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Biomedical subjects

J E Tomaszewski

Publications and source records attributed to J E Tomaszewski.

At least 163 records · Page 9Linked to original sources

Subpopulations of lymphocytes in maternal peripheral blood during pregnancy.

The fetus can be considered an allograft with up to one-half of its MHC antigens being potentially recognized by the mother as foreign. This study compares expression of OKT3, OKT4, OKT8, Kappa, Lambda and Ia antigens on lymphocytes in the peripheral blood of normal non-pregnant women, normal pregnant women, patients who are chronic spontaneous aborters and pregnant insulin-dependent diabetic women. Monoclonal antibodies and cytofluorometric analyses were used for these determinations. There were no significant differences (P = 0.01) between these groups for T-cell markers. A statistically significant (P = 0.001) increased ratio of cells bearing surface immunoglobulin to those expressing Ia antigen (K&L/Ia) was observed between normal non-pregnant controls and women with a history of chronic spontaneous abortion. It is concluded that T-lymphocytes in the peripheral blood do not demonstrate a phenotypic abnormality that would account for the non-rejection of the fetal allograft; however, women with chronic spontaneous abortion may have abnormal B-cell differentiation or T-cell activation that mediates chronic spontaneous abortion.

Abortion, Habitual↗

Mesonephric adenocarcinoma of the bladder.

Mesonephric adenocarcinoma of the bladder may be the malignant counterpart of nephrogenic adenoma. We report the third known case of this invasive, well differentiated, tubular neoplasm resembling nephrogenic adenoma. The invasive potential of nephrogenic neoplasms has altered our approach to the management of these lesions. Nephrogenic adenoma and mesonephric adenocarcinoma appear cytologically similar on a superficial bladder biopsy. The latter is excluded by deeper bladder biopsies. Muscular invasion may indicate a more aggressive behavior and may require radical cystectomy for cure.

Adenoma↗

Improved T cell subset monitoring by immunogold staining following renal transplantation.

Enumeration of peripheral blood T cells, functional T cell subsets, and B cells by immunogold staining (IGS) was compared with analysis by flow cytometry in 52 renal allograft recipients. Results by the IGS method compared favorably with those obtained by flow analysis. IGS is a simple, inexpensive technique that is readily adaptable to the setting of posttransplant immune monitoring.

Antigens, Surface↗

Binding of radioactivity after transplacental administration of tritiated N-nitrosodiethylamine to Syrian golden hamsters.

Tritiated N-nitrosodiethylamine (DEN) was administered to two groups of female Syrian golden hamsters on days 11 and 15 of pregnancy. Binding of radioactivity was measured in maternal and fetal organs after various intervals by liquid scintillation counting of dehydrated and combusted tissues. No bound activity was found in the fetal tracheas on day 11 of gestation, when transplacental administration of DEN is known to be noncarcinogenic for the offspring. On day 15, when DEN administration caused a 95% incidence of tracheal tumors in the offspring, bound radioactivity was found in the fetal tracheas. In the respiratory tracts of the mothers, the distribution of bound radioactivity correlated with the distribution of target cell types. Binding was high in segmental bronchi and bronchioles which contain numerous Clara cells, the major source of DEN-induced pulmonary tumors. No binding occurred in the main bronchi, which do not possess Clara cells.

Animals↗

Evaluation of metabolic activation of 7,12-dimethylbenz(a)anthracene in vitro by aroclor 1254-induced rat liver S-9 fraction.

Short-term assays for detection of chemical carcinogens frequently rely on an Aroclor 1254-induced rat liver S-9 fraction for metabolic activation of test compounds. The ability of this in vitro system to reproduce the activation occurring in target tissue was investigated by examining the DNA adducts produced when the polycyclic aromatic hydrocarbon carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), was incubated with the S-9 fraction and calf thymus DNA. Analyses by Sephadex LH-20 column chromatography of hydrocarbon-deoxyribonucleoside adducts obtained after enzymic digestion of the [3H]DMBA-modified DNA revealed that the products of binding of DMBA to DNA in the presence of the S-9 fraction vary with the relative concentration of DMBA to S-9 fraction. Further analyses of these adducts by high-pressure liquid chromatography in the presence of the diol-epoxide-DNA adduct (isolated from mouse embryo cells exposed to [14C]DMBA) and chemically synthesized ultraviolet-absorbing markers of DMBA 5,6-oxide-deoxyribonucleoside adducts showed that, at high DMBA-S-9 ratios, DMBA 5,6-oxide-deoxyriboiucleoside adducts were prominent among the products while, at low DMBA-S-9 ratios, the products included the diol-epoxide-DNA adduct found in target tissue. However, this adduct was always accompanied by other adducts not found in intact cellular systems. Inclusion of a metabolic inhibitor (1,1,1-trichloropropylene oxide) in the Salmonella mutagenicity assay demonstrated that high levels of revertants can be obtained from rat liver S-9 fraction-activated DMBA under conditions which should prohibit formation of the diol-epoxide. These results suggest that Aroclor 1254-induced rat liver S-9 fraction does not exactly reproduce the metabolic activation of this particular carcinogen in vivo and therefore should not be assumed to do this for other carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Comparison of metabolism-mediated binding to DNA of 7-hydroxymethyl-12-methylbenz(a)anthracene and 7, 12-dimethylbenz(a)anthracene.

