Cellular immunity in pyelonephritis: identification of suppressor cell activity of spleen cells in response to concanavalin A and inhibition of lymphocyte-mediated L cell cytotoxicity. A population of fast sedimenting spleen cells was identified as the cause of impaired in vitro response of spleen cells to concanavalin A (Con A) in acute pyelonephritis in rats. These fast-sedimenting cells responded to Con A by suppressing the DNA synthetic response of normal spleen cells to Con A. In addition, spleen cells from acute pyelonephritis rats were significantly less able to mediate in vitro cell destruction in xenogeneic aggressor lymphocyte: target L cell mixtures. On the basis of these findings, the hypothesis is proposed that a suppressor cell can protect the pyelonephritic kidney against immunologically mediated tissue damage.


Regualtion of the immune response to tumor antigens. I. Immunosuppressor cells in tumor-bearing hosts. A/Jax mice were rendered immune to the syngeneic and transplantable methylcholanthrene-induced Sarcoma 1509a by the surgical removal of the tumor 7 days after implantation; subsequent injection i.v. transfer of 10(7) to 10(8) washed thymus or spleen cells of tumor-bearing animals (TBA) to immune animals significantly inhibited the rejection of the tumor; this suppressive effect was entirely abolished by the treatment of these lymphocytes with anti-theta serum or anti-thymocyte serum (ATS) and complement before adoptive transfer. On the other hand, an equal number of thymus or spleen cells of normal animals or of animals bearing an unrelated tumor had no suppressive effect. Treatment of normal syngeneic animals with ATS after tumor cell inoculation or splenectomy of TBA resulted in the suppression of the tumor growth. The serum of TBA had no effect on tumor growth in immune syngeneic mice. Together these results suggest that TBA possess immunosuppressor T cells regulating negatively their immune response to the tumor.


Cytotoxic activity of lymphocytes. VI. Heterogeneity of cytotoxins in supernatants of mitogen-activated lymphocytes. Two different lymphotoxins synthesized by human blood lymphocytes stimulated with phytohemagglutin (PHA) are described. The two toxins are called alpha-LT and beta-LT relative to their elution order on gel chromatography. Their m.w. are 75,000 and 45,000 daltons, respectively. Both toxins appear as early as 7 hr after the addition of PHA, with the amount of beta-toxin exceeding that of alpha-LT initially. Both toxins are differentiated from a third toxin (adherent cell toxin, ACT) made by plastic-adherent cells without requiring mitogen-stimulation. Depletion of macrophages or B cells does not affect the synthesis of either lymphotoxin. Monospecific antisera were elicited to alpha-LT. Antisera elicited to beta-LT also neutralized alpha-LT but to a significantly lesser degree. Alpha-LT appears to be the lymphotoxin described by most other workers. Beta-LT is unstable at 37 degrees C which may explain why the low m.w. lymphotoxin has not been described previously.


Factors influencing the isolation of membrane immunoglobulins from T and B lymphocytes. 1. Detergent effects and iodination conditions. The optimal conditions for the extraction and isolation of immunoglobulins from the cell membrane (M-Ig) of T and B lymphocytes radioiodinated with lactoperoxidase were studied. A combination of 10M-urea, 1.5 M acetic acid and the non-ionic detergents Triton X-100 or Nonidet P-40 (NP-40) was found to overcome the tendency for membrane proteins to precipitate after extraction in urea-acetic acid alone. However, detection of T cell Ig was more dependent on detergent concentration than B cell M-Ig. Less T cell Ig was detected when the detergent concentration was increased from 0.1% to 1.0%, whereas the amount of B cell M-Ig was not affected by higher detergent concentrations.


Phytohemagglutinin-induced proliferation of guinea pig thymus-derived lymphocytes. I. Accessory cell dependence. The accessory cell requirement for mitogen-induced T lymphocyte proliferation has been investigated by using a population of guinea pig lymph node lymphocytes enriched in T cells and markedly depleted of macrophages and B lymphocytes. We have found that effective phytohemagglutinin-induced proliferation of T cells is dependent on the participation of accessory cells. Augmentation of PHA responsiveness was noted when cultural conditions were manipulated to increase cell density, suggesting that physical proximity between T cell and accessory cell is required for efficient triggering. Both syngeneic and allogeneic macrophages, as well as syngeneic fibroblasts, serve as accessory cells in this response whereas polymorphonuclear leukocytes or thymocytes do not. Thus, although PHA-induced T lymphocyte proliferation requires accessory cells, the specificity of these cells is strikingly less stringent than for antigen-mediated triggering of immune guinea pig T cells, a response which is dependent upon participation of syngeneic macrophages.


Phytohemagglutinin-induced proliferation of guinea pig thymus-derived lymphocytes. II. Accessory cell function. Accessory cell participation in PHA-induced thymus-derived lymphocyte DNA synthesis encompasses two distinct functions. The first consists of maintenance of the functional integrity of resting lymphocytes, and the second involves the direct induction and/or support of T cell proliferation in response to this mitogen. Whereas the reducing agent 2-mercaptoethanol can support an Mphi-depleted population of resting lymphocytes so that the latent biologic activity is maintained, it is not itself sufficient to allow the induction of lymphocyte proliferation in response to PHA. This latter function requires intact accessory cells.


Characterization of a subpopulation of human T lymphocytes reactive with an heteroantiserum to human brain. A rabbit antiserum to human fetal brain reacted after suitable absorptions with a subpopulation of human normal T cells. The distribution of reactive T cells varied according to the organ tested: 23% of peripheral blood lymphocytes, 5% of tonsil lymphocytes, and less than 1% of thymocytes were positive. Reactive cells did not transform after phytohemagglutinin or pokeweed stimulation but were at least weakly stimulated by allogeneic cells. T-derived neoplastic cells from one case of T acute lymphoblastic leukemia, two patients with Sezary syndrome, and from three out of five cases of T chronic lymphocytic leukemias (CLL) yielded negative results. In contrast, all the leukemic cells from two other patients with T-derived CLL were positive suggesting a proliferation of homogeneous cells arising from only a subpopulation of T lymphocytes.


Specific antigen-binding and antibody-secreting lymphocytes associated with the erythrocyte autoantibody responses of NZB and genetically unrelated mice. The receptor characteristics as well as incidence of antigen-binding lymphocytes (ABL) or B and T cell classes with membrane receptors specific for the exposed (X) and cryptic (HB) murine erythrocyte autoantigens were examined in NZB and nine control strains of mice. Whereas only NZB and NZB hybrid mice synthesize anti-X autoantibody pathogenetically implicated in the genetically determined autoimmune hemolytic anemia, the NZB as well as control strains synthesize the ubiquitous anti-HB anti-erythrocyte autoantibody. By utilizing immunocytoadherence assays, maximum numbers of specific ABL of both B and T lymphocyte classes were optimally demonstrated at erythrocyte:lymphocyte ratios of 20:1 and after lymphocyte fixation at 56 degrees C for 20 min. Surface membrane receptor specificity was established by inhibition with semi-purified soluble X or HB autoantigen. Inhibition of immunocyto-adherence with class specific antisera to mouse immuno-globulins demonstrated that the receptors on both B and T cells were of IgM class. Specific receptors regenerated in vitro after trypsinization which excluded the role of cytophilic antibody in the immunocytoadherence reactions. B lymphocyte ABL reactive with the X autoantigen were demonstrable in NZB, NZB hybrid, and control mice. Only in NZB and NZB hybrid mice, strains that uniformly synthesize anti-X autoantibody, were X ABL of T lymphocyte class demonstrated. The presence and incidence of T lymphocyte X ABL is compatible with the expression of a single dominant gene carried by the NAB strain. The incidence of B lymphocyte X ABL increased with age, suggesting proliferation of this cell population. HB ABL of both B and T lymphocyte classes were observed in all strains, concordant with the ubiquitous presence of humoral anti-HB autoantibodies. Differentiation of precursor B cells are evaluated by PFC assay of cells secreting specific autoantibodies. Anti-X PFC were observed only in NZB and NZB hybrid mice; and the observed frequency suggested that less than 3.5% of the specific ABL were differentiated for the secretion of anti-X autoantibody. Anti-HB PFC were observed in all strains and represented as high as 11.8% of specific ABL. Genetic determination of the anti-X anti-erythrocyte autoantibody response does not prescribe the presence of precursors of the antibody-forming cell, but rather appears to influence regulation of the differentiation of these cells. These data suggest that circumvention of immunologic tolerance to this specific erythrocyte autoantigen may occur at the level of the T lymphocyte; or alternatively, that T lymphocytes as well as B lymphocytes, are induced to proliferate and differentiate in the NZB strain.


Sensitization of T lymphocytes in vitro by syngeneic macrophages fed with tumor antigens. We investigated the interaction between T lymphocytes and macrophages in the vitro sensitization of lymphocytes against tumor cells. Spleen cells were sensitized in vitro by syngeneic peritoneal macrophages that had been fed with cell-free antigen preparation of syngeneic tumor cells. The sensitized T lymphocytes acquired specific cytotoxic cells. The sensitized T lymphocytes acquired specific cytotoxic activity in vitro and the capacity to inhingeneic fibroblasts, or the antigen preparation by itself were not able to sensitize the lymphocytes against the tumor.


Hereditary C2 deficiency: diagnosis and HLA gene complex associations. Nine families with genetically controlled C2 deficiency have been described where the propositii and family members are heterozygous C2 deficient. The diagnosis of hereditary C2 heterozygous deficiency was suspected on the basis of analysis for CH50, C2 protein, and C2 function, and then confirmed by family studies. Analysis of HLA antigens in these families supported the close association of C2 defiency and HLA-A10 and/or B18, particularly the latter. Analysis by MLC studies revealed recombination in one family between the HLA and B and D loci and in another family probable recombination between the D and C2 complement loci. Therefore, the order of the loci on the sixth chromosome is likely to be C2 complement, HLA-D, HLA-B, HLA-A.


