Influenzal pneumonia: early appearance of cross-reactive T cells in lungs of mice primed with heterologous type A viruses. Mice were first primed with a type A or a type B influenza virus and then challenged intranasally at least 1 month later with another type A virus. Potent cytotoxic T cell populations were found in lung, and effector T cell function was also demonstrated in blood, spleen and mediastinal lymph nodes. Lymphocytes isolated from all of these anatomical sites were active against target cells infected with the same, or with serologically different, type A influenza viruses. Also, prior exposure to another type A virus resulted in more rapid development of effector function than was seen in mice that had first been infected with B/Lee. Cytotoxic T cell populations generated in mice with influenza thus tend overall to be type-specific, and there is substantial localization of these effector lymphocytes in the pneumonic lung.


The effect of passive immunization against tetanus toxoid in man. The present study deals with the immunological response in man after passive immunization against tetanus toxoid. Treatment of man with equine antitetanus serum stimulates a rise of E rosette-forming T lymphocytes. The level of IgG also rises while the level of IgM falls. It is assumed that the foreign globulin acts as an antigen that evokes the T lymphocytes' co-operation for the humoral immune response with a switch from IgM to IgG synthesis.


Immune reactions associated with practolol therapy. A review of adverse reactions following practolol therapy is presented. The appearance of antinuclear antibodies seems to herald the clinical manifestations. Antinuclear antibodies were found in 30% of patients treated with practolol for prolonged periods. It is suggested that patients who develop an immune reaction following practolol metabolize the drug differently than those who do not.


Alterations in cardiovascular function during neurolept anesthesia for surgery on the coronary vessels. Induction of anesthesia for aortocoronary bypass surgery was accomplished by the administration of droperidol, morphine, oxygen and nitrous oxide-oxygen in 20 patients. They ranged from 40 to 69 years of age. Premedication consisted of diphenhydramine and morphine. Cardiovascular stability was the most important aspect of the technique. Heart rate changes were insignificant. Cardiac index increased substantially after droperiodol and remained unchanged after morphine. It stayed around control levels for the rest of the induction. A substantial decrease was observed while using mechanical ventilation. Mean arterial pressure dropped significantly after droperidol and again after morphine, then rose about 17% after oxygen to near control levels, where it stayed thereafter. Peripheral vascular resistance dropped substantially after droperidol. A significant increase occurred after oxygen, reaching almost control levels at this point. Mechanical ventilation caused a significant increase, similar to the decrease in the cardiac index. Decreased oxygen availability was compensated for by decreased oxygen consumption. Induction of neurolept anesthesia in the manner described appears to be void of the undesirable effects of either large doses of morphine, or nitrous oxide-oxygen following such morphine doses. Amnesia was complete in every patient.


Laser-coagulation of ruptured fixation suture after lens-implantation. Before it was known that polyamide tends to dissolve in tissue, nylon sutures were used to fixate 2-loop-Medallion-lenses to the iris. As was to be expected cases turned up in which the suture had ruptured. This situation entails the danger of contact between the end of the broken suture and the endothelium. By coagulation of the suture with a laser beam the danger was eliminated.


Corneal dellen following cataract extraction with lens implantation. Two cases of dellen following cataract extraction with implant insertion are described. Etiology may be based upon deprivation of nervous and vascular supplies, and possibly related to large corneal sections. Conservative therapy was found to be sufficient in restoring the corneal integrity.


A study of the mechanism of action of Taka-amylase A1 on linear oligosaccharides by product analysis and computer simulation. The action pattern and mechanism of the Taka-amylase A-catalyzed reaction were studied quantitatively and kinetically by product analysis, using a series of maltooligosaccharides from maltotriose (G3) to maltoheptaose (G7) labeled at the reducing end with 14C-glucose. A marked concentration dependency of the product distribution from the end-labeled oligosaccharides was found, Especially with G3 and G4 as substrates. The relative cleavage frequency at the first glycosidic bond counting from the nonreducing end of the substrate increases with increasing substrate concentration. Further product analyses with unlabeled and end-labeled G3 as substrates yielded the following findings: 1) Maltose is produced in much greater yield than glucose from unlabeled G3 at high concentration (73 mM). 2) Maltooligosaccharides higher than the starting substrate were found in the hydrolysate of labeled G3. 3) Nonreducing end-labeled maltose (G-G), which is a specific product of condensation, was found to amount to only about 4% of the total labeled maltose. Based on these findings, it was concluded that transglycosylation plays a significant role in the reaction at high concentrations of G3, although the contribution of condensation cannot be ignored. A new method for evaluating subsite affinities is proposed; it is based on the combination of the kinetic parameter (ko/Km) and the bond-cleavage distribution at a sufficiently low substrate concentration, where transglycosylation and condensation can be ignored. This method was applied to evaluate the subsite affinities of Taka-amylase A. Based on a reaction scheme which involves hydrolysis, transglycosylation and condensation, the time courses of the formation of various products were simulated, using the Runge-Kutta-Gill method. Good agreement with the experimental results was obtained.


Nonuniform distribution of concanavalin-A receptors and surface antigens on uropod-forming thymocytes. Uropods can form spontaneously in a variable fraction of mouse thymocytes incubated for 30--60 min in vitro at temperatures between about 8 degrees and 37 degrees C. The majority of the cells with a typical uropod are medium and large thymocytes. The "normal" distribution of concanavalin-A receptors and antigens recognized by a rabbit anti-mouse thymocyte serum was studied on these cells by electron microscopy using ferritin-conjugated lectin or antibodies. The cells were fixed with glutaraldehyde or formaldehyde before labeling. The distribution was essentially uniform on spherical cells. On the contrary, on cells which had formed a uropod the labeled receptors and antigens appeared to be preferentially concentrated around the nucleus, and depleted over the uropod, and especially over the constriction at the base of the uropod. Uropod formation and inhomogeneous distribution were inhibited or reversed by cytochalasin B, but not by vinblastine or colchicine. When the same ligands were applied to unfixed cells, the labeled and cross-linked components capped normally towards the cytoplasmic pole of the cell. These observations are described in relation to the ability of receptors and antigens to interact with an intracellular mechanical structure, and to the mechanism of capping.


Amino acid transport in thymic- and spleen-derived lymphocytes. We have examined the transport of amino acids by the sodium-dependent "A" and "ASC" system in thymic- and splenic-derived lymphocytes from the Long-Evans rat. Lymphocytes derived from the thymus transport amino acids by both the "A" and "ASC" systems, whereas lymphocytes from the spleen transport amino acids by the "ASC" system only. Thymic lymphocytes are capable of establishing a steady state distribution ratio of 7.9 for 2-aminoisobutyric acid, but splenic lymphocytes can attain only 3.5. The steady state distribution ratio of alanine was the same in both cell types. Sodium-independent transport is also different in splenic and thymic lymphocytes. But both cells move amino acids by a Na+-independent system for mediated exchange-diffusion. The studies show that lymphocytes derived from the spleen and thymus transport amino acids differently, and that the "T" lymphocytes from the spleen have membrane transport systems different from "T" lymphocytes from the thymus.


Extracellular matrix synthesis in blastula and gastrula stages of normal and hybrid frog embryos. IV. Biochemical and autoradiographic observations on fucose-, glucose-, and mannose-labelled materials. Normal Rana pipiens gastrulae show more incorporation of isotopically labelled fucose, glucose, and mannose into TCA-insoluble materials than blastulae. Interspecific hybrid embryos which undergo developmental arrest at the onset of gastrulation often synthesize reduced amounts of fucose-, glucose- and mannose-labelled materials. These materials are high-molecular weight and are degraded by Pronase into fragments which are included in Sepharose CL-4B but excluded from Sephadex G-50. Labelled materials contain label predominantly in fucose and galactose with little label in glucose or mannose. Labelled materials migrate slowly on cellulose acetate, bind to DEAE-cellulose and elute at low ionic strength and are precipitated by cetyl pyridinium chloride (CPC) without the addition of carrier compounds. Pulse-chase labelling experiments and light- and electron-microscopic autoradiography were used to examine the site of synthesis, mode of transport, and sites of deposition of fucose-, glucose- and mannose-labelled materials in different developmental stages of normal developing Rana pipiens embryos and interspecific hybrid embryos formed by fertilizing the eggs of R. pipiens with the sperm of R. catesbeiana. In both normal and hybrid embryos, after a 15-30-min pulse, grains are closely associated with juxtanuclear and cytoplasmic collections of membrane-bound vesicles which resemble the Golgi apparatus. In normal embryos following a 15-30-min pulse and a 60-min chase, grains are largely cleared from the cytoplasmic vesicles and deposited in the extracellular spaces or along cell surfaces. In contrast, arrested hybrid embryos given a 15-30-min pulse and a 60-min chase show a marked accumulation of grains over cytoplasmic structures such as the Golgi apparatus and vesicular elements in the cell cortex. Certain interesting features of regional variation in synthetic activity in developing normal embryos are also described.


Suppressor-cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction. To characterize the cell(s) responsible for the suppressor-cell dysfunction in active systemic lupus erythematosus (SLE), we fractionated blood mononuclear cells into thymus-derived (T), bone marrow-derived (B), and monocyte-depleted populations. Various cell populations from active SLE, inactive SLE, or normals, were activated with Concanavalin A, washed, and then co-cultured with active SLE cells. Soluble immune response suppressor (SIRS) from culture supernates of the activated cells was also used for the possible correction of the suppressor-cell dysfunction. Suppression was tested by enumerating DNA-binding cells by radioautography and by quantitating anti-DNA antibody in culture supernates by radioimmunoassay; and immunoglobulin was tested in cells and supernates by the immunofluorescence and the immunofluor techniques, respectively. Except for the numbers of DNA-binding cells, which were not suppressed, all the other three parameters in co-cultures with cells from active SLE patients were suppressed by Concanavalin A-activated cells (P < 0.001), or by SIRS (P < 0.05) from normals or inactive SLE patients. Concanavalin A-activated autologous or allogeneic active SLE cells and nonactivated cells from active or inactive SLE failed to suppress the various B-cell functions. Nonactivated normal cells suppressed levels of anti-DNA and immunoglobulin in supernates (P < 0.05). In characterizing the cells responsible for the suppressor dysfunction, it was clear from the results that T cells responsive to Concanavalin A activation are deficient in active SLE and fail to generate SIRS. On the other hand, monocytes from active SLE patients are responsive to signals from the activated T cells of normals or inactive SLE donors. Because SIRS suppresses active SLE cells in vitro, it might be considered therapeutically for the in vivo modulation of SLE.


