Barium delays the onset of rapid dark adaptation in bullfrog cones. The late receptor potential of the excised, perfused bullfrog retina was isolated with sodium aspartate. By employing a three-flash technique, cone responses were monitored without interference from rods. In cones barium ions were found to delay the onset of rapid dark adaptation, but the rate of recovery, once begun, was unaffected. We propose that barium ions act directly upon the enzyme system postulated to govern the onset of rapid dark adaptation of cones. In addition, barium was found to affect the amplitude of the rod receptor potential differently from that of cones, increasing the former but decreasing the latter. The effect of barium upon photoreceptor potential amplitude is discussed in terms of a reduction in the potassium conductance of the photoreceptors and the mechanisms postulated for photoreceptor excitation and rapid dark adaptation.


Significance of antibodies to double-stranded DNA in 30 systemic lupus erythematosus patients. Attention has been directed lately to antibodies reactive with double-stranded DNA (dsDNA) in systemic lupus erythematosus (SLE) patients, as these antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of the disease. In the present study, the clinical and laboratory evaluations of 30 SLE patients in various stages of disease activity were correlated with the levels of anti-DNA antibodies, as detected by the methods of Farr and of Aarden et al. Sera of 65 patients in relapse or remission were examined with both techniques, and a discrepancy was found in only nine sera. In addition, in six patients, a differential analysis of the immunoglobulin classes of anti-dsDNA was performed according to the method of Aarden et al. The data obtained with this assay correlate well with SLE activity and thus may add an important step to the evaluation of SLE patients.


Histiocytosis X in 9 children: clinical aspects and laboratory evaluations including an analysis of monocytopoiesis. Nine children with histiocytosis X were observed. The course of the disease largely depended upon the degree of dissemination at the time of diagnosis. Bone and skin involvement healed completely with a relatively simple therapy using prednisone in combination either with vincristine or vinblastine. Complete or long lasting partial remissions could be achieved up to involvement of 4 organs. Three patients demonstrating histiocyte infiltrations in 5 organs died. They all were less than 2 years of age. Hyperproliferation of monocytopoiesis was present in all patients manifesting itself by a rise in the fraction of mononuclear phagocytes in bone marrow. This variation was paralleled by monocytosis in the peripheral blood in 5 of 7 cases. Serum muramidase levels were increased in 5 of 6 patients. However, there was no clearcut correlation to the degree of disease dissemination.


Membranes of Rhodopseudomonas sphaeroides: effect of cerulenin on assembly of chromatophore membrane. The effects of cerulenin were investigated in Rhodopseudomonas sphaeroides to elucidate further the mechanisms controlling the assembly of the chromatophore membrane. When this potent inhibitor of fatty acid biosynthesis was added to photosynthetically grown cultures, there was an immediate cessation of phospholipid, bacteriochlorophyll a, carotenoid, and ubiquinone formation. Concurrently, there was also a marked decrease in the rate of incorporation of protein into the chromatophore membrane. In contrast, only a small decrease in the rate of soluble and cell envelope protein synthesis was observed and, in chemotrophically grown cells, protein continued to be incorporated into both the cytoplasmic and outer membranes. The removal of delta-aminolaevulinate from mutant H-5 of R. sphaeroides, which requires this porphyrin precursor, was reexamined to determine whether cerulenin-induced cessation of chromatophore protein incorporation was due solely to blocked bacteriochlorophyll a synthesis. In the deprived H-5 cells, inhibition of [35S]methionine incorporation into chromatophores was confined mainly to apoproteins of bacteriochlorophyll a complexes. Other minor chromatophore proteins continued to be inserted to a greater extent than in cerulenin-treated wild type where phospholipid synthesis has also ceased. These results indicated that the assembly of the chromatophore membrane is under strict regulatory control involving concomitant phospholipid, pigment, and protein syntheses.


Plasmid transfer in Haemophilus influenzae. Twenty-nine strains of Haemophilus influenzae highly resistant to ampicillin, chloramphenicol, or tetracycline were examined for the presence of plasmids. Agarose gel electrophoresis of ethanol-precipitated cell extracts revealed large plasmids in 11 strains, of which 7 were conjugative. Plasmid transfer by conjugation between isogenic strains was quite efficient, but transfer between different serotypes was nearly always much more inefficient. Type I or II restriction enzymes do not appear to be barriers to this transfer. Encapsulated cells can be both efficient donors and recipients. Small plasmids were seen in three strains, but only two of the three are resistance factors (RSF0885, pUB703). Thus, in 17 isolates antibiotic resistance genes are believed to be located in the bacterial chromosome. Most of these resistances could be transferred by genetic transformation into the widely used Rd strain. In some cases transfer of chromosomal resistance into conjugative plasmids was observed in both rec+ and rec host cells. Since transfer by conjugation seems to be the more efficient process, it is puzzling that in the majority of the 29 isolates studied resistance genes appeared to be in the chromosome.


Analyses of oligosaccharides by tagging the reducing end with a fluorescent compound. I. Application to glycoproteins. The reducing end sugar of an oligosaccharide and 2-aminopyridine were linked by means of reductive amination with sodium cyanoborohydride. The fluorescent derivative of the oligosaccharide thus obtained, which had a positive charge, was subjected to two-dimensional paper electrophoresis. In the first direction, the sugar derivative moved according to its degree of polymerization, and in the second direction, it moved according to the structure of the borate complex. In this way fluorescent derivatives of saccharides were mapped on a sheet of paper. The method was applied to some known mono- and oligosaccharides and to the saccharides obtained by nitrous deamination of the oligosaccharide portions of glycoproteins (fetuin, Take-amylase A, and ovalbumin). The fingerprints thus obtained were characteristic of the chemical structures of the original oligosaccharides.


Grafting of proteins onto polymer surfaces with the use of oxidized starch. A study has been carried out on the coupling of proteins onto crosslinked poly(vinyl alcohol) hydrogel membranes and ethylene-vinyl alcohol copolymer(EVA) films previously grafted with oxidized starches having many pendant aldehyde groups. The coupling reaction of proteins is based on the Schiff's base formation between the amino groups of proteins and the aldehyde groups of the oxidized starches which have been grafted onto the substrate membrane or film through acetalization of the aldehyde of starch with hydroxyl groups of the substrate polymers. The grafting of oxidized starches onto the EVA films seems to be restricted to the film surface, since no detectable change is observed in the weight and the attenuated total reflection infrared spectrum of the grafted films. The amount of grafted protein, determined by the ninhydrin method, reveals that, at least, plasma proteins such as serum albumin and fibrinogen are grafted to the film surface in a monomolecular layer without undergoing a marked denaturation. The alpha-amylase grafted onto the EVA film showed a distinct enzymatic activity in hydrolysis of amylose and starch, but the activity was very low compared with that of the ungrafted, soluble alpha-amylase.


A morphometrical study of the exocrine pancreatic cell in fasted and fed frogs. The influence of feeding on the ultrastruct of the frog exocrine pancreatic cell was studied by morphometrical procedures. Volume and surface of various cell structures were measured and expressed per unit cell volume. The average cellular size was not influenced by feeding. Though protein synthesis changes 5-to 10-fold (van Venrooij, W. J., and C. Poort. 1971. Biochim. Biophys. Acta. 247:468-470), no significant differences were observed in the amount of membrane that constitutes the rough endoplasmic reticulum (RER) and that represented  the major part of total cellular membranes. The appearance of the RER changed. When fasted, most of its membrane was arranged in stacks of tightly packed, narrow cisternae. Within 4 h after feeding, these cisternae were separated and irregularly dilated, and ribosomes became ordered in typical rosettes on their surface. The total volume of the Golgi system increased twofold after feeding. The vesicular and tubular elements at the Golgi periphery did not change, but the volumes of the Golgi cisternae and the condensing vacuoles increased 2.5- and 6-fold, respectively. The increased in the amount of membrane present in these structures was only 1.6- and 3.5-fold, which reflects the more distended appearance of the cisternae and the rounded shape of the condensing vacuoles after feeding. Feeding halved the number of secretory granules per cell, and signs of exocytosis were more common than in fasted animals. These findings suggest that, in the frog pancreatic cell, fluctuations in the production of secretory proteins are not accompanied by an important breakdown and renewal of cellular membranes. This may favor a rapid and strong response of the cell to feeding.


Effect of fasting and feeding on synthesis and intracellular transport of proteins in the frog exocrine pancreas. Frog exocrine pancreatic tissue was studied in vitro under conditions which maintain the differences between tissues from fasted and fed animals. Sodium dodecyl sulfate (SDS) gel electrophoresis after labeling with [14C]amino acids showed that feeding stimulated the synthesis of secretory proteins to the same relative degree as the overall protein synthesis. The intracellular transport of secretory proteins was studied by electronmicroscopy autoradiography after pulse-labeling with [3H]leucine. It was found that the transport route is similar under both feeding conditions. After their synthesis in the rough endoplasmic reticulum (RER), the proteins move through the peripheral elements and cisternae of the Golgi system into the condensing vacuoles. The velocity of the transport increases considerably after feeding. When frogs are fasted, the release of labeled proteins from the RER takes greater than 90 min, whereas after feeding, this happens within 30 min. Comparable differences were observed for transport through the Golgi system. The apparent differences between the frog and mammalian pancreas in the regulation of synthesis, intracellular transport, and secretion of proteins are discussed.


Bridging structures spanning the junctioning gap at the triad of skeletal muscle. The membrane systems of skeletal muscle were examined after tannic acid fixation. A new structure consisting of bridges spanning the junctional gap is described, and a model is proposed in which the cytoplasmic but not the luminal membrane leaflets of the transverse tubule and of the junctional sarcoplasmic reticulum (SR) are continuous. The globular particles (presumably the Ca-binding proteins) within the terminal cisternae were arranged in longitudinal rows and appeared adherent to the junctional membrane. The junctional gap was present in negatively stained, frozen thin sections of fixed muscles. Negatively staining material occured within the junctional gap. The cytoplasmic leaflets of the longitudinal, intermediate, and terminal cisterna regions of the SR exhibited a thick coat of densely staining material compatible with the presence of the Ca-ATPase. Similar bridges were also observed at the surface membrane-SR close coupling sites of vascular smooth muscle.