Eosinophils and immune mechanisms. III. Production of the lymphokine eosinophil stimulation promoter by mouse T lymphocytes. The lymphoid cell population responsible for production of eosinophil stimulation promoter (ESP), a lymphokine which increases migration of eosinophils, was investigated in murine Schistosoma mansoni infection. Con A challenge induced ESP production, whereas LPS did not. Prior treatment with anti-thetaC3H alloantiserum plus complement in vitro eliminated ESP production; in vivo treatment with rabbit anti-mouse thymocyte serum consistently reduced ESP production by splenic lymphoid cells, but affected lymph node cell ESP production only after exceptionally large doses. Thymocytes did not produce significant amounts of ESP; nor did lymphoid cells from congenitally athymic mice. Depletion of B lymphocytes and macrophages by nylon fiber adherence eliminated antigen-induced ESP production; this was partially restored by addition of non-immune, 72-hr peritoneal exudate cells. Con A-induced ESP production was not affected by nylon fiber treatment. These results demonstrate that ESP is  produced by an ATS-sensitive, peripheralized T lymphocyte population, and suggest a macrophage requirement for antigen-induced production of this lymphokine.


Replication of measles virus in continuous lymphoid cell lines. The replication of measles virus was studied in a T cell-like line, MOLT-4, and a B cell-like line, Raji. Both cell lines supported measles virus replication. The infected lymphoid cells were assayed for infectious virus and expression of measles antigens at timed intervals up to 84 hr after inoculation. At time 0, after a 2-hr adsorption period at 4 degrees C, both cell lines produced a maximum of 3% infectious centers and up to 22% antigen-positive cells. Eventually all cells in both populations became infected during the experimental period. When Raji and MOLT-4 cells were infected under similar conditions 100% infection of cells was achieved 12 hr earlier in Raji than in MOLT-4. Increasing multiplicity of infection (MOI) from 1 to 10 made no significant change in the number of infected cells during the early part of the cycle. Spread of virus was largely due to released virus and not cell to cell transmission. Since only a small proportion of the population absorbed the virus at any one time, and eventually all cells were infected, it was concluded that the receptors for measles virus were expressed at some phase of the cell cycle.


The active E rosette test: correlation with delayed cutaneous hypersensitivity. An active subpopulation of peripheral blood T lymphocytes, characterized by rapid (5-min) rosette formation with sheep erythrocytes (A-RFC), was measured in normal individuals after they were skin tested with microbial antigens. A significant rise in A-RFC occurred in all individuals who developed positive delayed cutaneous hypersensitivity (DCH) reactions, whereas skin test nonresponders showed no significant rise in A-RFC. No similar consistent changes occurred in populations of total T cells, characterized by longer (60-min) rosette formation with sheep erythrocytes, or in B cells, measured by immunofluorescence of surface immunoglobulin. The A-RFC response paralleled the DCH response in timing, but not in intensity. These results provide in vivo evidence for a biologically distinct T cell subpopulation, and focus attention on the A-RFC as immunologically active cells.


Regulatory substances produced by lymphocytes. III. Evidence that lymphotoxin and proliferation inhibitory factor are identical and different from the inhibitor of DNA synthesis. L cell mutant lines which were considerably more resistant to rat lymphotoxin (LT) than the original cell line were obtained by periodic additions of LT, partially purified from sensitized lymph node cell culture supernatants by DEAE-cellulose chromatography and Sephadex gel filtration. Addition of actinomycin D to cultures of these mutant cells abrogated resistance to LT, suqgesting that resistance was not due to a loss of LT receptors but probably to increased activity of a repair mechanisms. These mutant lines were also more resistant to the proliferation inhibitory effect of LT in low concentration and to that of diluted culture supernatants of lymph node cells stimulated with antigen (ovalbumin) than the original cell line, but they remained as sensitive to inhibitor of DNA synthesis (IDS) as the original line. The mutant lines also remained fully sensitive to both complement-dependent lysis by antibody and antibody-dependent cellular cytotoxicity, but showed increased resistance to the killing effect of rat lymph node cells sensitized with orginal L cells in vivo. These findings suggest that the lymphotoxic substance partially purified and characterized in this and in the previous paper may be an important mediator of T cell-mediated cytotoxicity.


Characterization of T and B antigen-binding cells for beta-galactosidase. II. T antigen-binding cells. The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.


Immune mechanisms in leukemia: protective capacity of the major lymphoid cell compartments. The capacity of immune spleen, lymph node, peritoneal, bone marrow, and thymic cells to protect C58/wm mice from syngeneic transplanted line Ib leukemia was quantified. Cells harvested 14 to 15 days after primary immunization were used for adoptive protection tests. Regression curves were computer analyzed and log10, PD50 values compared. For immune spleen, lymph node, peritoneal, bone marrow, and thymic cells the PD50 values were 4.53, 5.92, 4.88, 5.51, and 5.59, respectively. When immune spleen cells were treated with anti-Thy 1.2 serum the PD50 value was increased from 4.73 to 6.09, i.e., protection was reduced greater than or equal to 95%. Similar treatment of immune thymic cells reduced protection below measureable values. Anti-B cell sera (anti-IgM and anti-Ly 4.2) did not reduce the protective effect of immune spleen or marrow cells. These results indicate that a major protective cell population in each of these compartments was theta-positive. Experiments were carried out to characterize the cortisone (CS) and x-ray sensitivity of immune spleen, thymic, and marrow cells . When donor mice were treated with 12.5 mg of cortisone acetate/day for 2 days before lymphoid cells were harvested, the orotective effects of immune spleen cells, but not immune thymic or marrow cells, was reduced. When immune spleen cells were x-irrated in vitro, their protective effect was reduced by 350 R and abolished by 1000 R. When mice received whole boyd x-irradiation 24 hr before immune spleen cells were transferred their protective effect was reduced by 1000 R but only slightly lowered by 350 R. The possible significance of the multicompartmental nature of immunity to leukemia was discussed.


Partial purification of lymphokine activities by iso-electric focusing. A continuous cell-line has been shown to be adaptable to preparation of supernatants containing lymphokine activities. Separation and partial purification of migration inhibiting, colony stimulating and interferon activities from such preparations has been achieved by the use of density gradient iso-electric focusing.


Immunology of DNA. II. The effect of size and structure of the antigen on the Farr assay. The Farr assay for the detecton of antibodies to double stranded (ds) DNA is influenced by the DNA preparations used as antigen. To elucidate this the molecular weight of the antigen preparation, contamination with proteins and presence or absence of single stranded (ss) regions were studied with the following conclusions: 1) The degree of DNA binding by antibodies is linearly dependent on the molecular weight of the DNA, provided that this does not exceed 10 X 10(6). 2) Deproteinization of E. coli DNA by chromatography on methylated albumin-kieselguhr(MAK) columns results in lower binding by most sera. 3) ds DNA preparations sometimes contain ss regions which bind antibodies to ss DNA. The difference in behaviour of different ds DNA preparations may be ascribed entirely to these factors and not to differences in antigenic determinants. We have standardized the Farr assay and enhanced its specificity by the use of circular DNA isolated from bacteriophage PM2.


Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells. Friend leukemia virus (FV) suppressed the proliferative responses of spleen, lymph node, marrow, and thymus cell populations to various T- and B-cell mitogens. Cells taken from mice, e.g. BALB/c genetically susceptible to leukemogenesis in vivo were much more susceptible to suppression of mitogenesis in vitro than similar cells from genetically resistant mice, e.g., C57BL/6. Nylon wool-purified splenic T cells from BALB/c and C3H mice lost susceptibility to FV-induced suppression of mitogenesis but became suppressible by addition of 10% unfiltered spleen cell. Thus, FV mediates in vitro suppression of lymphocyte proliferation indirectly by "activating" a suppressor cell. The suppressor cell adhered to nylon wool but not to glass wool or rayon wool columns. Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function. Suppressor cells were not eliminated by treatment with rabbit antimouse immunoglobulin (7S) and complement (C). However, high concentrations of anti-Thy-1 plus C destroyed suppressor cells of the spleen; thymic suppressor cells were much more susceptible to anti-Thy-1 serum. Nude athymic mice were devoid of suppressor cells and their B-cell proliferation was relatively resistant to FV-induced suppression in vitro. The suppressor cells in the thymus (but not in the spleen) were eliminated by treatment of mice with cortisol. Thus, FV appears to mediate its suppressive effect on mitogen-responsive lymphocytes by affecting "T-suppressor cells." Spleen cells from C57BL/6 mice treated with 89Sr to destroy marrow-dependent (M) cells were much more suppressible by FV in virto than normal C57BL/6 spleen cells. However, nylon-filtered spleen cells of 89Sr-treated C57BL/6 mice were resistant to FV-induced suppression in vitro, indicating that the susceptibility of spleen cells from 89Sr-treated B6 mice is also mediated by suppressor cells. Normal B6 splenic T cells were rendered susceptible to FV-induced suppression of mitogenesis by addition of 10% spleen cells from 89Sr-treated B6 mice. Thus, M cells appear to regulate the numbers and/or functions of T-suppressor cells which in turn mediate the immunosuppressive effects of FV in vitro. Neither mitogen-responsive lymphocytes nor T-suppressor cells are genetically resistant or susceptible to FV. The genetic resistance to FV is apparently a function of M cells, both in vitro as well as in vivo.


Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems. Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.


The effect of anti-mu suppression of gammaM and gammaG on the production of gammaE. Newbonr mice were treated from the day of birth with either bovine gamma globulin or anti-mu chain sera. The latter was administered using a protocol known to produce suppression of gammaM, gammaG, and gammaA production. Subsequent immunization with ovalbumin (OA) in alum was attempted to see if suppression of gammaM, gammaG, and gammaA classes of antibody would also be accompanied by suppression of gammaE-producing capacity. gammaG and gammaM antibody to OA and mercaptoethanol-resistant (gammaG) antibody to OA were measured by passive hemagglutination; gammaG and gammaE anti-OA antibodies were measured by passive cutaneous anaphylaxis. Anti-mu suppression was achieved with significant reduction in gammaM and gammaG antibodies. gammaE antibodies were not affected, suggesting an ontogenetic development for gammaE-bearing lymphocytes independent of the previously described gammaM to gammaG to gammaA ontogenetic sequence.