Chronic myelocytic leukemia. Origin of some lymphocytes from leukemic stem cells. In three patients with chronic myelocytic leukemia who were heterozygous at the X-linked glucose-6-phospháte dehydrogenase locus, lymphocytes were studied to determine if they had the same stem cell origin as the leukemic myeloid cells. Normal tissues such as skin had both B and A glucose-6-phosphate dehydrogenase isoenzymes, but the leukemic myelogenous cells displayed only one isoenzyme type, consistent with their clonal origin. A population of cells with undoubted thymus-derived (T)-lymphocyte characteristics had both isoenzymes. Presumably, then, these T cells did not arise from the leukemic stem cell, either because they antedated the development of leukemia in that stem cell or, more likely, because they arose from progenitors not involved by the disease. In contrast, another population of lymphocytes showed only one isoenzyme type, suggesting that it arose from the chronic myelocytic leukemia stem cell. However, although this population contained many cells with the characteristics of bone marrow-derived (B) lymphocytes, it is not certain that the single enzyme produced by the cells over all can be attributed to B lymphocytes rather than to contaminating non-B-lymphoid cells.


Overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease. The deoxynucleotide, dATP, is elevated 50- to 1,000-fold above normal in erythrocytes, lymphocytes, and bone marrow from a child with adenosine deaminase deficiency and severe combined immunodeficiency disease. The child, when 17 mo of age, was also excreting approximately 30 mg of deoxyadenosine per day in urine (normal is less than 0.1 mg/day). Urinary excretion of uric acid was decreased. Elevated dATP levels in lymphocytes and bone marrow, and increased  urinary excretion of deoxyadenosine, persisted despite hypertransfusion of the child with irradiated erythrocytes from a donor with normal adenosine deaminase. Overproduction of deoxynucleotides by increased salvage of adenosine appears to be the primary metabolic abnormality in patients with adenosine de aminase deficiency.


General anaesthesia for periodontal surgery. A technique is described in which full-mouth periodontal surgery is carried out under general anaesthesia. The use of an endotracheal tube with inflatable cuff allows good visibility and access to all parts of the mouth unhampered by a throat pack; access is further improved by sloping the operating table foot-down. A system of haemorrhage control is used involving a combination of procedures: smooth anaesthetic induction and controlled carbon dioxide levels; intravenous injection of a fibrinolytic inhibitor (epsilon amino-caproic acid); foot-down tilt to the operating table and infiltration with local analgesic solution. The advantages and disadvantages of the technique are discussed.


Computer assisted ventriculography.

Computer assisted ventriculography. Computed tomography was performed following iothalamate meglumine (Conray) ventriculography in two cases of colloid cyst of the third ventricle. The application of this technique in the diagnosis of intraventricular mass lesions is discussed.


Cytotoxic activities of normal cultured human T cells. Normal human T cells grown in continued cultures in medium containing conditioned medium (CM) from PHA-stimulated lymphocytes were studied for their ability to manifest three known forms of cell-mediated cytotoxicity: lectin-induced cellular cytotoxicity (LICC), natural killer cell (NK) activity, and antibody-dependent cellular cytotoxicity (ADCC). The cultured T cells (CTC) were very effective mediators of LICC, being cytotoxic even at very low attacker-target cell ratios in the presence of different lectins, and against different types of targets. When tested without the addition of lectin, the CTC demonstrated a low degree of spontaneous cytotoxicity. This spontaneous cytotoxicity might not be due to conventional NK cells however, since the CTC failed to show significant numbers of cells with Fc receptors (FcR) for IgG, and had no detectable ADCC activity. CTC could represent a population enriched in polyclonal activated T cells with low spontaneous cytotoxicity against a variety of allogeneic target cells, which is greatly enhanced by the addition of lectins dur ing the 51Cr release assay.


Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses. Supernatants from concanavalin A-induced mouse spleen cells contain soluble factors which: 1) augment the anti-sheep erythrocyte hemolytic plaque-forming cell response of nude mouse spleen cells, 2) facilitate the generation of antigen-specific cytotoxic cells by alloantigen-stimulated thymocytes, and 3) enhance the mitogenic response of thymocytes in the presence or absence of phytohemagglutinin. The uninduced control spleen cell supernatants contained variable but significantly less biologic activity within the difference assay systems. The principle enhancing activity (apparent m.w. 35,000 to 38,000) in each of the assay systems was found to be inseparable after a multiple step purification scheme involving ammonium sulfate precipitation, two-cycle gel filtration, hydroxylapatite chromatography, and hydrophobic chromatography on Phenyl Sepharose. These results indicate that either a single factor (designated thymocyte mitogenic factor) augments both humoral and cell-mediated immune responses or, alternatively, the different biologic activities are mediated by different factors that share a common core structure.


Expression of human T lymphocyte antigens by killer cells. K cells, the effectors of antibody-dependent cell-mediated cytotoxicity, were found to express human T but not B lymphocyte antigens detected by rabbit anti-HTLA and anti-HBLA. Pretreatment of effector cells with anti-HTLA+C inhibited ADCC by specifically lysing K cells: no inhibition of ADCC by anti-HTLA occurred when deltaC was substituted for C. By contrast, pretreatment of effector cells with anti-HBLA nonspecifically inhibited ADCC, probably for forming antigen-antibody complexes with HBLA+ cells in effector suspensions: a) treatment with anti-HBLA deltaC was more inhibitory of ADCC than treatment with anti-HBLA+C, and b) the inhibitory effect of anti-HBLA on ADCC was either eliminated or markedly reduced if effector suspensions were first passed through a nylon fiber column, a procedure that removed most HBLA+ cells without affecting K cell activity. HTLA antigens expressed by K cells and NK cells are the same as HTLA antigens expressed by thymocytes since thymocytes completely absorb the anti-K cell and NK cell reactivity of anti-HTLA.


Lymphocyte-activating factor. I. Generation and physicochemical characterization. Lipopolysaccharide-activated murine peritoneal macrophages elaborate lymphocyte-activating factor (LAF) which is mitogenic for murine thymocytes. A method of LAF production is presented that permits the generation of a relatively homogeneous molecular species. LAF has an isoelectric point of 4.8 (range 4.7-4.9). The m.w. was determined by using several physical techniques. The apparent sedimentation coefficient (S20,w) was determined to be 2.0S by sucrose gradient ultracentrifugation. The Stokes (molecular) radius was determined by gel filtration on Sephadex G-75 to be 22 A (range 21.5 to 22.5); the calculated diffusion coefficient (D20,w) was 9.7 X 10(-7) cm2/sec (range 9.5 X 10(-7) to 9.9 X 10(-7). The buoyant density of LAF is 1.30 g/cm3 (range 1.27 to 1.33) as determined by CsCl isopycnic ultracentrifugation; the partial specific volume was estimated to be 0.72 (range 0.70 to 0.74). From these data, the m.w. was calculated to be 18,000 daltons (range 16,400 to 19,600) with the Svedberg equation. The frictional ratio was calculated to be 1.25.


Characteristics of complement receptor-bearing cells in the spleens of tumor-bearing mice. In the course of mammary tumor development, a population of nylon nonadherent cells with CR appears in the spleens of tumor-bearing mice although none are ever detected in normal mice. These cells apparently arise in response to immunologic stimulation. In a series of studies we have further characterized subsets of T cells (CR+ and CR-) with regard to their responses to mitogens in the lymphocyte transformation assay. Nylon column nonadherent cells from the spleens of tumor-bearing mice were rosetted in a complement receptor assay using EAC rosetting, and CR+ cells were separated from CR- by centrifugation in a discontinuous Ficoll gradient. CR+ T cells responded strongly to PHA and Con A and in addition responded to LPS, an activity not usually associated with conventional T cells. In contrast, CR- T cells from tumor-burdened mice responded to PHA but failed to respond to Con A or LPS.


In vitro studies of the rabbit immune system. VI. Rabbit anti-mouse cytotoxic T effector cells are inhibited by anti-rabbit T cell serum in the absence of complement. Xenogeneic rabbit anti-mouse cell-mediated cytotoxic activity could be generated by culturing lymphoid cells from mesenteric lymph nodes (MLN), spleen, or peripheral blood of rabbits primed 2 to 8 weeks earlier with mouse tumor or spleen cells. MLN cells, which provided the best source of activity after being cultured with 5 to 10 X 10(6) mitomycin C-treated mouse spleen cells for 4 to 6 days, produced 30 to 90% specific isotope release after 4 to 7 hr incubation with 15Cr-labeled tumor target cells. Xenogeneic cytotoxic activity was primarily H-2 specific and could not be blocked by immune complexes but was abrogated by treatment with goat anti-rabbit thymocyte serum plus complement (ATS + C) before or after culture. Therefore, the activity appeared to be mediated by cytotoxic T lymphocytes (CTL). Furthermore, ATS without C abrogated cytotoxic activity when included in the CTL assay at concentrations of 5 to 15 microliter/10(7) effector cells. The inhibitory activity of ATS was directed to the rabbit effector population and could be absorbed completely by rabbit thymocytes. Antisera to mouse T cells with comparable cytolytic activity in the presence of C did not inhibit murine allogeneic CTL.


Regulation of delayed-type hypersensitivity reactions by cyclophosphamide-sensitive T cells. The onset, intensity, and duration of DTH reactions elicited in mice immunized with either SRBC or products of the major histocompatibility complex can be altered significantly by pretreatment with CY 1 to 2 days before immunization. Such drug pretreatment tends to augment low DTH responses caused by the use of too much antigen and to diminish many responses that are optimal. Thus, pretreatment with CY does not specifically eliminate suppressor cells. Our results are most consistent with the notion that the cellular targets of low doses of CY are positive and negative feedback regulatory cells, which may consist of one population with two effects or, more likely, two distinct cell populations.