Rapid separation of mouse T and B lymphocytes using wheat germ agglutinin. A separation procedure has been developed for mouse splenic T and B lymphocytes which is based on their differential agglutination by wheat germ agglutinin (WGA). In the presence of 50-100 micrograms/ml of WGA, multicellular aggregates are formed which are enriched in B cells. These aggregates can be separated from monodisperse T cells by gravity sedimentation and subsequently dissociated into single cells by treatment with N-acetylglucosamine (NAG). Immunocytochemical analyses and mitogenic assays indicate approximately 10-15% cross contamination of the resultant B and T cell fractions. The separation procedure is not only convenient and rapid but also allows the simultaneous recovery of viable T and B cells from the same spleen preparation.


Interactions between purified GM-CSF, purified erythropoietin and spleen conditioned medium on hemopoietic colony formation in vitro. Preincubation of C57BL adult marrow cells or CBA fetal liver cells with a 250-fold excess concentration of purified GM-CSF failed to reduce the frequency of cells forming eosinophil, megakaryocyte or erythroid colonies in subsequent agar cultures. When excess concentrations of purified GM-CSF were added to agar cultures stimulated by pokeweed mitogen-stimulated spleen conditioned medium (SCM), no reduction was observed in the frequency of eosinophil, megakaryocyte or erythroid colonies. Addition of 4 units of purified erythropoietin (EPO) to cultures of fetal liver or adult marrow cells stimulated by SCM increased the number of erythroid colonies but did not reduce the number of non-erythroid colonies or the non-erythroid content of mixed erythroid colonies. Although neither GM-CSF nor EPO alone was able to stimulate erythroid colony formation in agar cultures of fetal liver cells, small numbers of large erythroid colonies were stimulated to develop in cultures containing both purified regulators. Purified GM-CSF was also able to support the survival in vitro of a small proportion of erythroid colony-forming cells in fetal liver populations cultured initially in the absence of SCM and the survival of some eosinophil and megakaryocyte colony-forming cells in similar cultures of adult marrow cells. The results do not support the hypothesis that GM-CSF and EPO compete for a common pool of uncommitted progenitor cells. On the contrary, the data indicate that GM-CSF und EPO are able to collaborate in stimulating the proliferation of some erythropoietic cells. Furthermore, purified GM-CSF appears to be able to support temporarily the survival and/or initial proliferation of at least some cells forming erythroid, eosinophil and megakaryocyte colonies, even though GM-CSF is unable to stimulate the formation of colonies of these types.


An unique form of osteomalacia associated with end organ refractoriness to 1,25-dihydroxyvitamin D and apparent defective synthesis of 25-hydroxyvitamin D. A 28-yr-old woman presented with hypocalcemia, hypophosphatemia, secondary hyperparthyroidism, and biopsy-proven osteomalacia despite treatment with vitamin D2, (17.5 mg/day). Three weeks after vitamin D2 treatment was stopped, she was found to have a low normal serum 25-hydroxyvitamin D (25OHD) and high serum 1 alpha, 25-dihydroxyvitamin D [1,25(OH)2D] of 18.6 ng/ml and 21.2 ng/dl, respectively. The fractional intestinal calcium absorption was low at 0.26. Treatment with 25OHD3 (20--50 micrograms/day) corrected the hypocalcemia and secondary hyperparathyroidism, raised intestinal calcium absorption, and reversed the skeletal lesions of osteomalacia. Serum 25OHD concentration rose to 51 ng/ml, while 1,25(OH)2D remained elevated. This case illustrates the probable operation of dual abnormalities in vitamin D metabolism. An impaired end organ responsiveness to 1,25(OH)2D was suggested by a low intestinal calcium absorption in the face of high serum 1,25(OH)2D. Moreover, there may have been a defective vitamin D-25-hydroxylase, since there was a relative refractoriness to treatment with large doses of vitamin D2, an inappropriately low serum 250HD after vitamin D2 therapy, and a responsiveness to treatment with 25OHD3.


Biochemical characteristics of 130 recent isolates from Haemophilus influenzae meningitis. A total of 130 Haemophilus strains, comprising virtually all isolates from Danish and Norwegian cases of Haemophilus meningitis occurring in the period from October 1975 through September 1976, were examined by biochemical and serological means. All isolates were identified as H. influenzae and, except for one noncapsulated strain, possessed a capsule of serotype b. The vast majority of strains (93%) belonged to biotype I, which, in contrast to biotypes II and III, is rarely encountered as a commensal of the upper respiratory tract. This finding is a strong incentive for studies of possible additional virulence factors associated with biotype I organisms. The results are discussed in the light of North American reports, which have suggested changes in the etiology of Haemophilus meningitis.


Hyper immunoglobulin M immunodeficiency. (Dysgammaglobulinemia). Presence of immunoglobulin M-secreting plasmacytoid cells in peripheral blood and failure of immunoglobulin M-immunoglobulin G switch in B-cell differentiation. The peripheral blood lymphocytes of nine patients with hyper immunoglobulin (Ig)M immunodeficiency were studied in an attempt to define the cellular basis of this disorder. B cells were normal in number but qualitatively abnormal in all patients. Approximately one-half of the B cell consisted of small lymphocytes (7-9 mum in diameter) bearing surface IgM and IgD, as well as C3 receptors. These cells were driven to secrete IgM but not IgG after in vitro stimulation by pokeweed mitogen. In the blood there were also large lymphocytes (10-14 mum in diameter) that possessed surface as well as intracytoplasmic IgM but lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. Such a subpopulation of lymphoid cells was not detected in normal peripheral blood and was unique for all patients with hyper IgM immunodeficiency studied.T cells from all patients were normal in number and in function both in vivo and in vitro and were able to generate adequate T-cell help to support IgG synthesis by normal B cells. No evidence was obtained for T cells capable of suppressing normal IgG synthesis in any of the patients after coculture with normal peripheral blood lymphocytes. The defect in hyper IgM immunodeficiency is intrinsic to B cells, which fail to switch from IgM to IgG synthesis.


Subset derivation of T-cell acute lymphoblastic leukemia in man. Normal human peripheral blood T cells can be characterized as belonging to either the TH+2 or TH-2 T-cell subset. Approximately 20% of T cells are TH+2, whereas 80% are TH-2 utilizing specific heteroantisera. To determine shether human T-cell acute lymphoblastic leukemia (T-ALL) cells belong to one or another T-cell subset, cell surface phenotyping was performed on tumor populations from 25 patients with T-ALL. Tmuor cells from these 25 individuals were either TH+1 or TH-2, but not both. 5 of 25 patients had TH+2 T-ALL cells. These TH+2 tumor populations were found exclusively in children and often without an accompanying thymic mass. TH-2 T-ALL, in contrast, occurred in both children and adults and was almost always associated with thymic enlargement. Although children with TH+2 T-ALL had as high or higher peripheral blast counts on presentation than their TH-2 T-ALL counterparts, overall survival was greater for the TH+2 group (greater than 36 mo) than the TH-2 group (less than 12 mo). These studies demonstrate that T-cell leukemias in man arise from distinct T-cell subsets and that cell surface characterization of T-cell malignancies may provide useful clinical data related to prognosis.


Computed tomography findings in ruptured arteriovenous malformations of the corpus callosum. Computed tomography (CT) is of proven value in the evaluation and localization of intracranial hemorrhage. The recognition of various patterns of subarachnoid, intracerebral, and intraventricular hemorrhage is necessary in order to provide accurate localization and to predict probable etiology of the bleed. We present three cases with angiographically proven ruptured arteriovenous malformations involving the midline of the corpus callosum. The clinical presentation and CT findings are discussed. We believe this represents a distinctive pattern of hemorrhage specific for this entity.


Neonatal intraventricular hemorrhage: a serial computed tomography study. Thirty infants weighing less than 1,500 g at birth and requiring assisted ventilation were studied by computed tomography (CT) as soon as possible after birth and at intervals thereafter. Hemorrhage were frequently detected within the first 48 hr of birth. Two infants had normal scans initially but developed intraventricular hemorrhage later. One infant had subependymal hemorrhage that later ruptured into the ventricles. Six deaths were due directly to intracranial hemorrhages. Hydrocephalus developed in seven and atrophy in two survivors. There was poor correlation between CT scan and clinical evidence of intracranial hemorrhage.


The target sign: a CT finding in tumors of the corpus callosum. An unusual computed tomography finding, the "target sign," is demonstrated in a patient with a corpus callosum tumor mass extending to the right lateral ventricle. The central low attenuation of the "target" is produced by the isolated part of the dilated lateral ventricle surrounded by tumor tissue, the dense area of the "target." The diagnosis of the tumor of the corpus callosum and the explanation of the "target sign" was made by polytome pneumoencephalography.


Immunologic reactivity in the hypereosinophilic syndrome. Because previous studies have suggested an important link between eosinophilia and immunologic reactivity, we investigated various components of the immune system in a large number of patients with the idiopathic hypereosinophilic syndrome (HES) to elucidate a possible role for immunologic phenomena in the etiology and pathogenesis of this disease. Immunoglobulin G, A, or M levels were only rarely abnormal. However, in 8 of 21 (38%) patients with HES, IgE levels were markedly elevated suggesting an association of an IgE-mediated mechanism with eosinophilia in this subgroup. Severe dermatographism was present in three fourths of patients, and 2 patients with intermittently elevated histamine levels manifested an unusual form of immediate-pressure urticaria. Serum complement determinations showed elevated C4 and C3 levels in 27% and 77% of patients, respectively. Antigen-antibody complexlike material measured by C1q binding was elevated in the serum of 7 of 22 (32%) patients; this finding may relate to the known ability of eosinophils to avidly phagocytose antigen-antibody complexes. When compared with normals, lymphocytes from patients with HES showed a variety of abnormalities of lymphocyte surface receptors and lymphocyte function. Thus, patients with HES demonstrate a variety of immunologic abnormalities which may be related primarily or secondarily to the pathogenesis of this syndrome.


Suppressor cell function in atopic dermatitis associated with elevated immunoglobulin E. Suppressor cell function was evaluated in 11 patients with atopic dermatitis (AD) and elevated IgE levels (mean, 4,554 IU/ml +/- 1,825 SEM) and compared to 11 matched nonatopic controls (135 IU/ml +/- 52 SEM). Two assays were employed to evaluate suppressor cell function. In the first assay, concanavalin A--activated suppressor cell activity of AD and control subjects were compared. In the second assay, peripheral blood mononuclear cells (PBM) from the same AD and control subjects were stimulated with varying doses of mitogen at day 0 and after 24 hr of preculture. In this system, increased proliferative response of precultured cells as compared to 0-hr cells has previously been shown in normals to represent loss of suppressor cell function in vitro. The lack of such an increase implies aberrant suppressor cell function. The data from both assays showed no significant difference in the degree of suppressor cell function of the patient population vs the control population. Thus, suppressor cell function as tested in these proliferative assays appears normal in AD patients with increased IgE.


