Enhanced lymphocyte-mediated killing of tumour cells after tumour irradiation in vivo. The effect of local X-irradiation of a syngeneic carcinoma of fibrosarcoma growing in the leg of W/Fu rats on the ability of host spleen lymphocytes to kill syngeneic and allogeneic tumour cells in vitro was examined. Lymphocytotoxicity was found to be enhanced one day after local X-irradiation (4000 R) when compared with unirradiated tumour-bearing rats (p = 0.05 to 0.01). This enhancing effect of local irradiation was not observed when the lymphocytes were tested 1 week or later after X-irradiation, nor when normal legs of non-tumour bearing rats were irradiated. Mechanisms which might possibly explain these results are a reduction in release of tumour-specific antigen which can act as an inhibitor of cell-mediated cytotoxicity, or depletion of suppressor cells in the lymphocyte population. These findings may be relavant to clinical studies of cellular immunity in patients undergoing radiotherapy of malignant tumours.


DNA synthesis and cell survival after X-irradiation of mammalian cells treated with caffeine or adenine. The expression of the transient depression in the rate of DNA synthesis normally observed after exposure of randomly-dividing Chinese hamster V-79 or Chinese hamster CHO cells to ionizing radiation can be postponed or diminished by a post-irradiation treatment with 1.0 to 1.0 mM adenine or 1.5 mM caffeine. Caffeine may exert its effect by creating additional sites for replication in irradiated cells. Cells treated with caffeine or adenine for 2 or 4 hours after exposure to 3000 rad of 300 kVp X-rays exhibit depressed synthesis only after the removal of caffeine or adenine. These alterations in the timing of the X-ray-induced depression of the rate of DNA synthesis have no effect on X-ray-induced cell killing. Although a 4 hour post-irradiation treatment of randomly-dividing Chinese hamster V-79 cells with 1.0 or 2.0 mM caffeine potentiates X-ray-induced cell killing, this reduction in survival is due primarily to effects on cells in S-phase.


[Incidence of gastric mucosal changes in multiple injuries]. In a prospective study the frequency of gastric mucosal lesions was investigated in patients with polytrauma. 23 out of 24 patients had mucosal lesions of different degrees of severity. 5 had petechiae only, 9 developed erosions and 9 ulcers. 11 had symptoms of gastrointestinal bleeding, 3 had to be operated.


[Effect of so-called electrodynamic potentials on experimental reactive pseudoarthroses in animal experiments]. Eelctromagnetic and a.c.-stimulation according to the method of Kraus was investigated using experimental hypertrophic delayed unions of the radius in beagles. We could not show any beneficial or adverse effect of the method of Kraus.


Impairment of cell-mediated immunity in ectodermal dysplasia with aplastic anemia. A case of ectodermal dysplasia and aplastic anemia is presented in which a cell-mediated immunodeficiency led to a fatal Pneumocystis carinii infection. Elevated levels of IgG, IgA and IgD were present with normal specific antibody titres. A deficient cell-mediated immunity was documented by low T cell numbers, poor in vitro mitogenic responses, negative skin tests and by the histologic finding at autopsy of thymic dysplasia.


Gelfoam and autologous clot embolization: effect on coagulation. An episode of disseminated intravascular coagulation following therapeutic gelfoam embolization to control bleeding from esophageal varices in a patient with liver disease is presented. We have since followed 13 patients prospectively (six control and seven gelfoam/autologous clot) to determine the effect of this procedure on clotting. We were unable to show significant differences between the two groups as measured by the prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and platelet count. However, fibrin (ogen) degradation products were significantly elevated (p less than .01) in the gelfoam/autologous clot group. We suspect this occurred secondary to clot lysis at the site of embolization. No subsequent bleeding diathesis attributable to this abnormality occurred in any of the patients.


Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.


Electrical stimulation of the cochlea in man: hearing induction and tinnitus suppression. Sensations induced by electrical stimulation of the cochlea in humans through a promontory or a round window electrode were studied in sixteen subjects. All the patients had total or severe hearing losses. Comparison of the results with the recordings of cochlear potentials gave valuable information in all cases about the site and degree of the disorder. The data on electrically induced auditory sensation are very similar to the general findings of other authors and support the attempts of rehabilitation of the deaf by this means. The most important result reported here is the cancellation of tinnitus during stimulation by positive pulses in most cases, without affecting simultaneous acoustical or electrical hearing. This phenomenon is very reliable and could lead to very important future developments.


alpha-amylase from five strains of Bacillus amyloliquefaciens: evidence for identical primary structures. The alpha-amylases from five strains of Bacillus amyloliquefaciens were compared to determine whether differences in primary structure are responsible for variations in catalytic properties previously reported among the enzymes. Amino acid analysis established virtually identical compositions for the proteins. Reaction with dimethylaminoaphthylene sulfonylchloride indicated the amino-terminal amino acid of each amylase to be valine. Carboxyl termini of the enzymes have been determined by digestion with carboxypeptidase A. The resulting kinetic data indicate tyrosine as the carboxyl terminus and leucine as the penultimate residue for all five proteins. Isoelectric focusing of the enzymes yielded isoelectric points in the pH range of 5.09 to 5.18. Tryptic digests of the enzymes chromatographed on a cation-exchange column showed identical elution patterns. It is concluded that the primary structure of the amylase from the five strains is identical or exhibits only conservative substitutions.


Crystal structure of monoclinic ribonuclease-S at 4 A resolution. The mode of binding of 4-thiouridylic acid and a fragment of folic acid, p-aminobenzoylglutamic acid. A four-A electron density map was calculated for the monoclinic crystal of ribonuclease-S (RNase-S) based on two heavy-atom derivatives. Close geometrical similarity was found between the two crystallographically independent RNase-S molecules (called molecules ZA and ZB) in this crystal and that (called molecule Y) in the trigonal crystal. Using the rotational and translational parameters relating these three molecules, it was established that the crystallographic two-fold symmetry between the two molecules ZA in the monoclinic crystal was exactly identical to that between the two molecules Y in the trigonal crystal, suggesting the tendency of RNase-S molecules to associate in this way although the interaction is weak. The 4-A difference Fourier maps calculated for the monoclinic crystal established the following conclusions. (1) 4-Thiouridine-2'(3')-monophosphates binds to the B1 and R1 sites like other pyrimidine nucleoside-2'(3')-monophosphates as expected from previous spectrophotometric studies, but not to the B2 site even at the concentration of 20 mM. An attempt to visualize the photoproduct generated by irradiation of near-ultraviolet light in this complex failed. (2) p-Aminobenzoylglutamic acid, a fragment of folic acid, seems to bind to RNase-S with its benzene ring close to the B2 site and the alpha-carboxylate group close to the p1 site. The model is compatible with most of the chemical results obtained by Sawada et al. ((1977) Biochim. Biophys. Acta 479, 188-197).


Studies on the substrate specificity of Taka-amylase A. XIII. Preparation of 6-deoxy-6-iodomaltooligosaccharides and their inhibitory action against Taka-amylase A1. O-alpha-D-Glucopyranosyl-(1 leads to 4)-O-6-deoxy-6-iodo-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose (6'-MT), O-alpha-D-glucopyranosyl-(1 leads to 4)-6-deoxy-6-iodo-D-glucopyranose (6-M), and O-6-deoxy-6-iodo-alpha-D-glucopyranosyl-(1 leads to 4)-D-glucopyranose (6'-M) were prepared and their inhibitory action against Taka-amylase A [EC 3.2.1.1, alpha-1, 4-glucan 4-glucanohydrolase, Aspergillus oryzae] was investigated. The inhibitor constants of 6'-MT and 6'-M were 10 mM and 54 mM, respectively, and both inhibitors showed mixed-type inhibition. 6-M scarcely inhibited the enzyme action.


Absence of the corpus callosum: computed tomographic evaluation in infants and children. Absence of the corpus callosum (ACC) has a characteristic finding on computed tomography of an elevated third ventricle interposed between the lateral ventricles. Ten children with ACC, 8 with associated craniocerebral lesions, are presented. The chief importance of computed tomography is in the accurate demonstration of ACC and its commonly associated intracranial lesions, some of which can be surgically treated. Secondly, the diagnosis of ACC implies, to the clinician, a greater degree of cellular brain maldevelopment.


The radiology of intracranial tuberculosis in children. Radiology provides valuable clues to the correct diagnosis of intracranial tuberculosis. Twenty-three children with this problem were reviewed. Fifteen had meningitis, 12 of whom had abnormal chest radiographs, nine of them suggestive of tuberculosis. Common neuroradiologic findings were minor suture separation, abnormal activity in the region of the sylvian fissure on brain scans, mild ventricular dilatation, and vasculitis. Among the eight patients with tuberculomas, abnormal chest radiographs were less common. Neuroradiologic abnormalities included evidence of increased intracranial pressure on skull radiographs, focal deep lesions on brain scans, and hydrocephalus and mass lesions on air studies. Most tuberculomas were calcified one year later.


Isolation of plasma and nuclear membranes of thymocytes. II. Biochemical composition. Thymocyte plasma and nuclear membranes obtained by the procedure described in the accompanying paper were analyzed for their biochemical composition. Plasma membranes were very rich in phospholipid, cholesterol, sialic aicd; they did not contain nucleic acids. In comparison, nuclear membranes had a lower phospholipid to protein ratio and contained much less sialic acid and cholesterol. 50% of the cellular cholesterol and of the membrane-bound sialic acid were found in the plasma membranes, 14% in the nuclear membranes. Live cells were labeled with 131I, and the acid-insoluble radioactivity was followed in the subfractions. A good correlation with the distribution and enrichment of plasma membrane market-enzymes was obtained. Label enrichment was about 50-fold in the two lightest of the three plasma membrane fractions. 60% of the label was contained in the plasma membranes, only 4% in the nuclear membranes. Cross-contamination of these two types of membranes was thus negligible. Sodium dodecyl sulfate-gel electrophoresis revealed three different patterns specific for, respectively, plasma membranes, the microsomal-mitochondrial fraction, and nuclear membranes. Each pattern was characterized by a set of proteins and glycoproteins, among which high molecular weight glycoproteins could be considered as marker-proteins of, respectively, 280,000, 260,000, and 230,000 daltons. 131I-labeling of live cells tagged with a very high specific activity three glycoproteins of mol wt 280,000, 200,000, and 135,000 daltons. Nuclear membranes prepared from labeled isolated nuclei had a set of labeled proteins completely different from plasma membranes.