Antigen recognition. IV. Discrimination by antigen-binding immunocompetent B cells between immunity and tolerance is determined by adherent cells. Mouse spleen cells capable of specifically binding intrinsically tritium-labeled polymerized flagellin (POL) (labeling by biosynthesis of flagellar protein) via IgM receptors were found to comprise a distinct population of about 20-50 cells per 10(6) lymphocytes. Evidence is presented that the majority of mouse spleen cells binding tritium-labeled POL undergoes blastogenesis after antigen capping, antigen shedding, and receptor reformation. Under conditions of tolerance induction in vitro, however, loss of antigen from the cell surface was inhibited. Such inhibition of antigen redistribution and shedding was reversed by a short pulse of colchicine and new antigen receptors were formed. In spite of this, colchicine had no effect on the tolerant state. However, tolerance could be broken, regardless of presence or absence of the alkaloid, with radioresistant theta-negative accessory (A) cells (adherent cells) from normal but not from tolerant spleen cell populations. "Tolerant" A cells, although they were incapable of cooperating in a response to POL, were capable of participating in a response to a second unrelated antigen. It is concluded that tolerance to POL in vitro is induced by mechanisms other than the physical blocking of bone marrow-derived (B) cell receptors by antigen. Most likely, the discrimination by the B cell between a tolerogenic and immunogenic signal is mediated by A cells.


Suppression of IgE antibody production in SJL mice. I. Nonspecific suppressor T cells. High titer and persistent antihapten IgE production in SJL mice can be obtained using appropriate immunization and radiation. Nonirradiated mice rapidly terminate this antihapten IgE production. Radiation was not necessary to prolong antihapten IgE production in other strains of mice. Termination can be obtained even in irradiated SJL mice by transferring normal SJL spleen cells. That the suppressor cells are T cells is shown by using thymocytes or cells treated with anti-Thy 1.2 and complement. No appreciable suppressive effect by normal spleen cells could be demonstrated on IgG1 production in SJL mice. The characteristic of low and transient IgE antibody response in SJL mice is inherited as a recessive trait controlled by a single Mendelian autosomal gene and is not linked to the H-2-gene complex. This characteristic does not depend on the infectivity of Nippostrongylus brasiliensis, the effect of anticarrier antibody, or the recognition of antigen.


The requirement for two complementing Ir-GLphi immune response genes in the T-lymphocyte proliferative response to poly-(Glu53Lys36Phe11). The antibody response to poly-(Glu53Lys36Phe11) (GLphi) has been shown to be under the control of two independent, major histocompatibility-linked immune response genes, designated alpha and beta. In the present work we demonstrate that the T-lymphocyte proliferative response is also under the control of these two immune response genes. Thus, mice of the H-2a, H-2b, H-2k, and H-2s haplotypes were all nonresponders to GLphi. In contrast F1 hybrids between these strains, such as (B10 X B10.A)F1 and (C3H X SJL)F1, as well as several recombinant mice derived from the nonresponder haplotypes, such as B10.1(5R), B10.HTT, and B10.S(9R), were all responders to GLphi. The complementation between nonresponder genomes appeared to be stronger in the cis position than in the trans position for some strain combinations. The failure of strains bearing only one of the two responder alleles to show a T-lymphocyte proliferative response to GLphi, argues strongly that neither gene can be expressed exclusively in B lymphocytes. This conclusion is discussed in relation to another two gene model which has recently been proposed.


Control of t-lymphocyte and B-lymphocyte activation by two complementing Ir-GLphi immune response genes. The possibility that the two complementing alpha- and beta-Ir-GLphi genes are independently responsible for controlling events in T lymphocytes and B lymphocytes, respectively, has been tested in double adoptive transfer experiments utilizing cells from appropriate inbred strains of mice. The results of these studies show that the functions of T lymphocytes and B lymphocytes and the cooperative interactions between T and B cells require the presence of both alpha- and beta-genes in each respective cell type. Moreover, evidence has been obtained in these studies that indicates a preference for the alpha- and beta-Ir-GLphi genes in the cis position to obtain the most effective T-B-cell interactions. The possible implications of these findings are discussed.


In vitro studies of the rabbit immune system. V. Suppressor T cells activated by concanavalin A block the proliferation, not the induction of antierythrocyte plaque-forming cells. The late B-cell proliferative phase of the in vitro antibody response by rabbit spleen cells is highly susceptible to suppression by activated T cells. The in vitro antisheep erythrocyte plaque-forming cell (PFC) response by spleen cells from normal or primed rabbits can be suppressed by adding concanavalin A (Con A), Con A-prestimulated peripheral blood or spleen lymphocytes, or supernates from Con A-prestimulated peripheral blood lymphocytes. The suppression is not mediated by a direct interaction of Con A with responding cells as shown by the effectiveness of prestimulated cells. Primed spleen cultures remain sensitive to Con A suppression as late as 72 h after initiation, and the addition of Con A after 24-72 h rapidly stops the increase in the number of PFC. T cells are required for Con A addition to be effective but the suppression can be induced at a time when T-helper cells are no longer necessary. Further, the suppressive effect of Con A addition is abrogated by specific antisera to rabbit T cells. We propose that Con A activates suppressor T cells which then exert their effects on proliferating PFC or their immediate precursor B cells. The early inductive or recruitment phase of the response is probably not blocked by suppressor cells. Also, there is an apparent relationship between the number of proliferating B cells and the number of suppressor cells required. Finally, the difficulties in inducing a stimulatory effect by Con A and the prolonged period that Con A addition is suppressive suggests that the rabbit has relatively more and/or longer-lived suppressor cells than the mouse and may be a particularly useful species for studying suppressive phenomena and their mechanisms.


B-lymphocyte alloantigens in Caucasians. Human B lymphocytes have been shown to have at least five polymorphic specificities defined by 32 antisera. The antisera were produced by absorption with pooled platelets to remove HLA activity and were selected out of over 400 tested sera. The sera that defined the five specificities had high correlation coefficients within a group (generally in the range of 0.6-0.9). As shown by the fit in the Hardy-Weinberg equilibrium, the five specificities appear to be determined by alleles at one genetic locus. No association between these specificities and HLA was noted.


Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells. Immune spleen cells from LCM virus-infected (CBA X C57BL/6)F1 radiation chimeras entirely repopulated with CBA-T6 lymphocytes were cytotoxic for allogeneic, LCM virus infected C57BL/6 mouse-derived target cells. Normal C57BL/6 targets were not lysed. CBA-T6 lymphocytes derived from (CBA X C57BL/6) radiation chimeras sensitized in vitro against TNP-conjugated C57BL/6 spleen cells lysed TNP-conjugated C57BL/6 targets. However normal C57BL/6 mouse-derived targets were not destroyed. The magnitude of virus-specific (or TNP-specific) cytotoxic responses against H-2 incompatible targets was lower compared to that against H-2 compatible targets. These data are considered to support and to extend the altered self concept, but are not consistent with the dual recognition concept.


Effects of membrane potential on the capacitance of skeletal muscle fibers. A method for measuring muscle fiber capacitance using small test pulses applied with the three-microelectrode voltage clamp is presented. Using this method, three membrane potential-dependent changes in capacitance were observed: (a) Capacitance of polarized fibers increased by 5--15% with depolarization from V less then -100 mV to voltages slightly below the contraction threshold. (b) Capacitance of fibers depolarized to -30 mV by 100 mM Rb solution decreased by roughly 8% with further depolarization to about +50 mV and increased with repolarization, exhibiting a maximum increase of about 10% at -80 to -90 mV. (c) Capacitance of fibers depolarized to -15 mV by 100 mM K solution increased by about 19% with further depolarization to +43 mV and decreased by about 23% with repolarization to -62 mV. Effects a and b are attributed to changes in specific membrane capacitance due to voltage-dependent redistribution of mobile charged groups within surface of T-tubule membranes. Effect c is caused by changes in the T-system space constant lambdaT due to the voltage dependence of K conductance (inward rectification). Analysis of c showed that in 100 mM K solution lambdaT congruent to 30 mum when inward rectification was fully activated by hyperpolarization and that the density of inward rectifier channels is about the same in surface and tubular membranes. Fiber internal resistance was found to be independent of voltage, a necessary condition for the interpretation of the capacitance measurements.


Computer mapping of brain-stem sensory centers in man. A computer program is described for use on-line with a two--stage stereotaxic technique in man. It has four capabilities. It transposes coordinates between a brain atlas and a stereotaxic frame, simultaneously adjusting for variations in individual brain dimensions. Corrections for electrode trajectories, and for any irregularities of placement of the stereotaxic frame in the head are also made. It plots an operative template that shows electrode trajectories and the sites from which physiological data are collected appropriately oriented upon a sagittal diagram of the brain. It graphically displays physiological data in the form of a Woolsey-type figurine chart that indicates threshold in milliamperes and, through the use of coded symbols, the quality of response and certain other data. It stores all this data in a tape library together with the locations of any lesions made. This makes it possible to replot any individual patient's operative data at any time. It also permits scanning of the stored protocols from all patients for any particular type of data either by itself or in combination with other data. This retrieved information is plotted on appropriate sagittal brain diagrams corrected for individual variations in brain size. Illustrations of the capabilities of the program are presented particularly with reference to the primary afferent pathways of the upper brain stem.


Otitis media caused by non-typable, ampicillin-resistant strains of Haemophilus influenzae. Strains of Haemophilus influenzae, which did not belong to any of the known capsular serotypes and which were resistant in vitro to ampicillin, have been isolated from middle ear exudates of two children with otitis media. These children failed to improve with ampicillin therapy, and the resistant organisms persisted at the site of infection. Patients infected with such ampicillin-resistant organisms require therapy with antimicrobial agents which are not susceptible to degradation by penicillinase.