Mechanisms of hypersensitivity: cellular interactions. Basophil arrival and function in tissue hypersensitivity reactions. Bone marrow-derived blood basophils are recruited into the tissues by immuno mechanisms in a variety of delayed time-course hypersensitivity responses. In the skin these are called cutaneous basophil hypersensitivity (CBH) reactions. In guinea pigs, it is now established that the elicitation of CBH is dependent on T cell- and/or (antibody)-triggered mechanisms. Both are subject to modulation. T cell-mediated CBH seems to be suppressed in basophil-poor tuberculin-type reactions. B cells mediate CBH via antibody of IgG1 isotype through mechanisms that involve Fc receptors, which can be competitively blocked. After basophils arrive at a CBH reaction they can be triggered by antigen to immediately release mediators such as histamine. Thus, one consequence of the arrival and accumulation of basophils at delayed hypersensitivity reactions is to augment the anaphylactic potential of a given tissue site. In reactions to parasites, release of mediators by tissue basophils seems to aid in the expulsion of these multicellular organisms, In addition, histamine released by recruited basophils, or by locally resident mast cells, may modulate some delayed reactions through stimulation of histamine-2 receptors on cells such as T lymphocytes. In mice, mast cell release of serotonin and subsequent stimulation of the local vasculature seems to be required to allow diapedesis and tissue accumulation of various bone marrow-derived accessory leukocytes in delayed-type hypersensitivity responses. Thus, basophils and mast cells, and their release of mediators such as vasoactive amines, are involved in the onset, development, and function of various tissue hypersensitivity responses.


Dendriform keratitis.

Dendriform keratitis. Since the cornea responds to various toxic stimuli by swelling and ulcerating, these changes may assume a dendriform pattern. A case of herpes simplex dendritic keratitis is presented along with its treatment. In addition, several other etiologic sources of an arborescent keratitis are discussed as to their differentiation and management implication.


Complement-mediated solubilization of immune precipitates prepared with antibodies of different avidity. Complement-mediated solubilization of immune precipitates prepared with HSA and rat IgG anti-HSA has been quantitatively analyzed. Early and late IgG anti-HSA antibodies were obtained 27 and 49 days after immunization, respectively. Immune precipitates prepared with early IgG anti-HSA were solubilized by rat serum to a larger extent than complexes prepared with late IgG anti-HSA. The affinities for HSA of the early and late antibodies were not significantly different. The quantitative differences in solubilization were neither due to differences in the Ab/Ag ratios of the immune precipitates, nor appeared to be brought about by changes in the distribution of the antibodies over the IgG sub-classes. The avidity of the late IgG anti-HSA antibodies was higher than the avidity of the early IgG antibodies. Presumably, the avidity of the antibodies greatly affected the complement-mediated solubilization of the immune precipitates. In addition, the solubilization was found to be dependent on the conditions employed to prepare the immune precipitates.


The chicken's femoral-lymph nodules: T and B cells and the immune response. Femoral lymph nodules (FLN), which are barely perceptible in normal birds, after a footpad injection of sheep red blood cells (SRBC) may either significantly enlarge (responder) or remain reduced in size (nonresponder). There were approximately 38% T cells and 53% B cells in the FLN of responder chickens. Significantly more plaque-forming cells (PFC) developed in the FLN than in the spleen after a footpad injection of SRBC. Total antibody, mercaptoethanol- (ME) resistant, and ME-sensitive fractions were significantly higher in birds given i.v. than in those given footpad injections. There were no differences in PFC and agglutinin titers between FLN-responders and nonresponders. The number of PFC in FLN exceeded the number of splenic PFC previously reported. The high PFC response of the FLN may reflect the large percentage of B cells in this lymphomyeloid tissue or the presence of antigen-experienced B cells in the FLN. Although FLN may influence a systemic immune response its major role appears to be restricted to a local response.


Fc receptors for IgA on human B, and human non-B, non-T lymphocytes. Recently, receptors for IgA were demonstrated on subpopulations of human T lymphocytes. In this report, TNP-modified ox erythrocytes coated with the IgA myeloma MOPC-315 were used to detect IgA receptor-bearing lymphocytes within the human non T cell lymphocyte population. A mean of 5.3% (range 2.9 to 12.4%) of E-rosette negative human lymphocytes bound IgA-coated indicator cells. Blocking studies with soluble IgA, IgG, and IgM demonstrated that the IgA receptors on the non-T cell populations were separate and distinct from the Fc-receptors for IgG and IgM. Fractionation of the non-T lymphocytes on anti-human (Fab)2 columns into sIg+ and sIg- populations or by rosetting with EAC to provide CRL+ and CRL- populations demonstrated that Fc-IgA receptors were present on a subpopulation of sIg+, CRL+ lymphocytes, and also on sIg- (non-T, non-B) lymphocytes.


Effects of concanavalin A-induced cells on the proliferative response of T cells. Concanavalin A-induced suppressor and amplifier cells to the proliferative response of human T cells to trinitrophenyl-modified autologous lymphocytes. Effects of Con A-induced human mononuclear cells on the proliferative response of peripheral T cells were examined by using TNP-modified autologous lymphocytes as stimulator cells. Cells induced by incubation with Con A contained both suppressor cells and amplifier cells. The former were induced from nylon wool-nonadherent T cells and these precursor cells were sensitive to mitomycin treatment. On the other hand, amplifier precursor cells were nylon wool-nonadherent T cells and were resistant to mitomycin treatment. Cell proliferation was required for the induction of suppressor cells but not for the induction of amplifier cells. Con A-induced suppressor effector cells were both nylon wool-adherent and nonadherent cells, on the contrary, Con A-induced amplifier effector cells were nonadherent cells. A small number of macrophages enhanced the suppressive activity of nonadherent T cells when added at the induction phase of suppressor T cells.


A methodological study of E-rosette formation using AET-treated sheep red blood cells. The influence of some of the well knwon technical variables on the E-rosette technique was examined using sheep red blood cells (SRBC) treated with 2-aminoethylisothiouronium bromide (AET). With AET treatment, E-rosette formation becomes less dependent on time and temperature and on the presence of serum. The mechanical stability of the rosettes is enhanced, and the number of SRBC attached to each rosette-forming lymphocyte (RFC) is markedly increased, leading to a sharper distinction between RFC and non-RFC. Ultimately, significantly more E-receptor carrying lymphocytes become detectable. Evidence is provided that the specificity of the E-rosette technique is unchanged after AET treatment of SRBC, in spite of the enhanced binding. A simple and reliable method for E-RFC identification is documented.


Secretion of plasminogen activator by bone marrow-derived mononuclear phagocytes and its enhancement by colony-stimulating factor. We have studied the production of plasminogen activator (PA) by mononuclear phagocytes derived from mouse bone marrow precursor cells (CFU-C) in culture. Bone marrow-derived macrophages (BMDM) obtained after 6-8-d cultivation in a liquid medium containing L-cell-conditioned medium (LCM), a source of colony stimulating factor (CSF), showed a high level of fibrinolytic activity comparable to that of thioglycollate medium-induced peritoneal macrophages (TPM) and at least 20-fold higher than that of resident peritoneal macrophages (RPM). Fibrinolysis was a result of active secretion of PA into the culture medium and plaques of caseinolysis could be detected by an overlay assay over all macrophage colonies formed after cloning of bone marrow cells in culture. When the fibrinolytic activity of BMDM harvested at different times was investigated, it was found that the level of PA activity of a given BMDM population correlated well with the incidence of cells (5-15 percent) able to proliferate and form colonies in agar after 7-14 d, somewhat more slowly than CFU-C. This correlation between the level of PA secretion and the incidence of agar colony-forming cells was also found with other mononuclear phagocyte populations. Active fibrinolysis and slow growing colony-forming cells were observed at the same time as adherent macrophages appeared, 2-3 d after the start of bone marrow culture, they persisted for 10 d before declining. Some of the factors which influenced PA production by BMDM were examined. Fibrinolysis could be enhanced two- to fourfold by exposing the cells for 4 h to concanavalin A (Con A), to medium conditioned by Con A-stimulated spleen cells and to LCM, but not by phagocytosis of latex particles. The substance in LCM that stimulated PA production appeared to be identical to CSF. Mononuclear phagocyte targets differed in their response to LCM, which stimulated fibrinolysis readily in BMDM, to a lesser extent in TPM and not at all in RPM. We conclude that CSF stimulates both proliferation and fibrinolytic activity in BMDM and that the level of macrophage activation, as defined by PA production, can be further enhanced by lymphokines. Induction of PA in BMDM provides a rapid and sensitive assay for measuring the activity of CSF and defining its role in macrophage activation.


Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin. Hemopoietic colony-forming cells committed to macrophage differentiation (M-CFC) are selectively and differentially inhibited by prostaglandin E (PGE). A hierarchy of sensitivity was observed among murine CFC stimulated by colony-stimulating factors (CSF) which differ in their ability to initiate proliferation of morphologically distinct colony types, or stimulated by CSF provided by macrophage feeder layers. Inhibition of macrophage colony formation to 50 percent levels occurred with PGE concentrations between 10(-8) and 10(-9) M, and was still evident at 10(-10) -10(-11) M PGE concentrations. The growth of mixed colonies containing both macrophages and neutrophils was less sensitive to the inhibitory effects of PGE, however, the monocytoid component of these colonies was reduced in the presence of PGE. Neutrophil progenitor cell proliferation was not influenced by PGE concentrations below 10(-6) M, regardless of time of addition of PGE, whereas clonal macrophage expansion, as well as clone size, was sensitive to inhibition by PGE when added as late as 3 d after culture initiation. Prostaglandin F(2alpha), was not inhibitory to colony formation. Experimental evidence for a selective role of macrophage PGE in the regulation of macrophage colony formation was directly provided by utilizing resident peritoneal macrophages as a source of CSF for bone marrow target cell overlays. Simultaneous morphological analysis of colonies proliferating in bilayer culture in response to increasing concentrations of macrophages, and direct measurements of PGE synthesized by an identical number of macrophages maintained in liquid culture demonstrate that a specific decline in macrophage colony formation occurs coincident with a linear increase in macrophage PGE synthesis. Inhibition of macrophage PGE synthesis by indomethacin results in the specific enhancement of macrophage colony formation. Furthermore, macrophage PGE synthesis is induced by CSF preparations with the selective capacity to differentially stimulate macrophage proliferation, but not by those which preferentially stimulate granulocyte colony formation. In comparison to the effects of PGE on M-CFC, polymorphonuclear granulocyte-derived lactoferrin (LF) reduces macrophage production of colony-stimulating activities for macrophage, mixed macrophage- neutrophil and neutrophil colony formation. The ability of LF to reduce macrophage PGE synthesis, presumably by decreasing CSF production, suggests that LF and PGE can interact in the control of macrophage and granulocyte proliferation.


