Lewis rat lymphocyte membrane antigens with two alloantisera, BN anti-Lewis and BN anti-Fischer have been studied. Three lines of evidence indicated that these antisera reacted with cell surface antigens homologous to Ia antigens of the mouse. 1) After absorption with Lewis platelets, the antisera killed only 40 to 50% of Lewis spleen cells. The majority of such cells were shown to be Ig-positive B cells by the examination of reaction patterns on lymphocytes after separation on nylon wool into T cell- and B cell-enriched subpopulations. 2) SDS-PAGE analysis of solubilized Lewis spleen cell antigens precipitated with these antisera revealed that the platelet-absorbed antisera reacted with molecules comparable in size to mouse Ia antigens (mw approximately equals 35,000 and 28,000). The unabsorbed sera reacted with these molecules and with additional molecules corresponding in size to mouse K and D antigens (m.w. = 45,000). 3) Neither of these antisera killed significant numbers of spleen cells from the partially congenic strain F.BN (seventh backcross homozygotes), a Fischer rat to which the Ag-B.3 allele is being transferred by repetitive backcrossing, indicating that the genes coding for these Ia-like antigens in the rat are linked to the Ag-B locus.


Studies on the generation of B lymphocytes in fetal liver and bone marrow. With the use of immunofluorescence techniques, cells containing cytoplasmic IgM (cIgM+), but lacking detectable surface IgM (sIgM+), have been identified in mouse fetal liver and adult bone marrow as a distinct cell population to sIgM+ B lymphocytes. We have shown that there is a considerable difference in the rate of entry of cIgM+ and sIgM+ cells into DNA synthesis in these locations. Moreover, within the cIgM+ population, the largest cells are the main group entering DNA synthesis. Our results are compatible with the notion that a pool of rapidly proliferating, large cIgM+ cells is present in fetal liver and adult bone marrow and that these cells give rise to populations of smaller cIgM+ cells, which move out of cell cycle, and convert to sIgM+ B lymphocytes. However, we recognize that this interpretation is speculative. Finally, we have shown that fetal bone marrow is a site of generation of sIgM+ B lymphocytes, but the question as to whether these cells are derived from Ig- precursors within marrow itself remains open.


Niridazole suppression of experimental allergic encephalomyelitis in Lewis rats. Administration of niridazole to Lewis rats beginning 2 days before sensitization with guinea pig spinal cord in combination with immunologic adjuvants exerted a dose related suppressive influence on development of experimental allergic encephalomyelitis (EAE). A daily dose of 75 mg/kg completely prevented clinical neurologic signs as well as markedly suppressed occurrence of immunohistopathologic manifestations of this autoimmune disease. A higher daily dose level of niridazole, i.e., 100 mg/k, also inhibited EAE but was associated with neurotoxic manifestations.


Sequential quantitation of circulating immune complexes in syngeneic and allogeneic rats bearing Moloney sarcomas. A Raji cell radioimmunoassay was employed to quantitate serially circulating immune complexes (CIC) in the sera of syngeneic BN rats and allogeneic Lewis rats bearing BN Moloney sarcomas. In syngeneic BN hosts the levels of CIC attained and the time-course of detection were related to the tumor dose, tumor mass, and regressive or progressive course of the tumor. In general, syngeneic rats that received larger tumor doses developed larger tumors and greater maximum levels of CIC. However, the amount of CIC was not always directly proportional to the tumor size, although this was nearly the case with regressor BN and Lewis rats. In rats with regressing tumors, CIC decreased to insignificant levels as the tumors disappeared. Progressor BN rats that received 20 and 10 X 10(6) tumor cells had higher and more sustained levels of CIC, but, shortly before the hosts died, despite an increase of tumor size, there was a decline of CIC. Progressor BN rats that received an initial inoculum of 0.5 X 10(6) tumor cells that grew to 44 mm maximum mean diameter had levels of CIC which were only slightly above levels of control rats. All allogeneic Lewis hosts rejected BN Moloney sarcomas, but had transient low levels of CIC coincident with tumor growth. Lewis rats had lower levels of CIC than BN rats bearing comparable masses of sarcoma.