An analysis of the action of atropine and scopolamine on the end-plate current of frog sartorius muscle. The effects of atropine sulfate and scopolamine hydrobromide were investigated on the end-plate current (EPC) of frog sartorius muscle by standard voltage-clamp techniques. Both atropine and scopolamine reduced the peak EPC amplitude although scopolamine was only one-third as potent as atropine. The reduction of amplitude became more pronounced with increasing membrane hyperpolarization resulting in nonlinear current-voltage characteristics. Atropine shortened the EPC duration and decreased the voltage-sensitivity of the falling phase; the latter, however, continued to remain a single exponential function of time as in the control. Scopolamine reduced the time to peak, and in addition, converted the falling phase to a double exponential function, consisting of a rapid initial phase followed by a slow terminal phase. Both phases of fall were altered by changes in drug concentration but only the terminal phase responded appreciably to changes in membrane potential. Atropine and scopolamine were without effect on the EPC reversal potential, indicating that the drugs do not exhibit a preference for the ionic species carrying the synaptic current.


Aerobic recovery metabolism following a single isometric tetanus in frog sartorius muscle at 0 degrees C. 1. Basal and recovery O2 consumption, delatO2, in frog sartorius muscles at 0 degrees C were measured with a polarographic electrode. Reproducible observations were made with the same muscle over many hours. 2. The experimental records had an exponential form except for the early phases of recovery following a single isometric tetanus. Diffusion of O2 within the muscle was adequate to account for this deviation from an exponential time course of recovery. The time constant of the recovery O2 consumption increased with the duration of tetanic stimulation from 5 to 20 sec. 3. Lactate synthesis was measureable in unstimulated aerobic muscles and increased in proportion to total O2 consumption as long as the muscle did not lack O2. The contribution of glycolysis to the total chemical energy production during recovery was 6-9%; for hypoxic muscles it was greater. 4. The resynthesis of phosphorylcreatine and the decrease in inorganic phosphate and free creatine following a tetanus showed an exponential time course similar to recovery O2. Initial concentrations were re-attained within 60 min following a 20 sec tetanus. 5. We conclude that recovery O2 consumpation is a useful and accurate measure of the net chemical energy utilization for a single contraction.


Relationship between initial chemical reactions and oxidative recovery metabolism for single isometric contractions of frog sartorius at 0 degrees C. 1. Measurements of intitial chemical changes and recovery oxygen consumption (deltaO2) were made in unpoisoned aerobic frog sartorius muscles at 0 degrees C to provide independent measures of the chemical energy used for isometric tetani of various durations. 2. DeltaO2 was measured polarographically and increased in a curvilinear fashion with stimulus duration. For stimulations longer than 4 sec deltaO2 was a linear function of the tension-time integral. 3. Measurements of the changes in the content of phosphorylcreatine, 'free' creatine and inorganic phosphate were made in muscles rapidly frozen during a tetanus. The average of these quantities, delta approximately P, was used to measure the initial 'high energy' phosphate utilization. No break-down of 'high-energy' phosphate compounds was detected up to 200 sec after relaxation of tension. Changes in the content of ATP were not observed except for a small decrease (-0-25+/-0-1 mumole/g) in muscles tetanized for 1 sec. 4. Delta approximately P also increase curvilinearly with tetanus duration and, for tetanic durations greater than 4 sec, was a linear function of the tension-time integral. 5. Both deltaO2 and delta approximately P were quantitatively related by a constant scaling factor of about 4-3 (delta approximately P/deltaO2) throughout the range of tetanic durations studied. The constancy of this ratio.provides evidence against the hypothesis that a significant 'missing reaction' provides energy during any one portion of the tetanus. Several hypothesis may account for the numerical value of the ration delta approximately P/deltaO2.


[Vertebral angiography and tumours of the posterior fossa in children. 29 cases (author's transl)]. With reference to 29 cases of tumours of the posterior fossa, the authors attempt to place the value of vertebral angiography amongst other diagnostic techniques and in particular in relation to ventriculography using iodised hydrosoluble contrast media. Whilst recognising the diagnostic possibilities offered by vertebral angiography, they feel that, in many cases, opacification of the IVth ventricle is necessary and that angiography does not therefore form part of the routine pre-operative assessment of such tumours.


The effect of caffeine and tetracaine on the time course of potassium contractures of single muscle fibres. 1. The time course of potassium contractures can be significantly prolonged by low concentrations of caffeine. 2. This effect of caffeine is not due to impairment of the fibre relaxing system. 3. Under conditions were contractile repriming is delayed (low temperature) an extra amount of activator can be released by caffeine, in addition to that released by potassium. 4. The source of this extra amount of activator is intracellular since its release can be shown in a O calcium EGTA medium. 5. Local anaesthetics, tetracaine, and to a lesser extent procaine, affect the release of contractile activator, without impairing the contractile machinery itself. 6. The results of the present paper support the view that the time course of potassium contracture is controlled by a membrane mechanism which is activated upon depolarization and later inactivates with time. 7. The effect of caffeine and local anaesthetics can be explained by assuming that the former prolongs the inactivation time course while the latter shortens it.


The accuracy of recording patient problems in family practice. In 1974 several studies were conducted on the validity of medical data recorded and computerized at family medical centers affiliated with the University of Western Ontario. Fifty-nine encounters were observed. An average of 2.54 somatic, emotional, or social problems were dealt with per encounter. The residents recorded an average of 1.51 problems and the observers 2.45. This difference is highly statistically significant (p less than .001). There was no significant statistical differences among the observers. The many questions this study raises may have a bearing on medical education, medical audit, research, medical computer systems, and perhaps even on quality of care since problem-solving is based on problem identification. Further studies and evaluation are needed.


Natural cytotoxic reactivity of rat lymphocytes against syngeneic Gross virus-induced lymphoma. Lymphoid cells from many normal W/Fu rats reacted in a 51Cr release cytotoxicity assay against (C58NT)D, a syngeneic Gross leukemia virus-induced tumor. The reactivity was maximal in young rats at 5-8 weeks of age and rapidly declined thereafter. Within reactive rats, the cytotoxicity was widely distributed among the various lymphoid organs. Since immunization of W/Fu rats with (C58NT)D was shown to elicit specific cell-mediated cytotoxic reactivity, studies were done to compare the characteristics of the natural reactivity with those of the immune reactivity. The specificity of both types of reactivity was analyzed in detail by an inhibition assay. The natural and the immune reactivities appeared directed against antigens associated with rat endogenous type-C viruses. The major differences between the natural reactivity and immune reactivity were the nature of the effector cells. Whereas immune reactivity was T-cell dependent, normal reactivity was not affected by treatment with antisera against T cells plus complement. Natural effector cells were not adherent and did not have macrophage properties. The active cells also did not have receptors for Ig or complement. The absence of detectable cell-surface markers on the natural effector cells was seen in studies of natural cytotoxic reactivity of mice, and it is proposed that the natural cytotoxicity in both systems is mediated by a unique subpopulation of lymphoid cells, tentatively designated "N" cells.


Bacterial lipopolysaccharides as helper factors for Friend spleen focus-forming virus in mice. Lipopolysaccharide (LPS) from several gram-negative bacteria significantly increased the spleen focus-forming efficiency of N-topic Friend virus complex in mice by different  mechanisms. One effect was associated with an increase in the number of availability of potential target cells for spleen focus-forming virus (SFFV) in fully susceptible mouse strains. This enhancing effect was optimal when LPS was injected 5 days before SFFV but was nil when LPS and SFFV were given at the same time. In contrast, in mice genetically resistant to the native helper virus of SFFV, the helper effect of LPS was optical when it was injected with SFFV and oil when given 5 days before or after the virus. LPS did not affect helper virus expression in a standard cell culture (XC) assay, but it did increase helper virus replication in mice. Mice lacking T cells or complete endogenous murine leukemia virus genomes were just as sensitive to the helper effects of LPS on SFFV expression as were control animals. Most of the helper activity of LPS is associated with the lipid A component. The mechanism of the helper effect of lipid A is still unknown, but hypotheses must take into account that this effect did not occur in fully susceptible hosts, but only in hosts carrying resistance alleles at either the FV-1 or the FV-2 locus.


The nonselective cytotoxic cell (N cell). When effector lymphocytes were reacted with cultured human tumors, the total cytotoxic reaction could be divided into selective and nonselective components. The nonselective part of the reaction was due to a cell type called N cells. Fractionation of effector suspension indicated that N cells were neither T nor B cells. Like B cells, N cells did not form rosettes with sheep erythrocytes; they were retained by columns coated with lg or antiserum to lg and died preferentially when stored at an ambient temperature. However, N cells were differentiated from B cells by their inability to form complement-receptor rosettes and by their survival when incubated at 30 degrees C. The effect of the nonselective cytotoxic cell must be differentiated from selective activity in studies of specificity for cell-mediated cytotoxicity.


Posterior fossa tumors with pathological laughter. Of two patients with posterior fossa tumor and pathological laughter, one had extrinsic compression of the brain stem; the other had an intrinsic brain-stem lesion. Surgical removal of the epidermoid from the cerebellopontine angle cured the laughter. The euphoria of multiple sclerosis with paroxysmal laughter and a feeling of joy is to be differentiated from cases in which pathological laughter is a presenting complaint.


Barium impaction as a complication of gastrointestinal scleroderma. Two patients with scleroderma of the bowel experienced life-threatening barium impaction after upper intestinal x-ray studies. Although the frequency of this complication is unknown, the difficulty of managing it when it occurs makes prevention imperative. X-ray studies should be performed only after careful consideration of the risks and benefits. When x-ray studies are performed, the patient should be vigorously purged soon thereafter, and a follow-up roentgenogram should be obtained to confirm adequate removal of barium.