Quantitative differences in immune responses during the various stages of  the estrous cycle in female BALB/c mice. The immune responsiveness of spleens from female BALB/c mice to PHA, Con A, and LPS was greater at proestrus and metestrus as compared with estrus and diestrus. The peaks of responsiveness corresponded to reported elevated levels of estrogen and pregnenolone during these phases of the cycle. Similar results were obtained with the IgM or direct plaque-forming cell responses, which were also increased at proestrus and metestrus. It appears that female hormones may directly or indirectly stimulate immune responsiveness in adult mice.


Particle counting immunoassay (PACIA). II. Automated determination of circulating immune complexes by inhibition of the agglutinating activity of rheumatoid sera. Antigen--antibody complexes were detected in patients' sera by inhibition of the agglutinating activity of rheumatoid sera toward IgG coated particles (latex). Precision, sensitivity (1--10 microgram/ml equivalents of heat-aggregated IgG), and reproducibility (maximum coefficient of variation of 11%) were obtained by measuring agglutination with an instrument counting the residual free particles. Automation allowed testing of 20 to 40 samples per hour. The inhibitory activity of spontańeously agglutinating sera was determined after inactivating endogenous rheumatoid factor by reduction with dithiothreitol. Non-aggregated IgG did not significantly interfere. The agglutinating activity of 6 rheumatoid sera was tested after incubation with the various immunoglobulin classes and subclasses polymerized by coupling to agarose, and all were found to be readily absorbed by IgG1, but poorly by IgG3, IgA1 and IgM. Reactivity with IgG2, IgG4 and IgA2 clearly differed for different rheumatoid sera. Among 70 sera from blood donors, 7 had abnormally high inhibitory activity. Six of these had also an abnormal protein profile, suggesting existence of latent disease. High inhibitory activity in 15 sera out of 18 from patients with systemic lupus erythematosus, and in 23 sera out of 46 from patients with breast cancer suggested that the rheumatoid factor inhibition test has a discriminatory capacity comparable with that of more sophisticated techniques requiring radioisotopes and/or cellular material.


Annual variations in the total lipid and protein content of the liver, fat body, ovary and plasma of the female frog (Rana esculenta L.). The concentrations of lipid and protein in the ovary, fat body, liver and plasma of the female frog (Rana esculenta L.) were found to exhibit marked seasonal variations. There was an interesting correspondence between the depletion of lipid in the plasma and fat body and an increased level of lipid in the ovary. It would appear that oestrogenic steroids stimulate and increase the concentrations of lipids in the plasma, whereas pituitary gonadotrophins influence the uptake of lipids by ovarian tissue for vitellogenesis.


Specific suppressive factors produced by hybridomas derived from the fusion of enriched suppressor T cells and a T lymphoma cell line. A cell fusion technique was used to produce hybridomas between the T lymphoma cell line, EL-4, derived from C57BL (H-2(b)), and an enriched population of human gamma globulin (HGG)-specific suppressor T cells prepared from the spleens of HGG-tolerant CBA mice (H-2(k)). Membrane fluorescence analysis of the hybridoma cells within 6 wk of cell fusion revealed expression of H-2(k) and I-J(k) gene products as well as H-2(b) antigens. Sonicates prepared from hybridomas which contained I-J(k) cells were tested for suppressive activity in vivo in irradiated mice given HGG-primed cells, dinitrophenyl (DNP)-primed cells, HGG-DNP, and horse erythrocytes. Among 18 such hybridoma lines, 6 showed specific suppressive activity, 5 nonspecific suppression, and 7 no suppression. Most lines progressively lost, with time, those properties derived from the normal parent cell. By about 3 mo after fusion few cells expressed CBA markers and only one cell line (number 77) retained some specific suppressive activity. In parallel with the losses was an alteration in chromosome number from near-tetraploid, soon after cell fusion, to near- diploid. Preliminary results with the T lymphoma-sensitive hypoxanthine aminopterin thymidine cell line, L5178, indicate retention of the expression of surface markers derived from the normal parent for 18 wk after hybidization. This suggests that T lymphoma cell lines may have to be screened for their capacity to produce hybridomas with stable properties.


Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. When cultures of normal mouse peritoneal macrophages were infected with the intracellular protozoan parasite Leishmania enrietti, the micro-organism was found to survive intracellularly for several days, apparently without multiplication. However, exposure of infected macrophages to certain stimuli led to rapid parasite killing and digestion, providing a sensitive assay with which the mechanisms of macrophage activation can be studied. Microbicidal activity was induced by incubation of macrophages with syngeneic spleen lymphocytes, which were stimulated either by allogeneic cells in mixed lymphocyte culture (MLC) or by the plant lectin concanavalin A (Con A). Cocultivation with MLCs led to parasite killing within 48-72 h, whereas exposure of infected cells to Con A-stimulated lymphocytes resulted in substantial destruction of the micro-organism within less than 24 h, an effect which was dependent on the presence of thymus-derived lymphocytes and was inhibited by alpha methyl-mannoside. Incubation with Con A-stimulated lymphocytes also led to lysis of part of the macrophage monolayer. However, parasite killing did not result from decreased macrophage survival, as destruction of the micro-organism was highest under culture conditions which were the least detrimental to the phagocytes. Conversely, excess numbers of Con A-stimulated lymphocytes were less efficient at inducing macrophage activation and displayed marked toxicity to the macrophage monolayer. When spleen cells were stimulated by Con A at concentrations above 10 mug/ml, a decrease was noted in the capacity of macrophages to destroy the parasite, probably reflecting a toxicity of the lectin for lymphocytes resulting in impaired activating capacity.


Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets. We have examined the ability of macrophages (Mphi) to transmit T-cell derived suppressor signals to other T cells. The suppressor signal studied is an antigen-specific factor which suppresses the ability of adoptively transferred, sensitized lymphocytes to express contact hypersensitivity in normal recipients. We have found that this factor binds to peritoneal exudate Mphi via cell surface structures which can be blocked with heat-aggregated gamma globulin. Dead (HK) Mphi bind the factor but fail to present it in a functional way to assay (immune) T cells, whereas live (L) Mphi perform both functions. Further, L Mphi can retrieve the factor in an active form from the surfaces of HK Mphi. Based on these and other findings (1-5), we discuss the possibility that Mphi may play as important a role in presenting T-cell communication signals to the cells of the immune system as they do in presenting antigen.


Role of the H-2 complex in induction of T helper cells in vivo. I. Antigen-specific selection of donor T cells to sheep erythrocytes in irradiated mice dependent upon sharing of H-2 determinants between donor and host. When purified CBA lymph node T cells were mixed with sheep erythrocytes (SRC) and filtered from blood to lymph through irradiated syngeneic mice for 1-2 days, the donor cells lost their capacity to stimulate anti-SRC responses by CBA B cells; the response to a third-party antigen (horse erythrocytes) was unaffected and active suppression was not involved. This process of specific negative selection to SRC also occurred when semiallogeneic mice were used as filtration hosts. By contrast, when allogeneic hosts were used the helper function of the donor cells was not reduced; this applied to both primed and unprimed T cells. Studied with congeneic resistant strains indicated that negative selection to SRC occurred only when the donor and host shared H-2 determinants. Studies with T cells depleted of alloreactive lymphocytes showed that negative selection to SRC in irradiated F1 hybrid mice was followed by a stage of positive selection where the donor cells gave greatly increased responses to the injected antigen. Positive selection did not occur in H-2-different mice, however, and the helper function of the donor cells remained unchanged. By these parameters it was concluded that homozygous T helper cells have no detectable capacity to recognize antigen in an H-2-different environment.


Adoptive transfer of allotype-specific suppressor cells inhibits thymus-independent immunoglobulin production in syngeneic athymic mice. (SJL X BALB)F1 suppressed mice have, in their lymphoid tissues, a population of suppressor T cells directed specifically against a paternal gamma G2a allotype (Ig-1b). Spleen or lymph node cells from these mice were injected into syngeneic nude mice and the effect on thymus-independent synthesis of Ig-1b in the athymic recipients was determined. After the injection of suppressor cells, Ig-1b disappeared from the serum of the recipients in a time course similar to that seen in normal mice. These results indicate that suppression occurs in the absence of thymus-derived helper cells, and they suggest that Ig-1b-producing B cells are the target of allotype-suppressor cells.


Regulation of cytotoxic T-cell reactivity to syngeneic tumors by the thymus. Adult thymectomy has been shown to result in the enhanced capacity of splenic T cells to respond to and lyse syngeneic tumor cells in vitro. In addition, T cells from thymectomized mice which kill syngeneic tumor cells do not lyse either normal lymphoid or mitogen-stimulated syngeneic lymphoblast target cells. These findings indicate that the thymus exports a subpopulation of T cells sensitive to adult thymectomy which regulates the generation of cytolytic T cells directed against syngeneic tumor cells.


Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host. The concept of adaptive (selective) differentiation preducts that early differentiation of lymphocytes is conditioned by the environment in which such differentiation takes place. These processes appear to involve selection of lymphocytes according to their self-recognition between interacting lymphocytes is, at least in part, controlled by major histocompatibility complex-linked genes, then adaptive differentiation is also controlled by these genes. In these studies, we have tested the capacities of helper T lymphocytes and hapten-specific B lymphocytes primed in the environments of various combinations of bone marrow chimeras prepared between two parental strains (i.e. A/J and BALB/c) and their corresponding F1 hybrid (CAF1) to interact with primed B and T lymphocytes derived from conventional parent and F1 donors as well as all of the corresponding bone marrow chimera combinations. The results demonstrate clearly that (a) F1 transplanted to F1 chimeric lymphocytes display no restriction in terms of cooperative activity with all of the various partner cell combinations; (b) parent transplanted to F1 chimeric lymphocytes manifest effective cooperative activity only for partner cells from F) or parental donors corresponding to the haplotype of the original bone marrow donor, thereby behaving phenotypically just like conventional parental lymphocytes; and (c) F1 transplanted to parent chimeric lymphocytes display restricted haplotype preference in cooperating best with partner lymphocytes sharing the H-2 haplotype, either entirely or codomimantly, of the parental chimeric host. The implications of these findings for understanding certain controlling mechanisms for lymphocyte differentiation are discussed.


