Peroxidase activity in mammary tumors - effect of tamoxifen.
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Biomedical subjects
Publications and source records attributed to J Levy.
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Normal mice can be induced by lipopolysaccharide to produce anti-polyadenylic acid (poly A) antibodies and xenotropic (X-tropic) type-C viruses. To determine whether these traits are genetically linked, high anti-poly A antibody, high virus-producing NZB mice were crossed with low anti-poly A antibody-producing, virus-negative SWR mice. All mice in the F1 generation could be induced by LPS to produce high levels of both anti-poly A antibodies and X-tropic virus. When F1 hybrids were back-crossed to the SWR parent, all offspring were high anti-poly A antibody producers, but one-third of the mice remained virus-negative. These results demonstrate that these two LPS responses of a B lymphocyte are not genetically-linked and the anti-poly A antibody response is multigenic.
Seventy-four cases of enterococcal bacteremia without endocarditis were reviewed retrospectively for the years 1963 through 1977. Thirty-nine patients had hospital-acquired infection, 27 had serious underlying disease, and 18 had polymicrobial bacteremia. The organisms isolated from the primary source of infection were similar in patients with pure enterococcal or polymicrobial bacteremia. The most common source was the urinary tract, followed by the abdomen, infected burns, and soft-tissue infections other than burns. The overall mortality was 34%, with significantly higher mortality in immunocompromised patients, including those with infected burn wounds. Mortality also was higher in patients with hospital-acquired infection. Eleven of the 25 deaths were considered directly related to enterococcal septicemia.
Patients with moderate-to severe dry skin of the lower legs bathed daily for 17 days using either an emulsified lanolin and mineral oil bath additive (Treatment Group) or their usual bath soap (Control Group). The affected sites were evaluated and photographed before and at selected times following treatment, using a standardized technique. The severity of the dry skin as it appeared in projected color transparencies was evaluated on a 10-point grading scale by a second investigator under blinded conditions. The differential response between treatment and control groups increased with time and was found statistically significant (p less than 0.05), demonstrating the sensitivity of the method as well as the apparent therapeutic effects of the bath additive.
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During levamisole therapy, 14 of 20 patients with previously unresponsive rheumatoid arthritis had significant improvement (P less than 0.05) in clinical measures of disease activity, erythrocyte sedimentation rate, and rheumatoid factor titer in a 32-week double-blind placebo controlled crossover trial. Levamisole was shown to alter antibody responses to tetanus and typhoid antigens, lymphocyte blastogenesis to phytohemagglutinins, and the number of null cells in peripheral blood. Agranulocytosis and rash resulted in discontinuation of the drug in one patient in each group. Though clearly effective, routine use of levamisole as a disease suppressant in rheumatoid arthritis must await more complete clarification of its association with agranulocytosis.
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A boy with mental retardation and physical abnormalities has an interstitial deletion of one chromosome 5:46,XY,del(5)(q13q15).
Tetracyclines are known to interfere with bone calcification. We therefore studied their effects on matrix vesicle production and initial calcification of cartilage. 15-day-old rats were injected intraperitoneally with oxytetracycline 100 mg/kg, 6 consecutive injections every 12 h. Epiphyseal plates were examined by scanning and transmission electron microscopy and compared to light microscopy findings. It was found that high doses of tetracyclines cause degeneration of the chondrocytes in the proliferating and hypertrophic zones. Chondrocytes had short processes with only few matrix vesicles covering their surface. In the chondrocytic lacunae of the longitudinal septa of hypertrophic and calcifying cartilage there were fewer matrix vesicles as compared to controls, and their ability to aggregate and form mineralized calcospherites was impaired. This was further proven when bones were immersed in 7% NaOCl or ashed, as minerals containing calcospherites were hardly seen. It is therefore presumed that interference with intracellular and probably extracellular accumulation of calcium by tetracycline might inhibit matrix vesicle production and aggregation, thus inhibiting calcification.