Molecular and biological properties of a macrophage colony-stimulating factor from mouse yolk sacs. A colony-stimulating factor (M-CSF) has been partially purified and concentrated from mouse yolk sac-conditioned medium (YSCM). M-CSF appeared to preferentially stimulate CBA bone marrow granulocyte-macrophage progenitor cells (GM-CFC) to differentiate to form macrophage colonies in semisolid agar cultures. By comparison, colony-stimulating factor (GM-CSF) from mouse lung-conditioned medium (MLCM) stimulated the formation of granulocytic, mixed granulocytic-macrophage, and pure macrophage colonies. Mixing experiments indicated that both M-CSF and GM-CSF stimulated all of the GM-CFC but that the smaller CFC were more sensitive to GM-CSF and that the larger CFC were more sensitive to M-CSF. Almost all developing "clones" stimulated initially with M-CSF continued to develop when transferred to cultures containing GM-CSF. In the converse situation, only 50% of GM-CSF prestimulated "clones" survived when transferred to cultures containing M-CSF. All clones initially stimulated by M-CSF or transferred to cultures stimulated by M-CSF contained macrophages after 7 days of culture. These results suggest that there is a population of cells (GM-CFC) that are capable of differentiating to form both granulocytes and macrophages, but, once these cells are activated by a specific CSF (e.g. M-CSF), they are committed to a particular differentiation pathway. The pattern of CFC differentiation was not directly related to the rate of proliferation: cultures maximally stimulated by M-CSF produced mostly macrophage colonies, but the presence of small amounts of GM-CSF produced granulocytic cells in 30% of the colonies. Gel filtration, polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and affinity chromatography with concanavalin A-Sepharose indicated that M-CSF from yolk sacs was a glycoprotein with an apparent molecular weight of 60,000. There was some heterogeneity of the carbohydrate portion of the molecule as evidenced by chromatography on concanavalin A-Sepharose.


Peritoneal exudate cells. V. Influence of age, sex, strain and species on the induction and the growth of macrophage colony forming cells. We investigated the effects of age, sex and strain in the induction of peritoneal exudate colony-forming cells (PE-CFC) in mice. Sex and age (ranging from 3 weeks to 12 months) had no significant effect on the induction of PE-CFC. However, we found significant difference between strains in terms of the number of nucleated cells and the proportion of PE-CFC in exudate cells. When we investigated the mechanisms behind this strain difference, we found that it was due to neither the type of colony-stimulating factor employed in culture, nor the type of stimulants used to induce the exudate, nor the difference in the kinetics of appearance of PE-CFC in the peritoneal cavity. We also studied the induction of PE-CFC in rats and hamsters and the growth of these cells in vitro. Unlike mouse cells, PE-CFC from rats and hamsters could also use media conditioned by cells from other species as a source of colony-stimulating factor.


Determination of benoxaprofen [2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid, LRCL 3794] in biological fluids. Benoxaprofen, a novel anti-inflammatory compound, is efficiently (greater than 95%) extracted from plasma and urine in the pH range 1 to 5 into either chloroform or ether. The compound is determined either by UV spectroscopy or by gas-liquid chromatography of the methyl ester (formed by reaction with diazomethane) on a column of 3% of silicone gum E-301 on DCMS-treated Chromosorb W, with detection by flame ionisation (limit 0.3 microgram/ml) or electron capture (limit 0.01 microgram/ml). For rapid routine use, the UV method (limit ca. 5 microgram/ml) gives good agreement with the specific methods.


The effects of ristocetin and von Willebrand factor on platelet electrophoretic mobility. Ristocetin will induce the agglutination of platelets in the presence of von Willebrand factor. In previous studies, an electrostatic mechanism was proposed for this phenomenon wherein first the platelet's surface charge is reduced by the binding of ristocetin and then the von Willebrand factor acts as a bridge between platelets. To test this hypothesis, the effects of ristocetin and von Willebrand factor, singly and together, on the electrophoretic mobility of normal, trypsinized, and Bernard-Soulier platelets was measured. Ristocetin alone, at concentrations of 0.5 mg/ml or more, produced a statistically significant reduction in the electrophoretic mobility of fresh or fixed platelets. Control experiments showed that the reduction was not due to changes in the ionic milieu of the solution. Therefore, the decrease in platelet mobility is evidence for binding of ristocetin to the platelet surface. Bernard-Soulier and trypsinized platelets also had reductions in mobility with ristocetin, suggesting that ristocetin binds to the platelet at sites other than the binding site for von Willebrand factor. The presence of plasma from a patient with von Willebrand's disease did not alter the reduction in mobility of normal platelets by ristocetin. However, the reduction was markedly enhanced in the presence of normal plasma. This enhancement did not occur with Bernard-Soulier platelets and was inhibited by anti-Factor VIII/von Willebrand factor antiserum or trypsinization of the platelets. Thus, the enhanced reduction appears to be associated with the binding of von Willebrand factor to the platelet surface. These studies indicate that platelets undergo two changes with ristocetin and von Willebrand factor, both of which facilitate agglutination: reduction in net surface charge and binding of von Willebrand factor, a large molecule which can serve as a bridge between platelets. In parallel studies, bovine von Willebrand factor, without ristocetin, agglutinated and reduced the electrophoretic mobility of normal but not Bernard-Soulier or trypsinized platelets; this indicates a similar mechanism of agglutination.


von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease. Factor VIII-related antigen (VIIIag) is deficient in plasma and platelets of patients with severe von Willebrand's disease. This study reports a second von Willebrand's disease antigen (vWagII), distinct from VIIIag, that is also deficient in the platelets and plasma of patients with severe von Willebrand's disease. VIIIag and vWagII are separable by molecular exclusion chromatography, sucrose density gradient ultracentrifugation, and crossed immunoelectrophoresis. They show reactions of immunologic nonidentity with each other, and thus, do not share a precursor-product relationship. vWagII is released from normal platelets during blood clotting, accounting for a fourfold higher concentration of vWagII in serum over plasma.


Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. I. General pattern of development. The development of Purkinje cells was studied in the bullfrog from prometamorphic tadpoles to 10-week-old postmetamorphic froglets by the Golgi-Kopsch method. In this species, the rate of Purkinje cell development is unusually slow and proceeds in two waves. The first wave of development begins prior to the establishment of the external granular layer (EGL), and proceeds slowly for two to three months during the formation of the EGL; then accelerating as metamorphosis is being completed, the cells reach near-adult dimensions a month later. Even prior to the formation of the EGL these cells are already present in the stage of dendritic orientation and flattening which, however, varies from the norm. The second wave of Purkinje cell development begins during metamorphosis and proceeds at a more rapid pace until two months after metamorphosis, at which time they appear to have reached adult dimensions. In these cells the development of the apical dendrite does not always coincide with the stellate stage but may proceed directly to the stage of dendritic orientation and flattening which, in accordance with the norm, is towards the pia and in the sagittal plane. Many variations are present in the dendritic trees and orientation of the dendritic branches of Purkinje cells throughout their development. These variations are similar to those seen in mammals, however, since the frog cerebellum consists of a simple plate, they cannot be attributed to a Cartesian transformation of dendrites to accomodate the curvatures of a folial pattern. Similarly, since these morphological variations occur in the course of normal development they cannot be attributed to a reaction to, or recovery from, injury during development.


Catecholamine innervation of the basal forebrain. III. Olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex. The catecholamine innervation of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex was studied in the rat using biochemical analysis and fluorescence histochemistry. Biochemical studies demonstrate a moderate norepinephrine (NE) content in all olfactory structures, a high dopamine (DA) content in the olfactory tubercle and a low DA content in the olfactory bulb, anterior olfactory nucleus and piriform cortex. Following locus coeruleus lesions NE content decreases 71% in the olfactory bulb, 82% in the anterior olfactory nucleus, 62% in olfactory tubercle and 77% in piriform cortex...


Retrograde responses of developing lateral motor column neurons. Removing the right hind limb of Rana pipiens larvae at different stages during development initiates diverse responses within lateral motor column (LMC) neurons whose axons have entered the limb and are forming neuromuscular junctions; Severing the hind limb at stage V inhibits the future differentiation of LMC neurons and, ultimately, 95% of the presumably injured cells degenerate; Ultrastructural observations indicate that the affected neurons become pyknotic, but display little evidence of lysosomal involvement. However, a quite different reaction is encountered when limb ablation is delayed to stage X. At this stage, LMC neurons rapidly disclose an intense retrograde response, which includes the genesis of numerous secondary lysosomes in degenerating cells; If, however, limb removal is postponed until stage XV or XX then a clasic chromatolysis can be recognized in axotomized neurons. The intensity of the chromatolysis appears to be inversely related to the age of the neurons. This investigation tends to support the premise that differentiating LMC neurons pass through three crucial stages in their development which can be identified following axotomy.


Allergy to a product(s) of ethylene oxide gas: demonstration of IgE and IgG antibodies and hapten specificity. Patient D.H., on chronic hemodialysis, developed severe allergic reactions after exposure to articles such as plastic tubing and hemodialysis supplies which had undergone cold sterilization with ethylene oxide (EO) gas. It was shown that human serum albumin (HSA) exposed to EO (EO-HSA) in the usual sterilization procedure selectively elicited positive skin tests and in vitro histamine release. It is now demonstrated that D.H. serum reacts selectively in a radioallergosorbent test (RAST) which utilizes discs coated with HSA and exposed to EO gas. In addition, D.H. serum contained IgG antibodies reactive with EO-HSA. This antibody activity was not detected in the sera of 27 normal subjects and 25 chronic hemodialysis patients. EO-HSA and ragweed RAST inhibition tests with a number of proteins in native form and after exposure to EO demonstrated the EO hapten specificity of the IgE antibody.


The hand in mixed connective tissue disease. The mixed connective tissue disease syndrome has been described in the medical literature. The clinical and serological characteristics of the syndrome are defined in this paper. The hands of these patients differ from the hands of patients with systemic lupus, rheumatoid arthritis, or systemic sclerosis. In 10 patients there were no erosive changes on radiological examination and all 10 patients had Raynaud's phenomenon. The most striking finding was tightness  in the flexors. Mild cases of flexor tightness improved with systemic steroids. One patient with severe flexor tightness required surgical release of adhesions from a chronic inflammatory process of fascia, muscle, and tenosynovium. Biochemical studies showed an abnormal collagen pattern that may be distinct for mixed connective tissue disease.