Reversal of nzb/nzw disease with total lymphoid irradiation. NZB/NZW mice spontaneously exhibit autoimmune disease similar to that seen in human systemic lupus erythematosus (SLE). We demonstrated that total lymphoid irradiation (TLI) reversed well expressed disease in 6-mo-old NZB/NZW females with a prolongation in survival, decrease in proteinuria, and decrease in anti-DNA antibodies as compared to control animals. Few side effects were observed in the treated group. TLI also prolonged survival in animals with advanced renal disease. These findings suggest that TLI may have application to the treatment of human SLE.


The time-course of energy balance in an isometric tetanus. Unpoisoned sartorius muscles of Rana temporaria were stimulated tetanically in isometric contractions lasting up to 20 s at 0 degrees C. The observed enthalpy (heat + work) production and the chemical changes in these contractions were measured, and a comparison was made between the observed enthalpy and the enthalpy that could be explained by the chemical changes. Like earlier workers, we found that the only net known reaction of energetic significance that occurred was dephosphorylation of n-phosphoryl creatine (PC), and we found a significant evolution of unexplained enthalpy (UE), a portion of the observed enthalpy which could not be explained by the extent of PC dephosphorylation. We measured the total quantity and the rate of production of the UE, and we found that its rate of evolution, which was most rapid during the first 750 ms of contraction, fell progressively to zero by the 8th s of contraction: i.e., after 8 s of contraction, all the observed enthalpy is adequately explained by PC dephosphorylation. The time-course of evolution of the UE was slower than that of the labile enthalpy (a component of the enthalpy evolved in isometric contraction whose rate of production declines exponentially at approximately 1 s-1). We conclude that, although the magnitudes of these enthalpy quantities may be similar, they are not derived from the same chemical reaction in muscle.


Accuracy of ventricular volume estimation. Sources of error in the estimation of ventricular volume from CAT scans are discussed and the accuracy of the measurement assessed. Two methods of calculating ventricular volume from an intraventricular injection of radioisotope are described and compared. Finally, the CAT scan and isotope methods are compared and contrasted. The error associated with a single measurement of volume by any of these techniques is between 20% and 30%. In patients with no ventricular catheter there is no choice other than to use CAT scanning, but if intraventricular injection is possible this method offers a potentially more accurate volume determination because of his higher signal-to-noise ratio.


The ability of color defectives to judge signal lights at sea. Measures were made of the ability of color-defective men to judge correctly the colors of navigation lights (red, green, or white) presented to them at night under realistic sea conditions. Eighty-one color-defective men were employed; they were categorized as to type and degree of defect using a battery of five color-vision tests. While the average performance of the color-defective men was considerably poorer than that of 24 color normals, there were large individual differences within each category of defect. Attempts to account for these differences in performance by variations in acuity, intelligence, and motivation failed. The extent to which the data can be accounted for by modern color-vision theory is discussed.


Dissolution rate of p-aminobenzoates from solid xylitol dispersions. Xylitol was studied as a carrier in solid dispersions because of its low melting point and stability up to 180 degrees. It is more stable than sucrose and does not enter into Maillard reactions. Solid dispersions were prepared from esters of p-aminobenzoic acid and xylitol by the melting method and were compressed into tablets. The p-aminobenzoate dissolution rates were determined by a modified beaker method. The increase in the dissolution rates was greatest at the lowest drug levels. When the dispersion drug content exceeded 20-30%, the dissolution rate per unit area remained nearly constant. In the latter case, the increase in the dissolution rate was primarily due to an increase in area. When the carbon chain length was increased in the homologous series, the dissolution rate from the xylitol dispersions showed a nearly linear decrease.


Membrane potential, contractile activation and relaxation rates in voltage clamped short muscle fibres of the frog. 1. Voltage clamped short (approximately 1.5 mm) muscle fibres of the frog can develop maximum tension of 4.3 kg/cm2. 2. The time course of contractile responses to prolonged depolarization is markedly dependent on the fibre membrane potential. With sufficiently long pulses the responses present a plateau and a spontaneous relaxation phase. 3. At room temperature (20--22 degrees C), and at membrane potentials of -10 mV the plateau duration is about 2 sec and the spontaneous relaxation rate is 0.50 sec-1. At membrane potentials of -35 mV the plateau duration is 4.6 sec and the spontaneous relaxation rate is 0.28 sec-1. 4. When the fibres are depolarized at room temperature with relatively short pulses (less than 2 sec), the contractile responses are cut short at the end of the pulse, and the fibres relax at a rate (11 sec-1) which is independent on the pulse amplitude and duration. 5. The relaxation rate after a short pulse can be affected by membrane potential only in the region near the contractile threshold where further release of contractile activator is expected to occur. 6. The time course of contractile responses to prolonged depolarization may be shortened by conditioning depolarization. 7. The system responsible for the release of contractile activator may be tentatively described by three states, resting, activated, and inactivated, in analogy with the model proposed by Chandler, Rakowski & Schneider (1976) to describe the possible configurations of the potential dependent charge movement in muscle.


Loss of extrasynaptic acetylcholine sensitivity upon reinnervation of parasympathetic ganglion cells. 1. The extrasynaptic acetylcholine sensitivity of frog cardiac ganglion cells was measured both after denervation and during the early stages of reinnervation by preganglionic axons. Sensitivity was measured by ionophoretic application of acetylcholine (ACh) to randomly chosen sites on ganglion cell bodies. 2. Extrasynaptic sensitivity rose gradually following denervation and after 3 weeks reached a mean value of approximately 1000 mV/nC. 3. Reinnervation of the cardiac ganglion began about 3 weeks after nerve crush. The ACh sensitivity of ganglion cells fell markedly during the 23--31 day period, to a mean of 184 mV/nC. None of forty-three neurones studied during that period received synaptic inputs sufficient to generate action potentials. 4. Twenty-nine of the forty-three neurones examined 23--31 days after nerve crush had not yet received detectable synaptic inputs, yet even these cells had markedly reduced ACh sensitivity. 5. When reinnervation of cardiac ganglia was delayed by resecting the preganglionic nerves, ACh sensitivity was reduced slightly (43%) between 14--21 and 23--31 days after surgery. Thus, most of the sixfold reduction in sensitivity that occurs during this time after nerve crush is a specific effect of reinnervation. 6. We conclude that loss of extrasynaptic receptors coincides with, or may even precede, the earliest physiological signs of synapse formation. Restoration of action potential activity in the ganglion cells is not essential to initiate this loss.


Effect of age and removable partial dentures on gingivitis and periodontal disease. The periodontal disease variables manifested in the individuals with partial dentures were more severe, which suggests that the contribution of denture status is significant. Age, while related to increased bone loss, did not appear to be of significance. Common sense suggests that poor oral hygiene in persons wearing removable partial dentures also is a contributing factor.


Glycerides as prodrugs. 1. Synthesis and antiinflammatory activity of 1,3-bis(alkanoyl)-2-(O-acetylsalicyloyl)glycerides (aspirin triglycerides). A series of 1,3-bis(alkanoyl)-2-(O-acetylsalicyloyl)glycerides (aspirin triglycerides) having aspirin at the 2 position of glycerol and fatty acids at the 1 and 3 positions was prepared. The compounds were administered orally and tested for efficacy in the rat paw edema test, and the stomachs were examined for the presence of lesions. The results showed that the members of this series in which the fatty acids are of intermediate chain length (C4-C12) do not cause gastric lesions and have essentially all the systemic activity associated with aspirin.


The electrogenic sodium pump of the frog retinal pigment epithelium. It was previously shown that ouabain decreases the potential difference across an in vitro preparation of bullfrog retinal pigment epithelium (RPE) when applied to the apical, but not the basal, membrane and that the net basal-to-apical Na+ transport is also inhibited by apical ouabain. The suggested the presence of a Na+ - K+ pump on the apical membrane of the RPE. In the present experiments, intracellular recordings from RPE cells show that this pump is electrogenic and contributes approximately - 10 mV to the apical membrane potential (VAP). Apical ouabain depolarized VAP in two phases. The initial, fast phase was due to the removal of the direct, electrogenic component. In the first one minute of th response to ouabain, VAP depolarized at an average rate of 4.4 +/- 0.42 mV/min (n = 10, mean +/- SEM) and VAP depolarized an average of 9.6 +/- 0.5 mV during the entire fast phase. A slow phase of membrane depolarization, due to ionic gradients running down across both membranes, continued for hours at a much slower rate, 0.4 mV/min. Using a simple diffusion model and K+-specific microelectrodes, it was possible to infer that the onset of the ouabain-induced depolarization coincided with the arrival of ouabain molecules at the apical membrane. This result must occur if ouabain affects an electrogenic pump. Other metabolic inhibitors, such as DNP and cold, also produced a fast depolarization of the apical membrane. For a decrease in temperature of congruent to 10 degrees C, the average depolarization of the apical membrane was 7.1 +/- 3.4 mV (n = 5) and the average decrease in transepithelial potential was 3.9 +/- 0.3 mV (n = 10). These changes in potential were much larger than could be explained by the effect of temperature on an RT/F electrodiffusion factor. Cooling the tissue inhibited the same mechanism as ouabain, since prior exposure to ouabain greatly reduced the magnitude of the cold effect. Bathing the tissue in 0 mM [K+] solution for 2 hr inhibited the electrogenic pump, and subsequent re-introduction of 2 mM [K+] solution produced a rapid membrane hyperpolarization. We conclude that the electrogenic nature of this pump is important to retinal function, since its contribution to the apical membrane potential is likely to affect the transport of ions, metabolites, and fluid across the RPE.


Infectious parotitis in Sjögren's syndrome: a case report and review of the literature. Infectious parotitis as a complication of the sicca syndrome has rarely been reported. A patient with bilateral parotitis due to H. influenza in reported and the literature regarding this rare complication of the sicca syndrome is reviewed. The host defense mechanisms which ordinarily protect normal individuals or patients with Sjögren's syndrome against purulent parotitis are discussed.


