Spontaneous rosette formation by lymphocytes. Differential effect of cytochalasin B on thymocytes and thymus-related peripheral blood lymphocytes in the guinea-pig. In the present investigation the differences in the capacity of thymocytes (Th) and thymus-related peripheral blood lymphocytes (TBL) of the guinea-pig to form spontaneous rosettes with rabbit erythrocytes (RRBC) were further evaluated. Cytochalasin B (CB) inhibited TBL rosette formation but was largely ineffective with respect to Th. This suggests that membrane modulation and microfilament function are requirements for the formation of TBL but not of Th rosettes. A certain critical RRBC receptor density on the lymphocyte may be necessary for a stable rosette. Our results suggest that different RRBC receptor densities on Th and TBL account for the differences in rosette forming capacity of these two cell types. In native Th, the receptor density may be high enough to warrant stable rosette formation. In TBL, however, active membrane movement and perhaps clustering of receptors may be necessary to achieve the local critical receptor density as prerequisite of a stable rosette.


Unusual roentgenographic manifestation of Pneumocystis carinii pneumonia. An immunologically deficient patient had two large nodular densities on the chest x-ray film. On autopsy, large solid accumulations and diffuse pneumonitis with Pneumocystis carinii were found. This represents an unusual manifestation of Pneumocystis carinii.


Primary choroid plexus papilloma of the cerebellopontine angle presenting as brain stem tumor in child. A case of a primary choroid plexus papilloma of the cerebellopontine angle in an 8-year-old female is presented. The clinical features of progressive cranial nerve palsies and cerebellar signs in the absence of intracranial hypertension initially suggested an intrinsic brain stem lesion. Whereas a radionuclide brain scan demonstrated abnormal uptake in the region of the pons, vertebral angiography and pneumoencephalography were diagnostic of an angle mass. At surgery, the tumor proved to be a choroid plexus papilloma that was totally confined to the cerebellopontine angle. This patient represents the thirteenth reported case of a primary cerebellopontine angle papilloma and the first such case occurring in a child.


[Endoscopic diagnosis and directed surgical treatment of the Mallory-Weiss syndrome using cardiatomy]. 18 cases of Mallory-Weiss-syndrome verified endoscopically are reported. The patient group is surveyed with regard to age and sex distribution as well as accompanying diseases responsible for vomiting. 16 patients were treated conservatively, 2 underwent surgery. Diagnosis, indication of surgical management by selective cardiomyotomy and fundal plasty are described in 2 cases.


[Massive gastrointestinal hemorrhage following internal drainage of pancreatic pseudocysts]. In operative treatment of pancreatic pseudocysts by inner drainage there is a risk of massive gastrointestinal bleeding particularly following an anastomosis to the stomach. In 10 patients in whom cystogastrostomy or cystoduodenostomy had been performed elsewhere a second laparotomy was necessary because of acute bleeding. In one patient a cystadenoma of the pancreas had been anastomosed to the duodenum by mistake at the previous operation. The leak of obliteration of the cyst is suggested to be the most important factor in the pathophysiology of bleeding. Inner pseudocyst drainage in a disconnected small bowel loop therefore principally should be performed at the lowest point of the cyst. The indication for an inner cyst drainage, however, must be closely examined since simultaneous pathologic changes in the pancreas often justify a resection to remove the origin of the cyst and, further, averting the complications of an inadequate inner pancreatic cyst drainage.


[Field study on the therapeutic value of trasylol in traumatic shock]. A report of the results of a multicenter study including 4686 patients concerning the therapeutic value of Trasylol (Aprotinin) in traumatic shock. The group treated additionally with Trasylol showed, beside a reduced overall mortality, a statistically significant reduction of mortality in those treated within the first 30 min after the injury. Surgery performed in the posttraumatic stage showed a lower mortality in the Trasylol group. The importance of a time factor in shock treatment and the effects of Trasylol in traumatic shock are emphasized.


Secondary cytotoxic allograft responses in vitro. II. Differentiation of memory T cells into cytotoxic T lymphocytes in the absence of cell proliferation. Murine cytotoxic T lymphocytes (CTL) were induced in "one-way" mixed lymphocyte cultures and their physical characteristics investigated by velocity sedimentation at 1 X g. The in vitro differentiation of progenitors of CTL into primary and secondary CTL was paralleled by characteristic changes in the size of the responder cells. Fractionated cells enriched for primary blast CTL reverted into clonally restricted "nonlytic" secondary T lymphocytes. Upon antigenic reexposure, these lymphocytes differentiated into secondary CTL within 18-32 h. This took place in the absence of cell proliferation and could be triggered by UV light irradiated allogeneic stimulator cells. It is suggested the different characteristics for the induction of either a primary or secondary cytotoxic T cell response reflect qualitative differences between unprimed T cells and memory T lymphocytes.


Rapid recovery of antigen-binding receptors on chicken B cells following anti-Ig serum treatment. Rosette-forming cells (RFC) from the peripheral blood of sheep red blood cell (SRBC)-immunized chickens were characterized as B cells which manifest antigen-binding receptors but no antibody secretion. Lymphocytes were pretreated at 0 degrees C with anti-Ig serum, washed, incubated further at various temperatures and harvested for the rosette-forming cells (RFC) assay. Anti-Ig treatment blocked all RFC formation and providing that the cells were maintained at less than 10 degrees C regeneration did not occur up to 6 h. Complete recovery of RFC formation occurred within 10 min at 37 degrees C following treatment with low but not with high concentrations of anti-Ig serum. However, recovery from inhibition by high-dose anti-Ig treatment was achieved by including chicken IgG in the incubation medium. The recovery of receptors was reduced following "sandwich" treatment of lymphocytes. When cells were treated with anti-Ig antibody, washed and exposed to various drug inhibitors of "capping" the regeneration of RFC was prevented; in contrast, inhibitors of protein synthesis were ineffective. The results were interpreted in terms of dissociation of anti-Ig antibodies from the Ig receptor at an early stage of the ligand-induced receptor redistribution process.


Requirement for accessory cells in the antibody response to T cell-independent antigens in vitro. The antibody responses of mouse spleen cells in vitro to three thymus-independent (TI) antigens namely, polymeric flagellin (POL) of Salmonella adelaide, DNP-Ficoll and "soluble" sheep erythrocyte (SRBC) antigen, were found to be dependent on adherent accessory cells (A cells) but to a lesser degree than the response to intact SRBC. Evidence for this comes from selective depletion of A cells from spleen cells and reconstitution with A cell-rich populations. Thus, depletion of A cells by adherence on glass resulted in abolition of the response to SRBC leaving the response to POL intact. More thorough removal of A cells by treatment with carbonyl iron powder was required for appreciable reduction of the responses to POL, DNP-Ficoll and "soluble" SRBC. This reduction in responsiveness was not due to poor cell survival after A cell depletion or to the loss of immunocompetent cells since 1) the recoveries of viable cells in all cultures were similar; 2) the contents of theta- and Ig-bearing cells and tritium-labeled POL-binding cells were unaltered after carbonyl iron treatment, and 3) responsiveness was fully restored by the addition of irradiated and anti-theta-treated A cells from the peritoneal cavity or the spleen. Hence, the hitherto A cell independence of TI antigens on which some theories of B cell activation are based is a result of inadequate depletion procedures, and the minimal model for B cell activation must take into account two cell types: B cells and A cells.


IgG response in vitro. I. The requirement for an intermediate responsive cell type. We have studied a secondary IgG anti-dinitrophenyl response in dissociated mouse spleen cell cultures which is comparable in magnitude to the responses detected after adoptive transfer. The data indicate that the responsive precursor cell is not a recirculating memory cell but is an intermediate B cell type which appears in vivo after antigen challenge of primed mice. Both antigen and T helper cells are required for in vitro stimulation of the intermediate cell type into the division and maturation steps leading to IgG antibody secretion. The buoyant density of precursor cells has been analyzed by bovine serum albumin density gradient centrifugation, and is consistent with their recent origin by division from memory cells.


Detection of anti-idiotype reactive cells in the response to phosphorylcholine. Upon immunization with phosphorylcholine (PC), BALB/c mice produce antibodies bearing mainly one idiotype which is identical to that of the TEPC 15 PC-binding myeloma protein. By coating sheep red cells (SRC) with TEPC 15 it was possible to detect anti-idiotypic plaques during the course of an immune response to PC. These plaques are detectable only after the anti-PC response has reached a peak and begun to decline. They are specific, since addition of free TEPC 15 and not MOPC 315 prevented their detection. It is suggested that such anti-idiotypic reactive cells might regulate the response to PC.


Studies on the lymphocytes of sheep. II. Some properties of cells in various compartments of the recirculating lymphocyte pool. The proportion of cells bearing surface immunoglobulin (Ig) and the normal lymphocyte transfer (NLT) reactivity of mononuclear cells obtained from the blood, afferent lymph, and efferent lymph from both somatic and intestinal nodes of sheep were measured. The proportion of Ig-positive lymphocytes was approximately 30% in blood and efferent lymph, but only about 10% in afferent lymph. The proportion of unlabeled lymphocytes (T cells) was about the same in all the preparations, as afferent lymph contains 15--20% macrophages. Despite this apparent uniformity in the T cell content, the NLT reactivity of efferent lymph was 3 to 5 times higher than that of blood or afferent lymph. No humoral factors could be detected by incubating cells in the various plasmas in vitro before injection. No inhibitory cells could be detected when mixtures of cell populations were used to initiate lesions. We suggest that lymphocytes in efferent lymph are more reactive than others because they are "groomed" by macrophages during their recirculatory passage through the substance of the node.


Fc-rosetting and nonrosetting T cells are killer cells. A fraction of T cells activated to H-2 determinants in vivo (ATO) express Fc receptors (FcR) on the cell surface. Those FcR can be detected by antibody coated red blood cells (EA rosettes). Nonrosetting and EA rosetting ATC could be obtained in highly enriched form (more than 99% pure) by separation by velocity sedimentation at unit gravity. Separately tested, both fractions of ATC showed killer cell activity against specific target cells. Possible explanations why only one population of T killer cells expressed FcR are discussed.