Nonspecific activation of murine lymphocytes. II. Parameters of the interaction between splenic lymphocytes and radiolabeled 2-mercaptoethanol in vitro. Recent evidence has indicated that addition of 2-mercaptoethanol (2-ME) to culture medium is able to activate murine lymphocytes to undergo blastogenesis, to synthesize polyclonal antibody, and to develop cytotoxicity to both autologous and heterologous target cells. In order to explore the basis for these phenomena, a study of the physical interaction between the cell and 2-ME was undertaken by using a radiolabeled preparation of 2-ME. Uptake of labeled 2-ME increased over the initial 24 hr of culture, after which a steady state was achieved. Cells were found to have maximal susceptibility to activation by 2-ME after incubation for 24 hr in the absence of the thiol compound. This observation was not explicable in terms of any alteration in the kinetics of 2-ME uptake. The amount of labeled 2-ME taken up was a function of the 2-ME concentration with which the cell was incubated, with the exception of the concentration range that is optimal for mitogenesis. At this range, the curve was suggestive of a saturation effect. Uptake by B cell cultures was found to exceed that by T cell cultures. Uptake was shown to result from interaction with protein, to be independent of metabolic energy, to be governed by temperature-dependent kinetics, and to be highly specific.


Patterns of expression of human "Ia-like" antigens during the terminal stages of B cell development. The "Ia-like" antigens characteristically present on the membrane of B lymphocytes were shown to be absent in most terminally differentiated Ig-producing plasma cells. This was most evident in analyses of myeloma plasma cells that uniformly lacked the Ia-antigens. Also, in B lymphoid cell lines, the lymphoblasts were uniformly Ia-positive but the plasma cells were negative. In contrast, however, the majority of plasma cells produced after pokeweed mitogen stimulation remained positive. Plasma cells in tonsil and in the tissue of peripheral blood of patients with Wladenström's macroglobulinemia were also sometimes Ia-positive although the majority were negative. Studies of membrane IgM and IgD indicated a similar loss in some instances. However, the SIg and Ia antigens were not invariably associated. These results lead to the conclusion that Ia-antigens are differentiation antigens for B cells and are usually lost by the end stage cells in this series.


Characterization of lymphocyte-activating factor (LAF) produced by a macrophage cell line, P388D1. II. Biochemical characterization of LAF induced by activated T cells and LPS. Unstimulated P388D1 cells, as well as P388D1 cells stimulated with PHA-activated guinea pig T lymphocytes or LPS, produced a lymphocyte activating factor (LAF). In order to have a chemical basis for comparing this LAF with the LAF produced by normal macrophages, we have analyzed several biochemical characteristics of the P388D1-derived LAF. Sephadex G-75 chromatography of concentrated LAF-containing supernatants from cultures of unstimulated and T cell stimulated P388D1 cells demonstrated that the cell line LAF had a m.w. of approximately 16,000. On DEAE cellulose, the T cell-induced LAF fractionated into at least three major peaks and one minor peak. By using hydroxylapatite chromatography, two of the major peaks of LAF activity were separated from residual contaminating Lowry positive material. LPS-stimulated P388D1 also produced LAF with a m.w. of 16,000. However, the LPS-induced LAF appeared to lack one of the DEAE peaks of LAF activity observed with the T cell-derived LAF. In contrast to LPS, T cells may induce the synthesis and/or release of an additional LAF component or enzymatically modify one or more of the LAF species that are produced in response to both stimulants. Based on the results of chemical characterization studies, the P388D1-derived LAF appears to be similar in size and charge to the lymphocyte activating factor produced by normal macrophages.


Tumor cell cytostasis by macrophages and antibody in vitro. I. Resolution into contact-dependent and contact-independent steps. In a murine system, macrophages, in concert with antibody, were shown to suppress iododeoxyuridine incorporation by tumor cells. The mechanism of suppression did not involve phagocytosis or lysis. The generation of suppressed tumor cells was resolved into a contact-dependent step and a contact-independent step. The first step was one-hit with respect to macrophages and multi-hit with respect to antibody.


Melanoma-associated immunosuppression through B cell activation of suppressor T cells. Using normal human lymphocytes isolated by sedimentation and cotton column adherence, we have developed a reliable assay of immunosuppression of PHA-induced blastogenesis by serum from selected melanoma patients. These lymphocyte cultures contained both responder cells (subpopulation x) and regulator cells (subpopulation y). Lymphocytes isolated by gradient centrifugation on sodium metrizoate-Ficoll contained responder cells (x) but no regulator cells (y). Cultures of lymphocytes isolated by this method were stimulated by PHA but were not suppressed by the addition of melanoma serum. When lymphocytes were isolated by a cotton column adherence/Lymphoprep centrifugation-double separation, subpopulations (x) and (y) were isolated. We have established that both subpopulations are necessary for suppression to occur, and that (y) operates as the regulator of (x). Finally, by manipulating B cell and T cell populations isolated by nylon column adherence or AET rosette separation, we have determined that the regulator ability of subpopulation (y) is the result of B cell activation of suppressor T cells.


Rabbit antiserum against Daudi-cell membrane fractions detects cell surface antigens present on subpopulations of human lymphocytes. An antiserum was produced by immunization of rabbits with membrane preparations of a human lymphoblastoid B cell line, Daudi. After absorption with a human endometrial carcinoma cell line, this antiserum appeared to be specific for antigen(s) present on adult and fetal thymocytes as well as on tonsillar lymphocytes but absent, or present in very small amounts, on normal or phytohemagglutinin- (PHA) stimulated peripheral blood lymphocytes (PBL). When T and B cell-enriched fractions from tonsillar lymphocytes were tested with the anti-Daudi serum, the reactivity was equally distributed in each population. Among 13 human lymphoblastoid cell lines tested, reactivity was demonstrated on three out of four T cell lines, and on four out of nine B cell lines. The positive reacting B cell lines were derived from two African and two American Burkitt lymphomas. The antigen(s) described does not seem to be related either to human Ia-type antigens or to Epstein-Barr virus-associated antigens because these antigens are not present on fetal or adult thymocytes. Reciprocal absorption experiments indicate that this anti-Daudi serum detects the same antigenic structures present on certain subpopulations of T and B lymphocytes.


Inhibition of the induction of cytolytic T lymphocytes with alloantisera directed against H-2K and H-2D gene products. Alloantisera directed at gene products of the H-2Kd or H-2Dd loci on the stimulator cell were shown to inhibit specifically the generation of cytolytic T lymphocytes to those antigens. Thus, masking the antigens of one H-2 locus on the stimulator cell inhibits the induction of CTL to products of that locus but does not inhibit the induction of CTL to antigens of another H-2 locus. Alloantisera inhibition of the induction of cytolytic T lymphocytes occurred with both normal and primed responder cells and also occurred when the stimulating antigens were on whole cells or purified plasma membrane. Absorption on the appropriate spleen cells removed the inhibitory capacity of these alloantisera.


Molecular identification of a surface structure on B cells (Lyb-3) and its relationship to B cell triggering. Lactoperoxidase-catalyzed radioiodination of cell surface proteins and immunochemical procedures are used to identify murine splenic lymphocyte membrane components bound by anti-Lyb-3 serum. This antiserum defines membrane components (Lyb-3) on a subpopulation of murine B cells that may function as a receptor for T cell signals. SDS-PAGE analysis of surface-labeled membrane components bound by anti-Lyb-3 serum demonstrated a single molecular species of 68,000 d. The polypeptides recognized by anti-Lyb-3 are not composed of disulfide-linked subunits and bear no antigenic relationship with known membrane immunoglobulins (IgM or IgD). Absorption of anti-Lyb-3 serum with the 68,000 d polypeptides removed the ability of anti-Lyb-3 serum to augment the in vivo immune response of mice to low doses of sheep erythrocytes. The latter provides formal proof that the 68,000 d polypeptide bound by anti-Lyb-3 serum is the target on the B cell membrane for the immunoenhancing activity of the antiserum.


Specific binding of T lymphocytes to macrophages. III. Spontaneous dissociation of T cells from antigen-pulsed macrophages. Peritoneal exudate lymphocytes (PEL) from immune guinea pigs that adhere to antigen-pulsed macrophages (MO) were cultured for 1 week to yield a population enriched in antigen-specific (selected) T cells. These cells bind specifically within hours to fresh autologous antigen-pulsed MO. Thd dissociation of these selected PEL from antigen-pulsed MO was studied. No evidence was obtained that factors in the culture medium play a role in dissociation. Lymphocytes that have dissociated from antigen-pulsed MO are usually fully capable of rebinding to MO freshly pulsed with antigen, suggesting that there is no deficiency in the lymphocytes ability to bind. In contrast, readding antigen to cultures during incubation prevents the predicted dissociation. Moreover, repulsing MO cultured without selected PEL restores their capacity to bind fresh selected PEL. These findings indicate that decay of antigen associated with with MO is the major mechanism underlying the observed dissociation.


Partial purification and molecular characterization of a lymphokine (costimulator) required for the mitogenic response of mouse thymocytes in vitro. We have partially purified a lymphokine, costimulator, which is necessary to induce mitogenesis in mouse thymocytes in vitro. Costimulator is released from mouse leukocytes exposed to Con A for 12 to 18 hr. It has been purified more than 100 X by gel exclusion chromatography and isoelectric focusing. Thymocytes from CBA/J mice respond to the mitogenic lectin Con A only if the costimulator concentration is above a certain level. Culturing such cells with Con A at a density below 1 X 10(6) cells/ml produces costimulator concentrations too low for mitogenesis. This system has been developed into a quantitative assay for costimulator, to monitor purification, recovery, and biologic activity in various methods of molecular characterization. The activity is trypsin sensitive, and has a buoyant density characteristic of protein or glycoprotein. However, for a protein, it is relatively heat stable. Its m.w., established by carrying out sedimentation, gel filtration, and buoyant density measurements, is 30,500, and its frictional coefficient is 1.45. Costimulator purified by isoelectric focusing is active at 10(-10) M or lower in tissue culture.