Effect of intracellular potassium upon the electrogenic pump of frog retinal pigment epithelium. We have studied the hyperpolarizing, electrogenic pump located on the apical membrane of the retinal pigment epithelium (RPE) in an vitro preparation of bullfrog RPE-choroid. Changes in RPE [K+]i alter the current produced by this pump. Increasing [K+]o in the solution perfusing the basal membrane increases RPE [K+]i (measured with a K+-specific microelectrode), and also depolarizes the apical membrane. The depolarization is due to a decrease in electrogenic pump current flowing across the apical membrane resistance, since it is abolished when the pump is inhibited by apical ouabain, by cooling the tissue, or by 0 mM [K+]o outside the apical membrane. Removal of Cl- from the solution perfusing the basal membrane abolishes the K+-evoked apical depolarization by preventing the entry of K+ (as KCl) into the cell. We conclude that the increase in [K+]i causes the decrease in pump current. This result is consistent with the finding that [K+]i is a competitive inhibitor of the Na+ - K+ pump in red blood cells. It is possible that the light-evoked changes in [K+]o in the distal retina could alter RPE [K+]i, and thus could affect the pump from both sides of the apical membrane. Any change in pump current is likely to influence retinal function, since this pump helps to determine the composition of the photoreceptor extracellular space.


Salicylate-induced gastrointestinal bleeding: comparison between soluble buffered, enteric-coated, and intravenous administration. Serum salicylate levels and blood loss in stools were compared in 94 patients after intake of various forms of acetylsalicylate. Four different oral soluble forms, an enteric-coated variety and an intravenous form were evaluated. Analysis of the results of blood loss measurement in stools showed that salicylate users could be divided into "bleeders" and "non-bleeders". Administration of enteric-coated and intravenous forms of salicylates showed less blood less than ingestion of soluble forms. Only after administration of enteric-coated or intravenous forms of salicylates was a relationship between serum salicylate level and blood loss in stools observed in "bleeders". This suggests a similar mode of action of both these preparations on gastric mucosa. We conclude that enteric-coated forms of salicylates cause gastrointestinal bleeding by a systemic action on gastric mucosa.


Saturable K+ pathway across the outer border of frog skin (rana temporaria): kinetics and inhibition by Cs+ and other cations. The reaction of abdominal skins of the frog species Rana temporaria on mucosal K+-containing solutions was studied in an Ussing-type chamber by recording transepithelial potential difference (PD), short-circuit current (SCC) and conductance (G). With Na-Ringer's as serosal medium, a linear correlation between PD and the logarithm of the mucosal K+-concentration ([K]o) was obtained. The K+-dependent SCC saturated with increasing [K]o, and could quickly and reversibly be depressed by addition of Rb+, Cs+, and H+. Li+, Na+, and NH4+ did not influence K+ current. A large scatter was obtained for kinetic parameters like the slope of the PD-log[K]o-line (18--36.5 mV/decade), the apparent Michaelis constant (13--200 mM), and the maximal current of the saturable SCC (6--50 microa . cm-2), as well as for the degree of inhibition by Cs+ ions. This seemed to be caused by a time-dependent change during long time exposure to high [K]o (more than 30 sec), thereby inducing a selectivity loss of K+-transporting structures, together with an increase in SCC and G and a decrease in PD. Short time exposure to K+-containing solutions showed a competitive inhibition of K+ current by Cs+ ions, and a Michaelis constant of 6.6 mM for the inhibitory action of Cs+. Proton titration resulted in a decrease of K+ current at pH less than 3. An acidic membrane component (apparent dissociation constant 2.5 x 10(-3) M) is virtually controlling K+ transfer. Reducing the transepithelial K+-concentration gradient by raising the serosal potassium concentration was accompanied by the disappearance of SCC and PD.


A morphometric study of the cochlea of the little brown bat (Myotis lucifugus). A detailed morphometric study of the basilar membrane was made from serial sections and graphic reconstructions of the cochlea of three little brown bats. Four distinct morphometric changes were observed within the basilar membrane. First, between 0-1.4 mm from the basal end of the cochlea, there is a rapid increase in width and cross-sectional area of the basilar membrane. Secondly, between 1.4-2.5 mm, there is little change in width of the basilar membrane (its cross-sectional area is at its greatest in this region). Thirdly, between 2.7-3.1 mm, there is a sudden decrease in cross-sectional area concomitant with an increase in the width of the basilar membrane. Finally, between 3.1 mm and the apex, there is a gradual decrease in cross-sectional area concomitant with an increase in the width of the basilar membrane. The magnitudes of the cross-sectional areas of the scalae media and vestibuli decrease from base to apex, but this is not true for the scala tympani. The cross-sectional area of the scala tympani appears to decrease from the base to 0.7 mm, then it increases up to 1.4 mm, and then it decreases to the apex. These morphometric changes in the basilar membrane of the little brown bat are compared to those in other echolocating and non-echolocating mammals. The significance of these changes is discussed in relation to the range of hearing in the little brown bat.


Arnold-Chiari malformation--some otoneurological features. Arnold-Chiari malformation was diagnosed in five patients with vertigo. Four were of anatomical type I. A case report is given of one patient who presented features of a unilateral cerebellopontine angle lesion. Downward beating vertical nystagmus was an important finding in three of the five patients. Other clinical and radiological features of the condition are discussed.


[Effect of hyperventilation on the vestibular system]. Nineteen normal subjects with no past history of hearing or balance impairment have undergone an electronystagmogram (E.N.G.), according to the usual technique in our laboratory. About one month or more after this first test, they underwent a second E.N.G. but this time with periods of hyperventilation distributed at certain precise moments of the test. Our analyses have not demonstrated that hyperventilation causes nystagmus or enhances in preexisting nystagmus in normal subjects, although the changes in the positional test were close to being significant.


Acute epiglottitis: 26 years' experience at the Montreal Children's Hospital. Two hundred and four cases of acute epiglottitis treated at the Montreal Children's Hospital between 1951 and 1978 are reviewed. The comparison of tracheostomy vs. nasotracheal intubation is discussed. Nasotracheal intubation has been found to be the treatment of choice as long as the necessary services are available in the hospital.


Gross hematuria associated with sickle cell trait and von Willebrand's disease. A case of recurrent gross hematuria, sickle cell trait and von Willebrand's disease is reported. The gross hematuria abated promptly after the institution of cryoprecipitate therapy. The importance of considering von Willebrand's disease in the differential diagnosis in patients with sickle cell trait and hematuria is discussed.


Metastatic carcinoma of the penis: complete remission after high dose methotrexate chemotherapy. A case of extensive metastatic epidermoid carcinoma of the penis is reported. Disseminated disease developed after penectomy and lymphadenectomy and it continued to progress while the patient received radiation therapy. Chemotherapy with high dose methotrexate followed by citrovorum factor rescue was instituted. After completion of 10 weekly cycles of treatment there was biopsy-proved complete regression of all lesions, which lasted 9 months when the patient suddenly died of pneumonia completely unrelated to the tumor or chemotherapy treatment. This chemotherapeutic approach deserves additional trial in patients with advanced stages of penile carcinoma.


Primary angiosarcoma of the heart.

Primary angiosarcoma of the heart. An unusual case of primary angiosarcoma of the left atrium in a heart with chronic rheumatic valvulitis is described. The tumor which was detected at autopsy 2 years after the second valvotomy operation was restricted to the endocardium only and metastasized to the brain.


Expression of KB cell alkaline phosphatase isoenzymes during growth in immunosuppressed LEW rats. Alkaline phosphatase isoenzyme expression of human tumor xenografts was studied by the growing of KB cells in immunosuppressed neonatal LEW rats. In culture these cells produced the oncoamniotic (FL) isoenzyme as the major form and the Regan isoenzyme as a minor fraction as well as a "hybrid" that shared properties of both of the other isoenzymes. Despite a reduction in specific activity, this isoenzyme pattern was essentially unchanged during in vivo growth. KB cells "pretreated" in culture with the glucocorticoid prednisolone in hyperosmolal medium exhibited a decrease in the levels of the oncoamniotic (FL) isoenzyme and an increase in the Regan isoenzyme. During growth of pretreated cells in vivo, a time-dependent resumption in the expression of the oncoamniotic (FL) isoenzyme was associated with the disappearance of the Regan isoenzyme. This shows that the expression of the oncoamniotic (FL) isoenzyme is not restricted to human tumor cells monophenotypic with respect to alkaline phosphatase.


Distribution of Lyb-4.1 and other membrane antigens on murine lymphoid tumors. The distribution of membrane antigens on 6 DBA/2-derived tumors (L1210, L5178Y, P815, ABLS 11, ABLS 12, and ABLS 13) was studied by direct cytotoxicity and quantitative absorption assays. Lyb-4.1 antigen was found solely on the L1210 tumor. Iad antigens were absent from all tumors, and H-2Kd and H-2Dd antigens were present on all tumors. Immunoglobulin was adsorbed to the ascites tumors and lost after 3 days or more in tissue culture. These studies were performed to characterize the distribution of DBA/2 membrane antigens on DBA/2-derived tumors as a base line for functional and chemical studies with these tumors and with their solubilized proteins.


[Ocular pathology related to intraocular lenses (author's transl)]. This study describes the ultramicroscopic alterations in several types of intraocular lenses removed from eyes with persistent ocular inflammation or elevated intraocular pressure. In some instances the alterations found in the lens material could have caused ocular disease. The corneal edema present in eyes with intraocular lenses sometimes is related to trauma at the trauma at the time of intraocular lens implantation. In most cases the alterations are similar to those found in Fuchs' dystrophy. The presence of warts in Descemet's membrane indicate previous corneal pathology, an obvious contraindication to the use of these devices.


[Congenital stromal cyst of the iris. A clinico-histopathological case report (author's transl)]. The clinical symptoms and the histopathology of a typical congenital stromal cyst of the iris are described. The difficulties of a correct diagnosis, especially in relation to a spontaneous luxation of the lens into the anterior chamber are pointed out. As to the origin of the cyst the development from transformed corneal endothelium should be taken into consideration.


[Herpes zoster-exophthalmus without ophthalmoplegia (author's transl)]. A case of exophthalmic myositis was identified by a secondary herpes zoster exacerbation. The herpes zoster exophthalmus in this case remained - in contrast to all other cases so far published - free of signs of ophthalmoplegia and retrobulbar neuritis with visual acuity loss.


Pathophysiological aspects of Hodgkin's disease. Hodgkin's disease is characterized by unique features setting it apart from other malignancies. Clinically, systemic symptoms are often prominent and spontaneous remissions may be seen. As major immunological aberrations, a reactive humoral response with hypergammaglobulinemia and a depression of cell-mediated immunity are observed. Pathologically, the diagnosis is based on the presence of pleomorphic morphology; this consists of an infiltrate of reactive inflammatory cells sometimes forming granulomatous lesions with or without varying numbers of the cells presumed to be malignant. The nature of these malignant cells remains undefined, with data supporting mainly B-cell, but also macrophage origin. Clear-cut evidence for monoclonality is available only in prognostically unfavourable histological forms.