Optimal conditions for the separation of rat T lymphocytes on anti-immunoglobulin--immunoglobulin affinity columns. The separation of rat T lymphocytes was investigated on anti-Ig--Ig columns. A simple and efficient method for the purification of rat Ig by precipitation of rat serum with sodium sulfate is presented. Protein binding characteristics of glass and plastic beads, as solid support of affinity columns, are described, as well as optimal parameters for coating beads with rat Ig (with  BSA, ribonuclease and lysozyme, as comparison). Binding of Ig was primarily dependent on the concentration of the Ig solution. Maximal strong binding of Ig (6.2 X 10(3) molecules per micron2 of bead surface) was reached a 400 microng per ml concentration of purified Ig solution during 20 min of incubation. Higher concentrations increased only the amount of loosely bound Ig on the surface of beads whereas the amount of firmly bound Ig remained unchanged. Fractionation of lymphoid cell suspensions on anti-Ig--Ig affinity columns prepared at optimal conditions resulted in highly purified T-cell suspensions containing less than 1% of lymphocytes bearing surface Ig receptors.


Cell surface immunoglobulin. XX. Antibody responsiveness of subpopulations of B lymphocytes bearing different isotypes. Murine spleen  cells were depleted of specific B-cell subpopulations bearing different immunoglobulin isotypes by means of complement-mediated cytolysis after treatment with antisera specific for micron- and gamma-chains. The functional effect of this depletion was measured by assaying both the primary and secondary plaque-forming cell responses of the residual cells after transfer to carrier-primed lethally irradiated hosts. The results suggest that cells bearing IgM are the progenitors of plaque-forming cells in the primary response and cells bearing IgG are the major progenitors of IgG plaque-forming cells in the secondary response. The quantity of IgM on progenitors of secondary IgM plaque-forming cells decreases markedly as the interval between primary immunization and antigenic challenge increases. Long-term memory cells for the secondary IgM response bear small amounts of both IgM and IgG.


The specificity of T-cell helper factor in man. Supernates of human T cells stimulated with TT antigen contain a factor that induces mitogenesis and immunoglobulin synthesis in autologous as well as allogeneic B cells. A fraction of the IgG produced has specificity against TT. The T-cell-derived LMF-TT eluted after albumin on Sephadex G 200 and did not contain immunoglobulin heavy chain determinants. LMF-TT was active on B cells from TT immune as well as TT- nonimmune individuals but in the latter instance the IgG secreted had no specificity against TT. B cells incubated with LMF-TT in the presence of a second antigen (DT) made IgG with specifity to that antigen provided the B-cell donor was immune to that second antigen. LMF-TT-containing supernates were depleted of TT antigen by Sephadex G 200 chromatography followed by passage over anti-TT immunosorbent columns. The antigen-free supernates were able to induce mitogenesis and IgG synthesis in B cells but the IgG produced failed to exhibit specificity against TT unless the TT antigen was readded to the B-cell cultures. The optimal concentration of LMF-TT (50 percent) inducing B-cell mitogenesis was different from the optimal concentration (20 percent) causing IgG synthesis by B cells. At low LMF concentrations (less than or equal 10 percent) addition of a second antigen to which the cell donor was immune caused an increase in the degree of B-cell mitogenesis. Submitogenic concentrations of LMF-TT (less than or equal to 5 percent) were still capable of inducingimmunoglobulin synthesis in B cells At these low concentrations of LMF-TT the proportion of anti-TT IgG over total IgG increased sharply. B cells from TT immune donors were separated on TT immunosorbent columns. Cells that bound to the column were more sensitive to the mitogenic and IgG synthetic effects of LMF-TT than unfractionated B cells. Thus, LMF is a nonspecific human T-cell helper factor which behaves like a polyclonal B-cell activator. However, in the presence of specific antigen (TT) the antigen-specific B cell is preferentially triggered by LMF. The experimental design of the present study does not rule out the additional presence of an antigen-specific helper factor in the supernates of TT-stimulated human T cells.