[Effect of temperature on excitation-contraction coupling of the bullfrog atrium (author's transl)]. Numerous studies have been reported on the effects of temperature on the electrical and mechanical properties of myocardium, and the augmentation of tension in low temperature has been generally considered to be simply due to a marked prolongation of the membrane action potential. In recent years, however, several kinds of the membrane currents such as INa1, INa2, ICa, IK1, IK2, IX1, IX2 and IC1 were discovered on the myocardium and the complicated processes of membrane excitation-contraction coupling (E-C coupling) were greatly analized in relation with the roles of these membrane currents and sarcoplasmic reticulum. Accordingly, the mechanisms of the inotropic effect of low temperature must also be reexamined on the basis of these lately developed knowledges. The present study, therefore, was undertaken to elucidate fundamental mechanisms of the action of temperature upon the membrane currents and E-C coupling processes, by examining the frog heart muscle with voltage clamp technique. The preparation used in the present experiments was the atrial muscle bundle isolated from the bullfrog (Rana cathesbiana). The thin muscle bundle was about 7 mm in length and 0.6-0.8 mm in diameter. The membrane potential, current and contractile tension were measured by means of the double glycerol-gap technique in voltage clamped conditions. The muscle chamber consisted of five compartments (1, 2, 3, 4 and 5). The large terminal compartments (1 and 5) were flowed with 200 mM KCl solution, the intermediate compartments (2 and 4) with isotonic glycerol solution, and the central compartment with Ringer or test solutions. The width of glycerol gap was 1 mm, and that of the central compartment ranged from 0.3 to 0.6 mm. The membrane potential was obtained as the potential difference between the central and terminal compartments (3 and 5), and the current, from the central compartment (3) which was kept at nearly earth potential by the aid of an operational amplifier (Philbrick, P65AU). The muscle tension was measured by the aid of a strain gauge (Nihon Kohden, SB-1T), the sensitive arm of which was connected to the end of muscle bundle in the terminal compartment (5). These potential, current and tension were recorded simultaneously utilizing by a triad-beam oscilloscope (Nihon Kohden, VC-7) and a inkwriting oscilloscope (Nihon Kohden, WI-180).


[Autolymphocytotoxins (CoCoCy) in different forms of hepatitis and cirrhosis (author's transl)]. Sera of altogether 282 patients with different forms of hepatitis and cirrhosis were screened for cold reacting complement dependant auto-lympho-cytotoxins (CoCoCy). These antibodies are 19S-IgM-immunoglobins and have no HLA-antigen-specificity. CoCoCy occurred in 48% of the patients with chronic aggressive hepatitis (CAH), in 14% of the patients with chronic persistent hepatitis (CPH) and in intermediate rates in the sera of patients with acute hepatitis. No correlations was found between CoCoCy and hepatitis B-antigen (HB-Ag). CoCoCy could be demonstrated also in 20% of the sera of a HB-Ag-positive and in 6% of a HB-Ag-negative control group. The serum concentration of CoCoCy is low. CoCoCy seems to be of T-cell-specificity and to reflect the overall-immunoreactivity without relation to the specificity of the antigenic stimulus. Thus demonstration of CoCoCy may be of pathogeneic and pathodynamic rather than of diagnostic interest.


[Allogenic and xenogenic aortic segmental transplants in inbred rats angiographically demonstrable vascular changes (author's transl)]. In order to make a systematic study of the significance of immunological reactions in vascular grafts, segments of abdominal aorta (4-5 mm long) were grafted into inbred rats. Four experimental combinations were used: I. syngeneic (CDF leads to CDF), II. weakly allogeneic (LEW leads to CDF), III. strongly allogeneic (BD 5 leads to CDF), IV. xenogeneic (guinea pig leads to CDF). After 100 days the gaft was macroscopically evaluated, angiographed and measured. Whereas no alterations of the vascular wall were found in group I, the degree of aneurysm formation increased significantly corresponding to the degree of histoincompatibility in the other groups: group II showed little aneurysm formation (medicum size 1.27 fold), group III more pronounced (1.71 fold) and group IV very pronounced (3.9 fold) with partial thrombosis in 3/5 of the cases. These findings are interpreted, as functional and morphological consequences of the immunogenicity of the aorta tissue. The conclusion was reached that the degree of histoincompatibility should be more carefully considered, also in vascular grafting.


Temporal bone histopathology in experimental hypovitaminosis A. Twenty-five years ago hearing loss was observed in some subjects during a comprehensive study of the effects of hypovitaminosis A on human volunteers. Experimental studies documenting histopathological changes in the temporal bone due to hypovitaminosis A are conflicting. Even the recent textbooks of otolaryngology and physiology make no mention of a role of vitamin A in the ear. To explore the role of vitamin A in the ear adult and weanling rats maintained on a diet totally lacking vitamin A were sacrificed at intervals. Their temporal bones were examined with the light microscope. After six weeks on a vitamin A free diet weanling rats showed hypertrophy of the periostial portions of the otic capsule. At 16 weeks a narrowing of the internal auditory canal due to bony exostoses was present. The neuroepithelia of the cochlea and the vestibular apparatus were histologically normal even in the longest surfiving animals. Adult rats maintained on a vitamin A free diet showed minimal thickening of the bone adjacent to the internal auditory meatus. The cochlea and the vestibular appartus in these animals remained normal throughout the 28-week experiment. Although we have demonstrated marked abnormalities of the otic capsule in hypovitaminosis A, our results do not support those of some earlier investigators who reported that atrophy of the cochlear and vestibular neuroepithelium occurred in the absence of dietary vitamin A.


[Hemobilia (author's transl)].

[Hemobilia (author's transl)]. Hemobilia is a syndrome caused by hemorrhage into the biliary ducts. It is characterized by colicky pains, jaundice, and intestinal bleeding; a correct diagnosis of this syndrome is made rather rarely. The most common cause is trauma; inflammatory or tumorous disease of the liver and bile duct system, bile stones and aneurysms of the hepatic artery are rarer causes. The diagnosis can be established and the arterio-biliary fistula localized by selective arteriography. A case is described, which shows, that, in addition, duodenoscopy with retrograde cholangiography is of diagnostic value. Other helpful diagnostic procedures are: splenoportography, liver scanning, and intraoperative cholangiography. Therapy must be surgical exclusively; palliative operations lead to high rates of relapses and letality. Best results are achieved by ligature of the hepatic artery in cases of central, or by partial resection of the liver in cases of peripheral localization of the fistula.


Chronic cutaneous lupus erythematosus (DLE)--a clinical and laboratory investigation of 80 patients. Clinical and laboratory data are presented from a study of a group of 80 patients with chronic cutaneous discoid lupus erythematosus. These data support the contention that if one selects patients with chronic scarring DLE who have no evidence by history or physical examination of extracutaneous involvement, then only a small percentage of patients will have detectable immunologic derangements. It is apparent that the clinical expression of lupus erythematosus depends, in part, upon the nature of the host's immune response.


[Angiographic diagnosis of non-neoplastic aqueductal stenosis in children (author's transl)]. Angiograpic diagnosis of non-neoplastic aqueductal stenosis in 4 children were described. The materials were selected from 160 vertebral angiograms of children below 15 years, performed at the Kyushu University Hospital from July 1967 to March 1974. There were 4 cases of angiographically demonstrated non-neoplastic aqueductal stenosis. These cases were confirmed by pneumoence-phalogram and/or pneumoventriculograms, which were performed before and after the Tolkildens procedure. Ages of the patients varied from 6 to 15 years with average of 11.8 years. All the angiographic findings of these 4 patients with non-neoplastic aqueductal stenosis were explained on the basis of 5 major morphological changes such as 1) marked symmetrical obstructive hydrocephalus, 2) dilatation of the third ventricle and aqueduct above the obstruction with resultant downward displacement and compression up the upper brain stem and posterior displacement of the precentral cerebellar fissure, 3) maintenance of normal shape and position of the lower half of the posterior fossa structure, 4) absence of midline shaft of the median and paramedian vessels, 5) morphologic changes of the subarachonoid cisterns. These angiographic findings coincided with the angiographic features as described by Huang et al. (1968), under the experience with 10 cases of non-neoplastic aqueductal stenosis of adults, averaging of 43 years. Special emphasis was placed on the diagnostic value of the small veins and arteries in the posterior fossa vascular system. We also emphasized that the vertebral angiography should be performed as the first investigative procedure using the contrast media in the posterior fossa lesions.


Measurements of the normal ventricular system with computer tomography of the brain. A preliminary study on 44 adults. The brains of 44 normal adults were examined by computer tomography (CT) with the fine matrix EMI scanner. Measurements of various parts of the ventricular system showed a sexual difference and an increase with age. Absolute measurements are preferred to indices or ratios. Comparison with the same parameters in pneumoncephalography and ventricular casts showed good correlation. The need for larger investigations of the normal population  is stressed.


[Ankylosing hemorrhagic arthropathy in a patient with Von Willebrand's disease (angiohemophilia A)]. A case of von Willebrand's disease with unusual clinical manifestations is described. The disease was characterized by the presence of insistently recurring haemarthroses, starting from infancy, involving a number of joints, ending in ankylosis. Bleeding time was lengthened and the patient presented antihaemophilic globulin deficiency and decreased platelet adhesiveness.


Relapse of Hemophilus influenzae type b meningitis after combined antibiotic therapy: report of a case. Antibiotic therapy of bacterial meningitis is being reevaluated due to reports of ampicillin-resistant strains of Hemophilus influenzae type b. The infant reported had a relapse of H. influenzae type b meningitis after an excellent clinical and bacteriologic response to an initial course of combined antibiotic therapy including chloramphenicol. This relapse is postulated to be due to localized cerebral vasculitis which was not treated for a sufficient period of time during the initial course of therapy. The patient responded well to a second course of penicillin and chloramphenicol. Since the use of pencillin and chloramphenicol will be increasing, the clinician should be aware that bacteriologic relapse of H. influenzae type b meningitis may occur with chloramphenicol therapy.


[Digestive tract hemorrhages of cirrhotic patients. Relation between hepatic insufficiency and the hemorrhagic lesion]. The cause of upper gastrointestinal bleeding was studied in 85 cirrhotic patients by emergency endoscopy. In every patient, one or several lesions were observed and the site of bleeding was ascertained in 59. The two main causes were oesophago-gastric varices (46 p.cent) and acute mucosal lesions(42 p.cent). The source of bleeding appeared to be related to the degree of liver function impairment. In patients with no or moderate liver function impariment, bleeding usually originated from varices or from drug-associated mucosal erosions. Patients with severe impairment of liver function most often bled from spontaneous acute oeso-gastro-duodenal ulcerations. These ulcerations resembled what has been described in "stress" hemorrhage. Because of the relationship between liver function and the cause of hemorrhage, mortality was lower in variceal bleeders (29 p.cent) than in patients with spontaneous ulcerations (83 p.cent). In patients with severely impaired liver function, portacaval shunt was rarely indicated since hemorrhage was generally due to acute mucosal ulcerations.