Suppression of polyclonal B cell activation in scrapie-infected C3H/HeJ mice. A consistent modification in B lymphocyte activation has been observed 1 month after infection of C3H/HeJ mice with scrapie. The mitogenic response to lipopolysaccharide of splenocyte cultures from experimental mice was reduced 30 to 60% as compared to controls. This reduction in mitogen responsiveness was transient but coincided with the onset of detectable splenomegaly and with the reported recovery of maximum yield of infectious scrapie agent in the spleen. The DNA synthetic response to lipopolysaccharide stimulation of splenocytes from scrapie-infected C3H/HeJ mice was depressed relative to controls only between 20 and 40 days after intracerebral inoculation. At all other times, experimental and control responses were identical. Scrapie-associated decreases in mitogenesis were found whether the spleen cell cultures contained splenocytes from individual mice, splenocytes pooled from several mice, or gradient-purified mononuclear cells. The responses of C3H/HeJ splenocyte cultures to phytohemagglutinin or concanavalin A stimulation were unaffected by scrapie infection.


Analysis of the cellular basis of idiotype-specific suppression. We have investigated the ability of B and T lymphocyte subclasses from donor mice that produce high levels of anti-Ar antibody but have been suppressed for one idiotypic component (CRI) to induce and maintain idiotypespecific suppression. Our studies indicate: 1) Memory B cells from such mice can preempt virgin CRI+ B cells present in the host from contributing to the anti-Ar response. 2) T cells can also adoptively transfer idiotypespecific suppression. 3) B and T cells do not act synergistically in this transfer of idiotype-specific suppression. 4) Extremely small numbers of Ly23 cells transfer suppression of idiotype and most probably represent true Ts cells. 5) Ly1 cells from hyperimmune idiotypically suppressed donors can induce idiotype-specific suppression. This latter result most likely reflects the induction of idiotype-specific suppressor cells in the host.


T cell growth factor: parameters of production and a quantitative microassay for activity. Several soluble factors have recently been associated with the proliferation and differentiation of thymus-derived lymphocytes. One of these factors present in medium conditioned by T cell mitogen-stimulated lymphocytes has the ability to promote the long-term culture of normal and antigen-specific cytotoxic T cells. We report a method to test for this proliferative stimulus in the form of a sensitive microassay based upon the tritiated-thymidine incorporation of continuous murine tumor-specific cytotoxic T cell lines (CTLL). The microassay requires microliter quantitites of sample fluid and is amenable to quantitative analysis. This highly reproducible,  quantitative assay for T cell growth factor (TCGF) has allowed investigation as to the kinetics of TCGF generation and has revealed that T lymphocytes are required for its production. Further investigation has supported the notion that this nonspecies-specific factor is actively removed from tissue culture medium by the proliferation of either T cell mitogen-activated lymphocytes or CTLL.


Studies on the question of conventional immunoglobulin on thymocytes from primitive vertebrates. I. Presence of anti-carbohydrate antibodies in rabbit anti-trout Ig sera. An unexpected cross-reactivity between trout immunoglobulin (Ig) and keyhole limpet hemocyanin (KLH) was observed. Rabbit antisera to KLH were capable of binding to radioiodinated trout Ig and, conversely, antitrout Ig reacted with KLH. The cross-reactive antibodies were not found in preimmune sera and did not arise because of a common contaminant in the two immunizing preparations. The molecular basis of the cross-reactivity was found to reside in the carbohydrate moieties. Isolated glycopeptides from KLH and trout Ig were efficient inhibitors of the cross-reactivity. Furthermore, L-fucose was capable of inhibiting the cross-reactivity, whereas other monosaccharides tested did not. Absorption of anti-KLH with trout Ig and anti-trout Ig with KLH effectively removed the cross-reactive antibodies and only slightly affected the titer to their respective homologous antigens. Antibodies with specificity for L-fucose were isolated from anti-KLH and anti-trout Ig sera by passage over affinity columns and elution with the monosaccharide.


A micro-procedure for quantitative precipitin tests. A new method for the quantitative analysis of antigens and antibodies has been based on (1) ultrafiltration of the antigen-antibody precipitates through silver membranes of 0.2 micrometer pore size in a specially designed multisample apparatus, and (2) spectrophotometric determination at 210 nm of the amount of proteins in the antigen-antibody precipitates dissolved in 0.01 N HCl. At this wavelength, the = C = O group of the polypeptide chains constitutes the main chromophoric group. In comparisons with the ninhydrin color reaction, protein determination by low UV spectrophotometry, e.g., at 210 nm, was shown to be about 6 times more sensitive, permitting analysis of samples containing from 1.0 to 35.0 microgram of antigen. The concentration range of protein solutions in 0.01 N HCl which is measured at low UV can be regulated by a factor of 8--10 by changing absorption between 200 and 230 nm. Comparison of the ultrafiltration microtechnique with the standard quantitative precipitin microtechnique involving centrifugation of precipitates was made in 4 different antigen-antibody systems. The new technique was found to be as accurate as the standard technique. It allows completion of analysis within only 5--6 h. The standard precipitin technique, by contrast, requires a 5--7-day reaction period for completion.


Presence of SLA and Ia-like antigen on boar spermatozoa. Several parameters for serological tests on boar spermatozoa were studied, and a reliable technique was developed and employed. Using SLA (the MHC system in pig) genotyped boars, and specific reagents, SLA and Ia-like antigens were demonstrated on the sperm using both the cytotoxic and the absorption test. No SLA activity was detected in the seminal fluid.


Heterogeneity of human colony-forming cells (CFU-C): differences in size, rate of colony formation, and responsiveness to colony-stimulating factor. Human bone marrow cells have been fractionated by velocity sedimentation at unit gravity. Fractions were analyzed for cell morphology, number of nucleated cells and myeloid colony-forming cells (CFU-C's). Colony formation was assayed with the following CSF preparations: serum-free HLCM and two electrophoretically distinct CSF fractions (CSF-A and CSF-B) purified from the same source. Two distinct CFU-C populations were found. One, a rapidly sedimenting (7.2 to 8.0 mm/hr), population exhibited colonies after 7 days of culture in response to HLCM and CSF-A only. The second, a more slowly sedimenting (6.5 mm/hr) CFU-C peak, did not exhibit colonies until 11 days of culture and did so in response to all three CSF's tested. The results indicate that human bone marrow CFU-C's are heterogeneous and that the two purified CSF fractions from human lung have different CFU-C specificity.


Selective impairment of hearing and vestibular function in a brain stem lesion. A case of sudden bilateral hearing loss in a diabetic patient is reported. Acoustic-vestibular examination indicated a lesion localized in the brain stem although no other neurological abnormality was found. Postmortem examination demonstrated severe vascular changes of the brain stem. Areas of fresh infarction and necrosis were found localized to the cochlear and vestibular nuclei. The case demonstrates that central vascular disorders may be the cause of sudden severe hearing loss even without other neurological symptoms or signs.


Optimal strategies in immunology. II. B memory cell production. After a first encounter with most antigens, the immune system responds to susequent encounters with a faster, more efficient and more strenuous antibody response. The memory of previous antigen contacts is carried by lymphocytes. Expanding on the model developed in Part 1 of this paper, we examine the optimal strategy available to the immune system for B memory cell production. We again find that the strategy should be of the bang-bang variety. The model we consider assumes that antigen triggers a subpopulation of B-lymphocytes. These triggered lymphocytes can proliferate and secrete modest amounts of antibody, or differentiate into non-dividing plasma cells which secrete large amounts of antibody, or differentiate into non-antibody secreting memory cells. Given injections of antigen at two widely spaced times we compute the strategy which minimizes a linear combination of the primary and secondary response times. We find that for all biologically reasonable parameter values the best strategies are ones in which memory cells are produced at the end of the primary response. Exerimental results which bear on the actual strategies employed are discussed.


Diffusion and consumption of oxygen in the resting frog sartorius muscle. Adaptations of the method of Takahashi et al. (1966. J. Gen. Physiol. 50:317-333) were used to test the validity of the one-dimensional diffusion equation for O2 in the resting excised frog sartorius muscle. This equation is: (formula: see text) where x is the distance perpendicular to the muscle surface. t is time, P(x, t) is the partial pressure of O2,D and alpha are the diffusion coefficient and solubility for O2 in the tissue, and Q is the rate of O2 consumption. P(O, t), the time-course of PO2 at one muscle surface, was measured by a micro-oxygen electrode. Transients in the PO2 profile of the muscle were induced by two methods: (a) after an equilibration period, one surface was sealed off by a disc in which the O2 electrode was embedded; (b) when PO2 at this surface reached a steady state, a step change was made in the PO2 at the other surface. With either method, the agreement between the measured P(O, t) and that predicted by the diffusion equation was excellent, making possible the calculation of D and Q. These two methods yielded statistically indistinguishable results, with the following pooled means (+/- SEM): (formula: see text) At each temperature, D was independent of muscle thickness (range, 0.67-1.34 mm). The activation energy (EA) for diffusion of oxygen in muscle was -3.85 kcal/mol, which closely matches the corresponding value in water. Together with absolute values of D in water taken from the literature, the present data imply that (Dmuscle/DH2O) is in the range 0.59-0.69. This value, and that of EA, are in agreement with the theory of Wang (1954, J. Am. Chem. Soc. 76:4755-4763), suggesting that with respects to the diffusion of O2, to a useful approximation, frog skeletal muscle may be considered simply as a homogeneous protein solution.


Kinetics of oxygen consumption after a single isometric tetanus of frog sartorius muscle at 20 degrees C. The time-course of the rate of oxygen consumption (QO2) has been measured in the excised frog sartorius muscle after single isometric tetani of 0.1-1.0 s at 20 degrees C. To measure deltaQO2(t), the change in QO2 from its basal level, a novel method was devised, based on the validity in this tissue of the one-dimensional diffusion equation for oxygen, established in the preceding paper. After a tetanus, deltaQO2 reached a peak within 45-90 s, then declined exponentially, and could be well fit by deltaQO2(t) = QO + Q1(epsilon -k1t - epsilon-k2t). tau2 (= 1/k2), which characterized the rise of deltaQO2, was a decreasing function of tetanus duration (range: from 1.1 +/- 0.28 min [nu = 5] for a 0.1-s tetanus, to 0.34 +/- 0.05 min [nu = 8] for a 1.0-sec tetanus). tau1 (= 1/k1), which characterized the decline of deltaQO2, was not dependent on tetanus duration, with mean 3.68 +/- -.24 min (nu = 46). A forthcoming paper in this series shows that these kinetics of deltaQO2 are the responses to impulse-like changes in the rate of ATP hydrolysis. The variation of tau2 with tetanus duration thus indicates the involvement of a nonlinear process in the coupling of O2 consumption to ATP hydrolysis. However, the monoexponential decline of deltaQO2(t), with time constant independent of tetanus duration, suggests that during this phase, the coupling is rate-limited by a single reaction with apparent first order kinetics.