Individual antigen-specific T lymphocytes: helper function in enabling the expression of multiple antibody isotypes. In recent years antigen-specific T cells have been shown to be capable of mediating a number of diverse functions in collaboration with B cells in humoral immune responses. One of the more intriguing roles attributed to helper T cells is the promotion of the synthesis of multiple immunoglobulin isotypes by B cells in T-dependent antibody responses. The experiments presented in this report were carried out to determine if an individual antigen-specific T lymphocyte has the capability to enable the production of antibodies of multiple immunoglobulin heavy chain isotypes. We describe an experimental system which allows for the isolation and antigenic stimulation of individual helper T cells in a splenic environment which provides an excess of primary B cells for collaboration with isolated T lymphocytes. Employing this system we have demonstrated that an individual antigen-specific T lymphocyte, specific for the PR8 strain of influenza virus, has the capacity to enable primary B-cell PR8-specific antibody responses of more than a single immunoglobulin isotype. The implications made by these studies regarding the problem of genetic restrictions regulating T-cell-B-cell interaction is discussed.


H-2 antigens of the thymus determine lymphocyte specificity. After immunization, normal H-2 heterozygous mice (for example H-2(b) x H-2(d)) generate two populations of cytotoxic effector T cells, one specific for target cells expressing H-2(b)-plus-antigen and the other specific for H- 2(d)-plus-antigen. With a multideterminant antigen, these two populations have about the same activity. We show here that the H-2 type of resident cells in the thymus determines the H-2 preference of cytotoxic T lymphocytes. F(1)(B 10 x B 10.D2) (H-2(b) x H-2 (d)) mice were thymectomized, lethally irradiated, and reconstituted with T-cell-depleted syngeneic hematopoietic cells. Groups of such ATXBM mice were grafted subcutaneously with neonatal thymus lobes from parental mice, either B10 (H-2 (b)) or B10.D2 (H-2(d)). 2-3 mo later, the mice were immunized against the minor histocompatibility antigens on F(1)(BALB/c x BALB.B) cells and assayed for cytotoxic T-cell activity. H-2(b) x H-2(d) ATXBM mice with H-2(b) thymus grafts responded to antigen-plus-H-2(b) much better than to antigen-plus-H-2(d), and vice versa for the mice with H-2(d) thymus grafts. As judged by antiserum treatment, the effector cells were of F(1) origin. To explore the possibility that the "thymus preference" may have been due to suppression of T-cell activity, nonimmune spleen and lymph node cells from normal H-2(b) x H-2(d) mice and cells from H-2(b) x H-2(d) mice bearing a homozygous thymus were mixed 1:1 and immunized in adoptive transfer. The mixture responded to antigen-plus-H-2(b) and antigen-plus-H-2(d) equally well, demonstrating that the cells that showed a "thymus preference" could not suppress a response to antigen in association with the nonthymic H-2 type. We conclude from these and other experiments that H-2 antigens present on resident cells of the thymus determine the spectrum of specificity of T cells which mature in that thymus and eventually make up the peripheral T- cell pool.


Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population. BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.


Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production. Lactoferrin (LF), the iron-binding protein present in the specific granules of mature granulocytes has been identified as colony inhibitory factor (CIF) which suppresses granulocyte--macrophage colony stimulating activity (CSA) production by monocytes and macrophages in vitro and rebound granulopoiesis in vivo. Separation of LF and CIF by isoelectric focusing confirmed that the regions of inhibitory activity corresponded in both to a pH of congruent to 6.5. In addition, the purified immunoglobulin fraction of rabbit anti-human LF antiserum, but not rabbit anti-transferrin (TF), inactivated the capacity of LF and CIF to inhibit CSA production, an effect blocked by prior incubation of anti-LF with neutralizing concentrations of LF. Suppression of CSA production correlated with the iron-saturation of LF; APO-LF (depleted of iron) was only active concentrations greater than 10(-7) M, native LF (8% iron saturated) was active at 10(-15) M, and fully iron-saturated LF inhibited at 10(-17) M. Suppression of CSA production occurred within a 1/2-h preincubation period with human blood monocytes but was reversed by bacterial lipopolysaccharide (LPS). This reversal was dependent on the relative concentrations of LF to LPS. Serum TF, a biochemically similar iron-binding protein which is antigenically distinct from LF, was only minimally active at concentrations greater than 10(-6) M. LF did not inhibit exogenously stimulated human granylocyte and macrophage colony-forming cells or erythropoietin-dependent human or murine erythroid colony- or erythroid burst-forming cells. Microgram quantities of LF acted in vivo to inhibit rebound granulopoiesis and CSA production in CD1 and C57Bl/6 mice pretreated with cyclophosphamide. These results strongly implicate LF as a physiological regulator of granulopoiesis.


Long-term culture of human antigen-specific cytotoxic T-cell lines. Long-term cultures of human cytotoxic T-cell lines (H-CTLL) were established. H-CTLL cells were strictly dependent on growth upon a T-cell growth factor (TCGF) produced by phytohemagglutinin-stimulated normal human peripheral blood lymphocytes. H-CTLL cells were maintained in TCGF-dependent exponential proliferative culture for over 4 mo during which time they continued to mediate stimulator antigen-specific cytotoxicity as measured by a 4-h 51Cr-release assay. H-CTLL cells recovered from cryopreserved stocks and re-established in long-term culture demonstrated similar high levels of antigen-specific cytotoxicity. H-CTLL cells were 95--100% E-rosette positive and expressed normal T and Ia-like cell surface markers. The ability to sustain differentiated antigen-specific T-effector cells in long-term culture may provide a new means for the study of both the mechanism and regulation of T-cell-mediated immunity.


Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. Purified Ly1 cells induce other T-cell sets to exert potent feedback inhibitory activity and this T-T interaction has been shown to play an important role in regulating in vivo immune responses. Approximately 2/3 of Ly1 cells also express the Qa1 surface phenotype (Ly1:Qa1+ cells). The experiments reported here indicate that Ly1:Qal+ cells are responsible for induction of feedback inhibition and that signals from both Ly1:Qal+ cells and Ly1:Qal- cells are required for optimal formation of antibody by B cells.


A medical information system for ambulatory care, research, and curriculum in an army family practice residency: 51,113 patient problems. Over a 16-month period, the Family Practice Residency at Madigan Army Medical Center coded 51,113 ambulatory problems using the International Classification of Health Problems in Primary Care (ICHPPC) coding scheme. The demography of this defined active duty, retired, and dependent population is described as well as the rank order of the major diagnostic categories and top 25 individual diagnoses. A plot of the major diagnostic categories seen by month over a 16-month period is presented. Comparisons between similar curves are made. Physician compliance to coding approached 75 percent and an average of 1.42 problems were dealt with (coded) per visit. Fifty percent of all patient problems recorded fell into 25 descriptive diagnoses. Ninety percent of all patient problems recorded fell into 163 descriptive diagnoses. These data compare favorably to the Virginia study. Comparison of the top 25 patient problems also revealed similarities between this and the Virginia study. Difficulties arise in comparing data because of the differences in coding schemes (RCGP vs ICHPPC). A universally adopted code for all family practice and ambulatory care research would help in overcoming this problem.


Information management in clinical practice. Information management is essential for optimal delivery of health care services to individuals and the community. Current information techniques--largely dependent on the individual patient record--cannot effectively store, process, retrieve, and communicate the vast amount of data and information which is integral to the comprehensive health care process. Computerized techniques similar to those which are an indispensable part of almost all scientific, commercial, and administrative sectors of society are urgently needed to support a fully effective health care system.


The red eye.

The red eye. The nonophthalmic physician confronted by a patient with a red eye should be able to distinguish common microbial or allergic conjunctivitis from potentially blinding disorders, such as acute angle closure glaucoma, uveitis, or herpes simplex keratitis, and should remain alert for an associated systemic disease, such as rheumatoid arthritis, polycythemia, or carotid cavernous fistula. The physician should approach the red eye systematically: take a careful history, including type of pain; measure visual acuity; observe the pattern of redness, the type of discharge, the shape of the pupil, and the opacities of the media; and measure the intraocular pressure.


Voltage- and time-dependent action of histrionicotoxin on the endplate current of the frog muscle. Histrionicotoxin, a toxin isolated from skin secretions of a Colombian arrow poison frog, Dendrobates histrionicus, decreased the amplitude and time-course of the endplate current, and altered the voltage dependence of the half-decay time. In addition, the toxin produced a characteristic nonlinearity in the current-voltage relationship of the endplate current when 3-s voltage conditioning steps were used. Reduction in time of the conditioning steps to 10 ms made the current-voltage relationship linear. The decrease in peak amplitude of the endplate current (epc) produced by histrionicotoxin measured during long hyperpolarizing conditioning steps was fitted by a single exponential function. The calculated rate constants ranged from 0.03 to 0.14 s-1 and varied with membrane potential at hyperpolarizing levels. The voltage- and time-dependent action of histrionicotoxin does not require an initial activation of receptors by acetylcholine (ACh). The characteristic of the current-voltage relationship can be accounted for by the observed voltage and time dependency of the attenuation of the endplate current amplitude in the presence of histrionicotoxin during long conditioning steps. These effects of histrionicotoxin on the peak amplitude, and on the voltage and time dependence of the epc were concentration-dependent and slowly reversible upon washing out the toxin. Thus, the voltage- and time-dependent action of histrionicotoxin at the endplate is related to an increase in the affinity between the toxin and the ACh receptor-ionic channel complex. This increase in affinity is postulated to be due to a conformational change of the macromolecule in the presence of histrionicotoxin which is demonstrated to be relatively slow, i.e., on the order of tens of seconds.


Influenza virus infection in newborn rats: a possible marker of attenuation for man. The growth of parent influenza viruses A/England/939/69 and A/PR/8/34, and clones 6, 7, and 64C, derived by recombination, was studied in newborn rats. Using an inoculum of 10(4.0) EID50, influenza virus A/England/939/69 produced the highest titres of virus in rat turbinates at 48 hours after inoculation; clones 6 and 7 and A/PR/8/34 grew to lower titres; and clone 64C grew to the lowest titre. These differences were less apparent when 10(2.0) EID50 of virus was used as an inoculum, and rats were not infected by smaller inoculum of any of the virus strains. Infection with 10(4.0) EID50 of all viruses produced lung infection; at 48 hours after infection, the highest titres were recovered from rats infected with A/PR/8/34 and A/England/939/69 virus. Prior infection with A/England/939/69 or A/PR/8/34 increased the incidence of bacteraemia and meningitis following intranasal inoculation of Haemophilus influenzae type b; infection with clone 64C did not enhance bacterial meningitis, while infection with clone 6 gave an intermediate result. Volunteer studies with these viruses have shown that influenza virus A/England/939/69 was virulent, clones 6 and 7 were attenuated, clone 64C was over-attenuated, and A/PR/8/34 virus was noninfective for man. The relative titres of virus recovered from turbinates taken 48 hours after infection with 10(4.0) EID50 of virus and the ability of virus infection to enhance bacterial infection correlated with the property of virus attenuation for man for four of the five strains tested; however, no correlation was seen for A/PR/8/34 virus, which is a result also found in other laboratory tests designed to measure virulence for man.