Immature T lineage lymphocytes in athymic mice. Presence of TL, lifespan and homeostatic regulation. Lymphocytes belonging to the T lineage were described in athymic nude mice. We showed previously that they were distinguished from usual peripheral lymphocytes by their low density of theta antigen, their slow electrophoretic mobility and their absence of recirculation through the thoracic duct. We now report that they also express the TL antigen, have a life span of 1 to 2 days, are produced in the bone marrow and are under the homeostatic influence of the thymus. Indeed they appear rapidly in surgically T-deprived mice and their production is blocked in both surgically or congenitally athymic mice receiving a thymus graft. This homeostatic control may be mediated via a humoral factor. Cells with similar characteristics are present in the thymus at early stages of embryogenesis. The characteristics of these T lineage lymphocytes strongly suggest that they may represent "pre-thymocytes", i.e. cells already committed to the T pathway independently of thymic influence but needing the thymus microenvironment to differentiate further.


Interference with histamine and imidazole acetic acid metabolism by salicylates: a possible contribution to salicylate analgesic activity? In man, rats and mice, the urinary excretion of the histamine and L-histidine metabolite, imidazole acetic acid, is increased and that of the conjugated metabolite, ribosylimidazole acetic acid, decreased by small doses of salicylates. In contrast to salicylates, other non-salicylate anti-inflammatory drugs, indomethacin, phenylbutazone, phenacetin and acetaminophen do not influence the excretion of the urinary metabolites of histamine and L-histidine. Since imidazole acetic acid is reported to have analgesic and narcotic activity, there is the inference that the analgesic properties of salicylate might be due in part to interference in imidazole acetic acid metabolism.


Ultrastructural identification of human tonsil T-lymphocytes by peroxidase-conjugated anti-HTLA serum. A horse anti-serum rendered specific for human T-lymphocytes was conjugated with peroxidase and used for ultrastructural identification of human tonsil T-lymphocytes. With T- and B-enriched suspensions, virtually all T-lymphocytes were labelled with Po-anti-HTLA, whereas no B-cells were stained with this conjugate. The labelling HTLA conjugate confirm the ultrastructural characteristics of thymus-dependant cells.


Independance of glucagon and insulin handling by the isolated perfused dog kidney. The effect of raising arterial plasma glucagon concentrations on kidney glucagon uptake was investigated using an isolated dog kidney perfused with whole blood. In addition, the effect of insulin on the magnitude of glucagon uptake by the kidney was studied at various glucagon concentrations. Renal vein plasma glucagon (V) has been found to be proportional to renal artery plasma glucagon (A). V and A were highly significantly correlated. In the absence of exogenous insulin infusion, V equalled 0.733 +/- 0.034 A, while in the presence of insulin V equalled 0.747 +/- 0.015 A. When kidney glucagon uptake was measured directly it increased as a function of arterial plasma glucagon. The calculated regression lines were similar in the presence and in the absence of insulin. The mean clearance rate of glucagon by the kidney was similar at low, medium or high concentrations of glucagon and was not affected by the presence of insulin at a mean concentration of 335.7 +/- 15.7 muU/ml. At this concentration of insulin, kidney insulin uptake was not affected by glucagon at concentrations ranging from 32 to 1600 pg/ml. Comparison of kidney glucagon uptake at similar arterial plasma glucagon concentrations, but with different renal plasma flows, indicated that kidney glucagon uptake is more dependant on arterial plasma glucagon concentration than on the quantity of glucagon entering the kidney per minute. It is concluded that: 1) kidney glucagon uptake increases as a function of arterial plasma glucagon concentration; 2) the clearance rate of glucagon is similar at low, medium or high arterial concentrations of glucagon; 3) at concentration of 300-350 muU/ml, insulin does not affect kidney glucagon uptake, and 4) at concentrations of glucagon up to 1600 pg/ml, renal insulin uptake is not affected by glucagon. These studies indicate that insulin and glucagon are handled independantly by the kidney of the dog.


Initial stages of differentiation of thymocytes in the plasma membrane. There is some evidence in the plasma membrane after binding of molecules triggering differentiation processes that different membrane areas exist possessing different functions. We have tried to isolate these different membrane areas, using a type of affinity chromatography on Con A-Sepharose. Our results from binding sites, affinity constant and fatty acid composition seem to reinforce the evidence that heterogeneous plasma membrane areas exist having different functions in the proliferation and differentiation process of thymocytes after triggering with Con A.


Detection of T-precursor cells in human bone marrow and foetal liver. Human lymphoid cells that have been incubated with conditioned medium from confluent monolayers of human thymic epithelium (HTCM) show an increase in cells forming rosettes with sheep erythrocytes at 4 degrees C (E-rosettes). Those cells demonstrating this in vitro conversion have been interpreted to be T-cell precursors. Separation of human bone marrow cells on discontinuous bovine serum albumin (BSA) gradients, and on a single-step 23% BSA gradient showed enrichment of these T-precursor cells, not only in bone marrow, but also in human foetal liver cells. Bone marrow precursor cells from a patient with Wiskott-Aldrich syndrome (T-cell deficiency) showed a normal in vitro response to HTCM, but no response was seen in cells from a patient with severe combined immunodeficiency disease.


The importance of clostridia in experimental intestinal strangulation. Hemorrhagic and ischemic strangulation of closed intestinal segments was sutdied in germ-free rats individually monocontaminated with one of eight separate species of clostridia. Ischemic strangulation was found to be as deadly as hemorrhagic strangulation in the presence of clostridia. Some clostridia were very toxic whereas others were relatively innocuous. The clostridia, ranked in the order of decreasing lethality, were: Clostridium perfringens type A, C. septicum, C. histolyticum, C. haemolyticum, C. bifermantans, C. sporogenes, C. tertium, and C. novyi type A. All species were readily established in the gastrointestinal tract of the nonoperated germ-free rat. The clostridia appear to be one of the most potentially lethal groups of organisms commonly found in the intestinal tract of human beings and animals.


Assessment of the accuracy of double contrast gastroduodenal radiology. The report presents an analysis of routine double contrast gastroduodenal radiology based on our experience with 1500 consecutive examinations. The value of this technique is illustrated by the demonstration of subtle abnormalities such as erosions, linear ulcers, and ulcer scars which are usually not demonstrated by the standard barium study. Two hundred and twenty-five of these patients have also been examined by endoscopy and radiological errors were found in 7%. This represents a marked improvement over the results obtained with the standard method. In the last 128 patients, a confidence level ranging from 3 (certainty) to 1 (uncertain) was assigned to the radiological diagnosis before endoscopy. It was found that the majority of radiological errors occurred in the few studies given the lowest confidence level. These findings indicate that the double contrast study of the stomach and duodenum can be a very accurate examination and that endoscopy can be applied more selectively to patients with inconclusive double contrast studies.


[Membrane receptors of lymphoreticular cells in hyperplastic and neoplastic diseases of the lymphatic system]. The results of T- and B-cell determinations are described in 105 cases of lymphoreticular and lymphoepithelial neoplasia, and are compared to similar investigations of 582 cases as published in the literature. In addition, T- and B-cell values are determined in blood of 35 healthy individuals, in 12 normal lymph nodes, as well as in hyperplastic conditions of lymph nodes from 30 patients and of tonsils from 85 patients. Cell characterizations are done by immunofluorescence and use of monospecific anti-immunoglobulin antisera (H chain specific), anti-thymus antiserum, as well as by the E-rosette test. While normal blood and normal and hyperplastic tissues show a polyclonal distribution or proliferation of lymphoreticular cells, neoplastic conditions are often characterized by an exuberant, possibly monoclonal proliferation of one cell type. According to this, lymphoreticular neoplasias are immunologically grouped into four main classes: B-cell neoplasias comprising most of the chronic lymphocytic leukemias, well differentiated lymphocytic lymphomas, BURKITT's tumor, follicular lymphoma BRILL-SYMMERS, and hairy cell leukemia. T-cell lymphomas represent a large part of poorly or undifferentiated leukemias of children, poorly differentiated lymphocytic lymphomas, prolymphocytic leukemia, and Sézary's syndrome. Monocytic neoplasias are malignant histiocytoses and leukemic reticuloendothelioses. A fourth group, which probably is not homogeneous and might be further classified in the future by use of more sophisticated methods, consists of tumors with T- and B-cell lack. Such tumors are histologically classified as Hodgkin's lymphomas, a certain number of histiocytic lymphomas, and mycosis fungoides. The prognostic and pathogenetic implications of a combined morphological and immunological classification of lymphoreticular neoplasias are briefly outlined.


[The effect of a flufenamic acid containing ointment in various rheumatic diseases. A double-blind study]. Of 100 patients suffering chiefly from soft tissue rheumatism 48 were treated in a double-blind study with an ointment containing flufenamic acid (Mobilisin) and 52 with a control preparation. The test ointment brought about good to very good results in 43 patients (89,5%) whereas only 26 patients (50%) of the control group showed a therapeutic effect. Either product was tolerated well; no side-effects have been observed in any of the cases.


[Progress in the diagnosis of cutaneous lymphomas. Enzyme cytochemical and immunocytological studies]. The term ""cutaneous lymphoma'' is used for lymphoreticular proliferative processes which primarily affect the skin. This term includes: mycosis fungoides, Sezary-syndrome and ""pagetoid epidermotropic reticulosis''; ""malignant reticulosis'', ""reticulum cell sarcoma'' and lymphosarcoma; in a wide sense of this term pseudolymphomas (lymphadenosis benigna cutis, benign lymphocytoma), specific skin infiltrates in leukemia and Hodgkin's disease might be included as well.


[Complications of Crohn's disease and their surgical treatment]. Crohn's disease is characterised by its unknown etiology and pathogenesis, its many complications and its extraordinary disposition of recurrence. The perforation of the small intestine, or of the colon, obstruction and massive bleeding are severe complications, requiring immediate surgical attention. Frequently specific formation of fistulae is indicative of the first sign of the disease. A radical operative treatment--by present results (approximately 70% of cases)--is the method of choice. The tendency to extend surgical procedures to the chronic stage of the disease has been discussed in recent years. Complications observed in patients under study have also been analysed.


[Spontaneous cholecysto-gastric fistula with massive gastrointestinal bleeding. Endoscopic diagnosis and concrement extraction]. A case of spontaneous cholecysto-gastric fistula is reported with penetration of a gallstone into the stomach leading to massive haemorrhage of gastric mucosa. The gallstone was removed endoscopically, the immanent complication of gallstone ileus could be eliminated. Mucosal bleeding was stopped by conservative methods, and thus enough time was won for optimal preparation for the ensuing operation. The problems of preoperative diagnosis are mentioned, also rate and early complications of spontaneous bilio-digestive fistulae and their poor prognosis concerning the increased letality at operation.