Inhibition of immunologic injury of cultured cells infected with lymphocytic choriomeningitis virus: role of defective interfering virus in regulating viral antigenic expression. The expression of viral antigens on the surfaces of lymphocytic choriomeningitis virus (LCMV)-infected L-929 cells peaked 2-4 days postinfection and thereafter precipitously declined. Little or no viral antigen was expressed on the plasma membrane surfaces of persistently infected cells, but LCMV antigens were clearly present in the cytoplasms of most of those cells. Cells early after acute infection (days 2-4) were lysed by both virus-specific antibody and complement (C) and immune T lymphocytes. To the contrary, antibody and C did not kill persistently infected cells, but T lymphocytes did kill such cells although at a lower efficiency than acutely infected cells. The expression of viral antigens on the surfaces of infected cells was regulated by the virus- cell interaction in the absence of immune reagents and was closely associated with defective interfering (DI) LCMV interference. DI LCMV, per se, blocked the synthesis and cell surface expression of LCMV antigens, and DI LCMV generation immediately preceded a precipitous reduction in cell surface antigenicity during the acute infection. Persistently infected cells produced DI LCMV but no detectable S LCMV. Peritoneal cells isolated from mice persistently infected with LCMV resembled cultured persistently infected cells in their reduced expression of cell surface antigens and their resistance to LCMV superinfection. It is proposed that DI virus-mediated interference with viral protein synthesis may allow cells to escape immune surveillance during persistent infections.


Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages. Frequencies of mitogen-reactive B cells have been determined in vitro under culture conditions which allow every growth-inducible B cell to grow and mature into a clone of Ig-secreting PFC. The frequencies of LPS-reactive B cells in the spleen of 6- to 8-wk old mice were between 1 in 3 and 1 in 10 splenic B cells from the following inbred strains of mice: C3H/Tif; BALB/c; BALB/c nu/nu; C57BL/6J; DBA/2J; C57BL/6J x DBA/(2J)F(1); and CBA and A/J. Very similar frequencies are found for lipoprotein-reactive B cells in BALB/c, BALB/c nu/nu, C3H/Tif, and C3H/HeJ mice. No LPS-reactive cells but normal frequencies of lipoprotein-reactive cells were found in C3H/HeJ mice, genetically nonreactive to LPS. SJL mice had significantly lower frequencies of LPS- and of lipoprotein-reactive B cells (1 in approximately 30 B cells). The number of LPS- and of lipoprotein-reactive B cells in spleen was dependent upon the age of the mouse. Newborn spleen contained approximately 10 percent of the number of reactive cells found at 6- to 8-wk of age. From there the frequencies declined again to drop below 5 percent of the maximal number at ages beyond 11 mo. LPS-reactive B cells yielding IgM- and IgG-PFC responses could be found in mesenteric lymph nodes, bone marrow, thymus, thoracic duct, and peripheral blood of 6- to 8-wk old mice. Their frequencies were one in three to five lymph node cells, 1 in 50 to 100 bone marrow cells, one in 10(5) thymus cells, and 1 in 20 to 40 thoracic duct or peripheral blood cells.


Ontogeny of B-lymphocyte function. III. In vivo and in vitro studies on the ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice. The ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice was studied in vivo, in a cell transfer system, and in vitro. Three different tolerogens were used: ultracentrifuged BGG, DNP(6)-D-GL, and ultracentrifuged DNP(22)-BGG. Irradiated thymectomized mice were reconstituted with B cells from fetal or neonatal liver or adult spleen or bone marrow. The mice were injected with tolerogen 1 day later. They were given normal thymus cells and challenged with either BGG or DNP(44)-BGG between 4 and 14 days after tolerance induction. With BGG no difference in ease of B-cell tolerance induction was observed in mice reconstituted with B cells from 17-day fetal liver, neonatal liver, 8- day-old spleen, adult spleen, or adult bone marrow. B cells from 14-day fetal donors are relatively resistant to tolerance induction. In contrast, with DNP(6)-D-GL and DNP(22)-BGG B cells from neonatal donors were clearly more susceptible to tolerance induction than were B cells from adult donors. Comparable results were obtained in studies on tolerance induction in vitro. Neonatal B cells were more susceptible than adult B cells to tolerance induction upon culture with DNP(6)-D-GL or DNP(22)-BGG. However, neonatal and adult B cells were identical with respect to ease of tolerance induction in vitro with deaggregated BGG. The results suggest that there are multiple mechanisms for B-cell tolerance induction. Immature B cells appear to be more susceptible to tolerance induction by some mechanisms but not by others. It is suggested that immature B cells are more susceptible to tolerance induction with moderately polyvalent antigens such as hapten-carrier conjugates. With antigens like BGG which do not haverepeated epitopes no difference between mature and fetal B cells in regard to ease of tolerance induction is observed. These observations raise questions about the importance of relative ease of tolerance induction in immature B cells as a mechanism controlling the normal induction of self tolerance.