[Clinical-functional emphysema diagnostics and immunological correlations (author's transl)]. By application of the correlation flow resistance/intrathoracic gas volume the lung emphysema is differentiated in quality within the scope of chronic obstructive lung diseases. For these groups immunoglobulins, the alpha1-trypsin activity in serum and the activity of further protease inhibitors were determined. There are no substantial variables in the different groups with regard to immunoglobulins. In the emphysema group alpha1-antitrypsin was a little reduced. This group included 2 patients with an alpha1-antitrypsin deficit. The two-dimensional separation of the inter-alpha-trypsin big inhibitor shows 3 areas which decrease significantly in case of severe emphysemata. The irritation of the inter-alpha-trypsin big inhibitor, i.e. in its turnover, parallel to the increasing degree of emphysema formation, is discussed.


[High-dose methotrexate therapy in osteogenic sarcoma: plasma pharmakokinetics to predict toxicity (author's transl)]. In 22 patients with osteogenic sarcoma, treated with 103 high-dose methotrexate infusions (6-8.5 g/m2 in 4-6 h) plasma methotrexate levels were measured with a specific and rapid radioimmunoassay. Nontoxic infusions were associated with methotrexate concentrations below 8.0 X 10(-6) mol/l at 24 h, 8.0 X 10(-7) mol/l at 48 h and 4.25 X 10(-7)/mol/1 at 72 h. All patients with 48 h methotrexate levels above 1 X 10-6 mol/l manifested severe toxicity with myelosuppression and stomatitis due to delayed methotrexate excretion. Rise of serum creatinine was not reliable to predict oxicity. Determination of 48- and 72-h methotrexate concentrations proved to be a valuable method for identifying patients at high risk for toxic side effects. Additional citrovorum factor may thus be given in time.


Internalization and processing of the EGF receptor in the induction of DNA synthesis in cultured fibroblasts: the endocytic activation hypothesis. The addition of EGF to cultured murine 3T3 cells produces a decrease in EGF binding activity with concomitant internalization and degradation of the initially bound EGF. When the EGF receptor on cultured 3T3 cells is affinity labeled with high specific activity 125I-EGF, and the fate of the affinity labeled EGF-receptor complex determined, the loss in binding activity was accounted for by receptor internalization and subsequent proteolytic processing of the EGF receptor molecules in the lysosomes. Studies of the effects of EGF concentration on EGF binding by cells, EGF-induced receptor internalization and EGF-induced stimulation of 3H-thymidine uptake into cellular DNA show that there is a direct correlation between EGF-induced receptor internalization and EGF-induced stimulation of DNA synthesis, but not between EGF binding and EGF-induced stimulation of DNA synthesis. This correlation is lost at high EGF concentrations, where stimulation of DNA synthesis is suboptimal. Optimal stimulation of DNA synthesis requires a minimum of 6 h of incubation of EGF with cells, and the suboptimal stimulation of DNA synthesis at high EGF concentration is intensified when the period of incubation of EGF with cells is less than 6 h. These data are consistent with a model of hormone signal transmission by Endocytic Activation, wherein the activation of EGF-induced processes requires constant EGF-induced internalization of receptor for a requisite 6-8 h period as an obligatory step in production of "second messenger" in the action of this hormone.


[Effect of limited mobility on vestibular function]. The hypokinetic effect on the nystagmic reaction and illusory sensations upon caloric and galvanic stimulations of the labyrinths was studied on six test subjects (professional gymnasts). Under normal conditions the sportsmen predominantly showed the nystagmic response to the caloric irritation of the left labyrinth. A 10-day hypokinetic exposure produced a noticeable decrease of the above asymmetric nystagmic reaction to the caloric irritation of both labyrinths. Simultaneously an enhancement of illusory sensations and a decrease of their thresholds in response to the firect current labyrinthine stimulation were noted. The above changes can be  attributed to the hypokinesia-induced decline of mechanisms of vestibular adaptation of sportsmen.


The effect of anticancer therapy on peripheral blood T and B lymphocyte counts and function. Patients categorized according to tumor type were compared to a control non-tumor population. Comparison of relative T cell values among the groups showed no significant differences; however, when absolute numbers of T cells/mm3 were compared, all cancer patients, whether from treated or untreated groups, had significantly depressed T cell values. No significant differences were observed in the relative or absolute numbers of B cells. Comparison of the total lymphocyte response to PHA showed no significant differences among the various cancer groups; however, response in all cancer groups whether from treated or untreated patients, was depressed by comparison to the control group. Patients categorized according to the type of treatment received showed significant depression in the white blood count, lymphocyte count, relative and absolute T cell counts and the absolute B cell count in the postsurgery, postadjunctive therapy group. The pretherapy group also showed significant depression in the absolute number of T cells/mm3 when compared to the controls. Response to PHA correlated with the absolute T cells values.


Ventricular pump performance during hypocalcemia: clinical and experimental studies. We have compared indices of ventricular function during rapid transfusion of citrated (1.5 ml/kg/min) or heparinized (1.5 ml/kg/min) autologous blood in six patients following discontinuation of cardiopulmonary bypass. Infusion of citrated blood was associated with a lowering of plasma ionized calcium concentration ([Ca++], from 0.90 +/- 0.04 to 0.71 +/- 0.4 mM, p less than 0.001) and an increase in pulmonary artery balloon-occluded pressure (PA0, from 9.4 +/- 2.6 to 15.5 +/- 1.7 mm Hg, p less than 0.u1), without a change in left ventricular stroke work index, stroke index, or cardiac index. Transfusion of heparinized blood caused no change in plasma [Ca++]. A rise in PA0, which was similar in magnitude to that observed during citrated blood transfusion, was associated with increased left ventricular stroke work index, stroke index, cardiac index, and mean arterial pressure. Although data obtained during citrated blood transfusion suggest the presence of transient left ventricular dysfunction, its magnitude is not readily expressed in terms of ventricular function curves when accompanied by a simultaneous change in [Cized closed-chest dog by volume loading during hypocalcemia, when mean arterial pressure, heart rate, and [Ca++] were in a steady state, both prior to and following beta blockade with propranolol. Function curves obtained during severe hypocalcemia ([Ca++] = 0.43 +/- 0.02 mM) were shifted significantly to the right and downward, when compared to those obtained during normocalcemia ([Ca++] = 1.06 +/- 0.03 mM). Hypocalcemia combined with beta blockade resulted in severe left ventricular failure, as demonstrated by a flat ventricular function curve.


Detection, prediction, and significance of perioperative myocardial infarction following aorta-coronary bypass. One hundred consecutive patients undergoing aorta-coronary bypass grafting (ACBG) alone, without ventricular venting, were prospectively studied to determine the incidence and consequence of perioperative myocardial infarction (PMI) and the clinical variables that were predictive of PMI. Incidence was determined by serial electrocardiography (ECG) 100 patients; serum CK, GOT, and LDH (100 patients). CK isoenzymes (qualitative 100 patients, quantitated 50 patients); vectorcardiography (VCG) (78 patients); and 99mtechnetium pyrophosphate scintigraphy (TcPyp) (52 patients). The incidence of PMI by ECG was 9%; an additional 8% of cases was diagnosed by enzymes alone. The incidence of diagnostic change by VCG was 19% and by scintigraphy, 25%. Using at least one changed variable of the remaining three as the reference standard, the relative sensitivity and relative specificity of given variables in the diagnosis of PMI were as follows: ECG 67% and 100%, respectively; VCG 85% and 94%; scintigraphy 92% and 97%; and serum enzymes 86% and 96%. By univariate analysis, unstable angina was the only significant predictor of PMI. The operative mortality rate was 2% and the mortality rate at 12 months was 5%. There was a significantly greater mortality rate in patients with PMI diagnosed by ECG (p less than 0.01), in patients with unstable angina pectoris before operation (p less than 0.05), and in women (p less than 0.05).


Concordance between medical records and observations regarding information on coordination of care. This study was designed to determine the extent to which the medical record contained evidence of coordination of care. Coordination of care was defined as the recognition of information (problems, therapies, intervening visits and tests) about patients from one visit to a follow-up visit. Overall, there was concordance between the medical record and independent observation of the physician-patient interaction in 70-85 per cent of instances. When there was clear indication that the practitioner recognized the information, the chart contained evidence of this recognition 68-85 per cent of the time, depending on the type of information. However, if the information was highly salient, the record contained evidence of recognition in a much greater percentage of intances: 95 per cent for distinctly identified problems, 83 per cent for problems which were contained within the text of progress notes, 96 per cent for major drugs, and 94 per cent for abnormal tests. The data from this study support the less direct evidence of others that the medical record adequately reflects extent of recognition of important information about patients by practitioners.


[Tracheal transplantation in inbred strains of rats.--III. The morphologic substratum of host-versus-graft reaction (author's transl)]. After isogeneic, allogeneic and allogeneic second-set tracheal transplantations gradually different morphological signs of a chronic host-versus-graft reaction in the wall of the transplants are observed. In no case there was a complete necrosis by rejection evident.


[Tracheal transplantation in inbred strains of rats.--IV. Histologic and histoautoradiographic findings in the epithelium (author's transl)]. In the first ten days after transplantation isogeneic and allogeneic tracheal transplants keep their epithelium, showing metaplasia as a sign of distinct regenerative activity in this time. In various degrees dependent on the constellation of experiments there are only signs of a weak chronic rejection. After more than 280 days again a stratified epithelium can be seen. In exeptional cases mucosa of second-set-transplants only show an obvious rejection reaction.


[Medico-legal assessment of vestibular disturbances (author's transl)]. In the medico-legal assessment of vestibular disturbances the degree of handicap in daily and occupational situations is to be considered. Therefore a five degree classification of everyday performances (physiological stimuli of daily life) involving the vestibular system and a grading of vestibular disorders based on subjective and objective symptoms have been compiled. A diagram relating intensity of vestibular disturbance with performance gives the percentage of reduction in working capacity (MdE).


