The Journal of experimental medicine
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This study identifies defects in the early stages of lymphopoiesis that may contribute to the abnormalities in the development and/or function of peripheral T and B lymphocytes in mice homozygous for the motheaten (me/me) and viable motheaten (mev/mev) mutations. The results indicate that in me/me and mev/mev mice prothymocytes in bone marrow are present in essentially normal numbers, as determined by intrathymic injection, but apparently lack the ability to home effectively to the thymus, as determined by intravenous transfer; early B lineage cells in bone marrow, identified by the B220 antigen, are markedly depleted, including immature B cells (sIg+), pre-B cells (cIg+, sIg-), and pro-B cells (B220+, cIg-, sIg-); TdT+ bone marrow cells, especially a subset that expresses the B220 B lineage antigen, are markedly depleted by two weeks of age; normal numbers of TdT+ thymocytes are present during the first 3 wk of postnatal life, but rapidly decrease thereafter. The results further indicate that neither the defective thymus homing capacity of prothymocytes nor the deficiency of TdT+ bone marrow cells is due to autoantibodies. The possible relationship of the defective development of lymphoid precursor cells to the premature onset of thymic involution and to the abnormalities of peripheral T and B lymphocytes in me/me and mev/mev mice is discussed; as are the results of in vitro studies (presented in a companion paper), which suggest that a primary defect in the stromal microenvironment of the bone marrow is responsible for the abnormal development of the lymphoid precursor cells.
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The autologous mixed lymphocyte reaction (MLR) is severely impaired in patients with acute infectious mononucleosis. Reactivity returned during the course of convalescence. ⋯ B cells from patients with infectious mononucleosis do not stimulate autologous T-cell proliferation, and this observation appears to explain the cellular basis of the impaired autologous MLR in infection. Two explanations for the B-cell defect were considered: (a) the influence of serum factors on B-cell function and (b) the effect of Epstein-Barr virus infection.
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The quantitative release of histamine by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the effect of peptidase substrates and inhibitors on the anaphylactic reaction. The anaphylactic release of histamine is prevented by chymotrypsin substrates and inhibitors but not by trypsin, carboxypeptidase, or leucine aminopeptidase substrates or the soybean trypsin inhibitor. The chymotrypsin substrates and inhibitors appear to be acting on an antigen-antibody-activated step because these substances fail to inhibit if the tissue is washed free of them prior to antigen addition, and because there is complete desensitization of the tissue without histamine release when the antigen is added in the presence of these inhibitors. ⋯ This indicates that diisopropylfluophosphate must be acting exclusively on an enzyme which exists in lung tissue in a precursor form resistant to diisopropylfluophosphate until activated by the antigen-antibody interaction. Thiol alkylating or oxidizing agents also prevent the anaphylactic release of histamine, but in contrast to the situation with diisopropylfluophosphate and the other chymotrypsin inhibitors, the phase of the anaphylactic reaction inhibited by N-ethylmaleimide is available prior to the antigen-antibody interaction. The similarities and differences between immune hemolysis and anaphylaxis in chopped guinea pig lung are considered in detail.
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The results of the experimental analysis reported in this and the two preceding papers (10, 11) indicate that in murine pneumococcal infections penicillin per se destroys the invading organisms only in those parts of the lesions where the bacteria are multiplying rapidly and are thus maximally susceptible to the bactericidal action of the drug. In areas where the bacterial growth rate is slowed, either because the pneumococci have reached a maximum population density, or because the accumulated exudate affords a relatively poor medium for rapid growth, the destructive effect of the antibiotic is greatly diminished. In such portions of the lessions the cellular defenses of the host are observed to play a major role in eliminating the bacteria. ⋯ They pertain only to the action of penicillin in acute infections caused by penicillin-sensitive bacteria which act in the host as extracellular parasites (16). The most common human infections included in this category are those caused by pneumococci and Group A beta hemolytic streptococci.(7) Whether they apply also to infections due to penicillin-sensitive staphylococci may be questioned because of recent evidence that certain pathogenic strains will survive phagocytosis (27). In diseases such as tuberculosis, brucellosis, and typhoid fever, which are treated with antibiotics having properties different from those of penicillin (28) and which are caused by bacteria capable of intracellular parasitism (28), factors other than those considered in the present analysis must certainly be involved in the curative effect of antimicrobial therapy.
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1. Renal blood flow is decreased by hypotension due to bleeding, and glomerular filtration rate is disproportionately decreased. After a first 40 minute stage of hypotension at about 60 mm. ⋯ Dogs with denervated kidneys respond to blood transfusion and restoration of arterial pressure by a disproportionately slow and incomplete return towards normal of renal clearance and, presumably, of renal blood flow. On the basis of these facts it is suggested that high spinal anesthesia may interfere with recovery of renal circulation in cases of shock treated by transfusion. 4. Profound or prolonged and repeated hypotension due to bleeding decreases the ability of normal and denervated kidneys of intact and anesthetized dogs to respond to transfusion and the restoration of arterial pressure by proportionately increased clearance and plasma flow, apparently because of renal vasoconstriction due to the release of humorally circulating vasoconstrictor substances.