Suppression of cell-mediated immunity by street rabies virus. Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.


Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes. Delayed-type hypersensitivity (DTH) transfer to GAT was restricted by the I-A region of the major histocompatibility complex (MHC). Sensitized cells from F1 hybrid mice between responder and nonresponder strains transferred DTH to syngeneic F1 mice and to naive parental strain recipients of the responder but not of the nonresponder haplotypes. These results are interpreted to favor the postulate that the MHC-linked Ir genes exert their effects by coding for components which allow interactions between particular I region gene products and the region to form stable structures immunogenic for DTH T cells.


Microelectrode studies of the active Na transport pathway of frog skin. When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V(O), concurrent with the observations that (a) a high resistance outer barrier R(O) accounting for approximately 75 percent or more of the transcellular resistance of control skins had been penetrated and that (b) 10(-5) M amiloride and reduced [Na] outside caused the values of V(O) to increase towards means value near -130 mV while the values of percent R(O) increased to more than 90 percent. It was of relationships were the same as the values of E(1) observed in studies of the current-voltage relationships were the same as the values of E'(1) defined as the values of voltage at the inner barrier when the V(O) of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of E(1), approximately 130 mV, represent the E(Na) of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of transepithelial voltage less than E(1) the V(O) was negative. These data can be interpreted with a simple electrical equivalent circuit of the active sodium transport pathway of the frog skin that includes the idea that the outer membrane behaves as an electrical rectifier for ion transport.


Arteriovenous malformations in the posterior fossa. We have operated on 12 of 14 cases of arteriovenous malformation (AVM) in the posterior fossa since 1968, with one death. The lesions were in the cerebellum in 10 cases (three anteromedial, one central, three lateral, and three posteromedial), and in the cerebellopontine angle in two; in two cases the lesions were directly related to the brain stem. The AVM's in the anterior part of the cerebellum were operated on through a transtentorial occipital approach.


Ventriculography with non-ionic water-soluble contrast medium, Amipaque (metrizamide). Comparative experimental and clinical studies. A non-ionic water-soluble contrast medium, Amipaque (metrizamide), was studied for use in ventriculography both experimentally and clinically, and identified as having markedly low toxicity. Twenty adult mongrel dogs were injected intraventricularly of intracisternally with 2.0 to 5.0 ml of Amipaque. It was found that Amipaque is safe compared with other water-soluble contrast media, especially relative to epileptogenic effect. The authors also carried out 17 clinical trials of ventriculography using 4.0 to 15.0 ml of Amipaque in 13 neurosurgical patients. There were no troublesome symptoms except for a mild headache as a side-effect in one patient, and Amipaque proved to be a satisfactory diagnostic contrast medium.


Cone pigments in human deutan colour vision defects. 1. The Nagel anomaloscope, neutral points and dichromatic matches to a spectral green light identified a population of seventy red-green dichromats. 2. The anomaloscope settings allow the calculation of the relative action spectrum of the match at the wave-length of the red (645 nm) and green (535 nm) primaries. The distribution of this ratio is bimodal; there are two clusters with a gap of about 0-75 long units between. Among the thirty-eight deuteranopes there are wide differences in anomaloscope matches; similar differences appear among the thirty-two protanopes. 3. Retinal densitometry of the foveas of fifteen of the deuteranopes is compared and contrasted with measurements on trichromats. In the former, only one photolabile pigment is found in the red-green region of the spectrum; normals always have two. The view of Rushton (1965a) that deuteranopes have erythrolabe but no measurable chlorolabe is confirmed for each member of this group. 4. Simple deuteranomalous show two red-green cone pigments. The difference spectra of extreme deuteranomalous are very similar to those found in deuteranopia. 5. Individual differnce in kinetics (photosensitivity, time constant of regeneration) and in the density and lambdamax of the difference spectrum of erythrolabe in deuteranopia are appreciable; the reasons for these differences are not clear.