Tibiae of young rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to study the origin and structure of matrix vesicles in periosteal bone. SEM studies have shown that periosteal osteoblasts have elongated processes with globular structures of 0.1 micron in diameter attached to the cell surface and processes. Similar structures were found to cover the inner surface of osteoblastic lacunae. The SEM studies have further shown that in the periosteal surface (forming bone) the above-described globules once mineralized, aggregated to form larger, nonhomogeneous mineralized spherules in which, by proper treatment with NaOCl, hydroxyapatite crystals could be exposed. Endosteal osteoblasts had fewer processes, devoid of the globular structures. Similarly, osteocytic and osteoclastic processes, although elongated and numberous, were not covered by the globular structures. In the matrix, collagen fibers of forming bone were randomly orientated, while in the deeper areas of bone they formed bundles with a longitudinal orientation. TEM studies have shown that the structures found on the osteoblastic surface and in the matrix are membrane-bound matrix vesicles which seem to be formed by budding from cell processes. Preformed membrane-bound vesicles were also observed by TEM inside sections of osteoblastic processes. These vesicles resembled the extracellular matrix vesicles in size and shape, thus giving the impression that at least some of the matrix vesicles are preformed cellular structures. While comparing SEM with TEM, it can be conducted that in bone, as in cartilage, matrix vesicles which probably serve as the initial locus of calcification, are formed directly by osteoblasts.
An empirical formula has been developed to calculate the de novo rate of synthesis of IgG in the central nervous system (CNS), based on physiologic principles that govern the passage of albumin and IgG across the blood-brain barrier (BBB). To validate the formula, radiolabeled IgG and albumin from pooled normal sera were followed from the blood to the cerebrospinal fluid (CSF) over 21 days in nine patients with definite multiple sclerosis (MS). IgG synthesis rates were calculated by the isotope exchange method and compared to values obtained with the empirical formula. There was excellent concordance, from a low rate of synthesis of 5 mg per day to a high rate of 120 mg per day. A double radiolabeled IgG experiment in two patients showed that the MS BBB processed normal serum IgG in the same way as IgG derived from autologous MS serum. Accordingly, the empirical formula, which requires only one sample of CSF and matched serum, can reliably and validly estimate the de novo rate of IgG synthesis in CNS of patients with MS.
The role of spironolactone in the aetiology of gynaecomastia was examined in terms of its ability to bind to the oestrogen receptor in cytosol, to cause specific oestrogenic effects in the absence of endogenous oestrogen and to be antioestrogenic in the presence of oestradiol. Tamoxifen, a non-steroidal antioestrogen, was chosen as an internal standard for comparison. Spironolactone and tamoxifen competitively inhibited the binding of oestradiol-17beta to its receptor in uterine and mammary cytosol, with inhibition constants of 2 x 10(-5) and 1 x 10(-7) mol/l respectively. To measure oestrogenic or antioestrogenic effects of the drugs five indices believed to be specific markers for oestrogen action were studied: uterine to body weight ratio, uterine protein content, oestradiol receptor in cytosol, progesterone receptor in cytosol and uterine peroxidase activity. Spironolactone, when administered for 3 successive days (40 microgram/day) to immature female rats, increased all of the five indices of oestrogen agonistic activity. The oestrogen-antagonistic properties of the drug were evaluated by comparing the oestradiol-injected group (5 microgram) to the oestradiol + spironolactone-injected group. A decrease was noted in all indices measured except for progesterone receptors in cytosol. Spironolactone appeared to be very similar to tamoxifen in its action both as an oestrogen and as an antioestrogen. The antioestrogenic effect of spironolactone cannot be explained by previously proposed mechanisms of action for the drug such as decreased synthesis of testosterone or inhibition of dihydrotestosterone binding to its receptor. These results suggest that spironolactone-induced gynaecomastia may be modulated by its action at both the oestrogen and dihydrotestosterone receptor in cytosol.
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A pericentric inversion of chromosome 12 was detected in an unborn baby by a second-trimester amniocentesis for prenatal diagnosis because of advanced maternal age. Subsequently, the identical pericentric inversion was found in the phenotypically normal father and a sibling. In this case of familial pericentric inversion, the parents were assured that their unborn baby was anticipated to be normal. The importance of banding studies for precise identification of structurally abnormal chromosomes and the need for chromosome study of family members for the peroper counseling of prenatal diagnosis of such a variant chromosome are discussed.