Limited effect of erythrocyte and plasma infusions in adenosine deaminase deficiency. A 10-month-old child with a profound deficiency of adenosine deaminase and severe combined immunodeficiency was treated for a period of 17 months with red cell and plasma transfusions containing normal amounts of the deficient enzyme. Following each transfusion, the plasma adenosine, red cell and lymphocyte ATP, urinary adenine, and urinary deoxyadenosine decreased transiently. During this period, the absolute blood lymphocyte count rose and a limited increased in the response of the lymphocytes to PHA-P was observed. Delayed hypersensitivity skin tests remained negative during the transfusion periods. A quantitative elevation of serum immunoglobulins occurred, but specific antibody formation was not elicited. In contrast to a previous report of successful therapy of ADA deficiency with red cell and plasma infusions, this patient responded poorly to enzyme replacement therapy. The difference may be related to a more profound enzyme deficiency in our patient.


Body rocking, head banging, and head rolling in normal children. Body rocking, head banging, and head rolling--three rhythmic behaviors that involve stimulation of the vestibular system--were studies in 525 normal children. Data analyses focused on two issues: (1) the prevalence and duration of these habits and their relationship to child and family factors and (2) the hypothesis that children who persistently displayed such behaviors would be reported as developmentally more advanced than "non-self-stimulators." Body rocking was the earliest to appear and most prevalent of the three habits. Head banging and head rolling had roughly the same prevalence and age of onset. Comparisons of "self-stimulators" with "non-self-stimulators" yielded no significant effects for birth order or SES; only for head banging was a significant (3:1) ratio of males to females found. A comparison of the ages at which 12 "milestones" first appeared supported the hypothesis of developmental precocity for the body rockers and the head bangers, but not for the head rollers.


Enhancement of mechanical performance by stretch during tetanic contractions of vertebrate skeletal muscle fibres. 1. Single fibres from the semitendinosus muscle of Rana temporaria were stretched during fused tetanic contractions and tension and sarcomere length (laser diffraction) responses were recorded. 2. Stretch of the fibres caused proportional increases in length of the sarcomeres. The force increased to a plateau value which was maintained during stretch or increased to a plateau value which was maintained during stretch or increased slightly. 3. The plateau value of force during stretch was dependent upon the velocity of stretch, was independent of the amplitude of stretch and was not proportional to overlap of thick and thin filaments. 4. There was enhancement of force after stretch compared with that produced at the same sarcomere length during isometric tetani. This force enhancement was independent of the velocity at which the stretch had been applied. 5. At sarcomere lengths between 1.9 and 2.3 micrometer, the force enhancement after stretch declayed rapidly, was independent of amplitude of stretch above approximately 25 nm per sarcomere not associated with a shift of the force--velocity curve. At sarcomere lengths above 2.3 micrometer the force enhancement after stretch decayed very slowly and was still present after 4 sec in long tetani. 6. At sarcomere lengths above 2.3 micrometer, force enhancement after stretch increased with amplitude of stretch and increased for any given stretch amplitude with sarcomere length. The force recorded after stretch was thus not proportional to overlap of thick and thin filaments. 7. At sarcomere lengths above 2.3 micrometer, the force enhancement after stretch was associated with a shift towards higher force value of the force--velocity curve. The velocity of shortening and zero load (V max) derived by hyperbolic extrapolation of the force--velocity curve was not affected.  8. Tension enhancement during and after stretch has a stabilizing effect in preventing dispersion of sarcomere length, particularly on the descending limb of the length--tension curve.


Reprimed charge movement in skeletal muscle fibres. 1. The three intracellular micro-electrode voltage-clamp technique was used to study the recovery of membrane charge movement in semitendinosus muscles of Rana pipiens. Muscles were placed in a hypertonic depolarizing solution to inactivate voltage dependent charge movement. Tetrodotoxin and tetraethylammonium ions (TEA+) were present to block voltage dependent ionic conductances. Rb+ and SO4(2-) were present to reduce inward rectification and leakage conductance. 2. The recovery ('repriming') of membrane charge movement was studied following hyperpolarizing pulses from a holding potential of -20 mV to membrane potentials from -30 to -140 mV for durations of 2--100 sec. The reprimed charge movement measured as the difference in membrane current required for identical voltage steps before and after long duration hyperpolarizing pulses was a linear function of membrane potential and symmetrical in shape. Reprimed charge is, therefore, simply the result of an increase in the linear capacitance of the fibre. 3. The mean value of the percent increase in capacitance for repriming at -100 mV was 12.3 +/- 1.7% (S.E. of mean) for 25 sec duration pulses and 27.8 +/- 2.9% for 100 sec duration pulses. If these data are corrected to the steady state and the surface contribution subtracted, the mean increase in 'volume' capacity is 40.3 +/-  3.6% (n = 21) for fibres with a mean diameter of 51 +/- 4 micron. 4. The increase in capacity can arise either by an increase in the transverse tubular length constant (lambdaT) or by gaining electrical access to additional linear capacitance within the fibre volume. If the capacitance arises solely from the transverse tubular system, the value of lambdaT before repriming can be no larger than 20 micron in order to explain the observed increase in volume capacity. A value of lambdaT as small as this seems unlikely. 5. The observation that reprimed charge is simply the result of an increase in linear capacitance is not consistent with the hypothesis that it is a gating mechanism for the activation of contraction.


Determination of dose-response curves by quantitative ionophoresis at the frog neuromuscular junction. 1. Quantitative ionophoresis at the neuromuscular junction is possible when (a) the drug is released from appropriate distances (15--20 micrometer for most drugs), (b) the topology of receptors is known and (c) high resistance drug pipettes (100--200 M omega) are sued. 2. With this method, drug concentration-endplate conductance relations were determined in voltage-clamped end-plates of the frog for the agonists ACh, carbamylcholine (CCh) and suberyldicholine (SubCh). 3. Based on the co-operative and independent model, theoretical dose-response curves were computed using as parameters the Hill coefficient nH, maximum conductance gmax., and apparent dissociation constant K. It was found that the co-operative model fitted the data much better than the independent model. 4. Based on the co-operative model, the mean maximum conductance for ACh was gmax. = 169 nS/micrometer, equivalent to 9000 ionic channels/micrometer length of a nerve terminal which can be opened at high drug concentrations. 5. The maximum conductance for CCh at--80 mV membrane potential was, on the average, 78% of that for ACh measured at the same end-plates. This value is termed the relative efficacy of CCh. 6. The mean values for the apparent dissociation constant K were 27.8 micrometer for ACh, 336 micrometer for CCh and 18 micrometer for SubCh. 7. The inhibition of the acetylcholinesterase activity by edrophonium (3--10 micrometer) affected only the local ACh concentration at the receptor sites, but not gmax. and nH. 8. Dose-response curves measured before and after removal of single nerve terminals in collagenase-treated muscle fibres showed no change in the nH, gmax. and K. A slight increase in gmax. to a value of 218 nS/micrometer observed comparing collagenase-treated and untreated end-plate. 9. Desensitization of receptors may occur in the range of several tens of milli-seconds.


An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions. 1. Frog neuromuscular junctions were viewed with Nomarski optics and voltage clamped. Agonist was applied ionophoretically and agonist concentrations were measured using a micro-electrode sensitive to quaternary amines. 2. The dose-response relationship was studied using the agonists carbamylcholine, suberyldicholine and hydroxyphenyl-propyltrimethylammonium. 3. With all of these agonists, it appeared that the ACh receptor could be active when either one or two agonist  binding sites were occupied. The receptor was much more likely to be active when both sites were occupied. Agonist dissociation constants and receptor activation probabilities were estimated by non-linear regression techniques for several possible receptor activation schemes.


A simple problem orientated record card for general practice. A simple way of introducing a problem orientated summary card into conventional NHS medical records is described.


Rheumatology in general practice--a survey in World Rheumatism Year 1977. Rheumatological complaints accounted for 10.6 per cent of new presentations in this general-practice survey. Spinal problems formed almost half of this total and led to a greater degree of disability than other locomotor system disorders. Active participation in the treatment of pain by the practitioner's use of manipulation and injection techniques is shown to be quite feasible in general. Forty-six per cent of all hospital referrals were simply requests for physiotherapy, and we suggest that physiotherapy departments should offer open access and so lead to a marked reduction in over-strained rheumatology consultant outpatient clinics.


Effects of antidiuretic hormone upon electrical potential and resistance of apical and basolateral membranes of frog skin. The effect of ADH upon the intracellular potential and the resistance of inner and outer borders of the transport pathway was investigated on isolated skins of Rana temporaria. Within 40 min after ADH (100--300 mU/ml), the intracellular potential under short-circuit conditions decreased to about 40% of the control value (--79 +/- 4 mV), concomitant with an increase in the short-circuit current to about 160% of the control value. Amiloride, applied when steady values under ADH had been reached, caused an immediate rise of the intracellular potential to values typical for control conditions. This confirms (i) the intracellular location of the microelectrode and the absence of impalement artifacts, and (ii) the ineffectiveness of ADH upon the electromotive forces of the inner border. ADH had no effect upon the intracellular potential after blockage of the Na entry by Amiloride. The equilibrium potential of the outer border was estimated to be about +20mV under the influence of ADH. As this value is considerably less positive than might be expected for the chemical potential of Na, a significant contribution of ions other than Na to the outer border conductance and equilibrium potential is implicated. The resistance of the outer border was more significantly decreased than that of the active transcellular pathway after ADH due to an increase in the inner border resistance, which exceeded that of the outer border after ADH. The effect of ADH upon the outer membrane characteristics would be underestimated by a factor of two, if the alterations of the electrical potential difference were not taken into consideration.