[Significance of variations in the size of Trichomonas vaginalis in patients with dysplasia, intrapithelial and invasive planocellular carcinoma of the uterine cervix]. The study of the size of Trichomonas vaginalis in 100 patients with dysplasia and intraepithelial or invasive planocellular carcinoma of the uterine cervix and in 100 controls with trichomoniasis alone has shown that the parasites are of a significantly smaller diameter in carcinoma in situ (9.57 +/- 0.35 mu) and invasive carcinoma (10.44 +/- 0.66 mu) than in dysplasia (13.71 +/- 0.35 mu). The analysis of the variance has shown that this difference is statistically significant. In the control group with trichomoniasis alone, the diameter of Trichomonas vaginalis was twice as large (21.46 +/- 0.66 mu) as that in carcinoma and still larger than that in dysplasia. This indicates that small forms of Trichomonas vaginalis are more pathogenic than large ones and might be one of the causative agents of the atypical transformation of the squamous epithelium of the uterine cervix.


[Vestibulo-ocular reactions by infants and young children (author's transl)]. Neurootological research demonstrated significantly different vestibulo-ocular reactions by infants and young children as compared to adults. Neurohistological research has demonstrated that the vestibular apparatus is developed by birth and therefore should be fully functional. Fifty full-term and healthy infants and children between 9 days and 24 months of age were placed on an electrically controlled rotating chair in order to determine the functional development of the vestibular system. The rotational test program consisted of a supraliminal acceleration stimulus of 3 degrees/s2, a constant rotation at 90 degrees/s for 3 minutes, and a final abrupt deceleration stimulus. The frequency and amplitude of the per- and post-rotatory nystagmus reaction were analysed from the electronystagmogram. The nystagmus frequencies demonstrate a low level in the first month. The per- and post-rotatory deviate clearly from each other in the following months. The amplitude values also start out low in the first month then climb thru the 7th month and finally stabilize or drop slightly in both the per- and post-rotatory phases. The accumulated results will be discussed and typical examples will be demonstrated.


Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Multiple sclerosis (MS) is a disease with no known treatment. In view of this and of its distressing nature patients are attracted by any new concepts. As a reaction to this neurologists are sometimes excessively sceptical and fail to consider new approaches seriously. Recent attempts have been made to treat multiple sclerosis with polyunsaturated fatty acids and with colchicine. This approach is not arbitrary and is firmly grounded in fundamental basic scientific concepts. In patients with multiple sclerosis there is evidence of both an abnormality in essential fatty acid metabolism and an abnormality in lymphocyte function. It is now apparent that the fatty acid abnormality may cause the lymphocyte abnormality and that both may be improved by dietary manipulation. There is also evidence that the demyelination may be associated with recurrent inflammatory episodes and with entry of calcium into the cytoplasm. In vitro colchicine has been shown to have actions compatible with regulation of cytoplasmic calcium and in two diseases characterised by intermittent inflammatory episodes (Behçets syndrome and familial Mediterranean fever) it has been found to prevent or to reduce the severity of such episodes. Preliminary results suggest that combined therapy with evening primrose oil and colchicine may be of considerable value.


[Localization by paper blotting technique of electrophoretic fractions on starch gel. Application to alpha 1 - antitrypsin (author's transl)]. The authors describe a paper blotting technique to reveal starch electrophoresis. After 3 minutes of contact between the paper band and the starch gel the former can be either dried during 5' at 90 degrees C then stained with nigrosine or sliced and revealed by an immunserum. This quick technique has been successfully applied to alpha-1-antitrypsin; on the one side phenotypes can be identified 24 hours earlier than with staining method using amido black 10 B and on the other side quality control of the fractionning can be done before the second stage of the Laurell type two-dimension separation.


The pineal and regulation of fibrosis: pinealectomy as a model of primary biliary cirrhosis: roles of melatonin and prostaglandins in fibrosis and regulation of T lymphocytes. Pinealectomy leads to increased formation of fibrous tissue in the abdominal cavity, increased skin pigmentation and elevated cholesterol and alkaline phosphatase levels. It also leads to reduced formation and/or action of prostaglandin (PG) E1 and thromboxane (TX) A2. PGE1 plays an important role in enhancing function of T suppressor lymphocytes which control overactive antibody-producing B lymphocytes. In primary biliary cirrhosis there are increased skin pigmentation, hepatic fibrosis, elevated cholesterol and alkaline phosphatase levels, defective T lymphocytes and hyperactive B lymphocytes. Primary biliary cirrhosis may be a pineal deficiency disease. Serotonin is important in the pineal and the serotonin antagonist methysergide may cause retroperitoneal fibrosis by interfering with pineal function. There is a good deal of other evidence which suggests that melatonin PGE1 and TXA2 are important in the regulation of fibrosis in other situations such as "collagen" diseases, lithium-induced fibrosis and cardiomyopathies. This suggests that enhancement of formation of PGE1 and TXA2 may be of value in diseases associated with excess fibrosis and defective T suppressor cell function. PGE1 levels may be raised by zinc, penicillin, penicillamine and essential fatty acids. TXA2 levels may be raised by low dose colchicine. These new approaches to treatment may prove safer and more effective than existing ones. They may be of value in disorders such as cardiomyopathy, Hodgkin's disease and other lymphomas, multiple sclerosis, Crohn's disease, atopy and other diseases in which defective T cell function is suspected.


Coronary bypass grafting in early stages of acute myocardial infarction. Acute coronary bypass surgery was performed in four patients with early anterior myocardial infarction due to severe proximal stenosis of the left anterior descending artery. Improvemnet of left ventricular anteroapical wall contraction was detected at the completion of the operation, in the early postoperative phase, and six to 18 months after surgery. It is concluded that critically ischaemic myocardium was salvaged by revascularization.


Ectopic production of human chorionic gonadotropin: a case report. The ectopic production of the beta-subunit of human chorionic gonadotropin (hCG) is described in a patient with an anaplastic carcinoma. After chemotherapy the marker decreased in a logarithmic fashion to undetectable levels but the neoplasm progressed and the patient died. The specificity of the beta-subunit of hCG is discussed. Discordance of the marker and clinical disease is pointed out, and several possible explanations are outlined. The lack of specificity of the beta-subunit of hCG and the discordance that it may exhibit means that its use in diagnosing and following disease progression may be limited.


Analysis of photoenzymatic repair of UV lesions in DNA by single light flashes. XII. Evidence for enhanced photolysis enzyme-substrate complexes by a 2-photon reaction. Yeast photoreactivating enzyme (PRE), preilluminated with wavelengths ranging from the near-UV to the red spectral region, forms with 254 nm-irradiated transforming DNA of Haemophilus influenzae enzyme-substrate complexes that are more efficiently photorepaired than complexes formed from non-preilluminated PRE. The action spectrum for this "preillumination effect", previously shown to have a maximum in the near-UV region, has another maximum near 577 nm. In complexes formed from non-preilluminated PRE the repair probability per incident photon is only about 25% of that in complexes formed from preilluminated PRE, if low-intensity photoreactivating light is applied continuously or as a sequence of flashes. However, photoreactivating light in the form of a single, high-intensity flash of 1 msec duration raises the repair probability to greater than 50%. Two light flashes, discharged with a delay of slightly more than a millisecond, may already achieve less photorepair than the same energy given as a single flash. These results are explained by the assumption that the great majority of PRE molecules in a non-preilluminated preparation have reduced activity (of the order of 1/4 of maximal activity). These less reactive molecules form enzyme-substrate complexes ("non-activated complexes") in which the repair probability per incident photon is considerably increased if 2 or more photons are absorbed within a time period of the order of milliseconds. This phenomenon, tentatively termed "2-photon photolysis" does not occur in "activated complexes" (i.e. those formed form preilluminated enzyme). The data are compatible with suggestion that the first absorption leads to a metastable excited state of the complex, during which the repair probability is increased by absorption of another photon. The generally observed heterogeneity of the photolytic response of enzyme-substrate complexes can be partly explained by heterogeneity of PRE molecules regarding their activity. In particular, uncontrolled exposure of enzyme to almost any kind of room light before its experimental use can enhance the heterogeneity.


Clinical utility of lymphocyte surface markers combined with the Lukes-Collins histologic classification in adult lymphoma. To determine whether analysis of lymphocyte surface markers adds clinically useful information to the Lukes-Collins classification of lymphomas, tumors from 107 adults were histologically classified and studied for surface markers. Ninety-six cases were histologically classified as Lukes-Collins B-cell lymphomas; 87 showed B and one showed T surface markers, whereas eight had neither marker. Eleven lymphomas were histologically T-cell tumors; four of the 11 showed T surface markers, and seven had neither marker. Both the Lukes-Collins classification and surface markers identified patient groups with different clinical characteristics, chemotherapeutic responsiveness and survival. However, by combining surface markers and histologic features, additional important therapeutic and prognostic information was obtained. In each histologic class, patients whose lymphomas failed to express immunologically the histologically predicted marker had fewer responses to chemotherapy and shorter survivals than patients whose lymphomas expressed the predicted marker. Our data suggest that the analysis of surface markers in combination with the Lukes-Collins classification identifies many patients who respond poorly to current therapy and who thus require new therapeutic approaches.


Persistence of inhibitory activity against normal bone-marrow cells during remission of acute leukemia. Bone-marrow cells from patients with acute leukemia in remission were tested for their capacity to produce a substance (leukemia-associated inhibitory activity, LIA) that inhibits the formation of granulocyte and macrophage colonies in cultures of normal, but not of leukemic, bone marrow. LIA was detected in extracts of whole marrow in only eight of 83 patients in remission. However, extracts of slowly sedimenting cells, separated by velocity sedimentation from the marrows of eight patients in remission whose whole marrow had produced no LIA, produced inhibitory material in all cases. Extracts of the more rapidly sedimenting cells from these marrows contained an inactivator of LIA. Three of six patients in remission whose unfractionated marrow was unresponsive to LIA had a subpopulation of colony-forming cells that was sensitive to the inhibitor. These observations suggest that certain cellular functions dot not completely return to normal during remission of acute leukemia.


[Arterio-veinous malformations located within the occipito-cerebello-mesencephalic dihedral (author's transl)]. About 4 cases of arterio-veinous malformations located within the occipito-cerebello-mesencephalic dihedral (which is this region of the brain including the cistern of Galen and the surrounding formations : the quadrigeminal bodies forwards, the splenium of the corpus callosum upwards, the upper face of the cerebellum and the pedonculus cerebellaris superior below) the authors related their own experience. These 4 cases are detailed from a clinical point of view. Them, a synthetic study is undertaken in which a comparison is done between the literature and the clinical features encountered : headache, sub-archnoid hemorrhage, impairment of consciousness, clinical features such as cranial nerve impairment, nystagmus motor impairment, cerebellar deficit, hydrocephaly. The value of angiography, ventriculography and CAT is discussed. All these patients have been operated upon as far as the authors think that a better chance can thus be offered to them. The choice of the technique is discussed. For one patient, the sub-temporal route was performed ; but it seems worth using the posterior inter-occipital route : this allows a better view on the lesion and an easier treatment of the malformation. These 4 patients suffered post operatively of a visual defect. The control angiography revealed no more arterio-venious malformation in two patients, a mild one in two others.


