Biomedical subjects
Publications and source records attributed to D Simon.
By spleen cell fusion with NS1 myeloma, a mouse hybridoma was obtained which secretes an antibody directed against human renin. This monoclonal antibody recognizes human and monkey renin, but neither hog nor mouse. Preliminary experiments demonstrate the potential of this antibody for renin immunopurification and characterization.
Despite widespread evidence that autoimmune mechanisms may contribute to the beta cell necrosis associated with type I insulin-dependent diabetes mellitus (IDDM), it has not heretofore been demonstrated that islet cell antibodies (ICAs), directed primarily against cytoplasmic antigens, are capable of specific lysis of beta cells. We utilized a readily accessible source of mouse pancreatic islets [CBA/J mice lacking exocrine pancreas (exocrine pancreatic insufficiency syndrome)] to experimentally induce ICAs inbred mice. Homogenates of these islets were injected weekly for four weeks into syngeneic (CBA/J) and allogeneic (A/J, C57BL/6J, C57BL/KsJ) recipients. Only C57BL/KsJ inbred mice showed the induction of a high titer (greater than or equal to 160) antiserum cytotoxic to 51Cr-labeled CBA/J lymph node target cells. Neither the immunized C57BL/sJ mice with circulating ICAs nor any of the other immunized strains showed any decrease in glucose tolerance as compared with vehicle controls. Moreover, no morphologic evidence of islet necrosis or atrophy was apparent. Thus the ICAs induced were reactive with alloantigenic determinants of the donor and unreactive with antigenic determinants of the recipient strain. The C57BL/KsJ antiserum was further screened for anti-islet cell cytotoxic activity using both a 51Cr release assay from CBA/J islet cell monolayer cultures, and immunocytochemical staining of sections of Bouin's fixed, paraffin-embedded pancreas. This antiserum was cytotoxic to CBA/J beta cells in monolayer culture, but not the other non-beta islet cell types. Immune lysis of the beta cell required rabbit complement. At a concentration of 1% antiserum and 4% complement, beta cell lysis was evident between 3 and 4 h at 37 degrees C. Ultrastructural examination of beta cells exhibiting cytopathic changes revealed cytoplasmic disarray rather than any obvious lytic events at the plasma membrane. Grossly distended, rough, endoplasmic reticulum containing intracisternal type A retrovirus was the most prominent feature distinguishing antiserum and control serum-treated beta cells. This model system suggests that ICAs which recognize beta cell cytoplasmic antigens are capable of specifically lysing beta cells via a complement-dependent mechanism. Immunocytochemical staining revealed that, in addition to islet beta-cells,, the antiserum (1/500 dilution) stained a macrophage-like cell in the spleen and lymph nodes, as well as an epithelial-like cell in the thymus. The possibility is discussed that this multiple specificity may have been due to passenger leukocytes present in the islet homogenates used to immunize.
The percentage of pancreatic-type isoamylase activity and the ratio of pancreatic to salivary-type isoamylase activity were determined in five control and 35 hyperamylasemic serum samples by means of an established simplified chromatographic method and a recently described inhibitor test. There was good correlation in the results, except at very high and at very low levels of P-type isoamylase activity. At these extremes, the inhibitor method yields imprecise quantitative results. The inhibitor test findings may also prompt misleading conclusions when elevated serum amylase activity is due to undetected macroamylasemia.
Explore the source record for details and available documents.
We have investigated the frequency of discordant results between the TRH test and classic dynamic tests of thyroid function (thyroid suppression and TSH stimulation tests) for patients presenting a diagnostic problem for hyperthyroidism. 12 patients in group I posed the problem of having a relapse of Graves' disease previously treated: a discrepancy between TRH and T3 suppression test results was observed in 17% of the cases. 10 patients in group II demonstrated the ophtalmopathy of Graves' disease without hyperthyroidism: discordance between tests results in this group was present for 20%. Finally, 25 patients in group III had a "hot" thyroid nodul apparent at thyroid scan: in 40% of the cases, the response to TRH did not lead to the same diagnosis that was suggested by the classical dynamic tests of thyroid regulation. The discrepancies observed in this work, between the results of the TRH test and those of classic dynamic tests, demonstrate that this two types of tests are not completely interchangeable, because they do not reflect exactly the same function.
Explore the source record for details and available documents.
Had markedly anarchic dietary behaviour with alternating anorexia and bulimia, or even self-induced vomiting. These disturbances in dietary behaviour fall within the context of an unusual neurotic syndrome, predominantly hysterical. There were also menstrual problems, most often amenorrhoea. The physiopathological relations between these symptoms and signs may be envisaged as follows: the initial psychological problems explain the dysorexia; the menstrual difficulties are related at one and the same time to the psychological problems and the dysorexia; the latter is responsible for the parotidomegaly and for disturbances in carbohydrate and lipid metabolism.
In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The authors report on the case of a 26-year-old woman and three members of her family suffering from a benign condensing osteopathy, of dominant autosomic transmission, characterized mainly by a non homogenous hyperopacity of the spine and the pelvis, without alcaline hyperphosphatasemia, and which seems to them different from the condensing ostepathies described up to now.
Explore the source record for details and available documents.
A 31-year-old female diabetic in hyperthyroidism, after ketoacidosis leading to a hypoglycaemic coma showed diffuse and persistent abnormalities of ventricular repolarization. Arguments are given for myocardial ischemia of metabolic origin by hypersecretion of catecholamines.
Explore the source record for details and available documents.
Previous studies of patients with lymphoid malignancies have suggested a relationship between survival and the presence of more than 40% hard-mirror cells in the bone marrow. This report represents the first detailed study of a patient with American Burkitt's lymphoma with numerous hand-mirror cells in the bone marrow during the course of the disease. The Burkitt cells were atypical because of their hand-mirror configuration in the bone marrow, the presence of cytoplasmic glycogen, the finding of an IgG surface marker, and a strongly positive acid phosphatase staining reaction. The presence of increased numbers of hand-mirror forms in the bone marrow during the course of the patient's illness may have clinical significance, because they were replaced by non-hand-mirror Burkitt cells in the terminal phase. More reports and investigations of patients with large numbers of hand-mirror forms in the bone marrow are needed to elucidate the full significance of this unusual cellular phenomenon.
DNA methylase has been purified 660-fold from nuclei from regenerating rat liver. The enzyme is able to methylate single stranded (ss) and double stranded (ds) DNA, the only reaction product being 5-methylcytosine. Previously unmethylated double stranded DNA from prokaryotes (M.luteus) as well as from eukaryotes (Ascaris suis) can serve as substrates. The synthetic copolymers (dG-dC)n . (dC-dG)n and (dG,dC)n are also methylated. While SV40 DNA is almost not methylated, PM2 DNA is a good substrate even in the supercoiled form. The enzyme methylates 1 in 17 bases in heterologous M.luteus DNA, but only 1 in 590 in homologous rat liver DNA. The high methylation level of M.luteus DNA, an analysis of the methylated pyrimidine isostichs and a preliminary dinucleotide analysis suggest that all the CpGs in a DNA can be methylated.
Explore the source record for details and available documents.