Altered carbohydrate content of alpha1-antitrypsin in patients with cancer. The glycosylation of IgG and alpha1-antitrypsin (alpha1-AT) was studied by their precipitation with concanavalin A in a codified serum panel from the National Cancer Institute (Bethesda, Md.) and the Mayo Clinic (Rochester, Minn.). The serum panel was composed of samples from 98 patients with cancer of the lung, prostate gland, or gastrointestinal tract, 50 samples from patients with benign inflammatory diseases from the same organs as those of the cancer patients, and 41 samples from apparently healthy smokers. The assay for alpha1-AT revealed statistically significant differences in levels between the patients with cancer, the patients with benign diseases, and the smokers. However, tests revealed no statistically significant difference in IgG levels among the three groups. These results suggest that cancer may alter the glycosylation of alpha1-AT. The possibility remains that the test for alpha1-AT can detect genetic differences among individuals, but studies of families are needed before a final conclusion can be made.


Homozygous alpha1 antitrypsin deficiency with unusual associations:  a case report. The rare association of protease inhibitor deficiency (Pi(zz) genotype) in a black American with chronic, obstructive pulmonary disease due to asthmatic bronchitis, rather than basal pan lobular emphysema, is presented. The late onset of symptoms, despite environmental exposures, is also unusual in this homozygote, as is his ethnic background.


Gastric candidiasis.

Gastric candidiasis. Two cases of candidiasis occured in the stomach. The first is a case of disseminated candidiasis with stomach wall involvement. The patient had Hodgkin's disease and responded to chemotherapy and amphotericin B. The second is a case of superficial invasion of Candida in a stitch ulcer. Systemic and local factors influence growth of Candida in the stomach.


The cost of coronary bypass procedures.

The cost of coronary bypass procedures. We reviewed the financial records of 200 succesive patients who had coronary artery bypass surgery in the first three months of 1976. The average hospital bill was $7,690 and the average length of stay was 18 days. The highest bill was $28,329 (79 days) and the lowest was $6,126 (11 days). The average total physician charge to the patient was $3,240. The total average hospital and physician cost was $10,930.


[Action of a new antiarrhythmia preparation, etmozin, on the contractile force, transmembrane action potential and the rapid incoming sodium flow of the frog atrial muscle]. The mechanism of the effect of ethmosine on the force of contraction, the membrane potential and the rapid incoming sodium flow of the frog atrium was studied by means of microelectrode technique and the method of potential fixation. It has been shown that in a concentration of up to 10(-5) g/ml ethmosine reduces the rate of increase of the foremost front of the action potential by 50%; has no substantial effect on the force of contraction, and on the shape and duration of the transmembrane action potential; inhibits the rapid incoming sodium flow by more than 50% by diminishing maximum conductivity of sodium ions; has no effect on processes of activation, inactivation and reactivation of the sodium flow. A comparison is made between ethmosine and other antiarrhythmic agents in their effect on the force of contraction and the electric parameters of cardiac cells.


[The diagnostic and prognostic value of alpha-1-antitrypsin measurement in tear fluid (author's transl)]. Bacterial infections of conjunctiva and cornea cause an increase of alpha-1-antitrypsin in tears. In 77 cases detections of this antiproteases were performed by immuno-chemical methods. We believed that the estimation of alpha-1-antitrypsin in tears may be an effective help in diagnosis of ocular inflamations.


[Anomalies of the colour vision of women as an indication of testicular feminisation (author's transl)]. When women show inborn anomalies of colour vision the syndroma of testicular feminization should be thought of as a possibility. In such cases the ophthalmologist should always ask the patient whether an amenorrhoea is present or ask for gynaecological examination.


[Diagnostik significance of cell membrane markers in childhood ALL (author's transl)]. Acute lymphoblastic leukemia (ALL) in childhood is not a homogeneous disease. By membrane phenotyping 6 groups of ALL in 66 children could be differentiated: Group I (38%) common ALL (anti-cALL+. Group II (32%) common ALL with T cell marker in addition (anti-cALL+, anti-T+). Group III (14%) T. cell ALL with E-rosette marker (anti T+, E+). Group IV (9%) T cell ALL without E-rosette marker (anti T+, E-). Group V (6%) undifferentiated ALL (anti-cALL-, anti-T). Group VI (1%) B cell typ (SmIg+). 19 or 20% of children in groups I and II opposed to 67 or 100% of children in groups III and IV had a white cell count at diagnosis of greater than 25,0 x 10(3)/mm(3) Mediastinal involvement was typical for groups III and IV. No significant difference was found so far for age or sex in the groups.


Demonstration of antinuclear antibodies in mercuric chloride-induced glomerulopathy in the rat. Serial administration of mercuric chloride to PVG/C rats induced a glomerulopathy associated with immune complex deposition along the glomerular basement membrane and in the mesangial area. These deposits could be demonstrated by immunofluorescence and electron microscopy 5 to 8 weeks after the first injection of mercuric chloride. At this time antinuclear antibodies could be demonstrated in the sera and in the eluates from the renal cortices from diseased animals. These findings suggest a possible role for antibodies directed against nuclear antigen in the pathogenesis of this type of experimental glomerular disease.


Results and patterns of perioperative myocardial infarction. Myocardial injury during a variety of cardiac surgical operations was determined in 57 patients by serial electrocardiograms (ECG's), serial determinations of serum creatine phosphokinase (CPK), and perioperative and postoperative technetium-99m stannous pyrophosphate (PYP) scans. ECG evidence of injury developed in four patients, whereas positive localized injury by PYP scan developed in ten. Twenty-one patients had elevated CPK enzymes postoperatively. The localization of injury by PYP scan correlated with ECG evidence of infarction in only one of four patients. Localized left ventricular injury by PYP scan without new Q waves on the ECG was common (5/12) in patients undergoing aortic valve replacement with perfusion of the coronary arteries. The injury in patients with congenital heart disease occurred at sites of ventricular incision or suggested possible air embolization of the coronary arteries. Perioperative infarction is frequently segmental and nontransmural and occurs in patients with coronary, valvular, and congenital heart disease.


Perioperative myocardial infarction in patients with coronary artery disease with and without aorta--coronary artery bypass grafts. The incidence of perioperative myocardial infarction (MI) was examined in 148 patients with known coronary artery disease (CAD) who underwent 226 noncardiac surgical procedures. In 168 operations in 99 patients who had prior coronary artery bypass grafting (CABG) there were no perioperative MI's whereas in the 49 patients who had not undergone prior CABG who underwent 58 noncardiac operations, there were three MI's (5 percent). The lower (p less than 0.02) incidence of perioperative MI in patients with CAD who had had prior CABG suggests a protective effect for subsequent noncardiac operation, which could not be explained by other differences in cardiac status between the groups. All three MI's occurred in patients with three-vessel CAD, evidence that this should be added to prior MI as a significant risk factor. The study indicates also that patients with prior CABG have less risk of MI during and following anesthesia and noncardiac operation than do patients without CABG who have had a previous MI.


Aorta--coronary artery revascularization with an expanded polytetrafluoroethylene vascular graft. A preliminary report. Patients requiring coronary artery surgery may have had bilateral saphenous vein stripping, and the arm veins may not be adequate for use for coronary artery grafting. The internal mammary artery may not be long enough for use for the circumflex or right coronary artery anastomoses. A suitable substitute would be most welcome for these patients or for those with marked varicosities of the saphenous vein. Five patients received expanded polytetrafluoroethylene (PTFE) grafts (Gore-Tex vascular grafts) for coronary artery revascularization because veins of adequate size or length were not available at the time of operation. These five patients are alive 9 to 14 months after graft insertion. Four of the five grafts were patent at the time of restudy 3 to 6 months postoperatively. More follow-up studies for far longer periods of time will be necessary before Gore-Tex vascular grafts can be recommended as the ideal material for coronary artery bypass surgery.


Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study. Seventeen of 34 consecutive patients undergoing coronary artery bypass grafting were randomly assigned to one of two methods of myocardial preservation. With the cold cardioplegic method (Group A), a 4 degrees C.  asanguineous solution with 30 mEq. of potassium per liter was infused into the aortic root for about 2 minutes immediately after aortic cross-clamping and again after about 45 minutes or when myocardial temperature rose above 19 degrees C. External cardiac cooling was provided by constant infusion of 4 degrees C. Ringer's solution into the pericardium. Seventeen patients were assigned to simple cardiac cooling by hypothermic systemic perfusion before aortic cross-clamping plus external cardiac cooling (Group B). Electromechanical activity ceased within 1 to 2 minutes in Group A but continued throughout the ischemic period in 14 patients in Group B. Myocardial temperature (mean for all observations) during aortic cross-clamping was 17.2 +/- 0.44 degrees C. In Group A and 24.0 +/- 0.70 degrees C. in Group B. Operating conditions were better in Group A. Card-ac function early postoperatively was good in both groups clinically and according to measurements, but only in the cold cardioplegic group (A) was cardiac index not adversely affected by longer cross-clamp time. Myocardial necrosis occurred in both groups but was probably less in the cold cardioplegic group. Thirteen patients (76 percent) in Group A had no electrocardiographic evidence of myocardial injury, compared with eight (47 percent) in Group B (p = 0.08). Eleven (65 percent of Group A had no or short-lived appearance of ceatine phosphokinase isoenzyme (CK-MB), compared with six (35 percent) of Group B (p = 0.08). Time-related CK-MB and SGOT mean levels were consistently lower in Group A.


Relation of preoperative use of aspirin to increased mediastinal blood loss after coronary artery bypass graft surgery. To evaluate the potential effect of aspirin, a platelet inhibitory agent, on postoperative bleeding complications after coronary artery bypass graft surgery, we compared each of nine patients who had taken aspirin within 7 days prior to operation to one or two control subjects (total 16 patients) matched for age, sex, extent of coronary disease, number of grafts placed total operative time, bypass time, and preoperative use of propranolol. Preoperative prothrombin time, partial thromboplastin time, and platelet counts were normal for all patients. Mean mediastinal blood loss was significantly greater in the aspirin group (919 +/- 164 ml., S.E.) than in the control group (437 +/- 61 ml., p less than 0.001). The degree of mediastinal blood loss did not correlate with patient age, total operative time, bypass time, number of vessels diseased, or grafts placed. In addition, compared to controls the aspirin group required prolonged chest tube drainage (33 +/- 5 hours versus 19 +/- 1 hour, p less than 0.001).