The influence of calcium-free EGTA solution upon membrane permeability in the crystalline lens of the frog. Potential difference, resistance, cation content, and 86Rb efflux were measured in frog lenses maintained in normal or calcium-free EGTA Ringer's solution. Exposure of the lens to calcium-free solution resulted in a rapid fall in potential and resistance, together with a twofold increase in 86Rb efflux rate. These rapid changes were not due to an alteration in cation distribution between the lens and its environment. However, the alteration in 86Rb efflux rate could be explained on the basis of the fall in potential. These findings suggested that removal of calcium from the bathing medium caused a rapid increase in sodium permeability alone. This suggestion was substantiated by the results of experiments where the response of the lens to low calcium solution was determined in a medium in which 90% of the sodium had been replaced by sucrose.


Studies on the mechanisms of vaccina virus cytopathic effects. I. Inhibition of protein synthesis in infected cells is associated with virus-induced RNA synthesis. The mechanism of vaccinia virus-induced inhibition of protein synthesis was studied in LLC-MK2, HeLa and L cells. Removal of cycloheximide (300 microgram/ml) from cells infected at a multiplicity of infection (m.o.i.) of 300 particles/cell at 4 h after infection resulted in the resumption of both host and virus protein synthesis in LLC-MK2 cells, but not in HeLa and L cells. In order to determine whether virus-induced RNA synthesis, which occurs in infected cells in the presence of cycloheximide, is related to the inhibition of protein synthesis, (cut-off), the rate of virus-induced RNA synthesis in the presence of cycloheximide was measured in all three cell types. In L cells and HeLa cells the rate of virus-induced RNA synthesis increased with time, whereas in LLC-MK2 cells it remained constant for at least 4 h. However, when higher multiplicities (900 and 2700 particles/cell) were used to infect LLC-MK2 cells, the rate of RNA synthesis in the presence of cycloheximide did increase with time and was greater at the higher multiplicity. Under these conditions there was a direct relationship between the extent of virus RNA synthesis and the degree of cut-off after the removal of cycloheximide. In HeLa and L cells infected at 300 particles/cell, the longer the exposure to cycloheximide, the greater was the cut-off observed upon removal of the drug. As was the case the LLC-MK2 cells, there was a direct relationship between the rate of RNA synthesis and the degree of inhibition of protein synthesis. Since virus-induced RNA synthesis occurs in the presence of cycloheximide, the effects of actinomycin D and cordycepin on host polypeptide synthesis were tested. Inhibition of host cell protein synthesis was virtually abolished when HeLA cells were infected in the presence of cordycepin (50 and 25 microgram/ml) or actinomycin D (20 microgram/ml). These results indicate that, as the rate of virus-induced RNA synthesis increased, regardless of the type of cell used, protein synthesis was inhibited at earlier times and to a greater extent. These observations are consistent with the hypothesis that the cut-off phenomenon is related to the synthesis of an early virus-induced RNA(s).


Effects on speech of chronic cerebellar stimulation in cerebral palsy. Chronic cerebellar stimulation of the anterior lobe is undertaken for relief of motor dysfunction in cerebellar palsy, but the effect on speech and vocal ability has been uncertain. The present study evaluated speech before cerebellar stimulation and during the immediate postoperative period in seven severely spastic/athetoid patients with congenital cerebral palsy and one patient with traumatic brain damage. Structured listening tasks were completed in blind fashion by a trained panel of speech pathologists. Group analysis revealed no significant improvement in speech intelligibility or articulatory accuracy after stimulation. With the exception of strain/strangle vocal quality, which improved considerably, vocal characteristics were not affected by cerebellar stimulation. In three of eight patients, however, improvement in certain speech characteristics was noted.


Studies of the third circulation. Amipaque CT cisternography and ventriculography. The techniques of Amipaque (metrizamide) computerized tomography (CT) cisternography and Amipaque CT ventriculography are described. Normal, intermediate, delayed, and obstructive cerebrospinal fluid circulation patterns are readily demonstrated by evaluation of ventricular stasis of Amipaque on serial CT scans. Both the morphological and physiological characteristics of intracranial cysts are accurately defined and a diagnostic classification is presented. The functional integrity of ventricular shunts can be appraised using the ventricular persistance of Amipaque as a primary criterion. Other applications of these modalities are described and their place in the neurodiagnostic armamentarium is discussed.


Thallium-201 myocardial perfusion scintigrams in the evaluation of aorto-coronary saphenous bypass surgery. The effect of aorto-coronary bypass graft surgery (CBG) upon regional myocardial perfusion (RMP) was studied in 23 patients using thallium-201 myocardial perfusing imaging after exercise. We compared the changes in RMP with the clinical status and ECG's during graded treadmill exercise (GTX) before and after CBG. After CBG, the New York Heart Association's "functional class" improved from 3.2 +/- 0.1 (mean +/- SE) to 1.2 +/- 0.2, p less than 0.005. The GTX performance of the patients was also significantly improved postoperatively as judged by the total exercise time (11.7 +/- 0.6 min postop, compared with 7.2 +/- 0.5 min preop; p less than 0.005). Postoperative improved Tl-201 scintigrams were observed in 19 patients, but in only nine patients did the perfusion distribution return to normal. Thus, Tl-201 exercise scintigrams following CBG demonstrate improved RMP in most patients. Failure of regional myocardial perfusion to improve postoperatively, however, does not preclude marked alleviation of angina and improved exercise tolerance.


Increasing incidence of ampicillin resistance in Hemophilus influenzae. The incidence of ampicillin resistance in Hemophilus influenzae and its medical significance have not been extensively determined. During 1975-1977, we tested for ampicillin resistance 489 consecutive middle-ear isolates of HI obtained from children in Huntsville, Alabama, and 719 consecutive laboratory isolates of HI from Children's Hospital, Boston. The annual incidence of Amp resistance rose progressively in each survey, from initial values of 1.4 to 5.3% in 1975, to 14 to 16% in 1977 (P less than 0.05), a mean annual rate of increase approximately twofold. Resistance was equally prevalent among type b and non-b isolates and among nasally carried and disease-associated isolates (from blood, CSF, middle ears). Patients harboring AmpR isolates were much more likely to have had recent exposure to beta-lactam antibiotics (P less than 0.01).


Coagulation abnormalities associated with localized hemorrhage in the neonate. Serial coagulation studies were completed on six neonates with apparent or inapparent localized hemorrhage. The sites of the hemorrhages were intracranial (2), gastrointestinal (2), subperiosteal (1), and pulmonary (1). The studies revealed an increased factor VIII level, decreased platelet count, and a short PTT. Since similar findings occur in disseminated intravascular coagulation, it is possible that coagulation abnormalities associated with localized hemorrhage result from similar mechanisms. These observations suggest that occult and clinically unrecognized hemorrhage can be suspected by serial coagulation studies of sick infants.


Biochemical and behavioral alterations in developing rats treated with 5,7-dihydroxytryptamine. Intracisternal administration of 5,7-dihydroxytryptamine (5,7-DHT) to immature rats produced a marked reduction of brain norepinephrine and serotonin. Accompanying these reductions of brain amines were a decrease in body weight and alterations in behavior. After treatment with 5,7-DHT at 3 days of age, locomotor activity was significantly elevated at 14 days of age, but was reduced at 28 days of age. 5,7-DHT alone also induced a significant deficit in acquisition of the shuttle-box avoidance response and blocked body movements observed after decapitation. Treatment with either pargyline or desipramine before injection of 5,7-DHT eliminated the effect of 5,7-DHT on noradrenergic fibers while enhancing the effects of 5,7-DHT on brain serotonergic fibers. These treatments also minimized the deficits of 5,7-DHT on growth and on acquisition of the avoidance response and reversed the blockade of decapitation convulsions. However, animals pretreated with pargyline or desipramine before they received 5,7-DHT still demonstrated hyperactivity at 14 days of age equivalent to that observed in neonates that received only 5,7-DHT. Furthermore, a behavioral syndrome induced by 30 mg/kg of 5-hydroxytryptamine was markedly potentiated by all of the 5,7-DHT treatments which suggest that serotonin receptors were supersensitive.


(2-Benzoylethyl)trimethylammonium chloride: a new, selective and stable inhibitor of human placental choline acetyl transferase. (2-Benzoylethyl)trimethylammonium chloride (BETA), a keto analog of acetylcholine, was synthesized and studied as an inhibitor of human placental choline acetyltransferase (ChA). It is a potent inhibitor of ChA with an 150 of 3.1 X 10(-6) M. The inhibition was rapid in onset and was slowly reversible. Upon dialysis of the inhibited ChA, 50% activity was recovered within about 4.90 hours. BETA was noncompetitive with respect to both substrates of ChA, acetyl-CoA and choline. BETA was selective for inhibiting ChA. It was about 100, and 50, times more potent for inhibiting ChA than acetylcholinesterase, and cholinesterase, respectively. Its activities at muscarinic and nicotinic receptors were negligible at the concentrations where complete inhibition of ChA was obtained. In contrast to the other ChA inhibitors, the styrylpyridines and halogenoacetylcholines, BETA is stable in solution. On prolonged storage (several days at 37 degrees C and pH 7.4), solutions of BETA decomposed partially into trimethylamine and vinylphenylketone. Beta was considerably more stable and more selective than other inhibitors of ChA.


The effects of 2,4,6-triaminopyrimidine (TAP) on sodium and potassium excretion by the rat kidney: comparison with amiloride. 2,4,6-Triaminopyrimidine (TAP) has been reported to be a blocker of the cation-specific paracellular conductance pathways of several epithelia. The compound is also known to inhibit sodium transport in the frog skin. Its effects on renal function were studied in clearance experiments in anesthetized rats and in isolated perfused rat kidneys and compared with the effects of amiloride. The effects of both compounds on electrical resistance of the frog gallbladder were also evaluated. Both TAP and amiloride caused modest natriuresis and a marked reduction in potassium excretion. Amiloride is approximately 1000 times more potent than TAP when compared on the basis of drug concentration in the urine. The concentrations of both substances in urine (at effective doses) correspond to concentrations reported to be effective against sodium transport in amphibian membranes. The urinary concentrations of TAP also correspond to the concentrations required to inhibit paracellular cation movement in the gallbladder. Amiloride at the level tested (10(-3) M) did not seem to influence the paracellular pathway. The results neither establish nor disprove a role of the paracellular pathway in potassium secretion. Both TAP and amiloride are secreted by the renal tubules.