Comparison of the binding to DNA of 7-hydroxymethyl-12-methylbenza(a)anthracene and 7, 12-dimethylbenz(a)anthracene (DMBA) catalyzed by mouse embryo cells in culture or by rat liver microsomes indicates that the products formed are different for the two hydrocarbons. Thus, the hydroxy compound is not an intermediate in the binding of DMBA to DNA in these systems. Binding of the hydroxy compound to DNA in mouse embryo cells is less efficient than for DMBA and is inhibited by 1,1,1-trichloropropylene 2,3-oxide, an inhibitor of epoxide hydrase. This and the fluorescence spectra of the hydroxy compound-DNA adducts indicate that the hydroxy compound is activated for DNA binding through the formation of a diol-epoxide in the 1,2,3,4-ring. As previously found for DMBA, this is consistent with the activation of this compound through a bay-region diol-epoxide.

9,10-Dimethyl-1,2-benzanthracene↗

Biochemical basis for cytotoxicity of 7,12-dimethylbenz(a)anthracene in rat liver epithelial cells.

When the effects of 7,12-dimethylbenz(a)anthracene (DMBA) on normal and malignant rat liver epithelial cells were compared in a colony inhibition assay, this carcinogen showed a preferential cytotoxic action on the normal cells. In investigations of the biochemical basis of this selective toxicity, it was found that both cell lines were similarly effective in binding DMBA to DNA and that both cell lines had the capacity to metabolize this carcinogen. However, the hepatoma cells were more efficient than were the normal cells in generating very polar metabolites (not organic solvent extractable). These studies suggest that the basis of the resistance of the hepatoma cells to the toxicity induced by DMBA lies in their ability to detoxify biologically active metabolites. Several phenols were examined as possible toxic metabolites of DMBA, but these were not toxic at dose levels at which DMBA kills most of the normal cells.

9,10-Dimethyl-1,2-benzanthracene↗

Metabolism of 7,12-dimethylbmethylbenz(a)anthracene by macrophages and uptake of macrophage-derived metabolites by respiratory tissues in vitro.

Cultured mouse macrophages and tracheal and lung tissue each produced the same ethyl acetate-soluble derivatives of 7,12-dimethylbenz(a)anthracene (DMBA). The derivatives produced in the different cultures were indistinguishable by thin-layer chromatography and by high-pressure liquid chromatography but differed in their relative proportions. The greatest difference was seen between lungs and macrophages. The predominant metabolite produced by lungs was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, while macrophages produced equal quantities of both 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and a second uncharacterized derivative, Metabolite B, at low DMBA doses (less than 0.05 microgram/ml medium) and primarily Metabolite B at higher DMBA doses (greater than 0.05 microgram/ml medium). Macrophages released the majority of the ethyl acetate-soluble metabolites that they produced into the surrounding medium. With the exception of 8,9-dihydro-8,9-dihydroxy-7,12dimethylbenz(a)anthracene, these derivatives were accumulated within tracheal and lung tissue when these organs were cocultivated with macrophages in the presence of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Comparison of the hydroxylation of zoxazolamine and benzo[a]pyrene in human placenta: effect of cigarette smoking.

The in vitro hydroxylation of zoxazolamine was compared with the hydroxylation of benzo[a]pyrene (BP) in full-term placentas from 11 nonsmokers and from 13 women who smoked cigarettes during pregnancy. Cigarette smoking increased the average zoxazolamine and benzo[a]pyrene hydroxylase activities 13- and 39-fold, respectively. A 59-fold range in benzo[a]pyrene hydroxylase activity and a 28-fold range in zoxazolamine hydroxylase activity were found in the placentas of cigarette smokers. A plot of these two enzyme activities showed that zoxazolamine hydroxylase activity was highly correlated, with benzo[a]pyrene hydroxylase activity in the 24 placentas studied (r = 0.98; p less than 0.001). A strong correlation between the above enzymatic activities was also found in 8 placentas which had been stored for 2 yr at -20 degrees C (r = 0.95; p less than 0.001). The results suggest that benzo[a]pyrene and zoxazolamine are metabolized in the human placenta by the same enzyme or by different systems that are under the same regulatory control.