A one-stage combined approach for the management of large cerebellopontine angle tumors. This paper reviews 180 cerebellopontine angle lesions in regard to results and complications of the surgical management with special emphasis on the diagnosis, surgical removal, and results in 60 large (4 cm. or greater) tumors of the CPA. The authors conclude that in their experience a one-stage combined translabyrinthine-suboccipital approach, which is explained in detail, is the procedure of choice in dealing with large tumors of the CPA.


The effect of the endolymphatic subarachnoid shunt operation on vestibular function. Preoperative vestibular function was studied in 56 patients undergoing the endolymphatic subarachnoid shunt procedure for Ménière's disease by electronystagmographic recording of bithermal air caloric stimulation. Fifty-two percent had normal vestibular function while 48% had a reduced vestibular response on the affected side using 20% difference as being significant. Best results of surgery with relief of vertigo were found in the group of patients with normal preoperative vestibular function (82%) while the group with reduced vestibular response preoperatively showed 63% with a good result. Postoperatively, 81% had a reduced vestibular response in the operated-on ear with 62% obtaining relief of vertigo. In patients with normal vestibular function postoperatively excellent relief of vertigo was obtained. Of patients with normal vestibular function preoperatively, 69% developed a reduced vestibular response postoperatively with only 55% having relief of vertigo. The results of surgery could be predicted more accurately using the results of vestibular function tests than audiometric data. It appears that for best results the endolymphatic subarachnoid shunt procedure should be performed early in the course of Ménière's disease when hearing is fluctuating and vestibular function is normal.


[Long term effects of splenectomy on the immune-status of Hodgkin's disease patients depending on the modality of treatment (author's transl)]. In a total group of 103 Hodgkin's disease patients the immune-status of splenectomized and non-splenectomized individuals is compared in subgroups characterized by the modality of treatment (RT, CT, RCT). The mitogenic stimulation of peripheral lymphocytes showed a decreased response of splenectomized patients in each therapy group. The percentage, but not the absolute number/mm3, of peripheral T-cells was reduced after splenectomy. Splenectomized patients, who received combined radiation and chemotherapy showed significantly lower IgM-levels than non-splenectomized patients after the same treatment. EBV-VCA-titers and skin-test-reactivity were not influenced by splenectomy.


[Production of mutants with an increased alpha-amylase synthesis]. A mutant characterized by elevated biosynthesis of alpha-amylase was obtained as a result of a three-stage induced selection using nitroso compounds. Changes of mutagens in the course of selection stages and the establishment of their effective doses causing the maximum accumulation of mutations yielded the mutant which produced 2.5 times more alpha-amylase than the parent strain of Aspergillus oryzae 762. The induced variability of the mutant can be registered on a solid growth medium and provides the high activity of alpha-amylase.


The association of serum proteins with peripheral blood cells at low ionic strength: ultrastructural examination. Peripheral white blood cells have been shown to bind serum immunoglobins when prepared in low ionic strength sucrose solutions. The presence and distribution of Ig on neutrophils, monocytes and lymphocytes was described using an immunoferritin probe and the electron microscope. It appears that this approach reveals immunoglobulins associated with peripheral white blood cells that are not observed by the usual methods of examining these cell surfaces after preparation at physiological ionic strength.


[Iron deficiency anemia caused by occult intestinal bleeding due to milk allergy (author's transl)]. With the passive hemagglutination method the authors proved antibodies against milkprotein fractions in three of nine patients with hypochrome anemia aged 7, 12 and 17 months. In these children the X-ray examination showed an intestinal allergy, presumably the reason for occult intestinal bleeding which inturn caused hypochrome anemia. After milk was eliminated from the diet iron therapy restored a normal haemoglobin content. Iron therapy alone only improved the anemia, since continuing intestinal bleeding prevented fullrecovery.


Comparison of incidence and prevalence of arrhythmias in acute myocardial infarction. Current methods of handling quantitative arrhythmia data deal primarily with the incidence (I) of arrhythmias and the relation of incidence to morbidity and mortality in patients with acute myocardial infarction (MI). To evaluate a new parameter, prevalence (P), and compare it with I, data from 345 patients with MI were analyzed from a computerized data base. I was defined as the number of patients in whom an arrhythmia had occurred and P as the number of days the arrythmia persisted. A high I/P ratio is generally associated with a low prevalence and a low I/P ratio with a high prevalence. Incidence, prevalence, and I/P ratios are shown for supraventricular, junctional, and ventricular arrhythmias, and AV block. Further analysis of the data from 98 patients showed that when inferior MI was compared to anteroseptal MI there was an increased incidence of AV block, and an increased incidence of ventricular tachycardia. A high I/P ratio is shown for arrhythmias associated with a high mortality in our previous studies. The data suggest the need for newer techniques for handling quantative arrhythmia data.


Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide. To evaluate the effectiveness of cyclophosphamide in the treatment of lupus nephritis, we designed a prospective study of patients with diffuse proliferative lupus nephritis. Twenty-six patients received prednisone (average dose, 40 mg per day) and 24 combined prednisone (average dose, 29 mg per day) and cyclophosphamide (average dose, 107 mg per day) for six months. Thereafter, all patients received maintenance doses of prednisone. Most of the patients improved (84 per cent) after six months of initial treatment with either program. Early progression of disease, ending mainly in end-stage renal disease, was equally frequent in the two treatment groups in patients with already advanced disease. In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs. However, the proportion of patients alive after four years with stable or improved renal function was similar in the two treatment groups.


A new Thy-1 alloantigen as a temporal marker of T lymphocyte differentiation. A new Thy-1 alloantigenic specificity is defined in the mouse. Antigen expression is restricted to 'mature' and memory T cells, with either helper or killer activity.


The use of Adriamycin and mehtotrexate in carcinoma of the cervix. The development of a safe effective regimen. The results of treating 59 patients with advanced carcinoma of the cervix with Adriamycin and methotrexate are given. Five combinations of the two cytotoxic drugs have been evaluated, differing only with regard to the methotrexate. One particular regimen has been shown to be effective with a relatively high remission rate coupled with a low rate of side effects.


Genetic resistance to helminths. The influence of breed and haemoglobin type on the response of sheep to re-infection with Haemonchus contortus. The influence of genetic factors on acquired resistance to Haemonchus contortus infections in sheep was investigated. Animals whose primary infections were terminated with an anthelmintic failed to develop any immunity against subsequent challenge as judged by worm numbers. Nevertheless, all were better able to retard the development and reduce the fecundity and haematophagic activities of their parasite populations than animals undergoing primary infections. High levels of resistance, as judged by all these parameters, were observed in most animals when the challenge larvae were superimposed on existing worm populations. The patterns of worm establishment and disease indicated that genetic factors operated in determining resistance, since fewer worms became established and less severe clinical and pathophysiological changes were observed in Scottish Blackface than in Finn Dorset sheep with the same haemoglobin type. Similar advantages were displayed by animals with haemoglobin AA and to a lesser extent those with haemoglobin AB over haemoglobin BB types. The importance of breed was further indicated by the occurrence of 'self-cure' in the majority of the Scottish Blackfaces but in only one Finn Dorset. There was no evidence that this reaction was associated with haemoglobin type.


[Comparative study of the peripheral lymphocyte count in controls and in patients with chronic lymphocytic leukemias 4 hours after injection of hydrocortisone (author's transl)]. The peripheral lymphocyte count was investigated prior to and 4 h after a single intravenous injection of 400 mg of hydrocortisone (HSHC) in 23 controls and 43 patients with chronic lymphocytic leukemia. A reduction in the peripheral lymphocyte count was observed in all normal controls, the mean decrease being 51.9%, with differences according to age.


DNA replication in Physarum polycephalum: UV photolysis of maturing 5-bromo-deoxyuridine substituted DNA. Combinations of 5-bromodeoxyuridine (BrdUrd) and 3H-deoxyadenosine (3H-DAdo) short pulses were given in the synchronous DNA-replication period of Physarum polycephalum. After a chase period, UV-photolysis products were analyzed on alkaline sucrose gradients. This strategy has allowed the following conclusions. a) at the time of master-initiation of DNA replication, points separated by 1.1-2.2x10(7) daltons of single strand DNA may initiate DNA synthesis. b) among these, only selected groups of replicons actually proceed in DNA replication at this time, while others appear to hold (later temporal sets of replicons). The origins of the ones that proceed in replication are separated from each other by a distance corresponding to 1.1-2.x10(7) daltons. c) regions in actual replication are separated from each other by increasing distances (up to 1.5x10(8) daltons single strand DNA) at later times in S.


[Preoperative detection of a bleeding Meckel's diverticulum by 99mTc-pertechnetate scinitigraphy (author's transl)]. A Meckel's diverticulum containing gastric mucosa was causing recurrent intestinal bleeding in a 5-year old boy. 99mTc-pertechnetate scintigraphy was used to demonstrate the heterotopic gastric mucosa preoperatively. Compared to intestinal radiography and angiography, 99mTc-pertechnetate scintigraphy is a mild and uncomplicated investigation without any risk and with a minimum of radiation exposure. Evaluating its results critically this procedure can be of great help in the preoperative diagnosis of intestinal bleedings of unknown origin.


Juvenile polyp in a 10-month-old infant. A 10-month-old boy had episodes of apparent colic with bloody diarrhea. On investigation after prolapse of a rectal mass, a pedunculated polyp was found and removed by transanal ligation. The abdominal pain had been caused by the polyp intussuscepting the sigmoid colon into the rectum. Although rectal bleeding in children under age 1 is rarely caused by rectal polyps, physicians should consider this diagnosis in children of any age when recurrent colic and blood-streaked diarrhea occur.


Painful joints. Clues to early diagnosis. Many cases of joint pain may be diagnosed from clinical findings alone. A careful history and physical examination are essential. Of all diagnostic laboratory tests for joint disease, none is completely specific. Results of latex fixation tests, antinuclear antibody (ANA) tests, and uric acid tests are all strongly suggestive when positive but do not rule out disease when negative. The most valuable laboratory procedure is examination of the synovial fluid. X-ray examination seldom is helpful in differentiation of early joint disease but may be very helpful in later stages.