Modification of electroshock convulsive responses and thresholds in neonatal rats after brain monoamine reduction. Modification of electroshock (60 Hz; a.c.) convulsive responses and thresholds by monoamine-reducing drugs was investigated in developing rats. Throughout postnatal development, tetrabenazine (TBZ) reduced brain monoamines and increased the severity of motor responses to electroshock. The predominant maximal response in control pups progressed from hyperkinesia (day 1) to clonic convulsions (day 3) and tonic forelimb (day 7) and hindlimb (day 19) extension. The pattern in TBZ-treated pups progressed from tonic forelimb extension (day 1) to tonic hindlimb extension (day 7). On day 7, TBZ reduced the thresholds for clonic (CT) and tonic convulsions (TT) to 41 and 24% of control, respectively. Reserpine (1.25 mg/kg, 24 hours) decreased the TT but not the CT; TBZ, 4 hours before reserpine, prevented this decrease. A higher dose of reserpine (2.5 mg/kg) decreased both the CT and TT. On day 8, TBZ (25 mg/kg, 4 hours) decreased the TT (46% control); L-dihydroxyphenylalanine, but not 5-hydroxytryptophan prevented this decrease. Intracisternal 6-hydroxydopamine reduced the TT on day 8, while intracisternal 5,7-dihydroxytryptamine had no effect despite a 46% reduction in serotonin. The results indicate that in the neonatal rat brain, monoaminergic systems are sufficiently mature to attenuate electroshock convulsive responses, perhaps by limiting propagation of seizure discharge.


[Haemorrhage from the duct of Wirsung : emergency arteriographic diagnosis. One case (author's transl)]. The authors report a case of haemorrhage from the duct of Wirsung related to a pseudocyst of the pancreas ulcerating into a branch of the splenic artery. The diagnosis was made as an emergency by arteriography. 45 cases exist in the literature. Arteriography was performed in 10 cases. An arterio-canalar communication was demonstrated in only 3 cases.


Mechanistic possibilities in prebiotic thiophosphate chemistry. Two types of reactivities of thiophosphates have been demonstrated: one being nucleophilic displacement by the P-S moiety of nucleoside phosphorothioates and the other, phosphorylation via P-S cleavage as the driving force. We have designed a system where both displacement on carbon and P-S cleavage are possible. Adenosine derivatives have been synthesized with 5'-deoxy-5'-chloro and 5'-O-tosyl substitutions as leaving groups utilizing the 3'-O-phosphorothioate as the biphilic center. The main products of cyclization were 5'-O-tosyl and 5'-chloroadenosine 2':3'-cyclic phosphate. Formation of 3':5'-S-phosphorothioate was slow even using an excellent leaving group. This is possibly due to hydrogen bonding between the 2'-OH and the neighboring P-O.--KOH hydrolysis of the cyclic phosphorothioate yielded 2'(3') phosphorothioates in a 1:1 ratio. The 2' and 3' isomers were separated and used to study the relative rates of cyclization. The cyclization via P-S cleavage of 2'(3')-O-phosphorothioates showed that the 2' isomer was more reactive. This is the first report of superior reactivity of the 3'-OH of a ribonucleoside.


Platelet-suppressant therapy in patients with coronary artery disease. Platelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary atherosclerosis, acute myocardial infarction, unstable angina, and sudden cardiac death. In addition, platelets may contribute to saphenous vein aortocoronary graft occlusion. Of 104 men with coronary artery disease, platelet survival (SURV) (chromium51 labeling) was shortened in 68% (3.1+/-0.03 days [average+/-SEM]; normal, 3.7+/-0.03 days; P greater than .001). Three platelet-suppressant drugs, sulfinpyrazone, clofibrate, and dipyridamole increased SURV. Saphenous vein graft occlusion was associated with shortened SURV. Of 36 men with occlusion of at least one graft, SURV was shortened in 35 (2.5+/-0.08 days), whereas in 19 with all grafts open, SURV was shortened in six (3.5+/-0.10 days; P less than .01). These drugs increased SURV (2.3 +/- 0.08 to 2.7 +/- 0.11 days; P less than 0.1) and were associated with improved graft patency (four of 32 grafts after initial bypass vs 30 of 34 grafts open after second operation).


Rapid penetration of potassium and other salts into the frog tongue papilla. The permeabilities of the frog tongue epithelium for potassium and other ions during a short time span were investigated electrophysiologically. The fungiform papilla of the bullfrog tongue was suctioned into a U-shaped glass suction electrode, through which Ringer solution was circulated. Compound nerve action potentials were recorded antidromically from the electrode following electrical stimulation of the glossopharyngeal nerve. When more than 5-10 mM potassium salts, 30 mM RbCl, 30 mM CsCl, 0.025 g in dl solution tetrodotoxin, 0.1 g in dl solution lidocaine hydrochloride or 3 g in dl solution ethanol, each of which was dissolved in Ringer solution containing 1.9 mM KCl, were flowed through the suction electrode, only the negative components of action potentials were gradually reduced and finally disappeared. The time needed for 50% reduction of negative components was about 10 sec for 0.1 M potassium salts and longer for the nonelectrolytes. A single suctioned papilla, which was flowed with various test solutions, was stimulated electrically and the change in current threshold of the papillary nerve was measured by recording orthodromic action potentials from the glossopharyngeal nerve. The threshold decreased within 10 sec after 0.05 M BaCl2 was flowed, but increased within 10 sec after 0.1 M KCl was flowed. The reduction of negative components of nerve action potentials may be due to the conduction block induced by potassium and other ions invading to the space around axons terminals. The threshold change also may be induced by the ions reaching the axon. These results suggest that chemical substances can rapidly penetrate the tongue epithelium of the frog, reach the papillary nerve fibers and contribute or modify gustatory informations.


Cadmium-induced decrease in the outer facing skin resistance of a bullfrog (Rana catesbeiana). Effects of cadmium on the electrical properties of frog skin were investigated by using the microelectrode technique. The epidermal application of 2 mM Cd for 5 min increased both the short circuit current and the skin potential, and decreased the skin resistance (RM). Cadmium also decreased intracellular potential with reference to the epidermal solution (PDi) and the electrical resistance between the epidermal solution and the tip of a microelectrode (RM1) located in the stratum germinativum. deltaRM that is RM,Cd-RM, control seemed to approximately coincide with deltaRM1 which is RM1,Cd-RM1,control. Comparing with our previous results, i.e., Cd decreased RNa (the resistance to the active Na current) and increased Rsigma (the resistance to the passive ions) but did not altered ENa (the electromotive force of active Na current) in the later stage (15 min or later). Cd seemed to decrease the RNa component at the epidermal side of the skin in the early stage (less than 5 min).


Aortic valve replacement and aorta-coronary bypass surgery. Results with perfusion of proximal and distal coronary arteries. The results in 80 patients undergoing simultaneous aortic valve replacement and aorta-coronary saphenous vein bypass grafting were analyzed to assess the effect of operative technique. The over-all operative mortality rate of 6.3% (five of 80) did not differ significantly from our results with aortic valve replacement alone. All patients who had isolated aortic valve replacement were operated upon with moderate hypothermia. The combined operation was performed in two ways. Thirty-one patients had aortic valve replacement prior to bypass grafting with intermittent coronary ostila perfusion. There were two deaths (6.5%), and five myocardial infarctions (16.1%) were diagnosed by standard electrocardiographic and enzyme criteria. More recently, 49 patients have undergone bypass grafting prior to aortic valve replacement. The proximal ends of the grafts were either anastomosed high on the aortic root or else individually cannulated to provide continuous distal perfusion during subsequent aortic valve replacement, with continuous coronary ostial perfusion. There were three operative deaths (6.1%) and one myocardial infarction (2.0%). The risk of combined aortic valve replacement and coronary bypass need be no greater than the risk of aortic valve replacement alone. Our experience suggests that myocardial perfusion distal to significant coronary artery stenoses reduces the risk of myocardial infarction in patients with coronary artery disease requiring aortic valve replacement.


[Reaction to physical load in persons with a varying vestibular-autonomic resistance]. The level of vestibular stability (tolerance to the double rotation test according to I. I. Bryanov) was compared with the pattern of changes in the heart rate and arterial pressure during exercise tests (20 squatting per 30 sec). The test subjects were 136 healthy male volunteers--representatives of different professions, aged 21--40. The subjects with high vestibular stability showed greater changes in heart rate (+29%) and a relatively stable diastolic pressure. The subjects with low vestibular stability displayed, on the contrary, greater changes in the diastolic (-9%) and pulse (+71%) pressure and a relatively low increase in heart rate. The time of recovery of the pressure level was significantly longer in the susceptible people. The possibility of predicting vestibular tolerance on the basis of responses to exercise tests was explored. Mathematical formulas of the theory of image recognition were used to develop a rule that makes it possible to identify 84.4% subjects with low vestibular stability in a given group.


Survival after coronary surgery.

Survival after coronary surgery. A 4.4 year follow-up study has been done on a previously reported group of 200 consecutive patients who underwnet coronary bypass. The yearly mortality rate has been 1% (8/200 in 4 years). Our total group of 1,038 surgically treated patients has had an operative mortality rate of 1.3%, and an early graft patency rate of 89.6% has been recorded in the 60% of patients consenting to restudy. These results are compared to natural history studies with and without angiography. Comparison with recent prospective randomized studies of patients with chronic stable angina and those with unstable angina suggests that a low operative mortality rate and optimal technical performance are necessary to improve the survival rate of patiens with symptomatic obstructive coronary disease.


Risk factors in patients undergoing a second aorta-coronary bypass procedure. A group of 38 patients with a second revascularization procedure was studied for factors which may have contributed to the reappearance of angina after the first operation. Our data indicate that these patients usually have the first operation at an earlier age and had fewer bypasses at that time. In addition, they had inadequate control of the plasma triglyceride and cholesterol levels.