Differential sensitivity to x-ray of chromosomes of blood T-lymphocytes and B-and T-cell lines. Normal T-lymphocytes, B-cell line (CCRF-SB) and T-cell line (CCRF-HSB-2) cells, all diploid in their chromosome constitution, were exposed in vitro to various doses of X-ray and analyzed at their first mitotic division for structural chromosome abnormalities. The irradiation effects were determined also by a viability test of the cells, using trypan blue dye. The irradiated T-cell line (CCRF-HSB-2) showed a remarkably high frequency of chromosome aberrations, including chromosome and chromatid deletions, chromatid exchanges, dicentrics, rings and acentric fragments. On the other hand, the chromosome aberrations observed in the irradiated B-cell line and normal T-lymphocytes consisted mainly of dicentrics, rings, deletions and acentric fragments; the frequency of chromosome and chromatid deletions was low as compared to that of the T-cell line. The cell viability test showed a singificantly higher percent reduction of viable cells at every dose of X-ray in the irradiated T-cell line than in the B-cell line or the normal T-lymphocytes. It is possible that the increased radiosensitivity of the T-cell line is related to the original malignant nature of the cells, which originated from the lymphocytes of a patient with acute lymphoblastic leukemia.


[The aetiology of rheumatoid arthritis (author's transl)]. An ineffective aetiology for rheumatoid arthritis and other connective tissue diseases has been frequently postulated but never proven. Despite the failure to obtain firm evidence of viral infection in most patients with these disorders for several reasons this theory should not be discarded. Firstly several mechanisms have been discovered by which virus infections can persist in lymphocytes and other tissue thereby provoking inflammation without the production of complete readily detectable virus particles. Secondly there are numerous ways in which host resistance to virus can be subverted with the perpetuation of an ineffective or inappropriate immune response. Thirdly the immunopathological features of these diseases are entirely compatible with an infective aetiology. The main problem is likely to prove the difficulty in attributing a primary pathogenetic role to any isolated virus rather than regarding it as a passenger virus which has been non-specifically activated by the disease process. However preoccupation with a viral aetiology should not blind one to other possibilities since many environmental allergens can produce immunopathological disease of highly protean nature.


[Classification of non-Hodgkin's lymphomas on the basis of Morphological and immunological features shared by normal and neoplastic lymphatic cells (author's transl)]. A review is given of the new Kiel classification of non-Hodgkin's lymphomas (NHL) and of the findings which led to its development. The Kiel classification of NHL is based on morphological and immunological features shared by normal and neoplastic cells. Therefore, the origin, maturation, and reaction of nonneoplastic T- and B-cells together with their immunological, enzyme-cytochemical and morphological features are discussed first. In the T-cell system T-precursor cells, prothymocytes, T1/T2-cells, and T-immunoblasts can be distinguished on the basis of the given features. The B-system is primarily composed of cells of the two antigen-dependent B-cell reactions, the germinal center reaction, and the plasma cell reaction. These cells can be distinguished both morphologically and through demonstration of the complement receptor in frozen sections. We differentiate the following entities of NHL, divided into six groups for better understanding: 1. lymphocytic lymphomas: chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, hairy cell leukemia, mycosis fungoides, and Sézary syndrome; 2. secretory immunoglobulin-producing lymphomas: plasmacytoma and lymphoplasmacytoid immunocytoma; 3. germinal center cell tumors: centroblastic/centrocytic lymphoma, centrocytic lymphoma, centroblastic lymphoma, Burkitt's lymphoma, and lymphoma of the Burkitt type; 4. lymphoblastic lymphomas: "convoluted cell" type and "unclassified" type; 5. immunoblastic lymphoma; 6. reticulosarcoma. B-cell characteristics are revealed by more than 80% of the NHL, namely by 97% of the cases of CLL, by all secretory immunoglobulin-producing lymphomas, by all germinal center cell tumors, and by most immunoblastic lymphomas. More than 50% of the B-cell tumors are evidently derived from germinal center cells. The following are T-cell tumors: a few rare forms of CLL, mycosis fungoides Sézary syndrome, about 50% of the lymphoblastic lymphomas, and a few immunoblastic lymphomas. It could be shown that the cells of lymphoblastic lymphoma, "convolted cell" type with strong acid phosphatase reactivity have the same features as fetal thymocytes. So far, we have not observed any cases of true reticulosarcoma as described by Roulet and Rappaporti, i.e. tumors of phagocytic reticulum cells. The morphological features which could be defined for the entities distinguished in the Kiel classification of NHL are so characteristic that most of these entities can now be diagnosed on the basis of their histological and cytological pictures alone.


Immune interferon production by lymphoid cells: role in the inhibition of herpesviruses. Bovine peripheral blood lymphocytes (PBL) obtained from infectious bovine rhinotracheitis (IBR) virus- and tuberculin-immunized animals produced large quantities of interferon within 24 h of in vitro stimulation by IBR and purified protein derivative antigens. Separation of PBL into populations enriched in T lymphocytes or B lymphocyte provided the antigen-specific step for immune interferon production. A 2- to 10-fold increase in interferon occurred when lymphocytes were combined with autologous macrophages. Although macrophages, even if treated with antilymphocyte serum to remove any contaminating lymphocytes, could produce some interferon, the augmented interferon produced by macrophage-lypmhocyte cultures was not dmpocytes. Direct physical contact between macrophages and lymphocytes was required for the production of enhanced levels of interferon. Antigen-antibody complexes of irradiated virus-infected cells in the presence of antibody were as efficient or better at stimulating interferon than was free antigen. Because IBR virus was inhibited by interferon levels stimulated in cultures by IBR antigen, it was suggested that the local production of interferon by immune cells might play a similar role in curtailing virus dissemination in vivo, thus leading to recovery from disease.


Genetic analysis of lymphocyte activation by lipopolysaccharide Endotoxin. A genetic study of in vitro lymphocyte blastogenesis by the B-cell mitogen lipopolysaccharide endotoxin has been performed, using both low-responder C3H/HeJ mice and high-responder CBA/J mice. The crossbreeding of these strains produced F1 progeny that were intermediate in responsiveness. Responder types from the backcross of the F1 to the C3H/HeJ strain segregated into intermediate- and low-responder phenotypes, whereas intermediate- and high-responder phenotypes were produced from the backcross of the F1 to the CBA/J strain. The F2 generation consisted of all three responder phenotypes in frequencies that fit the classical Mendelian ratio of 1:2:1, indicating that the mitogenic response to lipopolysaccharide endotoxin in mice is most likely governed by a pair of autosomal co-dominant genes.


Identification and quantitation of capsular antigen in capsulated and noncapsulated strains of Haemophilus influenzae type b by crossed-immunoelectrophoresis. Sonicated preparations of capsulated Haemophilus influenzae type b, two of its spontaneous mutants, one containing patches of capsules (class I variant) and the other noncapsulated (class II variant), and a noncapsulated strain of H. influenzae type d were analyzed by crossed-immunoelectrophoresis using unadsorbed antiserum to capsulated H. influenzae type b. Twenty common antigens were present in all four cultures. Two type b-specific antigens were also identified in the three H. influenzae type b cultures when antiserum adsorbed with H. influenzae type d sonicates (AdR) was used. One of these, the type b capsular antigen, cross-reacted with an antigen of Bacillus pumilus. Further adsorption of AdR with the B. pumilus sonicate reduced, but did not eliminate, the antibodies to the type b capsular antigen, although all antibodies to B. pumilus were removed. Sonication sheared the type b capsular antigen, resulting in an increase in its electrophoretic mobility in agarose gel. The capsular antigen from all three H. influenzae type b cultures had the same electrophoretic characteristics. Reproducible quantitation of sheared and unsheared capsular antigen was demonstrated by rocket immunoelectrophoresis. As little as 2.5 ng of polyribophosphate pentose was identified and measured. Capsulated H. influenzae type b contained 78 ng of polyribophosphate pentose per mug of cell protein; class I contained 20 ng and class II contained 4 ng. The small amount of type b capsular antigen present in the class II variant may account for its lack of detection in this organism before now.


Lymphocyte populations in acute viral gastroenteritis. Viral gastroenteritis was induced in 16 of 24 normal volunteers after oral administration of either the Norwalk or Hawaii agents. Clinical illness lasted for 24 to 48 h and resolved spontaneously. During acute illness, a transient lymphopenia was noted which involved all lymphocyte subpopulations (thymus-and bone marrow-derived, and null cells). No circulating lymphocytotoxins were detected, and the lymphocytes remaining in the circulation responded normally to mitogenic stimuli. The acute lymphopenia occurred at the time that mononuclear cell infiltration of the jejunal mucosa has been noted. These findings are consistent with the occurrence of a redistribution of circulating lymphocytes during acute illness, with accumulation of lymphocytes at the site of infection in the gut.


Immunodepression by Rowson-Parr virus in mice; lymphocyte markers and capping response of spleen and lymph node cells after infection. Infection with Rowson-Parr virus (RPV) induced a rapid reduction in the number of immunoglobulin-positive and theta antigen-positive cells detectable by immunofluorescence in the spleens of susceptible BALB/c mice. The changes produced by RPV infection in the lymph nodes were different, since the number of immunoglobulin-positive cells was increased and the proportion of theta-positive cells remained unchanged. However, the ability of immunoglobulin-bearing cells to redistribute their receptors into caps was reduced in both types of lymphoid tissue. A similar pattern of changes was produced by infection with Friend leukemia complex, from which RPV was originally obtained. These effects of RPV and Friend leukemia complex may contribute to the immunodepressed state of infected mice.


Platelet aggregation by hepatitis B surface antigen-antibody complexes. Platelet aggregation indicating antigen-antibody complex formation was observed when hepatitis B surface (HBs) antigen and antibody were mixed. Platelet aggregation titers were determined for serum specimens found positive by radioimmunoassay for either HBs antigen or HBs antibody. From these determinations, incidence of HBs antigen-antibody complexes was found to be higher in HBs antigen seraas than in HBs antibody sera. There was an inverse correlation between platelet aggregation titers and radioimmunoassay values that was statistically significant for HBs antigen sera but not for HBs antibody sera. The incidence of anti-complementary activity was twice as high for platelet aggregation-positive HBs antigen and antibody sera as for platelet aggregation-negative sera. HBs antigen sera that were positive by platelet aggregation exhibited nearly three times the incidence of anti-complementary activity as did HBs antibody sera. However, the low incidence of anti-complementary activity was distributed about equally between HBs antigen and antibody sera that were negative by platelet aggregation. Additional HBs antigen preincubated with HBs antigen-positive sera effectively inhibited platelet aggregation, whereas additional HBs antibody was somewhat less effective. On the other hand, preincubation of HBs antigen sera with anti-IgG serum effectively enhanced platelet aggregation, whereas preincubation of HBs antigen sera with HBs antibody did not.


