[Cerebrovascular disorders in pregnancy and the puerperium].
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Biomedical subjects
Publications and source records attributed to L C Yang.
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Erythroderma and exfoliative dermatitis developed in a 17-year-old boy following therapy with phenytoin sodium. Immunologic studies performed early in the course of the dermatitis disclosed panhypogammaglobulinemia and a marked increase in T lymphocytes that responded poorly in vitro to T-cell mitogens. After therapy with prednisone, the dermatitis improved somewhat, and the patient's lymphocytes proliferated in vitro when exposed to phenytoin. We speculate that our patient's acute hypersensitivity reaction may have been mediated by an excessive number of phenytoin-sensitized suppressor-cytotoxic T lymphocytes and may represent a disorder of immunoregulatory T cells.
A severe illness developed gradually in a healthy boy following administration of live measles vaccine at age 14 years. Killed measles vaccine had been given at age 2. Panniculitis began near the site of live vaccine injection, extended contiguously to involve the entire upper arm, and then began to appear in distant subcutaneous sites. He was febrile, leukopenic, anemic, and lost weight rapidly. Evidence of a cause-and-effect relationship between the lesions and the measles vaccine included biopsy findings of particles closely resembling measles nucleocapsids and complete virions by electron microscopy, positive fluorescence after staining with two anti-measles nucleocapsid sera, and immunologic aberrations. The lesions regressed after various treatments and completely remitted on two occasions, but recurred. He became severely malnourished and finally died 29 months after the measles vaccination. At autopsy, pannicultitis was found in the subcutis and mesentery, without evidence of involvement of the brain or other vital organs.
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Human fibroblast and Syrian hamster embryo cells were induced to synthesize interferon (IF) with rIn . rCn and rIn . rCn + DEAE-dextran, respectively. Following induction, these cells synthesized IF for only a short time before entering into a repressed state and shutting off the synthesis of IF. Homologous and heterologous whole cell translational systems were developed to investigate the molecular basis for the shut-off of IF synthesis. These systems allowedd for the introduction of exogenous hamster and human IF-mRNAs into intact normal and repressed hamster and human cells via an improved CaCl2 precipitation technique. Human IF-mRNA was translated in normal human and hamster cells and in repressed hamster cells but not in repressed human cells. In contrast, the hamster IF-mRNA was translated in normal human, normal hamster, and repressed human cells but not in repressed hamster cells. These results indicate that a species-specific mechanism inhibiting translation of IF-mRNA is directly responsible for the shut-off of IF synthesis in human fibroblasts and Syrian hamster embryo cells.
Serial sera from 50 marrow transplant recipients were examined for their spectra and titers of antibodies to EBV-specific antigens. Immediately before or after transplant, blood products passively transferred antibodies to EB viral capsid antigen (VCA) and EBV nuclear antigen (EBNA). In most recipients, passively-transferred antibodies were replaced by endogenous antibodies regardless of whether donor or recipient had EBV antibodies before transplantation. Commencement or resumption of endogenous EBV antibody production was not associated with signs of infectious mononucleosis or heterophil antibody responses. Antibodies to VCA rose to abnormally high titers, followed successively by antibody to early antigens (EA), and disproportionately low levels of anti-EBNA. Unusually high anti-VCA and anti-EA levels persisted when tests of immune function returned to normal. Antibodies to other herpes group viruses showed no consistent changes. We conclude that (1) EBV does not cause significant clinical problems in marrow transplant recipients; (2) persistent EBV infection can become established or reestablished in the presence of antibodies to EBV; (3) marrow transplant recipients show the same exaggerated immune response to EBV as other immunodeficient patients; and (4) the pattern of EBV-specific antibodies may be a more sensitive measure of defective cell-mediated immunity than most conventional tests of immune function.
Quantitative determinations of cryoglobulins (IgG, IgA, IgM, and C3) were performed by a laser nephelometry microtechnique on 250 serum samples from a group of pediatric patients suspected of having immune complex-mediated disorders. Approximately 50% of these samples were cryoglobulin positive. Patients with cryoglobulins were examined as three separate groups: systemic lupus erythematosus, presumptive autoimmune disorders, and chronic bacterial or viral infections. Nearly all of these patients have mixed cryoglobulins. The relation of cryoglobulinemia with serum hypocomplementemia and renal involvement was examined in a group of systemic lupus erythematosus patients. High levels of cryoglobulins were found in patients with hypocomplementemia and anti-DNA antibodies without clinical evidence of nephritis. Highly significant correlations were oberved between C1q binding activity, presence of cryoglobulins, and serum hypocomplementemia in systemic lupus erythematosus patients. Only 60% of the cryoglobulin positive samples had immune complex demonstrable by C1q binding. Cryoglobulin analysis using the laser nephelometry microtechnique permits screening of pediatric patients for the presence of immune complex, permits detection of low levels of cryoglobulins, allows quantitative determination of the specific imunoglobulin classes in the precipitate, and requires only a very small amount of blood suitable for the pediatric population.
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A patient with Behçet's syndrome manifested by optic atrophy, purulent conjunctivitis and orogenital ulcerations presented with a high fever and pericardial effusion. A mixed cryoglobulinemia (immunoglobulin A (IgA)-immunoglobulin G (IgG)) was observed. Treatment with indomethacin resulted in rapid defervescence, resolution of the pericardial effusion and the orogenital ulcerations, and disappearance of the cryoglobulinemia. Discontinuation of indomethacin therapy was followed by a recurrence of the oral and genital ulcerations that responded promptly to the reinstitution of indomethacin treatment.
We have demonstrated that T lymphocytes from the spleens of adult guinea pigs sensitized to group A streptococcal antigens are cytotoxic for cultured fetal guinea pig heart cells. Lymphocyte cytotoxicity, measured by 51Cr release from target cells, was stimulated by sensitization in vivo with group A whole cells, cell walls, and purified protoplast membranes emulsified with complete Freund's adjuvant (CFA). Sensitization with group C streptococcal antigens in CFA or CFA alone produced lymphocytes with little or no specific cytotoxic activity. Target cells of cultured fetal skeletal muscle, liver, or skin were relatively refractory to effector cell cytotoxicity. The presence of antigenic determinants on the membranes of cultured myofibers, cross-reacting with group A streptococcal cellular antigens, was confirmed by immunofluorescence. These data are discussed in terms of a model for poststreptococcal rheumatic myocarditis in which cell-mediated autoimmune mechanisms may participate.
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Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (i.e., cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membrane-bound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [(3)H]leucine and of [(3)H]choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, [(3)H]leucine incorporation into cytoplasmic membranes was inhibited, while [(3)H]choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.