Potassium-induced cardioplegia. Additive protection against ischemic myocardial injury during coronary revascularization. Potassium-induced cardioplegia during anoxic arrest was utilized in a study of 190 consecutive patients undergoing revascularization (average 2.8 grafts per patient) from August, 1975, through August, 1976. Surgical technique, moderate systemic hypothermia with intermittent anoxic arrest, and the surgeon were the same for all patients. One hundred thirty-five patients (KC1-treated) received a bolus (150 ml.) of potassium solution injected into the proximal aortic root whenever the aortic cross-clamp was applied; 55 others served as control subjects. The mortality rate was 2.2% (three of 135) in the KCl-treated group and one of 55 in the control group. New Q waves appeared in 5.9% (eight of 135) of the KCl-treated patients and 11% (6 of 55) of control subjects (p = N.S.). Catecholamine drips were required after bypass in 4.4% (six of 135) of patients given potassium and 18% (10 of 55) of control patients (p less than 0.05). Profound myocardial relaxation was of added technical value with potassium. It is our impression that hearts treated with potassium exhibited more prompt cardioversion, separated from cardiopulmonary bypass with less need for inotropic support, and exhibited less myocardial injury during the revascularization procedure.


Delirium after coronary artery bypass surgery. The incidence of postoperative delirium following coronary artery bypass surgery was 28%. This rate is comparable to that after open-heart surgery. However, of those variables which were previously found to correlate with delirium in the open-heart group, only severity of postoperative illness in the recovery room significantly correlated with delirium in patients having bypass. The relationship between personality type and delirium, previously found to be signficant, was suggestively associated in these patients. A history of myocardial infarction prior to surgery was significantly associated with delirium.


Directional selectivity and colour coding in the frog retina. The impulse discharge of ganglion cells was recorded with extracellular micro-electrodes in the excised and opened eye of the common frog, Rana temporaria. The responses of different ganglion cell types to a standard moving spot with various spot-background contrasts are described. Information about such stimulus parameters as the size and contrast as a moving object is given by different classes of ganglion cells with preferences for different stimulus features. Of 171 sustained cells with small receptive fields 29 were found directionally selective, i.e. they responded well to movements only in some directions. Experiments with double stimulus fields suggest that this selectivity is due to an amacrine cell-mediated lateral inhibition nonsymmetrically arranged around the centre of the receptive field. The dichromatic colour vision of the frog is based on partly opponent signals from yellow-sensitive cones and blue-sensitive green rods. These opponent inputs make the ganglion cells respond to blue spots moving against a yellow-green background, irrespective of the relative intensities of the two colours. When the green rods are stimulated with blue light the ganglion cells produce long "on"-responses with significantly lower impulse frequencies than the short cone-mediated responses.


[Spontaneous and provoked nystagmus as a criterion of the duration of effect of hypnotics and narcotics in ambulant surgery (author's transl)]. A testing of usefulness of systematic search for spontaneous and provoked nystagmus relative to the duration of effect of several hypnotics and narcotics showed in 83% positive vestibular findings in 150 non-selected, ear sound patients. Vestibular nystagmus was still detected 2 hour p.o. in 74%, 3 hours p.o. in 30% and 4 hours p.o. in 7% of cases. 78 times (52%) a convergent or divergent posture nystagmus was recorded and 47 times (31%) a vertical nystagmus. The subjective sensations of the test persons are out of proportion to the objective findings. The localisation of the pharmacotoxic lesion is discussed.


[Normal values of the caloric test (author's transl)]. Normal values of the caloric test are reported in 202 healthy subjects; besides the absolute values, these comprise the degree of side-difference of excitability and of directional preponderence in percent of the total reaction. In addition to mean values with standard deviations, the median values and the interquantile areas 80, 90, 94 and 100% have been reproduced in tabular form, because, according to statistical calculations, there is no normal distribution of the values in the strict sense. The problematic nature of borderline values for the separation of physiological from pathological responses is discussed in detail. In vieu of the considerable scattering, a knowledge of normal distribution areas appears to be absolutely necessary for an accurate evaluation of the caloric test in patients.


[Experimental investigations of vestibulary hypoxia (author's transl)]. In an experiment with alert rabbits the inspired gas mixture was altered to obtain hypoxia. A significant reduction from the normal nystagmus reaction was observed. This reduction in the amplitude (about 50%) is immediately reversible by giving oxygen. These experiments were repeated with each animal several times, the results being reproductible. There is a significant decrease in nystagmus amplitude through the influence of hypoxia.


The spectrum of the Mallory-Weiss tear.

The spectrum of the Mallory-Weiss tear. A Mallory-Weiss tear is a mucosal laceration occurrring at or near the esophagogastric junction and is most often associated with vomiting. This is a common cause of upper gastrointestinal bleeding; in our series, 14% of patients presenting to the hospital because of upper gastrointestinal bleeding had Mallory-Weiss tears. Massive hemorrhage is not characteristic and 37% of the patients required no blood transufsions. A classical history of nonbloody emesis followed by hematemesis was found in only 29% of patients. The most common story was the appearance of blood with the first vomiting. In 35% of our patients with Mallory-Weiss tear, an additional potential bleeding site was identified, and, in approximately half of these patients, it was actually bleeding. Most Mallory-Weiss tears stop bleeding spontaneously and supportive treatment is all that is required. If bleeding continues, infusion of vasoactive substances into the celiac artery or into the left gastric artery often obviates the need for operation.


Coronary artery surgery in Australia, 1974-1976. A report by the National Heart Foundation of Australia. This is a report of the total Australian experience in coronary artery bypass graft surgery over a two year period from October 1, 1974, to September 30, 1976. It provides data on the results up to discharge from hospital. There were 2349 patients undergoing operation in 9 units in all mainland States. Each of the nine participating units reported preoperative data on age, sex, symptoms, previous history, indications for surgery and special investigations including results of X-ray examination, electrocardiography (ECG), ventricular and coronary angiograms and left ventricular end diastolic pressure as well as details of surgery which was carried out, and patient status at the time of discharge. The data were collated and analysed at National Heart Foundation headquarters in Canberra.


The natural history of chronic middle ear disease in Australian Aboriginals: a cross-sectional study. One hundred and sixty-three Australian Aboriginals, who were aged from four months to 60 years, were examined clinically and otologically. Audiometric tests were completed on 110 of these subjects. On the assumptions that the aural health of these people has remained stable for many years, the cross-sectional data which were obtained have been used to infer the natural history of ear disease. Seromucinous otitis media is manifest as a disease of early childhood, which recovers spontaneously in most cases and has no obvious sequelae. Perforated tympanic membranes likewise seem to heal spontaneously in the majority of cases. The evidence suggests that hearing loss is the main problem and treatment should be directed towards the level of hearing loss and its effects.


[Diagnosis of von Willebrand's disease]. 31 patients with the diagnosis or presumed diagnosis of von Willebrand's disease were reinvestigated by means of Ristocetin cofactor-activity and factor VIII-associated antigen. In addition a family with a variant of von Willebrand's disease is described. Ristocetin cofactor-activity was found the most reliable test, its value for the diagnosis of mild forms and of variants of von Willebrand's disease is further established by these results.


[Complications of antithrombotic prophylaxis with acetylsalicylic acid (ASS) in polycythemia (author's transl)]. Eight patients with polycythemia whose main complaints resulted from vascular complications were prophylactically treated with ASS. 4 patients tolerated the treatment without any side effects, 4 patients had an acute upper gastrointestinal hemorrhage, which was fatal in 2 cases. Correlations between the thrombohemorrhagical syndrome in polycythemia on one hand and the side effects of ASS on the other hand are discussed. As a result of this antithrombotic prophylaxis with ASS is not indicated in polycythemia even in predominance of vascular complications and absence of bleeding tendency. In life-threatening situations antithrombotic therapy with heparine should be preferred.


[Unusual skeletal changes in acute lymphoblastic leukemia in children (author's transl)]. During the early phase of their disease three children with acute lymphoblastic leukemia showed unusual skeletal changes radiologically. Mainly osteolysis in the lower jaw, opacity of the sinus, decreased hight of the vertebrae, and a unilateral necrosis of the head of the femur. These skeletal alterations are much more common in other diseases than in acute lymphoblastic leukemia.


[Number of hydrogen bonds in the structure of collagen]. The kinetics of hydrogen exchange of collagens from different animals was studied by the radioisotopic method (tritium) and infrared spectroscopy (deuterium). It has been shown that collagens from different animals (rat, pike, cod, carp, frogs) differ in amino acid composition and thermostability but are similar in the amount of slowly exchanged hydrogens. All the studied collagens have (1.00 +/- 0.05) very slowly exchanged hydrogens per triplet and (0.6 +/- 0.1) slowly exchanged hydrogens per triplet. Identifying the quantity of slowly exchanged hydrogens with the quantity of hydrogen bonds in the macromolecule, it can be concluded that collagens differing in stability do not differ by the quantity and composition of intramolecular hydrogen bonds.


[Improvement of zoster therapy by adamantine]. In the course of 3 years we observed a considerable improvement of herpes zoster in 44 patients being treated with amantadine. The periods of pain and efflorescence were shortened to 1/3 of the values usually experienced and painful post-zoster complications did not occur. The therapeutic effect depends on a) beginning treatment with high doses as early as possible, b) combination of local and systemic administration of adamantine, c) continuation of treatment for several weeks with gradually reducing doses. Harmless side-effects which are easily controlled are dryness of mouth, slight fall in blood pressure and insignificant general stimulation. In old people half the standard dose should be given in the beginning and particular attention paid to symptoms of restlessness on account of a possible delirium. Severe disorders of renal function are a contraindication.


[Neurosurgical treatment of trigeminal neuralgia]. Sweet's method for thermocoagulation of the Gasserian ganglion is a real advance in the operative treatment of trigeminal neuralgia. The advantages of this method are obvious: minimum operation risk, minimum complication rate, short postoperative convalescence, shorter confinement to hospital and finally the possibility of repeating the operation without risk in the event of a relapse.


[Indomethacin retard 75 mg in the treatment of coxarthrosis]. A single dose of 75 mg Sustained-Release Indomethacin proved to be an effective medication in the treatment of osteoarthritis of the hip. It was generally well tolerated; two patients reported moderate gastrointestinal side effects, no CNS related side effects. The gastric tolerance appeared to be better than with Amuno. The convenience of the single dose therapy was spontaneously expressed by all patients.


[25 years of surgical treatment of femur neck fractures. Report on 1000 cases]. 1000 operative treatments of fractured neck of the femur in hospital in 25 years were analyzed. In addition to a rise in frequency of admission, a progressive aging of the patients was observed. The operative technique developed into osteosynthesis, principally with the Pugh nail and hip joint alloplasty. 19% of the patients died.