Morphology and time course of experimental listeriosis in nude mice. Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, listeric infection in congenitally dysthymic nude (nu/nu)  mice does not proceed in clear-cut phases, develops more slowly, displays a chronic tendency from the beginning, and shows a considerably different morphology. The inability of nude mice to effectively control and terminate infection by Listeria monocytogenes obviously results from the lack of T lymphocytes.


Transactions of an international conference. Worldwide concern: better dental care for more people. An international collaborative study. How the study was designed. The study originated from the common need felt by the United States Public Health Service and the World Health Organization for objective information about various national dental care delivery systems and their effectiveness in the societies in which they were used. The relationships between consumers, providers and administrators within each system were emphasized rather than the comparison between systems since each operated within a specific biological and ecological environment. Six systems all of which had been in existence for at least twenty years were originally selected for study to encompass those dependent on a majority of government or private enterprise, use or non-use of auxiliaries, differeing systems of financing and of definition of target groups for receipt of services. The countries originally taking part were Australia, the Federal Republic of Germany, Japan, New Zealand, Norway and Bulgaria, though Bulgaria withdrew early in 1975.


Preparation of various fractions from Mycobacterium smegmatis, their arthritogenicity and their preventive effect on adjuvant disease. Cell walls of Mycobacterium smegmatis were able to produce much more severe arthritis in rats than the delipidated cells, whereas cell envelope and cell membrane fractions were unable to produce the disease. The lysozyme-solubilized product was able to produce mild disease with only 30% of incidence with an optimum dose, whereas the higher and the lower doses did not produce the disease. The rats immunized with cell envelope, cell membrane fraction and nonarthritogenic doses of lysozyme-solubilized product were protected against the subsequent homologous and heterologous challenge of delipidated cells. It was discussed that this preventative effect can be the result of antigenic competition between the arthritogenic and nonarthritogenic components of M. smegmatis. On the other hand, all the fractions separated here were able to serve as an immunoadjuvant in terms of inducing delayed hypersensitivity to ovalbumin in guinea pigs.


Arthritogenicity of Mycobacterium smegmatis subfractions, related to different oil vehicle and different composition. Arthrigenicity of Mycobacterium smegmatis subfractions appeared to be remarkably potentiated in oil vehicles such as squalane or mineral oil, while water-in-oil emulsions containing Arlacel A appeared to decrease or suppress their arthritogenicity. It seems that Arlacel A can exert a suppressive effect on the arthritogenicity of the subfractions. Poly I:C and acetylated wax D potentiated the arthritogenicity of lysozyme-solubilized product, while cord factor was unable to do so. When given together with either cell membrane fraction or cell envelope, the lysozyme-solubilized product produced much more severe disease than that of lysozyme-solubilized product alone. Cell walls lost much of their arthritogenicity when mixed with lysozyme-solubilized product.


Dose-related effect of hydrocortisone treatment on the electrokinetic properties and mitogen responsiveness of mouse thymocytes. The electrophoretic mobility (EPM) and the ability to synthesize DNA in vitro either spontaneously or in response to concanavalin A (Con A) and phytohemagglutinin (PHA) were investigated on thymocytes from adult female Swiss/B mice which had received intraperitoneally, 2 days previously, various doses (10-750 mg/kg body weight) of hydrocortisone acetate (OHC). A first group of thymocytes, highly sensitive to OHC, rapidly decreased in proportion following administration of increasing doses of OHC (10-125 mg/kg body weight) and included the totality of low-EPM thymocytes (EPM less than 1.0 mum sec-1 V-1 cm) together with about 70% of the high-EPM thymocytes encountered in the normal thymus. The second group of thymocytes (4% of the initial cellularity), which resisted to OHC at 125 mg/kg body weight and was only reduced by half with doses of OHC 6-fold larger, was composed essentially of high-EPM cells. The mean EPM of both groups tended to increase with increasing doses of OHC which suggests that among these two groups thymocytes are all the more OHC-sensitive as they possess a low surface charge. Spontaneous DNA synthesis, measurable on the first 24 h of in vitro cultivation, markedly dropped after treatment with OHC at doses higher than or equal to 62 mg/kg body weight. This loss of early spontaneous proliferation coincided with the disappearance of medium-EPM thymocytes. By contrast, proliferative response of thymocytes to mitogens was enhanced by OHC pretreatment of donors and roughly paralleled the enrichment in high-EPM cells. However, administration of the largest amounts of OHC diminished this mitogen responsiveness, although PHA reactivity was less affected than Con A reactivity.


Radiosensitization of mammalian cells by diamide. The effect of diamide on the radiosensitivity of T-cells was investigated under oxic and anoxic conditions. The compound was found to sensitize the cells under both conditions. Under oxic conditions, exposure for 10 min before and during irradiation to 0.1, 0.5 and 1.0 mM diamide produced dose-modifying factors of 0.81, 0.60 and 0.55, respectively. Under anoxic conditions, exposure for 10 min before and during irradiation to 0.5 mM produced a dose-modifying factor of 0.34. When the cells in oxic conditions were exposed for just 20 min before irradiation, the sensitizing effect was smaller, but some sensitization effect was still apparent after a 120 min interval between diamide treatment and irradiation. Diamide also sensitized the cells after irradiation, but this effect was less than when it was present during irradiation. The presence of whole rat-blood in the incubation medium prevented sensitization. No sensitization could be detected in the whole animal. It is proposed that sensitization is due to lack of capacity for repair of radicals by hydrogen transfer and biochemical repair processes.


Control of DNA repair linked to neuroblastoma differentiation. Mouse neuroblastoma cells, which can be induced to undergo reversible differentiation in culture, have been used as a model to investigate the effects of ultra-violet (U.V.) radiation on terminally-differentiated nerve cells. Differentiated neuroblastoma cells were found to be extremely sensitive to U.V.-radiation when compared with proliferating cells from the same clone. However, normal resistance was regained if the differentiated cells were allowed to proceed to the next G1 phase of the cell-cycle before irradiation. Neuroblastoma cells in the differentiated mode are capable of carrying out soem excision repair of DNA damage, but they appear to lack a repair mechanism present in proliferating cells.


Studies on the radiosensitivity of the function of the Golgi complex. The uptake of 3H-glucosamine into primary human-embryo fibroblasts and into the Golgi-rich fraction isolated from liver of mice labelled in vivo was studied, after various doses of X-radiation, by autoradiography and biochemical methods. A dose of 90 rad resulted in an increased precursor uptake in interphase cells at 24 hours and in mitotic cells at 48 hours after irradiation; 226 rad had virtually no effect on the grain counts of interphase cells, but reduced the labelling of mitotic forms. The characteristic intracellular localization of the grains were not influenced by these doses. Although no immediate radiation-induced reaction could be observed in liver cells either, significant stimulation of the 3H-glucosamine incorporation was measured in isolated Golgi-rich fractions 24 hours after whole-body irradiation with 90, 450, or 905 rad. This phenomenon is discussed as a part of the somatic regeneration of membrane structures.


Effects of ionizing radiation and cysteamine (MEA) on activity of mouse spleen adenyl cyclase. In mice X-irradiated with doses of 200 R and 400 R, there was a substantial increase in spleen adenyl cyclase activity; there was similar activation by MEA. In mice given MEA before irradiation, an additive effect of radiation and the radioprotective drug was observed. On the other hand, a dose of 800 R given either alone or after pre-treatment with MEA failed to elicit any change in cyclase activity. The results indicate the importance of the adenyl cyclase system in the response of cells to irradiation and action of MEA.


Change in the radiation responses of oogonia in the embryos and fry of the fish Oryzias latipes. Embryos of the fish Oryzias latipes were irradiated with 1000 R of X-rays 1 day before hatching,and the post-irradiation change in the female germ-cell population was observed. Scarcely any reduction in the number of oogonia was observed, but their proliferation was inhibited. Repopulation occurred between 12 and 20 days after hatching. These responses were quite different from those of germ cells in the irradiated fry (Hamaguchi and Egami 1975). Embryos and/or fry were also exposed to 1000 R of X-rays 1 day before hatching and 0, 1, 2, and 3 days after hatching. A comparison of their responses suggested that the change in the radiation responses of oogonia is correlated with the initiation of meiosis.


Histochemical characterization of cholinesterase activity in the frog brain with special reference to its localization on the wall of blood vessels. The nature of the cholinesterase activity present on the wall of blood vessels in amphibian brain has been studied histochemically. It is concluded that the enzyme involved is acetylcholinesterase rather than butyrylcholinesterase, which more frequently occurs in the blood vessels of the brain of other vertebrates. The histochemical results are in agreement with most biochemical data concerning substrate specificity and inhibitor response for both acetylcholinesterase and butyrylcholinesterase. The two main hypotheses put forward by others in order to explain cholinesterase activity in brain vessels are discussed briefly.


Mechanism of DNA degradation by the ATP-dependent DNase from Hemophilus influenzae Rd. The rate of production of acid-soluble material during degradation of duplex DNA by Hemophilus influenzae ATP-dependent DNAse (Hind exonuclease V) has been shown to be directly dependent upon the Mg2+ concentration in the reaction mixture. At high concentrations of Mg2+ (5 to 20 mM), DNA degradation to acid-soluble products is rapid and the rate of ATP hydrolysis is slightly depressed. At low concentrations of Mg2+ (0.1 to 0.5 mM), the enzyme rapidly hydrolyzes ATP and converts up to 35% of linear duplex DNA to single-stranded material while degrading less than 0.2% of the DNA to acid-soluble products. We refer to this enzymatic production of single-stranded DNA as the "melting" activity. Under the conditions of our assay, the initial melting reaction is processive, lasting about 70s on phage T7 DNA. Using DNAs with several different lengths, we have established that the duration of the initial reaction is dependent upon DNA length, requiring approximately 1 s per 0.18 mum. The products of the initial reaction on phage T7 DNA are somewhat heterogeneous, consisting of short duplex fragments approximately 0.5 mum long, purely single-stranded products up to 7 mum long, and longer duplex fragments 3 to 11 mum in length, some of which have single-stranded tails. Nearly half of the single-stranded material remains linked to a duplex segment of DNA after the inital processive reaction. We propose that Hind exo V initiates attack at the DNA termini and then acts in a processive manner, migrating along the DNA molecule, converting some regions to single-stranded material by the combined action of the melting activity and limited phosphodiester cleavage, while leaving other regions double-stranded. At the completion of its processive movement through a single DNA molecule, it is released and then recycles onto either intact molecules or the partially degraded products, continuing in this manner until the DNA is finally reduced to oligonucleotides.