Benzopyrene Hydroxylase↗

Deuterium isotope effects during formation of phenols by hepatic monoxygenases. Evidence for an alternative to arene oxide pathway.

The in vivo and in vitro metabolisms of normal and deuterated aromatic substrates have been investigated in ratsmsignificant isotope effects (k(H)/k(d) = 1.3-1.75) were associated with in vivo formation of meta-hydroxylated metabolites from 1:1 mixtures of normal and perdeuterio-(aryl ring) nitrobenzine, methyl phenyl sulfide, and methyl phenyl sulfone. Since isotope effects of this magnitude are incompatible with arene oxides as intermediates in the formation of phenols, the results provide evidence that multiple pathways are responsible for the formation of phenols in mammals. Significant isotope effects were not associated with the formation of the other phenolic isomers of nitrobenzene, methyl phenyl sulfone, or methyl phenyl sulfide or with the formation of phenolic products from anisole, bromobenzene, chlorobenzene, fluorobenzene, benzonitrile, naphthalene, zoxazolamine, acetanilide, biphenyl, diphenylhydantoin, benzene, o- and p-xylene, toluene, and mesitylene. Significant isotope effects might not be observable with the latter substrates if the kinetic parameters for oxidation of substrate change or if the arene oxide pathway greatly predominates. Furthermore, extensive in vivo metabolism of any substrate would make isotope effects unobservable by the procedure employed, namely the analysis of isotope content in metabolites formed from 1:1 mixtures of normal and deuterated substrates.

Animals↗

Prenatal characteristics of congenital nephrosis: results of a survey.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.

Female↗

Mucinous carcinomas involving the prostate: atypical findings at MR imaging.

The magnetic resonance (MR) imaging findings in four patients with mucinous tumors involving the prostate are presented. The MR appearance of these tumors differed from that of typical prostatic adenocarcinomas in that the signal intensity on T2-weighted images approximated or exceeded that of the uninvolved peripheral zone. The unusual appearance of mucinous prostate tumors may present problems in diagnosis and staging with MR imaging.

Adenocarcinoma, Mucinous↗

Effect of nonanticoagulant heparin (Astenose) on restenosis after balloon angioplasty in the atherosclerotic rabbit.

PURPOSE: To determine whether intravenous administration of Astenose, a high-molecular-weight nonanticoagulant heparin, can reduce restenosis following balloon angioplasty in a rabbit model. MATERIALS AND METHODS: Focal atherosclerosis was induced in 54 rabbits (89 vessel), and angioplasty was performed after animals were randomized into five groups. Group 1 vessels (control) were treated with lactated Ringer solution for 28 days (n = 19); group 2, Astenose at 0.10 mg/kg per hour for 28 days (n = 16); group 3, Astenose at 0.33 mg/kg per hour for 28 days (n = 16); group 4, Astenose at 0.60 mg/kg per hour for 28 days (n = 17); and group 5, Astenose at 0.33 mg/kg per hour for 14 days (n = 21). Arteriograms were obtained to measure minimal luminal diameters before, immediately after, and 28 days after angioplasty, and the rabbits were killed for histologic analysis. RESULTS: Angiographically demonstrated restenosis was significantly reduced in groups 3 (18.9% +/- 3.7, P = .04) and 4 (20.2% +/- 3.1, P = .04) compared with the control group (32.4% +/- 4.8). Group 5 showed a nonsignificant trend toward reduced restenosis (23.1% +/- 2.9, P = .09), and group 2 showed restenosis similar to that in group 1 (31.0% +/- 2.5, P = .80). However, quantitative histopathologic analysis detected no differences among the groups in absolute plaque area. Medial area was significantly smaller in groups 2 and 5 (P < or = .002) than in group 1, and there was a nonsignificant trend toward reduced medial area in groups 3 and 4 (P = .12). CONCLUSION: Long-term intravenous Astenose therapy resulted in a modest but statistically significant reduction in angiographically demonstrated restenosis after angioplasty in this atherosclerotic rabbit model.

Angiography↗

Cytapheresis in a patient with Sezary syndrome.

A patient with Sezary syndrome underwent cytapheresis on the IBM 2997 cell separator. Four procedures were performed over a 12-day period. A total of 8.3 x 10(10) Sezary cells were removed. The patient's skin lesions and lymphadenopathy regressed. Transient thrombocytopenia occurred, requiring platelet transfusion. Although a significant number of platelets were removed by pheresis, this was not sufficient to explain the thrombocytopenia. The patient subsequently died of causes unrelated to the cytapheresis.

Cell Separation↗