[Epididymitis after prostatectomy (author's transl)]. Complications which prolong hospitalization occur after 10% of prostatectomies, depending on the type of operation. Epididymitis develops after prostatectomy especially in postoperative urinary tract infection, and in patients with risk factors (retention of urine, recurrent residual urine, infected urine, and after adenomectomy). In comparison with the time before specific antibiotic therapy, postoperative epididymitis has fallen by 50% with preliminary antibiotic treatment. Postoperative epididymitis very rarely occurs under treatment with gentamicin.


[Etiological assessment of aseptic femoral head necrosis from blood serum metabolic parameters (author's transl)]. The etiological assessment of aseptic femoral head necrosis in adults is facilitated by investigation of the uric acid level and of fat metabolism parameters. From 98 of our own patients it appears that femoral head necrosis after trauma, irradiation therapy and caisson disease and after massive doses of cortisone only exceptionally shows pathological serum levels. Femoral head necrosis with manifest metabolic diseases shows 53.3% hyperuricemias and hyperlipemias or dyslipidemias. Of femoral head necroses without concomitant diseases, prior physical effects and administration of cortisone, 91% had hyperuricemia and 65% hyperlipemia or dyslipidemia.


[Cholesterol deficiency. A pathogenetic factor in chronic anemias? Preliminary report of a study in three states (author's transl)]. It has been shown in several studies that there is a statistically confirmed connection between cholesterol and Hb levels in the sense that hypocholesterolemia and anemia occur together particularly frequently. This was demonstrated in an epidemiological cross-section study of 3958 patient data, and also that in a retrospective case control study of 159 anemias there wasa concurrent hypocholesterolemia. It is explained by the fact that cholesterol deficiency leads to rigidity of the erythrocytes.


[Somatic therapy of endogenous psychoses (author's transl)]. In pursuit of the idea of the scientific concept of disease, the aim of somatic treatment of the endogenous psychotic patient should be a specific causal therapy without aggravating and therapeutically useless side effects. Modern psychopharmacotherapy approaches this requirement. Insulin coma therapy and psychosurgical procedures have rightly been abandoned. Electroconvulsive therapy, on the other hand, in certain indications and observing certain precautions is still applicable. Under the influence of ideological critics with no experience of the method, its dangers are immeasurable over-emphasized and its therapeutic efficacy underestimated.


[Psychophysiological aspects of mastalgia. Psychometric studies (author's transl)]. After exclusion of clinical causes for intermittent mastalgia, psychosocial factors should be thought of as a study of 533 women showed: 1. Women with intermittent pains in the breast differed statistically significantly from other women without mastalgia in 8 out of 12 personality characteristics (FPI). 2. Mastalgia occurred more frequently with increasing age, in women without partners, in painful experiences with menarche and menstruation. 3. Women with mastalgia examined their breasts regularly, they were confident that they could feel nodules and went more frequently for medical treatment of their breasts. 4. In mastectomy patients with a history of mastalgia particular attention should be paid to a psycho-social status.


[Duodenal ulcer therapy with cimetidine. A clinical endoscopic study in 76 patients (author's transl)]. 34 patients were treated with cimetidine and placebo in a double blind trial and 42 were treated with cimetidine alone. Criteria investigated were the pain response, consumption of antacids when required and especially the endoscopically demonstrated scarring of the duodenal ulcer. Compared with placebo, cimetidine is capable of soothing pain and also reducing the consumption of antacids more quickly and to a greater extent. The differences are statistically significant. Complete anatomical healing of the ulcer was established in the double blind study in 80% of the patients in the cimetidine group and in 40% of the placebo group. Similar results were also shown in the group which received cimetidine alone.


[Immune defects as a cause of septic complications in leukemias and malignant lymphomas (author's transl)]. Septicemias, especially those due to gram-negative pathogens, frequently occur in leukemias, malignant lymphomas and other malignant or metabolic diseases leading to inanition. The causes are disturbances of cellular defense and humoral immune defects. The immune reaction can be affected by disordered antibody function. In addition to a disturbance of leukocyte function due to reduction of granulocytes (granulocytopenia) disturbances of leukocyte function also occur with a normal cell count (granulocytopathy) especially under cytostatic therapy. Besides specific antibiotic therapy it is important to improve the defense position of the organism by treating the primary disease and to assess the disordered immune status correctly.


[Effect and tolerance of Biarison (proquazone) in rheumatoid arthritis (author's transl)]. Biarison was tested in 24 patients mainly with classical rheumatoid arthritis for its efficacy and tolerance. There was a distinct improvement in the course of the 4 weeks' therapy with a mean dosage of 900 mg/day (it was in the meantime raised to a maximum of 1500 mg/day in isolated cases) especially in the pain, stiffness and functional capacity. Biarison caused few gastrointestinal side effects: the tolerance may be said to be good on the whole.


[Therapy of alcoholism. The use of thiamine, ATP and magnesium and the control of clomethiazole sympathetic blockade (author's transl)]. Substitution therapy with thiamine, ATP and magnesium which, just like that with clomethiazole has a parasympathomimetic action, is based on the principle of suppression of the sympathetic system. If these patients are no longer capable for any reason of continuing to take the endogenous substances (thiamine, ATP and magnesium) by mouth, the treatment is continued with clomethiazole an an infusion. But since the intravenous administration of clomethiazole is not seldom accompanied by a parasympathetic coma with respiratory and cardiac depression and miosis, treatment of a sympathetic blockade with dextrose solution containing salt is proposed.


Role of helper, suppressor and B-cell defects in the pathogenesis of the hypogammaglobulinemias. We investigated suppressor and helper T cells in 19 patients with variable immunodeficiency to assess the possibility that defective interactions among these cells and B lymphocytes are the chief cause of the inadequate plasma-cell development and hypogammaglobulinemia characterizing these syndromes. We accomplished functional separation of the two T-cell subsets, using irradiation, which selectively inactivates T-cell suppressors. The patient B lymphocytes were usually capable of some differentiation into plasma cells when co-cultured with T cells manipulated to optimize helper effects. Eighteen of 19 patients showed quantitatively poor plasma-cell production even under these conditions. However, only one had defective enough helper function, and only one sufficiently excessive suppressor activity for these factors to be considered the major pathogenetic process in each case. Since neither an absolute defect in B cells nor consistent abnormalities in modulator T cells were demonstrable in most patients, other explanations must be sought for the mechanisms underlying this form of primary immune deficiency.


Calcium transients in aequorin-injected frog cardiac muscle. The Ca2+ -sensitive bioluminescent protein aequorin was microinjected into cells of frog atrial trabeculae to study intracellular calcium transients associated with excitation-contraction coupling. The amplitude of the aequorin signal increased with extracellular Ca2+ concentration and stimulus frequency, but decreased with stretch. Isoprenaline and acetylstrophanthidin both increased the amplitude, but had strikingly different effects on the time course of the signal.


Endocrine control of appetite: gastrointestinal hormonal effects on CNS appetitive structures. Permanent semi-microelectrodes were implanted in the ventromedial hypothalamus (VMH), lateral hypothalamus (LH), amygdala (AMYG), medial forebrain bundle (MFB), anterior hypothalamus (AH), inferior colliculus (IC), and caudate nucleus (CN). Average evoked responses were recorded simultaneously from the above sites in freely behaving rats before and after administration of pentagastrin (100 microgram/kg), secretin 1 microgram/kg or cholecystokinin octapeptide (CCK-OP) (1 microgram/kg) in search of satiety signal. Gastrin and secretin had little effect while it appears that CCK may perform a regulatory function in a neurohumoral feedback mechanism.


Comparison of metrizamide and iodophendylate for cerebral ventriculography: a long-term ultrastructural study of the ventricular wall in the rat. Cerebral ventriculography was performed on adult albino rats to compare the effect of metrizamide and iodophendylate on the ependymal wall. The animals were killed by vascular perfusion 1 month and 4 months after ventriculography. The ependymal layer and the underlying brain tissue were examined with the electron microscope. After the use of metrizamide the tissue appeared completely normal. The use of iodophendylate provoked accumulation of phagocytozing macrophages on the ependymal wall and storage of iodophendylate in the ependyma and underlying brain tissue. These changes were present both 1 and 4 months after ventriculography.


Morphological changes in the CNS after Dimer X ventriculography. The brains of 89 cats were investigated after the stereotactic injection of Dimer X into the ventricular system. The animals were sacrificed after 6, 24 and 48 h and after 7 and 30 days. Morphological changes were found in the ependyma, choroid plexuses, subependymal zone and in the brain tissue. They were most intense within 2 days of the experiment and some lesions (subependymal inflammatory infiltrates and ependymitis granularis) persisted up to 30 days. Similar changes were revealed postmortem in the brains of 20 patients in whom Dimer X ventriculography had been performed.


[Use of thymus hormone in the demonstration of acute T-null cell lymphocytic leukemia]. The Authors studied the effect of the human serum thymic factor on the peripheral-blood leukocytes from ALL patients, by testing the frequency of the E+cells by means of the e rosette assay before and after cell incubation with the above mentioned factor. In 3 out of 24 patients tested, the thymic factor incubation of peripheral-blood mononuclears increased the number of E+cells. The shift from R to E+cells caused by the human serum thymic factor occurred among null cells (E-, SM-Ig-). The possible value of the test in investigating whether a T0 leukemia might really exists is pointed out, as well as its prospective importance in monitoring the variations of the immature T cell counts in relationship to the patient's treatment and his disease course.


The spectrum of Chandler's syndrome: an often overlooked cause of unilateral glaucoma. Eleven cases of unilateral glaucoma are summarized. The typical presentations of these cases are (1) unilateral; (2) middle-aged women; (3) blurred vision; (4) corneal endothelial guttae (unilateral); (5) corneal edema; (6) stromal iris atrophy; (7) pupil abnormality; (8) peripheral anterior synechias;(9) elevated intraocular pressure; and (10) if previously diagnosed, the diagnosis is likely incorrect. Variations in these may occur. The disease can occur in men. Some patients may have nodular iris nevi. All of them represent the spectrum of Chandler's syndrome. Accurate diagnosis is important particularly in view of the optimistic prognostic implications for the fellow eye.


Congenital cholesteatoma.

Congenital cholesteatoma. Congenital cholesteatoma of the temporal bone may be encountered by the otologist in the cerebellopontine angle, petrous bone, or middle ear cleft; the latter occurrence seems most likely. The etiology, epidemiologic factors, location of intracranial occurrence, clinical features, methods of diagnosis, differential diagnosis, gross and microscopic pathologic features, and surgical treatment of congenital cholesteatoma are presented. Our personal experience is described. The advantages and complications of various operative approaches are discussed.