Unidirectional K+ fluxes in rat thymocytes stimulated by concanavalin A. Unidirectional K+ fluxes were estimated in isolated rat thymocytes by 42K exchange kinetics. The cells were either preloaded with isotope and the release of it measured during incubation for one hour at 38 degrees C, or the cellular uptake of isotope during a similar incubation was measured. The influx rate of untreated thymocytes was: 2.3-10(-12) moles cm-2-s-1 and efflux rate: 1.8-10(-12) moles cm-2-s-1. When con A was added to the cells, influx was raised 74% and efflux 65%. Maximal effect was obtained when the concentration of con A was 15 mug/ml, but concentrations as low as 0.75 mug/ml were effective. Hydrocortisone resistant thymocytes responded at least was well as untreated cells to con A, which also raised RNA synthesis rate in the former cells 2.5 times. Using an extracellular marker, 51CrEDTA, intracellular concentrations of some ions was estimated in the thymocytes after one hour incubation: Na+: 30 mmoles/kg water, K+: 177 mmoles/kg water and Cl-:43 mmoles/kg water. Cellular water content: 69%. These values were not found significantly altered when con A was present. Since con A raised influx and efflux to the same extent and no net flux of K+ could be detected, it is proposed that both active and passive transport of K+ was increased by con A. The increased fluxes induced by con A, can apparently not be reversed by removal of con A from the incubation medium or by addition of the inhibiting hapten, alpha-methyl-D-mannoside.


Genetic control of lipopolysaccharide induced generation of serum colony stimulating factor and proliferation of splenic granulocyte/macrophage precursor cells. Administration of bacterial lipopolysaccharides (LPS) to mice causes a rise in tissue and serum colony stimulating factor (CSF) levels and in bone marrow and splenic colony forming cells (CFC). Two inbred strains of mice differing in their response to LPS were used to study the genetic control of LPS induced granulopoietic responses: a high responder strain (C3H/eB) which reacts to LPS by an elevation in serum CSF and by an increase in splenic CFC levels, and a low responder strain (C3H/HeJ) which fails to show these responses. The ability to generate serum CSF after administration of LPS is controlled by a single autosomal dominant gene, while the splenic CFC response to LPS follows the characteristic patterns of a polygenic inheritance control. The associated relationships of CSF and CFC responsiveness have been investigated in backcross (F1 X C3H/Hej) and F2 mice. Most mice which generated high levels of CSF showed a high or intermediate CFC response and most mice which did not generate any detectable levels of serum CSF showed a low splenic CFC response. The results suggest that CSF may play a physiologic role in vivo as a granulopoietin. In addition it was shown that the genetic control mechanisms governing the CSF/CFC responses are determined by the lipid A-KDO portion of the LPS molecule, suggesting that lipid A is the active part of the LPS molecule in stimulating granulopoiesis.


Hemophilus influenzae, type b, antibody frequencies determined with bactericidal and radioimmunoassay tests. Bactericidal and radioimmunoassay (RIA) antibodies to Hemophilus influenzae, type b, were measured in the sera of 85 children aged 18 through 71 months. Bactericidal antibodies were present in only 21% of those over 60 months; RIA levels rose linearly with increasing age (P less than 0.005). Bactericidal antibodies were present in nine of 29 sera with RIA levels greater than or equal to 0.7 mug/ml and in only four of 56 sera with RIA levels less than 0.7 mug/ml (P less than 0.01). The discrepancies between the two tests probably reflect their measurement of different antibodies. Results of the RIA fit the clinical observation that H. influenzae meningitis becomes less frequent with age.


Comparison of isolation of Haemophilus vaginalis (Corynebacterium vaginale) from peptone-starch-dextrose agar and Columbia colistin-nalidoxic acid agar. A total of 447 cervical or vaginal specimens were inoculated in parallel onto peptone-starch-dextrose (PSD) and Columbia colistin (10 mg/ml)-nalidixic acid (15 mug/ml) (CNA) agar and were incubated for 48 h at 35 degrees C in an atmosphere with 2 to 10% CO2. One hundred (22.4%) of the cultures were positive for Haemophilus vaginalis. Forty-eight of the isolates were recovered from both PSD and Columbia CNA agar, five from PSD only, and 47 from Columbia CNA agar only (P less than 0.001). On Columbia CNA agar, 76 of the isolates were detected after 24 h of incubation, and the remainder were detected within 4 days of incubation.


The paradox of Hemophilus infuenzae type B bacteremia in the presence of serum bactericidal activity. We investigated the role of serum bactericidal activity in Hemophiplus influenzae type b infections in infants with meningitis and in a rat model. In infected infants, 13/22 admission sera had bactericidal activity against the infecting strain, and bacteremia was as frequent in those with bactericidal activity (54%) as those without (56%). The coexistence of bactericidal activity and bacteremia was reproduced and studied in experimentally infected weanling rats. Serum from such rats kills in vitro 95% of conventionally broth-grown bacteria within 10 min, but does not kill organisms obtained from the infected animals. Thus bactericidal activity as conventionally determined for H. influenzae b may have no relevance in vivo, Incubation of broth-grown bacteria in normal rat serum for 30 min at 37 degrees C produces a resistance like that of in vivo organisms. This phenotypic conversion depends on factors that are of molecular weight less than 1,000, stable to 100 degrees C, but destroyed by ashing. When injected intravenously into nonimmune animals, broth-grown bacteria are quickly cleared, while serum-preincubated bacteria are not. The latter, however, are cleared when injected into bacteremic rats (half-life 30 min). Bacteremia in the rats may persist despite this capacity for clearance because bacteria are entering the blood from extravascular fluids, which contain greater than 90% of the total bacterial burden.


Experimental evaluation and clinical application of intraoperative counterpulsation without balloon pumping. Cardiac assistance in the form of counterpulsation (CP), created by intraaortic balloon pumping (IABP), has recently been utilized to wean patients from cardiopulmonary bypass (CPB) after conventional modalities have failed. The use of IABP, however, is often delayed because it is not part of the standard CPB setup and requires an additional cutdown, an arterial graft, and the retrograde insertion of a foreign body into the arterial tree. To eliminate the disadvantages of IABP, an alternate technique for CP has been developed. A pneumatially actuated external blood reservoir connected via a "Y" connector to the standard arterial line of the CPB circuit can provide pulsatile flow, and when synchronized with the EKG, CP with or without CPB. Experimental evaluation with dogs comparing this technique with IABP has shown that the former can create comparable CP pressure curves to the latter. The technique was applied to 11 patients undergoing either aorto-coronary bypass surgery and/or valvular surgery. Two of the 11 patients could come off CPB only with the assistance of CP. Coronary bypass graft flow, when measured, increased by 25% due to CP in two out of seven patients. The arterial CP technique has proven to be easily adapted to clinical settings and provides immediate and effective CP when required.


Ontogenetic shift of spectral phototactic preferences in anuran tadpoles. Tadpoles of three species of anurans initially had a midspectrum ("green") preference in laboratory phototactic tests, which was shown experimentally to involve a form of true color vision in one species and probably in the other two as well. During development, the preference shifted to shorter wave-lengths (higher frequencies) until a short-wavelength ("blue") preference predominated in the pre- and postmetamorphic stages and in the adults of six species tested; color vision was involved in all of these stages. The green preference of young tadpoles is ecologically adaptive, in that it directs larvae to green plants that provide food or shelter. Tadpoles observed in a pond congregated heavily in vegetated areas rather than in open water. Spectroradiometric field measurements showed that pond illumination in vegetated areas had a more highly saturated yellow-green spectral dominance compared with a desaturated white illumination in open water. During all ontogenetic stages and as adults, the animals had a preference for high illuminance of white light, which correlates with the high illumination of their habitat. Microspectrophotometric data from Liebman and Entine suggested that the green rods are active receptors in tadpoles, making unlikely Muntz's hypothesis that the ontogenetic shift in spectral preferences is due to premetamorphic maturation of these receptors. However, the visual pigments of all five types of photoreceptors shifted from vitamin A2- to vitamin A1-based chromophores during ontogeny, and the resulting shift in spectral response of the receptors might be related to the spectral shift in phototactic preferences.


Immunoglobulin E synthesis in parasite infection. The infection of rats with Nippostrongylus brasiliensis (Nb) larvae enhanced IgE synthesis prior to the formation of IgE antibody specific for parasite antigens. As early as the eighth to tenth day of infection, IgE-bearing lymphocytes appeared in lymph nodes and spleen. At this time, even bone marrow contained IgE-bearing blast cells. The IgE-forming plasma cells were detected in the lymph nodes and spleen at the tenth day and their number reached maximum at the fourteenth day. The proliferation of IgE-bearing lymphocytes in the lymphoid tissues was observed in neonatally thymectomized animals, indicating that T cells are not essential for the development of IgE-B cells in the infected animals. It appears, however, that T cells are involved in the differentiation of IgE-B cells to IgE-forming plasma cells. Nonspecific proliferation of IgE-B cells and their differentiation to IgE-forming plasma cells may explain potentiation of IgE antibody formation against unrelated antigens after infection with N. brasiliensis (Nb). It was also found that T cells specific for parasite antigens were primed by infection with Nb. Evidence was obtained tht Nb-specific T cells raised by the infection collaborated with hapten-specific IgE-B cells and IgG-B cells for the secondary antihapten antibody responses. By contrast, T cells primed by immunization with parasite antigen included in alum exerted the helper function for IgG antibody response but failed to collaborate with IgE-B cells. Dissociation between the helper function for IgE and IgG antibody response indicated that parasite infection generated a favorable condition for priming T cells for the IgE antibody response.