Immunotherapy: concepts and nursing implications. Concepts of immunlogy and the human immune system are essential for an understanding of the rationale of immunotherapy. Immunotherapy is presently being investigated as adjunct therapy for patients with cancer. It is therefore essential for the professional nurse to become cognizant of the various modalities and possible complications of immunotherapy in order that the nursing implications may be incorporated into clinical practice.


Effect of concanavalin A on expression of cell surface sialyltransferase activity of mouse thymocytes. Incubation of mouse thymocytes with mitogenic concentrations of concanavalin A causes a 2-fold increase in cell-surface-associated (but not total cell) sialyltransferase activity (ectosialyltransferase, CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) as judged by incorporation of [14C]sialic acid into endogenous cell acceptors and into added desialylated fetuin acceptor. The concanavalin-A-induced enhancement of enzymic activity is essentially complete within 1 hr after addition of mitogen and remains at elevated levels for 12 hr, declining rapidly thereafter. Intact cells labeled previously with [14C]sialic acid and then incubated briefly with hydrolytic enzymes, including neuraminidase and insoluble trypsin, released 43-66% of total cell-associated radioactivity without appreciably changing cell viability. Alterations in sialyltransferase activity due to concanavalin A treatment could not be explained by a mitogen-mediated (a) uptake of radioactive precursors, (b) cell death, (c) increased product catabolism, or (d) activation of sialyltransferase by mitogen binding to the enzyme. Furthermore, the process does not require active protein synthesis. The results are consistent with a rapid concanavalin-A-induced exposure of potential enzymic activity that was previously inaccessible to substrate.


Novel mechanism for translational control in regulation of ferritin synthesis by iron. Poly(A)-containing RNA was isolated from the polyribosomal and post-ribosomal fractions of the livers of normal and iron-treated rats. These RNA fractions were then translated in a wheat germ system to provide a measure of the amount of ferritin mRNA present in each fraction. Following iron administration, there was a 2-fold increase in the amount of ferritin mRNA in the polyribosomal fraction. This increase was not inhibited by prior treatment of the rats with actinomycin D or cordycepin, suggesting a cytoplasmic control mechanism. In normal rats, the post-ribosomal fraction contained an amount of ferritin mRNA equal to that in the polyribosomes. When iron was administered, this untranslated ferritin mRNA became reduced to negligible quantities, thus accounting for the doubling of the ferritin mRNA content of the polyribosomal fraction. A scheme is proposed in which translation of the ferritin mRNA in the post-ribosomal fraction is prevented by adhering ferritin subunits. Iron administration removes this inhibition of the translation of ferritin mRNA by promoting aggregation of these subunits into ferritin.


Immediate short-time effects of ethacrynic acid on frog gastric mucosa in chloride-free solutions. The presence of ethacrynic acid in the nutrient sulphate solution produces, generally in less than 3 min, a decrease in resistance accompanied by an increase in transmucosal PD. These results strongly suggest that the dominant effect of ethacrynic acid is not on the Na+ pathway of the nutrient membrane, but without further knowledge of the resistance of other ionic pathways, it cannot be inferred whether the effect predominates on the K+ pathway as in Cl- media.


Evidence for clustering of H-2K, H-2D, and the Fc receptor on the membranes of B cells. Alloantisera to H-2K, H-2D, and Ia antigens markedly inhibited the binding of EA but not FITC-IgG by the B cell Fc receptor. EA rosette formation approached normal levels when masked H-2 but not Ia specificities were allowed to cap on the membranes of B cells. beta2-mu coated SRBC were bound by the Fc receptor, and high concentrations of soluble beta2-mu were found to moderately inhibit EA rosette formation while lower concentrations enhanced binding. The data support the concept of Fc/Ia identity, and they suggest that H-2K, H-2D, and the Fc receptor may be closely grouped on the membranes of B cells. Further, these observations suggest that the beta2-microglobulin associated with H-2 could serve to link T cells with the Fc receptor of B cells during the inductive phase of antibody synthesis.


Use of low intensity direct current in management of ischemic skin ulcers. A clinical investigation of the use of low intensity direct current (LIDC) in treating ischemic skin ulcers was conducted at the University of Missouri. The purpose of the study was to evaluate the effect of LIDC on altering the healing rate of ischemic skin ulcers. One hundred ulcers were treated with LIDC. Six of the patients had bilateral symmetrical ulcers which provided the control group. The six control ulcers were managed exactly the same as their counterpart  except that LIDC was omitted. The mean healing ratio of the control ulcers was 14.7 percent per week compared to 30 percent per week of the treated counterpart. The mean healing rate of the 100 ischemic skin ulcers treated with LIDC was 28.4 percent per week. The data indicated that ischemic skin ulcers treated with the current responded with a healing rate approximately twice as fast as those ulcers that did not receive LIDC treatment. The authors concluded that the use of LIDC added an effective modality to the armamentarium of the physical therapist for the treatment of ischemic skin ulcers.


Effect of concomitantly administered drugs on the control of long term anticoagulant therapy. The stability of control of long term anticoagulant therapy was studied in a group of 277 patients with respect to drug interactions. Increased instability (changes of dose/month of therapy) was related to the number of concomitant drugs taken irrespective of, and in addition to, known specific interactions. Fluctuating cardiac status in patients requiring digoxin and diuretic therapy was a major factor in stabilizing anticoagulant control.


[Radiological evaluation of the course of pneumocystosis (author's transl)]. Serial chest X rays were performed on 124 infants in an orphanage with endemic Pneumocystic carinii infection. The infection was serologically and autoptically proven in 98 cases. The interstitial infiltrate in the lungs is not specific for Pneumocystis carinii infection, but is the result of the host reaction, which persists after the antigen has been destroyed. The interstitial infiltrate is therefore neither time-related nor diagnostic and cannot be used as a guideline for therapy. The treatment of the patient is completed, while the unspecific infiltrations persist.


[Rheumatological calcinoses].

[Rheumatological calcinoses]. The different types of calcinosis observed in rheumatic patients are described : those most frequently found are periatricular and tendinous ; others that are less frequent are subcutaneous and result from tissue attack (filariasis, repeated microtraumatisms) ; diffuse dystrophic calcinoses of the Thibierge and Weissenbach syndrome ; and lasty, in contrast to the preceding examples, diffuse, dystrophic, and metabolic articular chondrocalcinosis. The etiopathogenesis of these calcinoses remains obscure, but the phenomenon of calciphylaxis seems to be involved.


Massive extra-enteric gastrointestinal bleeding: angiographic diagnosis. Two patients with massive gastrointestinal bleeding are reported. One bled from an aneurysm of a branch of the left hepatic artery, the blood reaching the bowel through communication with the biliary tree. The second had an aneurysm of a branch of the splenic artery which communicated with the pancreatic duct. This type of bleeding is intermittent and, consequently, actual extravasation of contrast media is not always seen. Therefore, if one sees an aneurysm of a visceral artery, even if it does not directly supply the enteric tract, one should consider the possibility that it is the origin of the hemorrhage. Pathogenesis, diagnostic modalities, and therapeutic implications are discussed.


Environmental Radioactivity in Denmark in 1974. The present report deals with the measurement of fall-out radioactivity in Denmark in 1974. Strontium-90 was determined in samples from all over the country of precipitation, soil, ground water, sea water, grass, dried milk, fresh milk, grain, bread, potatoes, vegetables, fruit, total diet, drinking water, and human bone. Furthermore, 90Sr was determined in local samples of air, rain water, grass, sea plants, fish, and meat. Caesium-137 was determined in soil, sea water, milk, grain products, potatoes, vegetables, fruit, total diet, fish, and meat. It was also measured by wholebody-counting of a control group at Tisø. Estimates of the mean contents of radiostrontium and radiocaesium in the human diet in Denmark during 1974 are given. The gamma-background was measured regularly at locations around Risø, at ten of the State experimental farms, in one area in Zealand, one in Jutland, and along the shores of the Great Belt. Finally the report includes routine surveys of environmental samples from the Risø area.


Environmental Radioactivity in the Faroes in 1974. Measurements of fall-out radioactivity in the Faroes in 1974 are presented. Strontium-90 (and 137Cs in most cases) was determined in regularly collected samples of precipitation, grass, milk, fish, sea water, bread, and drinking water. In addition, analyses were made of spotsamples of lamb, potatoes, sea plants, vegetables, eggs, and human bone. Estimates are given of the mean contents of 90Sr and 137Cs in the human diet in the Faroes in 1974. Whole body measurements were made on six individuals from the Faroes.


Environmental radioactivity in Greenland in 1974. Measurements of fall-out radioactivity in Greenland in 1974 are reported. Strontium-90 (and Caesium-137 in most cases) was determined in samples of precipitation, sea water, vegetation, animals, and drinking water. Estimates are given of the mean contents of 90Sr and 137Cs in the human diet in Greenland in 1974. Three Greenlanders were measured by wholebody counting.


[Demonstration of Australia antigen in a rheumatologic population]. The authors looked for Australia antigen in a population of 578 rheumatic patients, 300 of whom were polyarthritic, by electrosyneresis and complement fixation methods. Australia antigen was found in 26 patients, and anti-Australia antibodies in 33 patients. Most of these patients were suffering from rheumatoid polyarthritis--22 presented hepatic disturbance, and 28 had undergone surgical operations, blood transfusions, and repeated hospitalization. The presence of Australia antigen did not in any case appear to play a role in the development of the lesions, apart from the occurrence of signs of hepatic lesions, but appeared to be an indicator of a form of hospitalization.


Electroimmunoassay of alpha1-antitrypsin with high precision. A modification of the electroimmunoassay of alpha1-antitrypsin is described. A fixed amount of the antigen is removed by addition of antibody to standards and samples before elctrophoresis. By changing the dilution procedure, the whole area of the gel plate is used for measurements within a small concentration interval. The measurement range can be changed by the addition of different amounts of antibody. The precision is increased about three fold, with a coefficient of variation within series of 0.6% to 1.2% and between series of 0.6% to 0.7%. This improvement in precision can be used to increase the significance of measured differences in alpha1-antitrypsin concentrations. The possibility of obtaining the same precision by an increased number of replicate analyses by the normal electroimmunoassay is discussed.