[Stimulation of the periaqueductal gray matter for pain : electrical activity and evoked potentials (author's transl)]. There is some evidence that stimulation of the periaqueductal gray matter produced analgesia is accomplished by the activation of neuronal systems where endorphins are thought to be transmittors. However, the neurophysiological mechanism of this stimulation is not elucided. In this preliminary paper, the spontaneous and the evoked electrical activity has been studied in 3 patients operated on with implantation of an electrode in the periaqueductal gray matter for chronic pain. Particularly interesting are the pronounced decrease of the evoked potentials in the sensory nucleus of the thalamus after stimulation of the periaqueductal gray matter.


[Transcutaneous electroanalgesia and naloxone. Clinical aspects (author's transl)]. Recently, Mayer (1977) and Adams (1976) proved that both acupuncture and direct electrostimulation of deep encephalic structures produce an analgesic effect releasing a neurotransmitter similar to morphine (endorphine). We have verified this hypothesis, using the transcutaneous electrotherapy in five patients with chronic pain at the back (postherpetic neuralgia in 3, pain cancer in 2). All patients related a certain analgesic effect during electrotherapy, with a reduction in pain of more than 50 per cent. During electroanalgesia we administered Naloxone (an antagonist of morphine). In 3 cases we observed a clear, although short, return of algic symptomatology. At the contrary, in other two patients Naloxone caused briefly a further and clear reduction in the pain.


Effect of administration of 5-hydroxytryptophan and an inhibitor of L-aromatic amino acid decarboxylase on glucose metabolism in rat brain. The effect of 5-hydroxytryptophan (5-HTP)--the precursor of serotonin (5-hydroxytryptamine, 5-HT)--and of an inhibitor, N-(DL-seryl)-N'-(2,3,4-trihydroxybenzyl)hydrazine (Ro4-4602), of L-aromatic amino acid decarboxylase on the metabolism of glucose to amino acids in brain tissue was investigated. Labeled glucose (20 muCi, 0.24 mg in 0.2 ml 0.9% saline) was injected intravenously into fed rats pretreated with Ro4-4602 (50 mg/kg intraperitoneally) either alone or in combination with 5-HTP (30 mg/kg intravenously) or with the appropriate vehicle. After the injection of Ro4-4602 plus 5-HTP, the concentrations of 5-HT and 5-HTP in brain were increased, but the increase of 5-HTP was more pronounced and prolonged than the increase in 5-HT. This suggested that Ro4-4602 slightly inhibits the reaction of decarboxylation in the brain, although at the dose used the drug is usually considered to act only peripherally. After administration of Ro4-4602 alone or combined with 5-HTP, the concentration of glucose in plasma was not significantly increased. However, the concentration of glucose in brain was markedly increased with such treatments. The administration of Ro4-4602 alone or combined with 5-HTP reduced the flux of 14C from labeled glucose to amino acids in brain. The concentrations of amino acids in brain were little changed by these treatments.


Subcellular distribution of corticotropin-releasing factor in the medio-basal hypothalamus of the rat. Subcellular fractionation of the mediobasal hypothalamus (MBH) and frontal cerebral cortex was performed by differential and discontinuous sucrose gradient centrifugation. Corticotropin-releasing factor (CRF) activity of the different fractions was evaluated by bioassay. Significant CRF activity was found in acidic extracts of the MBH but not of the cerebral cortex. About 80% of the MBH effect on adrenocorticotropic hormone release was recovered in the crude mitochondrial pellet (P2) which contains synaptosomes. After further fractionation, distribution of CRF activity paralleled that of lactate dehydrogenase activity, a marker of the soluble cytoplasm. It is concluded that most CRF in the MBH is located in nerve endings as already shown for several other neurohormones.


Cortical atrophy, ventricular enlargement and intellectual impairment in the aged. Fifty-nine subjects over age 60 had a computerized tomography (CT) scan and completed four neuropsychological tests. Measurements of ventricular size and sulcal enlargement were compared to test performance. Performance of the elderly subjects was also compared to that of subjects aged 16 to 40 years. Subjects over 60 years of age had significantly more brain atrophy and more impaired test performance than younger subjects. Subjects aged 80 to 99 had more atrophy and impaired performance than those 60 to 79 years. Our results suggest that, with aging, the brain atrophies and loses its abilities as measured by neuropsychological testing. However, CT evidence of atrophy only weakly predicts impaired mental function independently of age.


[Correlations between splenoportographic findings and risk of digestive hemorrhage in portal hypertension]. In 102 cases examined by splenoportography (93 cirrhosis with patent splenoportal axis and 9 splenoportal thrombosis without appreciable liver changes), the occurrence of episodes of digestive haemorrhage was statistically correlated with age, sex, type of portal impediment, type of collateral circulation, and the presence or otherwise of ascites, and with portal pressure values measured by splenomanometry. The only statistically significant correlation was that concerning the type of hepatofugal collateral circulation, as digestive haemorrhage proved gradually less frequent in patients with gastro-oesophageal collateral circulation, in those with so-called infraportal collateral circulation and, finally, in those where angiography was unable to demonstrate the presence of any collateral circulation at all.


[Aneurysms of the coronary arteries. Apropos of a case of bilateral aneurysm successfully treated by surgery]. Successful surgical management of multiple aneurysms of the coronary arteries by means of an aorto-coronary by-pass was later followed by equal success in the treatment of a double aneurysm of the carotid siphon. The literature appears not to contain any previous report of such an association. The pathogenesis, complications and therapeutic management of this uncommon branch of coronary pathology are discussed.


[Problems in emergency surgery: segmental portal hypertension]. Three typical cases of segmental portal hypertension due to occlusion of the splenic vein are reported. This syndrome may be asymptomatic for a very long time and then present suddenly in the form of a serious picture of high digestive haemorrhage due to rupture of the varices of the fundus of the stomach as a result of hypertrophized submucous collateral drainage circulation. Useful for diagnosis are oesophagogastroduodenoscopy, which points to stomach varices, and splenoportography or superselective arteriography of the splenic artery with venous phase, which highlight pathognomonic dilatation and tortuosity of the gastroepiploic veins. Surgical exploration typically shows: presence of large epipolic vessels, splenomegaly, absence of changes in the liver and in the portal and mesenteric circulation. Resolutive treatment of choice is splenectomy.


Tissue culture of adult human neurons.

Tissue culture of adult human neurons. Dissociated neurons from adult human trigeminal and superior cervical ganglia were cultured in vitro for more than 2 months. Immediately after dissociation by incubation in 0.06% collagenase for 15--18 h, the cultures consisted of single neurons or clumps of neurons and degenerating fragments of myelinated or non-myelinated axons. After 7--10 days, bipolar Schwann cells, large neurons and fine nerve fibers were observed. Electron microscopic examination of these neurons revealed all the ultrastructural features of healthy adult neurons including those of lipofuscin pigments. By electrophysiological technique, extracellular recording to action potentials generated by these neurons were obtained indicating the neurons were alive and healthy. The availability of adult human neurons in culture should provide a model system for investigation related to the pathomechanism of lipofuscin formation and aging in general.


Direct septo-hypothalamic projections in the rat. Axonal projections from neurons located in the medial and lateral septal nuclei (MSN and LSN) were traced autoradiographically. The MSN projected bilaterally via a midline route to the diagonal band of Broca (DBB), the preoptic area (POA), the suprachiasmatic (SCN), paraventricular (PVN), ventromedial (VHM) and arcuate (ARC) nuclei including the median eminence (fiberous zone). Lateral coursing fibers traveled with the medial forebrain bundle (MFB) to the supraoptic (SON) and pre- and supra-mammillary nuclei. The majority of LSN axons projected to, and terminated in, the MSN. Fibers projected ipsilaterally through the POA, SON, SCN, ARC, ME and MMN with axonal projections observed throughout the MFB. In summary, the neurons of the MSN project to the medial hypothalamic nuclei via a midline route while LSN axons projected strongly to the MSN with the remaining fibers coursing along the ipsilateral MFB to terminate in several hypothalamic nuclei. These data indicate that a direct septo-hypothalamic pathway exists in the rat.


Visual prognosis in bacterial endophthalmitis treated with intravitreal antibiotics. Eleven of 16 cases of human culture-proved endophthalmitis have been successfully treated with the intravitreal administration of 400 micrograms of gentamicin sulfate and 360 micrograms of dexamethasone with concomitant use of systemic antibiotics and prednisone. Seven of the 16 eyes (44%) had final visual acuity of 20/400 or better. Four additional eyes had residual useful vision after treatment. The visual prognosis in these cases is directly related to the exotoxin and proteolytic enzyme activity of the organisms. Delay of more than 36 hours between onset of symptoms and intravitreal treatment adversely affects the visual outcome. If a highly virulent organism has been isolated or if treatment has been delayed, vitrectomy to treat acute endophthalmitis is indicated. The comparatively high rate of recovery in this series is probably related to the high dose of intravitreal gentamicin utilized and the concomitant intraocular use of dexamethasone.


Relationship of oral complications to peripheral blood leukocyte and platelet counts in patients receiving cancer chemotherapy. Patients undergoing cancer chemotherapy often suffer from oral complications as a result of their disease and its treatment. The effects of the chemotherapy on the bone marrow and oral mucosa, coupled with the patient's immunosuppressed state and altered oral microbial flora, predispose these patients to oral mucositis, infection, and hemorrhage. The oral mucosa appears to mirror the effects of the chemotherapy on the bone marrow, as there appears to be a direct relationship between the changing peripheral blood counts and the status of the oral mucosa.


Acute intracranial vascular accidents.

Acute intracranial vascular accidents. Cerebellar hemorrhage, cerebellar infarction, pontine hemorrhage, and pontine infarction are four clinical conditions representative of intracranial posterior fossa accidents, which can mimic acute vestibular disturbances. It is exceedingly important to recognize these clinical entities early and to differentiate them from peripheral vestibulopathies so that appropriate diagnostic tests and therapeutic measures can be instituted early to prevent the high mortality rate seen without appropriate treatment. It is appreciated that without computed axial tomography, rapid diagnosis of these clinical syndromes is more difficult, but it is still possible on the basis of the clinical clues mentioned if their potential significance is recognized.