Comparative anatomy of cerebellar catecholamine innervation from teleosts to mammals. The cerebellar innervation of the catecholamine (CA) neurons was experimentally investigated with histofluorescence method in the brains of the vertebrates from teleosts to mammals. In the teleosts the source for the cerebellar CA are composed of three CA neuron groups. Hypothalamic CA neuron group contributes mainly to innervation in the valvula cerebelli whose development is dependent on the high degree of the development of the lateral-line organ. CA neurons in the medulla oblongata might innervate the vestibulo-lateral lobe and corpus cerebelli. These two CA neuron groups appear to constitute the main source for the cerebellar CA, though it is certain that rhombencephalic CA neurons also send their axons to innervate the cerebellum. In the tailless amphibian which is devoid of the lateral-line nerves, cerebellar CA especially in the corpus cerebelli is supplied mainly by the rhombencephalic CA neurons which still remain in less developed stage in phylogenetic scale. In the bird, ascending CA neuron system is maintained by long axons and the anlage of locus coeruleus (LC) appear first in this class. A large number of CA nerve terminals in the cerebellum of the bird are supplied by both CA neurons of the dorsal part of the tegmentum and CA neurons disseminated in the tegmental reticular formation. In the mammals showing the highest development of the cerebellar and cerebral cortices, LC is well developed and cerebellar CA is supplied mainly by LC, though cerebellum is innervated by other CA neurons besides LC. Possible significance of the CA neurons on the development of the cerebellum in phylogeny was discussed.


Comparative anatomy of the locus coeruleus. II. Organization and projection of the catecholamine containing neurons in the upper rhombencephalon of the frog, Rana catesbiana. The organization and projection of the catecholamine (CA) containing neurons in the upper rhombencephalon were experimentally investigated with histofluorescence method in the brain of the bullfrog, Rana catesbiana. A small number of catecholamine containing neurons are located in the upper rhombencephalon. These neurons do not send ascending fibers to contribute CA projection to the forebrain, but give rise to relatively short axons to innervate the cerebellum and neighbouring reticular formation. Judging from their anatomical aspects, it seems that the structure homologous to the mammalian locus coeruleus is not present in the amphibian brain.


Single step separation of human T and B cells using AET treated srbc rosettes. A technique for the single step separation of human thymus derived (T) and Bursa equivalent (B) lymphocytes was developed. Density separation of B lymphocytes and T lymphocyte-sheep red blood cell (SRBC) rosettes on Ficoll-Hypaque was modified by pretreatment of the SRBC with 2 aminoethylisothiouronium bromide hydrobromide. This modification yielded significantly purer populations of T and B cells. Up to 15 X 10(7) were separated without increasing contamination allowing for the recovery of B lymphocytes as well as T lymphocytes in sufficient numbers to use in functional assays.


A simple method for screening human T and B lymphocyte alloantibodies. An sRBC-hemolysin monolayer was employed for separating human lymphocytes into two sub-populations, adherent cells (predominantly B cells) and non-adherent cells (predominantly T cells). The separated cells were then tested simultaneously against predispensed sera by complement-mediated cytolysis for the presence of alloantibodies to either T or B cells. A total of 372 sera were screened. Antibodies specific for B cell antigens were found in 19 sera and 9 sera were found to contain antibodies to T-specific antigens.


The sealed capillary migration technique and thymocyte migration in vitro. The in vitro migration of thymocytes in sealed capillary tubes was influenced by cell number, temperature, cell viability and oxygen supply. Migration was successively slower over a 24 h period. There was no major influence of gravity or the degree of initial packing of the cells by centrifugation. Migration was inhibited by cytochalasin B, although the cells escaped from this effect after 8 h. A transient stimulatory effect on migration was seen after addition of serum or supernatants from cultured thymocytes. There was no effect of isoproterenol, theophylline or carbacholine. A paradoxic effect was obtained with high doses of some metabolic inhibitors, which produced increased migration in spite of cell death. The technique may be used for studies on lymphocyte migration in vitro, but care must be taken to exclude a toxic influence of added substances, and expected effects should preferably be looked for early after onset of migration, since cell viability is gradually decreased.


Ototoxicity of tobramycin: a clinical overview. In a survey of data on 3,506 patients treated with tobramycin, the 21 cases of drug-related ototoxicity are reported and reviewed. In seven patients the effects were auditory only, in nine vestibular only, and in five both auditory and vestibular. Effects subsided in 14 of the 18 patients who were available for monitoring after therapy. High-frequency audiometric losses persisted in three patients, and a hearing decrease persisted in one. In only one of the three patients did audiometric losses exceed 40 decibels. The patients with drug-related ototoxicity were compared to a group of 49 patients for whom both audiometric testing (before and after therapy) and clinical observation showed that no ototoxic reactions had occurred. Preexisting renal impairment, prior and/or concomitant therapy with other possibly ototoxic drugs, and therapy for 10 days or more with a dose of greater than 3 mg/kg per day were found to be associated with ototoxicity.


Frog lysozyme III. The effects of metamorphic inhibition on Rana pipiens lysozyme ontogeny. The inhibition of Rana pipiens metamorphosis by thiouracil altered the ontogeny of lysozyme. Certain isozymes of the enzyme remained absent. There was, nevertheless, an increase in tissue lysozyme concentration.


[A case of Turner's syndrome in 45,X/46,XXp- mosaicism associated with colour-blindness (author's transl)]. We have reported the study of a young girl aged 19 suffering from a gonadal dysgenesis the chromosomal complement of which is 45,X/46,XXp-. The analysis of the transmission of Xg group was insufficient to demonstrate with certainty the origin of the pathological X. The tests indicating the ability to discriminate colours (Ishihara's test and anomaloscopy) showed a protanopia, probably of paternal origin. Hence, the Xp- probably comes from the mother.


Habituation of a monosynaptic response in frog spinal cord: evidence for a presynaptic mechanism. 1. Using the isolated spinal cord of bullfrogs (Rana catesbeiana), intracellular correlates of habituation-like depression of the monosynaptic response elicited in motoneurons by lateral column (LC) stimulation were investigated. The following properties of the motoneuron were compared before and after response depression produced by stimulation of the LC at 0.5/s: resting membrane potential, membrane conductance, critical firing level, and rheobasic current. No alteration was found in any of these parameters. 2. To determine whether transmitter release mechanisms were changing over trials, the LC was stimulated with pairs of stimuli separated by 6 ms presented at 0.5/s. While the amplitude of the first EPSP declined (74% of initial value), the amplitude of the second EPSP increased (111% of initial value). Facilitation ratios thus increased. 3. The following conclusions can thus be drawn: 1) habituation involves a process intrinsic to the LC-motoneuron synapse; 2) habituation is not totally mediated by receptor desensitization; 3) habituation is not mediated by a mechanism extrinsic to the LC-motoneuron synapse that depolarizes terminal endings, e.g., presynaptic inhibition or accumulation of extracellular potassium; 4) habituation is not produced by transmitter depletion. Any of these possibilities has as a necessary consequence that facilitiation ratios remain unchanged. 4. Possible mechanisms that could mediate habituation are: 1) alterations in mobilization  and/or release of transmitter; 2) decreased probability of invasion of terminal branches of the presynaptic fiber by the action potential.


Sound localization in anurans. I. Evidence of binaural interaction in dorsal medullary nucleus of bullfrogs (Rana catesbeiana). 1. The response patterns of single cells to monaural and binaural acoustic stimuli were studied in the dorsal medullary nucleus of the bullfrog (Rana catesbeiana). This nucleus represents the first ascending center in the anuran's central auditory nervous system. 2. Of the 142 cells isolated, 75 units responded only to monaural stimulation. Approximately 80% of these monaural cells could be excited by the ipsilateral ear, while the remaining 20% received their excitatory input from the contralateral ear. The other 67 units responded to binaural stimuli. Of these binaural cells, 14 could be excited by either contralateral or ipsilateral stimuli, and the threshold and best excitatory frequency were similar for each ear (EE). The other 53 binaural cells (EI) could be excited by stimulation of one ear and inhibited by stimulation of the other ear; for almost all of these cells the contralateral ear was excitatory and the ipsilateral ear was inhibitory. The best inhibitory frequency for one ear was approximately the same as the best excitatory frequency for the other ear, and the threshold for inhibition was near the threshold for excitation. 3. The tuning curves for all of the cells in the dorsal medullary nucleus were unimodal with "Q" values ranging from 0.4 to 4. The excitatory thresholds were widely scattered between 22 and 115 dB SPL. 4. The distribution of best excitatory frequencies for the monaural cells comprised three groups: 200-300, 500-800, and 900-1,600 Hz. The best excitatory frequencies of the binaural cells were scattered over this entire range, with a broad peak around 200-800 Hz. 5. Approximately 80% of the cells in the dorsal nucleus responded tonically throughout the duration of an excitatory tone burst. The remaining 20% of the cells responded phasically during the transient stages of a tone burst over a wide intensity range. 6. Response latencies were compared for the two types of monaural cells to tones at their best exciatatory frequencies at 10 dB above threshold. The latencies for the contralaterally excitable cells were just a few milliseconds longer than the latencies for the ipsilaterally excitable cells. For binaural cells the latency for contralateral stimulation was only 1-2 ms longer than for ipsilateral stimulation. It was concluded that the contralateral input to the dorsal medullary nucleus is not of efferent descending origin from higher auditory centers. 7. All of the binaural EI cells were sensitive to small interaural intensity differences and many were also sensitive to minute interaural time differences. These cells likely play a role in localization of sounds of significance to anurans.


Transverse-section radionuclide scanning in cisternography. By applying the technique of transverse-section radionuclide scanning to cisternography, the structure and relationships of the basal cisterns and other subarachnoid spaces of the brain can be visualized more clearly and with more detail than is possible with routine imaging techniques. The ability of this method to separate overlapping areas of radioactivity ensures improved definition of space-occupying processes within the basal cisterns. In the evaluation by cisternography of patients with hydrocephalus and dementia, the transverse-section images clearly separated various normal and abnormal patterns, whereas the routine cisternogram images were equivocal.