Variation in the action spectrum of erythrolabe among deuteranopes. 1. Eight deuteranopes matched a mixture of a monochromatic light on the long wave side of the neutral point and a violet (450 nm) primary to a fixed white as well as a monochromatic light on the short wave side of the neutral point mixed with a red (650 nm) primary, to the same white. For lambda greater than 530 nm, the former set of matches defined the action spectrum of the long wave sensitive foveal cones, and for lambda less than 480 nm, the latter that of the short wave sensitive cones. 2. Individual differences in the former matches were approximately correlated with the respective ratio of the sensitivities of the wave-length of the anomaloscope primaries, in a way that individual differences of the latter were not. 3. Assuming that eye media differences alone account for the differences in long wave sensitive foveal action spectra, the spectral reflectivity of the foveal fundus was predicted for these deuteranopes. The prediction is inconsistent with measurement. 4. Thirteen deuteranopes matched monochromatic spectral lights with a green (535 nm) and a blue (460 nm) primary. The result were analysed by von Kries' method in which differences in matching due to differences in eye media absorption are obviated. The matches of five differed significantly from one another when so analysed. It was concluded that at least one of two action spectra of the foveal cones of every one of these five differed from that of all of the others. 5. The canon that deuteranopes accept normal colour matches was evaluated by confronting a single normal with five deuternopes in the analytical anomaloscope of Baker & Rushton, set in the mode of each of the five in turn. Obvious differences existed between this normal's matches and those of four of five deuteranopes. 6. Explanations for differences in the spectrum of erythrolabe in different deuteranopes are evaluated. The possibilities that all have the identical visual pigment but (a) in cones with different optical funnelling properties or (b) in different optical densities are considered. Preliminary results are not in agreement with the expectations of either of these ideas. 7. It is suggested that the visual pigment in the foveal long wave sensitive cones of different deuternopes (and of different normals) may have different extinction spectra. The idea is consistent with micro-spectrophotometric measurements of rhodopsin in individual rods from different frogs (Bowmaker, Loew & Leibman, 1975).


The red and green cone visual pigments of deuternomalous trichromacy. 1. Three "simple" deuteranomalous trichromats match with abnormally low "red" tristimulus values throughout the spectrum and abnormally high "green" tristimulus values in the long wave end of the spectrum which become normal (and then low) in the yellow-green. The spectrum locus of this transition differs from one anomalous to the other. Differences in the matches of two of these cannot be due to differences in eye media transmissivities alone. Therefore these two deuteranomalous have different cone visual pigments. 2. The analytical anomaloscope was used in the confrontation of one deuteranomalous with six deuteranopes in turn. In each confrontation the deuteranope set the anomaloscope in his mode and adjusted the intensity of the monochromatic light for a match. Deuteranomalous matches were rejected by four of these six deuteranopes. 3. They were accepted by two of the six. These two rejected each other's matches in a way not attributable to differences in eye media transmissivity. 4. Three different psychophysical techniques were used to measure the action spectra of the long wave cones of these two deuternopes. All three methods reveal small but systematic differences in lambdamax and shape of the curve for the one deuteranope compared with that of the other. 5. In red-green spectral range, these spectra are accurately described by different linear combinations of the color matching functions of the same deuteranomalous whose matches the two deuteranopes accept. Linear combinations of those of a second deuteranomalous, with at least one different kind of cone, fit less well. 6. The wave length discrimination curve of the former deuteranomalous was measured with a new method. The curves of two normals were also obtained for comparison. Wave-length discrimination predictions from the Stiles (1946) line element theory were compared to the anomalous curve. The deuteranopic action spectra were used in the line element to compute this deuteranomalous' discrimination. There is reasonable first order correspondence between prediction and observation, but the prediction is sensitive to small changes in the derivatives of the logarithms of the action spectra. 7. Line element prediction of the deuteranomalous step-by-step luminous efficiency curve is insensitive to such uncertainties. The agreement with expectation from the above assumptions and the measured step-by-step deuteranomalous luminous efficiency curve in the red-green part of the spectrum is therefore good. 8. It is concluded that the erythrolabe in one deuternope's long wave cones has the action spectrum of this deuteranomalous' long and the erythrolabe in the other deuternope's long wave sensitive cones has that of this deuternomalous' medium wave cones. This leads to a general hypothesis about the nature of all forms of red-green colour vision defects transmitted recessively on the X chromosome.