Acquired von Willebrand's syndrome and thrombopathy in a patient with chronic lymphocytic leukaemia. This paper reports the biological data found during an acquired bleeding disorder occurring in a 65-year-old woman affected with chronic lymphocytic leukaemia. They consists of haemostatic abnormalities which resemble an presently undescribed association of an acquired von Willebrand's syndrome with a thrombopathy. von Willebrand abnormalities were temporarily corrected by infusion of normal cryoprecipitate and reproduced in vitro by the incubation of normal platelets with the patient's IgA. The platelet defect was partially corrected after corticotherapy. The possible relationship of the associated defects is discussed.


Pulmonary circulation in alpha1-antitrypsin deficiency investigated by cinedensigraphy. The series consisted of eight cases of severe serum alpha1-antitrypsin deficiency (Piz homozygosity) and eight lung patients with a heterozygous level of the compound. The regional blood pulsation pattern in the lungs in the recumbent position was compared with the pattern in a group of normal controls using a cinedensigraphic device specially constructed for lung circulation studies. In the homozygous group, pulsation in the lower part of the lungs was significantly weakened to the benefit of the apical part. Individual variations occurred. The disturbance observed was not altered with oxygen breathing. This phenomenon is analogous to the redistribution of the blood flow demonstrated by scintigraphic methods. The heterozygous group did not differ significantly from the normal controls with regard to regional pulsation pattern.


Visual tracking and the primate flocculus. Purkinje cells in the primate flocculus discharge specifically in relation to visual tracking, effectively generating a velocity profile of the target during pursuit. It is suggested that these neurons supply oculomotor centers with the velocity command signals needed to support pursuit eye movements.


A cytoplasmic factor promoting oocyte maturation: its extraction and preliminary characterization. Cytoplasm of maturing amphibian oocytes possesses a factor that induces germinal vesicle breakdown. This factor was extracted from Rana pipiens eggs and assayed by microinjection in Xenopus laevis oocytes. The activity of this factor is Mg-dependent, Ca-sensitive, and associated with heat-labile protein. Centrifugation on a sucrose density gradient revealed that the factor exists in three different molecular sizes.


Carbohydrate deficiency of the factor VIII/von Willebrand factor Protein in von Willebrand's disease variants. Study of the normal human factor VIII/von Willebrand factor reveals a macromolecular glycoprotein composed of apparently identical subunits. This purified glycoprotein has procoagulant, antigen, and von Willebrand factor activities. In three patients with a variant of the von Willebrand's disease syndrome, their factor VIII/von Willebrand factor protein was present in normal amounts and had normal procoagulant and antigen activities; however, this protein was deficient in both carbohydrate and von Willebrand factor activity. The carbohydrate portion of the factor VIII/von Willebrand factor glycoprotein is of major importance in its interactions with platelets or the blood vessel wall, or both.


In vitro lymphocyte reactivity and T cell levels in patients with melanoma: correlations with clinical and pathological stage. In vitro lymphocyte reactivity (LR) to phytohemagglutinin (PHA) and peripheral blood thymus-dependent lymphocyte (T cell) levels were determined in 42 tumor-bearing patients with clinically operable melanoma and were compared to 41 age-matched normal controls. Patients with tumors clinically confined to the primary site (Stage I) as a group had normal immune reactivity and T cell levels, and those with regional metastases by clinical assessment (Stage II) had relatively impaired LR and T cell levels. In six of 24 patients with clinical Stage II tumors, widespread metastases (Stage III) subsequently were found. The severe immune defects in this group with occult disseminated melanoma accounted for the impaired LR and low T cell levels in the group with clinical Stage II tumors. Although overlapping levels of LR and T cells in the patients with pathological Stage II and III tumors prevent use of the data as a determinant of tumor extent in individual patients, the results show that these in vitro assays define a relation between cellular immunocompetence and tumor burden in patients with melanoma.


Suppressor activity of the human spleen and thymus. Both the spleen and thymus of man contain a population of cells which can suppress the mixed lymphocyte reaction. Splenic cells suppress the MLC 58 +/- 4.8 percent, and the thymus is able to suppress the MLC 90 +/- 2.6 percent. However, splenic cells require stimulation by vegetable mitogens before suppressor activity can be observed, and the thymus displays spontaneous suppressor activity without prior stimulation. The suppressor effect is linearly related to the log of the cell dose (r = 0.8, p less than 0.01), and at low doses the suppressor cells stimulate rather than inhibit the MLC. The cells are exquisitely sensitive to immunosuppressive drugs, and blood levels encountered in clinical organ transplantation abrogate their suppressive activity. The suppressive activity of the cells is nonspecific, and they are able to inhibit the MLC between individuals totally unrelated to the spleen or thymus donor. Since these cells likely play a role in the development of tolerance, further characterization of their properties is required.


Gastric infarction after therapeutic embolization. A case of extensive gastric necrosis after therapeutic transcatheter embolization of the left gastric artery with fragments of gelatin sponge for recurrent massive upper gastrointestinal hemorrhage is reported. Although future modifications in technique and in choice of embolic agents undoubtedly will be forthcoming, postembolic ischemic necrosis may prove to be a major limitation of this technique. Until more widespread experience is accumulated and the frequency of postembolic ischemic necrosis is known, it would seem prudent to reserve this procedure for those patients presenting prohibitive surgical risks.


[Reconstruction of the diaphragm with a pericardial flap after radical pleuropneumonectomy for malignant pleural mesothelioma (author's transl)]. Pleuropneunomectomy with resection of the diaphragm only offers acceptable therapeutic results in patients with multifocal malignant mesothelioma of the pleura. Diaphragmatic replacement on the right side can be satisfactorily achieved by fixation of the liver to the thoracic wall. On the left side many homologous and heterologous tissues and prosthetic adjungts have been suggested with varying success. This report describes technique and results in two patients where the broad pedicled left hemipericard was successfully used to replace the resected left diaphragm.


[Complications after thoraco-retroperitoneal nephrectomy (author's transl)]. We are of the opinion that for large kidney tumors in the upper region as the afflicted venous portions, the most advantageous incision is a thoraco-retro- peritoneal one. It allows the surgeon total freedom of movement and ensures reliable radical tumor-nephrectomy, as well as reconstruction possibilities in the large vessels. Of course, use of this incision is not without complications. They appear, however, not as often as opponents of this method would suppose. There are other statistics to support our convictions (4). From the check-ups of our thoraco-retroperitoneal nephrectomy patients, we are able to surmise the following: - The post operative mortality rate is not increased with this method. The cause for the mortalities are, as far as one can tell, old age and/or a generally poor condition piror to nephrectomy. - Post operative complications due to access though the thorax are very few. Not one patient had to be re-operated, punctured, or treated using suction drainage. No respiratory difficulties were observed. - Post operative complications from the wound were naturally relative to the extent of the incision. It was also here unnecessary to perform a second operation except in one case of a retroperitoneal hematoma from heparinization. This complication was not the result of this particular incision.


[Pulmonary glomangiosis (author's transl)]. The clinical aspects, differential diagnosis and aetiology of the rare pulmonary glomangiosis are described by means of four cases observed in our clinic. It is a hamartogenous stenosing disease of the lungvessels, appearing predominately in children who suffer from congenital heart disease. It leads to pulmonary hypertension. The pulmonary glomangiosis is of practical importance: By palliative operation as the banding of the pulmonary artery the demand hypertension in the pulmonary circulation is suppressed artificially, so that in heavy cases a sufficient oxygenation is not provided, and the children die in the postoperative period. From the surgical aspect such a disease of the pulmonary vessels has to be supposed when the blood pressure distally of the experimentally banded pulmonary artery drops insufficiently. The authors recommend to exclude the disease of the vessels by excicion of lungtissue and immediate histologic investigation before the final banding is performed.


[Meningial hemangiopericytoma with two-term late metastasis in lung and thoracic wall (author's transl)]. A case of two-term thoraco-pulmonary late metastasis after a meningial hemangiopericytoma which had been treated surgically 16 years before is described. Histological features, biological behavior, and problems of late metastasis and of surgical treatment of metastasis are discussed.


[Secondary isophageal reconstruction after resection of a cardia carcinoma (author's transl)]. Following abdomino-thoracical total gastrectomy and partial resection of the esophagus performed because of the presence of a stomac cancer located in the upper part of the organ an attempt was made to execute from a left sided thoracotomy an esophago-jejunostomy. During which it was found that the previously prepared loop of the jejunum was too short. The execution of a colon interposition in this particular operational state would have been too demanding on the patient; therefore the operation was concluded with a blind closure of the distal end of the esophagus and a jejunostomy (discussion of the resultant problems included in paper). The reconstruction of the digestive tract by retrosternal colon interposition a few weeks after the resection of the cancer proceeded without complication and with consequently excellent functional effect.


[Esophagopleural fistula associated with postprandial syncopes. A late complication after pneumonectomy (author's transl)]. A case of esophagopleural fistula in a 54-year-old man who underwent pneumonectomy for bronchogenic carcinoma is described. As uncommon and hitherto unknown complications postprandial syncopes and a letal arrosion of the right cardiac atrium occurred. The pathogenesis of the esophagopleural fistula, the clinical features, and the pathophysiological mechanism of the swallow syncope are discussed.


[Diagnostical and therapeutical aspects of post-traumatical endobronchial bleeding (author's transl)]. Post-traumatic endobronchial bleeding is a serious concomitant injury in thoracic traumas. Untreated cases are threatened early with pulmonary insufficiency caused by the displacement of a blood clot with in the respiratory tract. Pathophysiology, diagnosis and treatment of the post-traumatic endobronchial bleeding are discussed. Conservative and surgical measures are discussed on the basis of 15 observations. The prognosis of the endobronchial bleeding depends decisevly on the length of its existence and intensity. Conservative or operative procedure should be decided on the basis of repeated endoscopical controls. A liberal attitude towards the operative therapy is recomended.