Gas-liquid chromatographic determination of vitamin D in multivitamin preparations containing excess amounts of vitamin E. Gas-liquid chromatographic (GLC) determination of vitamin D in multivitamin preparations containing excess amounts of vitamin E (a more than 2,500 weight ratio of dl-alpha-tocopheryl acetate to vitamin D) was investigated and a simplified routine method was established because the method reported previously (1) could not be applied to such special preparations. After applying the unsaponifiable matters of a sample to a phosphate-treated alumina column chromatography prepared according to MULDER et. al. (2), the eluate was evaporated and the residue was subjected to thin-layer chromatography (TLC) and GLC. When this method was applied to model preparations made by mixing vitamin D2 and dl-alpha-tocopheryl acetate (excess amounts), good results were obtained. Since the results on a commercial multivitamin preparation containing excess amounts of vitamin E were also satisfactory, it was confirmed that the proposed method could be used for simplified routine determinations.


Induction of transporting sites in a sodium transporting epithelium. 1. Frogs (Rana temporaria) were bathed for 1 week in solutions containing 1-1 mM sodium chloride and either one or both of amiloride (10(-4)M) and spironolactone (10(-5r both of amiloride (10(-4) M) and spironolactone (10(-5) M). This procedure was designed to deplete the sodium transporting compartment of the skin epithelium of sodium, while at the same time antagonizing the effects of endogenous aldosterone. 2. After 1 week the skins were used in vitro to measure the level of sodium transport (short-circuit current) and the density of sodium entry sites in the mucosal surface of the epithelium ([14C]amiloride binding). 3. Sodium deprivation for 1 week caused approximately a doubling of both sodium transport and the density of sodium entry sites in the mucosal surface of the epithelium compared to control skins. 4. When the results for sodium deprived and control skins were pooled there was a highly significant correlation between the density of sodium entry sites and sodium transport. 5. Mechanisms by which sodium deprivation leads to an increase in the density of sodium entry sites are discussed.


[The effect of ATP and acetylcholine on the sodium transport in bullfrog large intestine (author's transl)]. By Ussing's flux chamber method the effect of ATP and acetylcholine (ACh) on the sodium transport was studied in bullfrog colon. The results obtained are as follows; 1. ATP added to the mucosal medium caused biphasic changes in the transmural potential difference (P.D.) and short-circuit current (S.C.C.), although serosal ATP was ineffective. After an initial rapid and transient rise, both the P.D. and S.C.C. increased in parallel to reach a peak in about 10 min suggesting that the tissue conductance is little affected by ATP. Addition of ouabain to the serosal fluid depressed both the P.D. and S.C.C. and abolished the electrical responses to ATP. The application of ouabain to the mucosal side did not cause any significant depression. These results can be explained in terms of stimulation of sodium pump by ATP added to the mucosal medium. 2. ACh added to either the mucosal or the serosal medium caused increased in the P.D. and the S.C.C. The serosal application was more effective than the mucosal application. The increase in S.C.C. was more remarkable than that in the P.D., indicating an increase in the tissue conductance. It is suggested that ACh stimulates ion transport systems by changing the membrane permeability of the colon.


Selective decrease in the rate of cleavage of an intracellular precursor to Rauscher leukemia virus p30 by treatment of infected cells with actinomycin D. The cleavage  of an intracellular 67,000- to 70,000-dalton precursor, termed Pr4 to Rauscher leukemia virus (RLV) p30 protein proceeded at a slower rate when virus-producing cells were treated with actinomycin D (AMD). Treatment with AMD also caused a slight accumulation of Pr4 in purified early virus particles produced by a cell line which usually produces virions that contain little Pr4. The cleavage of other intracellular viral precursor polypeptides was not affected by treatment with AMD. Treatment of infected cells with cycloheximide, on the other hand, allowed the cleavage of Pr4 to proceed at the usual rate for a short period of time before further cleavage was drastically slowed or prevented. The cleavage of several other viral precursor polypeptides was also inhibited by treatment with cycloheximide. Different lines of evidence suggest that the mechanism of action of AMD is not due to a possible indirect effect on protein synthesis. Thus, the rate of cleavage of Pr4 was not affected by the length of pretreatment with AMD between 1 to 8 h. In addition, the combined effect of AMD and cycloheximide, at their maximal inhibitory concentrations, was greater than the effect of either drug alone, indicating the involvement of two at least partially different mechanisms in the action of AMD and cycloheximide. Furthermore, AMD did not affect the pulse labeling of viral precursor polypeptides. These results suggest that the interaction with viral RNA, whose production is inhibited by AMD, accelerates the cleavage of Pr4 to p30 during virus assembly. A hypothetical model is presented to illustrate th possible advantages of having a step in virus assembly in which genomic RNA interacts with a precursor to capsid proteins before the cleavage of that precursor.


Microelectrode study of spreading depression (SD) in frog retina--general observations of field potential associated with SD. Using microelectrodes, the field potential change associated with SD (SDP) was recorded from frog retinas conditioned with Cl-free Ringer's. In such retinas, SDP was induced by light or chemical agents such as glutamate, aspartate and K+. The chemicals, when applied iontophoretically, produced a local graded response which eventually triggered SDP. A potential similar to the local response to chemicals was often discerned on the rising phase of SDPs produced by light or occurring spontaneously. The SDP was maximal across an innermost retinal layer 50 mum or less in thickness with the intraretinal polarity predominantly negative, indicating that the major sink of SDP is in the inner plexiform layer. The influence of SDP on the receptor potential was relatively small, but the other components completely disappeared at the beginning of SDP, recovering gradually thereafter. Concomitantly, a strong depolarization occurred in the ganglion cells. Stimulation of the optic nerve could induce SDP, but nerve impulse activity is not important for SDP because tetrodotoxin was unable to prevent SDP due to light or chemical agents.


Microelectrode study of spreading depression (SD) in frog retina-Müller cell activity and [K+] during SD--. By means of K+ microelectrodes, K+ potentials and [K+] were studied in frog retinas conditioned for SD by CL--free Ringer's. A marked increase in [K+]o was observed during SD, the increase being maximal in the inner plexiform layer (up to 50 mM or more) and subsiding towards the distal retina. The extracellular K+ potential change during SD and also the graded K+ potential changes produced locally by iontophoretic injection of SD-stimulant chemicals resembled the membrane potential changes in Müller cells under the same conditions, suggesting that the Müller cells act as K+ electrodes. In retinas conditioned by Cl--free Ringer's Müller cells were swollen. This allowed intracellular recording with K+ electrodes in Müller cells to reveal that upon SD the Müller cells immediately start to cleanse the extracellular space of excess K+ which is probably a product of pathologically enhanced synaptic activity in the inner plexiform layer. The mechanism of SDP, the field potential change associated with SD, is discussed from a proposed model.


Corynebacterium vaginale (Hemophilus vaginalis) bacteremia: clinical study of 29 cases. Twenty-nine patients with bacteremia due to Corynebacterium vaginale, an inhabitant of the female genital tract, are described. Four were newborn babies. Nineteen were healthy young women delivered at full term by an operative procedure, cesarean section, or episiotomy. Within 48 hours fever and bacteremia developed. While receiving antibiotics the fever returned to normal, usually within 48 hours. The remaining cases were associated with septic abortion, tubal pregnancy, an intrauterine device, hydatidiform mole, and cellulitis. None of the adults showed evidence of brain abscess, meningitis, or endocarditis. Corynebacterium vaginale is an opportunistic minor pathogen that apparently gains access to the blood stream via an exposed vascular bed rather than as the result of immunosupression.


[Nature of changes in the sympathico-adrenal system and certain indicators of homeostasis in patients with chronic coronary insufficiency during the process of surgical intervention]. A study of some aspects of homeostasis and hemodynamics in surgical interventions for chronic coronary insufficiency helped reveal a difference in the nature of their changes depending upon the severity of the course and outcomes of the operation. With the latter running an uneventful course there is observed, as a rule, a moderate rise of the blood catecholamines level and their abundant passage with urine, which appears as a prognostically favourable sign. In operations complicated by the "syndrome of low cardiac ejection" terminating lethally there was definable, on the contrary, a high blood catecholamines content in conjunction with their reduced passage with urine. This was considered a prognostically adverse sign.


[Various indicators of the kinin and sympathico-adrenal systems in patients with recurrent myocardial infarct]. The interrelationship between the kinin and sympathoadrenal systems of blood was studied in 45 patients with repeated myocardial infarctions of different clinical course. Complicated repeated infarctions with rhythm disorders, cardiac asthma, pulmonary oedema, cardiogenic shock were accompanied by a more distinct elevation of the blood catecholamines level and the kinin system activity, than the non-complicated ones. The changes in the activity of the kinin and sympathoadrenal systems were found to parallel each other. Some diagnostic and more promising prognostic importance of the determined parameters was revealed.


[The clinical picture of metastatic myotic endophthalmitis (author's transl)]. Mycotic Septicaemia (especially with the Candida species) is not an uncommon hazard of hospitalized patients, especially those on intravenous hyperalimentation. Two such patients with endogenous mycotic bilateral endophthalmitis are presented. In spite of typical ocular symptoms diagnosis was delayed. Two further unilateral cases of a more atypical form of endogenous mycotic endophthalmitis in otherwise seemingly healthy patients are also described. Correlating histopathological findings in three of these 4 cases to the clinical histories, conclusions are drawn to aid an early diagnosis which is of paramount importance if the necessary antimyotic treatment is to preserve visual function.


[Legal security in the determination of the "anomalous quotient" (author's transl)]. By testing individuals as well as a group seasonal oscillations of the Anomaloscope's mixing screw regulation could be observed. For that reason further standardization of research methods is requested.


[On the so-called inferior, sickle-shaped edematous corneal dystrophy (author's transl)]. The inferior, sickle-shaped, edematous corneal dystrophy described by Bietti has not been further reported in the literature. A similar corneal lesion in a 44-year-old patient provided the stimulus to express some thoughts as to the etiology and pathogenesis of this form of dystrophy.


[Histiocytosis-X of the orbit (author's transl)]. After reviewing the syndrome of histiocytosis X, the special problems of an attack on the eye are discussed with regard to clinical, histological and radiological findings. By means of two cases, all aspects important for the diagnosis and treatment of histiocytosis X are discussed with reference to the literature. A histologically verified histiocytosis X in the area of the orbita is described in an almost 2 year old girl and another girl aged 7 years and 3 months. In both cases, the disease began with an edema of the upper eyelid and swelling of the lateral orbital margin. The second case showed in addition the clinical symptoms of a dacryoadenitis. The X-ray pictures of the skull revealed a large triangular osseous lesion in the area of the orbital margins. Blood chemistry, hematological tests and the bonemarrow puncture did not yield any pathological findings. The diagnosis of histiozytosis X could be made only by a biopsy from the tumor area. The swelling in the area of the eyelids and the lateral orbital margin disappeared under cytostatic therapy with Vincristin and Prednison.