A-band length, striation spacing and tension change on stretch of active muscle. 1. Single muscle fibres of the frog were stretched during tetanus and filmed down the interference microscope. 2. Sarcomere lengths and A- and I-band widths were measured from cine films taken of the experimental sequences. 3. When a fibre was stretched during a tetanus, its A-band widths remained constant while its I-band widths changed according to the extent of the stretch. This behaviour is identical with that of a fibre stretched at rest. 4. Sarcomere lengths remained uniform along the fibre during a tetanus plus stretch, increasing as the I-band widths increased when the fibre was stretched. 5. At sarcomere lengths longer than LPmax (the length corresponding to greatest isometric tetanus tension) where the isometric tension diminishes as the fibre is lengthened, if the stretch was imposed during a tetanus the tension was higher after the stretch than before, showing a plateau which lasted for the duration of the tetanus. 6. This effect increased with longer sarcomere lengths and was not due to increased resting tension.


The passive electrical properties of frog skeletal muscle fibres at different sarcomere lengths. 1. The passive electrical properties of frog skeletal muscle fibres have been measured at a number of different sarcomere lengths (from 2-1 to 4-0 micron). The geometrical outline of each fibre was determined from optical cross-sections and sarcomere length was measured by laser beam diffraction. 2. When fibres were stretched to long sarcomere lengths the membrane capacity, Cm, of both normal and detubulated (glycerol-treated) fibres was significantly less than the Cm of fibres at rest length. A significant reduction in membrane conductance of fibres held at long sarcomere lengths was only seen with detubulated fibres. 3. Membrane capacity and membrane conductance have a significant dependence on the cross-sectional area of normal fibres but are independent of cross-sectional area after detubulation. 4. It has been shown that membrane geometry depends on the sarcomere length of the fibre and it is suggested that the passive membrane properties are related to sarcomere length because they depend on membrane geometry. 5. The specific membrane capacity, calculated from the data from detubulated fibres, is 0-8 micronF/cm2. 6. The internal resistivity, Ri, of normal fibres, also depends on sarcomere length between 2-1 and 3-0 micron. At a sarcomere length of 2-1 micron the average Ri is 122 +/- 3 omega. cm (mean +/- S.E. of mean) and at a sarcomere length of 3-0 micron the average Ri is 210 +/- 17 omega. cm (mean +/- S.E. of mean). No further increase in Ri was observed with further increases in sarcomere length.


Histocompatibility antigens (HLA) in rheumatic diseases in Iran. One hundred and sixty-six patients with different forms of rheumatic diseases were tissue typed for 26 antigens of the A and B locus of the HLA system, using a modified KN cytotoxicity test. Among 25 patients with confirmed ankylosing spondylitis, 23 had HLA B27 (92 per cent), compared to 2.5 per cent in the normal controls. This confirms the strong association of HLA B27 with ankylosing spondylitis. Eight patients had doubtful AS, five of whom were positive for B27. In 21 patients with mechanical disorders of the spine no B27 was found. Thirty-six patients with osteoarthrosis of the knee joints did not show any significant relationship with any HLA antigens. Twenty-one patients with systemic lupus erythematosus showed an increase of HLA B13 and B17.


A dynamic primary care curriculum based on the problem-oriented system. The audit of behaviors of health care providers is a valuable tool for learning the essentials of primary care and health care delivery. At the University of Vermont a dynamic curriculum has evolved from the student audits of the practice sites where the training takes place. Evaluation studies to date indicate a positive effect on career goals leading to primary care specialties and a desire to practice in rural settings in underserved areas. This approach to teaching primary care has proven to be effective and has gained high acceptance with the students. They learn that audit is a valuable means of self-education as well as method for providing quality assurance to the patient.


Masking of receptors for sheep erythrocytes on human T-lymphocytes by sera from breast cancer patients. Sera from 140 breast cancer patients and 38 controls were tested for their ability to inhibit sheep erythrocyte (E) rosette formation by normal, allogeneic lymphocytes. Inhibition of rosette formation by greater than 20% was found with 65% of stage I sera, 91% of stage II sera, 56% of stage III sera, and all stage IV sera. In contrast, only 13% of control sera was inhibitory. The inhibitory factor was found to bind to only a proportion of T-lymphocytes and could be removed from these lymphocytes by mild proteolytic digestion or extended washing. Examination of the properties of the inhibitory factor indicated that it differed from other substances that reportedly inhibited E-rosette formation.