[Serum factors inhibiting cellular immunity in systemic lupus erythematosus]. Forty three patients with systemic lupus erythematosus (SLE) were divided into three groups, inactive, active without treatment and active on treatment with steroids. T lymphocytes from peripheral blood were determined and the results compared with those of twenty five normal individuals. In further experiments, the mitogenic capacity of SLE lymphocytes to Con A and the serum's activity of these patients upon normal lymphocytes were analized. Decreased T lymphocytes were found in all groups of patients with SLE. There were no difference between the mitogenic response of SLE patients and controls when the lymphocytes were incubated with normal human AB serum. When normal lymphocytes were incubated with serum from SLE patients with active disease, and inhibition of mitogenic response to Con A was observed. These results suggests that the decrease cellular immunity observed in SLE is due to serum factors rather than to intrinsic T cell abnormality.


Modulation of macrophage tumoricidal capability by polyene antibiotics: support for membrane lipid as a regulatory determinant of macrophage function. We have examined the effects of the sterol-binding polyene antibiotics on macrophage tumoricidal capability. Incubation for 2 hr of activated macrophages from bacillus Calmette-Guérin-infected mice with amphotericin B at 0.5--2 microgram/ml or amphotericin B methyl ester at 0.5--10 microgram/ml enhanced the capability of activated macrophages to kill 3T12 cells. These polyenes did not make normal or stimulated macrophages tumoricidal. Experiments with the ionophores gramicidin, alamethecin, nigericin, and valinomycin indicate that the ionophoretic properties of amphotericin B may not account for its enhancing effect on macrophage tumoricidal potential. Two polyenes with a smaller ring structure, filipin and pimaricin, were also ineffective suggesting that stereospecific modifications in membrane lipid organization underlie the enhancing effect of amphotericin B. The results suggest that the clinical efficacy of amphotericin B in promoting resistance to fungal disease and possibly to neoplasia may operate in part through potentiation of macrophage effector functions.


Actin may be present on the lymphocyte surface. Lymphocytes were assessed for the presence of surface actin and myosin by lactoperoxidase-catalyzed iodination and indirect immunofluorescence using antisera against purified pig skeletal muscle actin and pig smooth muscle myosin. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of 125I-labeled pig, mouse, and human B lymphocytes revealed an intense radioactive band of 43,000 molecular weight, whereas pig and mouse T lymphocytes gave a much less intense band. This band comigrated with actin, was nonglycosylated as judged by lack of binding to lentil lectin-Sepharose, was bound specifically by myosin fibers, and could be distinguished from a polypeptide of similar mobility derived from the major histocompatibility antigens. These results suggest that actin is present on the surface of B lymphocytes and, to a lesser extent, on T lymphocytes. Pig, mouse, and human Ig-bearing cells were stained by antiactin and antimyosin antisera, as judged by indirect immunofluorescence, whereas non-Ig-bearing cells were not stained. Antibody binding, however, was depleted by adsorbing the antisera with Ig-Sepharose. It was concluded that the immunofluorescence results are misleading and reflect the presence of antibodies that crossreact with Ig.


Venom coagglutinin: an activator of platelet aggregation dependent on von Willebrand factor. A platelet-aggregating activity was found in many snake venoms, predominantly those of the genus Bothrops, that is apparent only in the presence of the platelet-aggregating von Willebrand factor of plasma. It is designated "venom coagglutinin." The coagglutinin can be largely separated from the thrombin-like enzyme of the venoms by ion-exchange chromatography. The venom factor acts on formaldehyde-fixed platelets and is effective with decalcified, heparinized, and afibrinogenemic plasmas but not with severe von Willebrand disease plasmas or with normal plasmas in which the von Willebrand factor has been neutralized by specific antibodies. Use of this coagglutinin permits the assay of von Willebrand factor without the many disadvantages of the ristocetin test. The coagglutinin is active with human, dog, pig, and bovine plasmas and with platelets of any one of these species. This broad-spectrum activity without regard to species contrasts with the ristocetin-resistance of many combinations of plasma and platelets from various species. The assay provides a procedure for studying human, porcine, and canine von Willebrand disease. The lack of species specificity of the coagglutinin suggests that it may be a universal activator of the von Willebrand factor-platelet reaction.


Serotonergic reduction of dorsal central gray area stimulation-produced aversion. Stimulating electrodes were implanted into the dorsal central gray area (DCG) of rats. The animals were trained to bar press to decrement the aversive DCG stimulation current. Rats treated with 5-hydroxytryptophan (5-HTP), 75 mg/kg or 150 mg/kg, showed a dose-dependent reduction in decremental bar pressing. In a second study, animals received either chlorimipramine, 15 mg/kg, protriptyline, 15 mg/kg, or 5-HTP, 150 mg/kg. Chlorimipramine, a strong blocker of serotonin reuptake, and 5-HTP produced significant reductions in decremental bar pressing. Protriptyline, a weak serotonin reuptake blocker, produced no significant effect. These results suggest that serotonin reduces aversive neural mechanisms associated with the dorsal central gray area.


Changes in ingestive behavior following interruption of a noradrenergic projection to the paraventricular nucleus: histochemical and neurochemical analyses. Histochemical investigation of the paraventricular nucleus (PVN) identified the tractus filiformis lateralis (TF) as a major noradrenergic preterminal pathway to the PVN. Bilateral knife cuts transecting the TF resulted in a discrete deafferentation of 56% of the noradrenergic input to the PVN region. TF transection also resulted in hypophagia and hypodipsia during the first four days after surgery. A marked hyperdipsia developed between postoperative Days 11 and 13 and persisted until sacrifice on Day 17. The results suggest that the TF contains a noradrenergic system which innervates the PVN and is involved in mediation of ingestive behaviors.


Antinuclear antibodies, affective disorders and lithium therapy. The prevalence of positive antinuclear antibody (ANA) was investigated in a group of patients suffering from recurrent affective disorders who had been treated for more than one year with lithium carbonate. There was no  increase of ANA in these patients (8%) as compared with a group of patients suffering from affective disorders (7.5%), but untreated with lithium salts, or with the prevalence of ANA in the general population (9%) of the same age group.


Doxepin as a blocker of central serotonin receptors. The antidepressant drug-Doxepin (DX) was examined in order to investigate its central antiserotonin activity. The drug antagonized the behavioral syndrome elecited by L-5-hydroxytryptophan in rats and mice, but did not affect the pinna reflex. In the flexor reflex preparation, DX acted like other sero-tonin receptor blockers: By itself, it had no influence on the flexor reflex but it prevented the potentiation induced by serotonergic agents (fenfluramine, LDS, mescaline). The hyperthermia provoked by serotonergic agent (fenfluramine, LSD)in rabbits was antagonized by DX. DX abolished the syndrome induced by oxotremorine. The results obtained indicate that DX blocks central 5-HT receptors, like the two other antidepressants, mianserin and danitracen.


[Inflammatory pulmonary lesions: resolutions and residuals (author's transl)]. There are different patterns of development and resolution of inflammatory alveolar and interstitial pulmonary lesions. Delayed resolution of peripheral pneumonia results in lung shrinkage mainly towards the mediastinum and the apices with distortion and atypical distribution of pulmonary vasculature and compensatory hyperinflation. Resolution in perivascular and peribronchial parts is often delayed and results in scarring. Interstitial pneumonia may result directly in pulmonary fibrosis with loss of volume and honeycombing. With varying microorganisms and varying immunity chronic and atypical courses are observed more frequently.


Percutaneous transhepatic obliteration of gastroesophageal varices: some technical aspects. Two cases of bleeding from gastroesophageal varices treated by variceal obliteration illustrate multiple routes of variceal supply, and alert embolizing angiographers to the presence of spontaneous portosystemic shunts which should be kept open. In one case, variceal obliteration required embolization of the left gastric vein and a transhepatic collateral originating from the left hepatic portal branch and contributing substantially to variceal filling. A second patient with a relatively large spontaneous splenorenal shunt had recurrent variceal bleeding two months after a successful embolization of the coronary vein and a short gastric vein. A repeat study revealed the recurrent varices were supplied by enlarged right gastric and gastroepiploic veins. Superior mesenteric venography was necessary for their visualization.


Detection of hemorrhage in a patient with cecal varices using 99mTc-sulfur colloid. Colonic or ileal varices secondary to portal hypertension or superior mesenteric vein obstruction may present with significant hemorrhage which is difficult to diagnose by angiography. In a patient with lower gastrointestinal hemorrhage and colonic varices, a 99mTc-sulfur colloid scan demonstrated the varices and extravasation into the cecum. Extravasation was not demonstrable by angiography.


Suppression of cone signal in the dark-adapted frog retina as indicated by the electroretinogram. Electroretinogram (ERG) cone acitvity is depressed in the dark-adapted frog retina. The strength of this effect is examined over a large range of flash energy, for 618 nm flashes extending up to about 4 log10 units above the "threshold" (10-25 micron V b-wave) of the cone ERG "released" in the early stage of rapid dark-adaptation (RDA). Cone signal depression is remarkably strong over this flash energy range. The cone ERG is practically absent for flashes up to about I log unit above cone RDA threshold. For stronger flashes, the suppression becomes time-dependent, that is, cone signal is very small for the first few hundred msec. after the flash, cone intrusion then becoming detectable. The results suggest that the cone suppression phenomena arises distally in the retina, probably near the receptor layer, and that cone signal intrusion a few hundred msec. after a strong flash may be due to light-adaptation of rods by the flash itself.


[Association of Sjögren's syndrome and mixed connective tissue disease (Sharp's syndrome) in an adolescent (author's transl)]. The authors present the case of an adolescent who, despite his youth and relatively unaffected lacrimo-salivary secretion, was classified within the context of Sjögren's syndrom on the basis of paraclinical investigations, in particular the detection of salivary and lacrimal immunoglobulins. During a long course, the progresssive appearance of new lupoid type signs led to further complex immunological examinations, including examination for anti-E.C.T. antibodies. This case would appear to be an incomplete Sharp's syndrome and should be classified amongst the mixed connective tissue diseases.