Histological findings in rabbits which died with symptoms of mucoid enteritis. Histological and aetiological similarities between rabbit mucoid enteritis and human ulcerative colitis are briefly discussed. Escherichia coli seems to be associated with the rabbit disease, and treatment aimed at this organism has been followed by a period of 4 years free from mucoid enteritis.


Information factors affecting problem follow-up in ambulatory care. The influence of information factors on the follow-up of patient problems was studied in six ambulatory clinics providing primary patient care. By means of chart review, the encounter notes were examined for two consecutive visits to the same clinic to determine problems identified at the first visit and detect evidence of follow-up of these problems at the second visit. In those clinics using a problem list, at the front of the chart, those problems on the problem list had a higher follow-up rate than those not on the list particularly at longer intervals between patient visits. An encounter note written in the problem-oriented format did not enhance follow-up. Since information factors as well as clinical factors affect the follow-up of patient problems these factors must be carefully considered when designing information systems to serve ambulatory care.


Format review: evaluating implementation of the problem-oriented medical record. As interest in the problem-oriented medical record (POMR) develops, and more medical settings begin to implement the system, many observers are expressing a desire to know how well the system is being used and accepted. Moreover, settings currently using the POMR system have a need to document the effectiveness of their POMR program as a means of insuring continued progress and for addressing difficulties and obstacles affecting its use. Format review is a technique for reviewing patient records and describing patterns of POMR use. Patient records of an institution are reviewed concurrent to the patient's contact with the institution. Data collected from each record is summarized to provide an overview on patterns of POMR use and to identify areas of difficulty. These findings can serve as the basis for educational and administrative intervention to improve use of POMR. The format review technique is explained and examples of its application are given. The technique has been used at Michael Reese Hospital and Medical Center over the past two years, and has proven to be a useful tool in describing the implementation progress of POMR.


[Report of 125 esophageal carcinomas (author's transl)]. This report concerns our experience in the treatment of 125 patients with carcinoma of the esophagus during 17 years (excluding the cardiac region of the stomach). In our material predisponsing factors had no effect upon the age of the patients. The symptomatology is described, the causes of postoperative complications and mortality are discussed. The principal indications are mentioned and technical considerations are summariced. Radical tumor resection resulted in a 2 year survival rate of 23 percent. Palliativ resections in cases of advanced carcinoma are refused because of the high mortality rate and the small expectation of life.


[Technique of submucous sclerosing in patients with bleeding esophageal varices -- therapeutic results (author's transl)]. Acute hemorrhage from esophageal varices is becoming more and more frequent, implying a poor prognosis for the patient and necessitating dramatic therapeutic procedures by the physician or the surgeon. Regular endoscopic controls of patients with liver cirrhosis and portal hypertension are necessary before the first bleeding occurs in spite of negative X-ray findings of the esophagus, since long-term therapeutic results may be inproved by such controls. Sclerosing the esophageal wall does not occlude the esophageal veins, which do remain open consequently; they are just "displaced" deeper into the mucosa. There are no risks or complications of this procedure especially when esophageal varices are just beginning to form and when the esophageal mucosa is still being intact. Therapeutic results are encouraging, and they are better as compared to the results of emergency shunt or elective shunt surgery. Until short time ago sclerosing the esophageal wall was sort of a preliminary preoperative therapeutic procedure. Today it is a well established therapy in its own right, although it is, as is shunt surgery, symptomatic therapy. It does seem to be superior however to all other forms of therapy aimed at preventing or treating esophageal bleeding, since primary mortality seems to be lower and longterm results seem to be better.


A family with congenital deutan and tritan defects. A family has been found with deuteranopia and a tritan defect which is not sex-linked. It is proposed that there is also an autosomal dominant gene for tritan defects showing variable expressivity.


Colour vision deficiencies and haemophilia. Our investigations have following results: In the Rath-von Verschuer family, which is so extraordinary that the authenticity sometimes had been doubted, we found that crossing overs which were present in 50% of the cases were shown by the combination of protan defect and haemophilia B. This corresponds exactly to the observation of Whittaker and co-workers, who starting from that fact, concluded that there was a remarkable distance between the protan gene and haemophilia B gene on the chromosome. The observation enlarges the number of pedigrees with the combination of protan defect and haemophilia B. At the same time, however, we are doubtful that there might be a probable preference for this combination. With regard to the question whether manifestation of protanopia and protanomaly in any given form could be influenced by an additional factor in the X-chromosome, our present investigations give no reliable data.


A consideration of the racial incidence of congenital dyschromats in males and females. The female incidence of congenital dyschromats corresponds to the square of the males in the Northern European populations, but this relation is not always true in the non-white races. The above-mentioned facts in the non-white races which are theoretically strange are considered to be caused by an anti-glare factor of pigment epithelium in their eyes, on the assumption that the abnormal color sense of color defectives may be a special form of visual dysfunction glare pointed out by IINUMA.


Data concerning colour vision deficiencies amongst 29,985 young Greeks. In this survey, 29,985 young Greek employees were screened by the Ishihara plates and if necessary by further more detailed methods (including anomaloscope). The examination of 21,231 young males revealed 212 (1.00%) protanopes, 241 (1.14%) deuteranopes, 254 (1.20%) protanomalous, 978 (4.61%) deuteranomalous and 2 with monochromatic vision. In total, 1,678 males (7.95%) had a colour vision disturbance. The examination of 8,754 young females revealed 1 (0.01%) protanope, 2 (0.02%) deuteranope, 3 (0.03%) protanomalous and 31 (0.35%) deuteranomalous; no case of monochromatic vision in females was detected. In total, only 37 (0.42%) females had a detectable colour vision disturbance with applied screening method. These results are discussed and compaired with the available bibliographic data.


A new screening method for detecting colour vision deficiencies. Diagnostic colour vision examinations are generally administered with the anomaloscope. But this instrument requires a lot of time and experience for the tests as well as for the interpretation of the results. In practical use, it will be sufficient in most cases to know whether normal colour vision is present or not, and it is not necessary to use sophisticated devices. So it was considered desirable during the TCU conference on colour vision defects held in London in March 1973 [1] to have a testing method for practical use which is both accurate and time saving. At the time when this demand was brought up, a new colour vision test was being developed by Rodenstock [2]. It enables semi-skilled personnel to perform the test independently of ambient light condition in only 20-30 sec and to effect a classification of the type of colour vision at the same time [3].


Visually evoked cortical potential (VECP) in dichromats. The fundamental spectral sensitivity functions in man were studied by recording the visually evoked cortical potential (VECP). Using steadily presented strong blue-green and purple adaptation lights, two different spectral sensitivity functions were obtained with peaks in the green (540 nm) and in the red (590 nm) part of the spectrum. Only one peak (540 nm) was found in protanopia. The specific shift in deuteranopia and the influence of a blue-sensitive mechanism is discussed.


Experimental alteration of the red cone photoreceptor process. In our experiments, intense monochromatic coherent light (647.1nm) was used to permanently alter the red cone process. As the turtle (Pseudemys) is very sensitive in the red region of the spectrum, it was chosen as an appropriate animal model in which to study initially experimentally induced protanopia. Dark adaptation and spectral sensitivity functions were measured for ERG criteria using a vector voltmeter. Successive dark adaptation functions were measured for chromatic light adaptation levels from full bleach to about two log units above full bleach, where the dark adaptation was abruptly altered in its dynamic range by about one log unit. Pre- and post-exposure measurements showed the action spectra suppressed in sensitivity by about one log unit from 600 to 660 nm. A small depression in the short wavelength region (420-500nm) was also observed.


Unilateral colour vision defect resembling tritanopia. A case of unilateral tritan defect is described. Colour-naming experiments showed that the tritanopic eye could perceive multiple colour hues. Although the defect resembled congenital tritanopia, it was considered to be acquired secondary to retinal pathology.


Mutation induction by MNNG in a bacteriophage of Haemophilus influenzae. Three temperature-sensitive mutants of the Haemophilus influenzae phage HP1c1 were tested for reversion to wild type (ts leads to ts+). Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) produced revertants at levels up to 0.1% of the total progeny phage from treated lysogens. Cells treated with MNNG after infection with whole ts phage produced progeny phage with similar reversion frequencies, but when the uninfected cells or the phage were treated alone no reversion was induced. Fixation of premutational lesions was shown to occur with no evidence for host-cell DNA synthesis, indicating that phage DNA synthesis may be responsible for fixation of mutation in phage DNA. Evidence is given which shows that prophage DNA replicating by the cells' replicating system after treatment and before induction, produces the same number of revertants per survivor as phage DNA which is replicated outside the host genome. Two of the phage mutants (ts1 and ts2) reverted at similar frequencies, while one of the mutants (ts3) exhibited a much lower induced reversion frequency.


[Immunobiology of tuberculosis].

[Immunobiology of tuberculosis]. R. Koch showed in 1882 in his so-called fundamental experiment that tuberculous guinea pigs exhibit a vigorous immunity against re-infection. In investigations in 1930--40 we showed that this immunity is not mediated by humoral antibodies. It is a cellular process, a local and general activation of the macrophage system (the system of mononuclear phagocytes). The tuberculous granuloma consists of activated macrophages and their descendants (epitheloid and giant cells), which inhibit the growth and spreading of tubercle bacilli. The role of the specific and unspecific activation of the macrophage system could be demonstrated in experiments on rats, infected with Bartonella muris ratti. These early results are related to the recent knowledge concerning cellular immunity and granulomatous inflammation, especially to the cooperation between the lymphatic and macrophage system.


[Rapid atrial stimulation in therapy of atrial flutter]. Personal experience in 12 cases of atrial flutter treated with various types of atrial electrostimulation is reported. In 6 cases the sinusal rhythm was obtained immediately. In the remaining cases sinusal rhythm was also obtained with atrial fibrillation from a minimum of 2 minutes to a maximum of 48 hours.


The widened spectrum of multiple cartilaginous exostosis (MCE). 2 brothers with possible homozygous multiple cartilaginous exostosis (MCE) are reported. The MCE-PD-(Peripheral Dysostosis) syndrome is discussed. A family (father, daughter and son) with Metachondromatosis is presented, and the tendency to spontaneous remission in this condition is emphasized. A "second thought", when considering the diagnosis of mce, seems worthwhile.