[A different approach in the treatment of aneurysms of the ascending aorta (author's transl)]. A safe method in therapy of the ascending aortic aneurysm by partial resection and reconstruction combined with reinforcement by a nylon net is described. Seven patients were operated upon without hospital mortality. Early operation is recommended, when there is only slight aortic insufficiency. In such a situation it is possible to reinforce the ascending aorta without ECC, to stabilize the progress of widening the ascending aorta and the aortic root.


[Surgery for atrial septal defect in patients over 40 years of age (author's transl)]. Between 1961 and 1972, 354 patients with atrial septal defect ware treated surgically. Of these 80 patients were aged over 40 years at the time of operation. The hospital mortality was 5%. 2 of these patients had a increased preoperative pulmonary artery systolic pressure (50-75 mmHg), the other 2 had a mitral or tricuspid incompetence. At late follow-up 82% of patients were symptomfree, 18% had slight clinical signs of breathlesness on exertion. The heart size decreased in 37 of 40 patients, the electrocardiographis signs of right ventricular hypertrophy in 23 patients. There was no influence on preexistant dysrhythmias by the operation. It is concluded that patients with atrial septal defect in this age group benefit from surgical closure of the defect.


[Ethiology and treatment of pleural empyema after thoracic surgery (author's transl)]. Between 1961 and 1974 a total of 29 patients have been treated for empyema after lung resection. Pneumonectomy for bronchus carcinoma had been previously performed in 19 patients, partial resection of the lung in ten. In the majority of cases a technical insufficiency was at last partially responsible for appearance of empyema. Differentiation between empyema after pneumonectomy and empyema in patients with residual lung parenchyma has proved to be of advantage. As to predisposing factors, treatment and prognosis of empyema in cases with residual parenchyma is comparable to regular pulmonary empyema. Empyema after pneumectomy however is different in treatment and prognosis. Irrigation of the infected thoracic cavity either by repeated punction and/or by continous through-drainage is helpful and improves the otherwise poor prognosis.


[Ultrastructure of an atrial myxoma (author's transl)]. Electron microscopic examination of a surgically removed atrial myxoma showed, besides fibrocytes and fibroblasts, mainly isolated smooth muscle cells arranged in solid cellstrands. They are responsible for collagen-and elastin-synthesis. They are presumed to arise from subendocardial smooth muscle cells and considered to be neoplastic.


[Microparticles in heart operations with extracorporal circulation (author's transl)]. Disturbances of the microcirculation during extracorporal circulation are not yet clearly understood. Many authors think that microembolism is reposible. In two groups of patients with different perfusion techniques we were looking for microparticles with a new constant pressure filtration method using the Agglometer r apparatus. During the by-pass no particles were found. Yet, we found particles in the priming when blood was used, in the suction blood and in special blood samples after contact with the pericardium. In these cases it was always possible to eliminate the particles with special filters. The particles in the suction blood seemed to originate from the extracardial blood portion coming from the pericardium. This portion seemed to be responsible for postoperative complications such as hemolysis and petechia. These complications could not be seen when extracardiac suction blood was eliminated or filtrated.


[Traumatic hämolysis of verious heart-lung-machines on oxygenators (author's transl)]. 1250 protocols of heart-lung-machines, taken between 1962-1974, underwent a variance analysis. The results show that rollerpumps with high pumpvolumes (80 ccm) are not significantly lower hemolytic than rollerpumps with a pumpvolume of 40 ccm. The hemolysis stands in direct proportion to the blood flow. Membranoxygenators effect a less traumatisation than screen- and bubbleoxygenators. Furthermore the use of fresh ACD-blood shows a lower hemolysis than hemodilution and older ACD stored blood. Type and age of the vitium have no influence on the traumatic hemolysis. The use of the orthograde perfusion is significantly better than the retrograde perfusion; the use of blood-filters is no cause for traumatic hemolysis. The above mentioned results are in accordance to literature, but the facts cannot be objectivated that easily than in invitro experiments.


[Effectiveness of local and parenteral antibiotics in infection of aortic dacron grafts (author's transl)]. The effectiveness of local and parenteral antibiotic prophylaxis in infections of aortic dacron grafts was tested in animal experiments. In 20 foxhounds Dacron-interpositions, 4 cms in length, were inoculated with 50 million Staph aureus bacteria and then treated in 4 different ways: Nr. 1-5 no antibiotic treatment. Nr. 6-10 local antibiotic (Nebacetin, R) treatment. Nr 11-15 parenteral treatment with Gramaxin (R) i.m. Nr. 16-20 combined Nebacetin (R) and Gramaxin (R) treatment. The untreated dogs developed infection of laparotomy wounds, peritoneum udn prosthesis. Nebacetin gave improved results, whereas Gramaxin led to complete eradication of the infection. It is concluded, that antibiotic prophylaxis should be applied in vascular surgery, whenever alloplastic, homologous or autologous implants are used.


[Acupuncture analgesia for open heart surgery (author's transl)]. The first clinical results of 100 patients, operated since November 1973 using ECC and acupuncture anesthesia are reported. The method of combined chinese and european procedures of analgesia is described. Advantages and problems of the new method are discussed.


[Compromised lumen of ectopic left circumflex coronary artery by prosthetic valve (author's transl)]. Implantation of an aortic valve prosthesis in patient with aberrant left circumflex coronary artery arising from the initial portion of the right coronary artery resulted in compression of this vessel by the prosthetic valve and in pump failure after interruption of cardiopulmonary bypass. Incidence and significance of variations in coronary artery origin and course are mentioned.


Release and retention of labelled DNA in the thymus and spleen of irradiated mice. The process of release and retention of labelled DNA in thymus and spleen of normal and irradiated (60Co) mice has been studied after administration of 3H-thymidine. The results indicate that the dividing fraction of lymphoid cells is more resistant to radiation than the fraction of nondividing lymphocytes. The time courses of the specific activities of DNA in thymus and spleen were different especially after irradiation with lethal doses. It is suggested that the process of depletion in the lymphoid series is probably similar for both thymus and spleen but, the different cellular composition of these organs led to apparently unrelated results.


[Membrane model in the presentation of surface immunoglobulin on human lymphocytes with peroxidase cabeled antibodies]. For the demonstration of B-lymphocytes the direct immune peroxydase technique with anti-human IgM was used. In contrast to the biochemical and immunological controls in 11.1% of 30 normal persons positive membrane reactions could be proved without doubt. A certain distinction from other white blood cells and falsely positive contrast reactions is possible by means of counterstain with genuine nuclear red and after contrastation with osmium tetroxyde. The method described has a large number of advantages compared with other methods of the determination of B-cells, which appear usable for the clinician above all on account of the relevance to practice.


[Rheumatic diseases: a public health problem (author's transl)]. This study surveys the main quantitative data of the literature concerning the morbidity and the functional and socio-economic influence of rheumatic diseases. The cost of medical care and the functional and socio-economic repercussions entailed by these diseases represent a heavy burden on the community. In France, epidemiological surveys must be carried out, which will include medical attendance rates, sickness incapacity and statistics on disability. Once the amplitude of this problem is determined, it must be communicated to the general public, using sanitary education techniques, and an influence must be exerted on the authorities to undertake a general campaign against rheumatic diseases.


[Changes in the cytokinetics of Mott's cells following sensitization to BCG under conditions of preliminary treatment of rats with soluble antigens of Mycobacterium tuberculosis]. The effect of pretreatment with tuberculins on BCG sensitization of rats was expressed in the transformation of precursors into Mott's cells. The tuberculins, particularly the old tuberculin, inhibited the MC-reaction; this seems to be connected with the tolerogenic action of the mycobacterial polysaccharides. An attempt was made to interpret the results from the point of view of the three-component system of the lymphoid cell cooperation during the formation of humoral antibodies, taking into account the competitive antagonistic relations between the delayed hypersensitivity (DH) and the humoral immunity. It postulated that this competition is effectuated through the repression of the B cell function by the T1 lymphocyte killer effectors of the DH committed to the same antigen against which the "blasts" or the plasmoblasts (subsequently transformed into MC) were produced. The author believes the latter to be the cells in which specific antiboty synthesis was blocked in the statu nascendi due to ectopic (not in the Golgi zone, but in the cisterns of the rough reticulum) and an excessive complex assembly of polysaccharides with the peptide chains of immunoglobulins.


[Study of the immunodepressive effect of passive immunization on a model of adaptive immunity]. The effect of various doses of specific serum administered in passive immunization on the formation of primary and secondary adaptive immunity in mice of the CBA strain was studied. Primary and secondary response was more sensitive to passive immunization on a model of adaptive immunity than in vivo. Most sensitive to the immunodepressive action of specific antibodies IgM and IgG were plaque-forming cells, and most resistant -- rosette-forming cells and cells. This led to a supposition that antibodies administered in passive immunization depressed the development of the immunological response acting at the level of T- and B cells.


[Stimulation of immunoglobin synthesis and rheumatoid-factor production by rheumatoid synovial effusions and by supernatants of synovial tissue cultures]. Factors capable of stimulating the synthesis of immunoglobulin by circulating human lymphocytes, as measured by a radioactive immune coprecipitation method, have been demonstrated in rheumatoid synovial eeffusions but not in effusions from patients with other arthritides. The activity of the ffusions was localized in two fractions eluted from an agarose A 5m column: fraction II eluting with IgM and fraction E eluting with albumin. Fraction II enhanced immunoglobulin synthesis only in circulating rheumatoid lymphocytes, while fraction V enhanced immunoglobulin synthesis in both rheumatoid and normal lymphocytes. Similar active fractions were found in culture supernatants of rheumatoid synovial tissue. Enhanced immunoglobulin synthesis was also observed following addition of aggregated IgG to rheumatoid lymphocytes. Finally, increased synthesis of anti-IgG (rheumatoid factor) was observed following addition of fractions II and V to rheumatoid but not to normal lymphocytes. The possible relationship of the active material in fraction II to IgG-containing immune complexes and the active material in fraction V to a T cell produced lymphokine-like mediator of T cell function are discussed. The findings presented provide evidence that in addition to antigenic stimulation, the action of one or more enhancing factors liberated by antigen stimulated mononuclear cells, possibly T lymphocytes, plays a role in the immunoglobulin synthesis observed in rheumatoid synovial tissue.