Showing papers by "Texas Medical Center published in 1990"

A comparison of DNA adduct formation in white blood cells and internal organs of mice exposed to benzo[a]pyrene, dibenzo[c,g]carbazole, safrole and cigarette smoke condensate.

Abstract: Measurement of tissue/cell DNA adducts represents a suitable monitor of carcinogen exposure because the majority of chemical mutagens/carcinogens react with DNA, forming covalent adducts, a key event in the initiation of chemical carcinogenesis. Investigations of DNA-adduct formation in vivo in white blood cells (WBC) versus target tissues, i.e. internal organs for most carcinogens, is expected to yield useful information about the suitability of WBC for biomonitoring and risk assessment. For this purpose, female ICR mice were given 0.4 mmole/kg benzo[a]pyrene (BP), 0.045 mmole/kg dibenzo[c,g]carbazole (DBC) or 2.47 mmole/kg safrole by oral gavage or 4 daily doses (equivalent to 3 cigarettes) of cigarette-smoke condensate (CSC) by topical application. At 24 h after dosing, DNA adducts were detected by a nuclease P1-enhanced 32P-postlabeling assay [M.V. Reddy and K. Randerath, Carcinogenesis, 7 (1986) 1543] in WBC and internal tissues treated with individual carcinogens, while CSC treatment elicited aromatic adducts in most tissues but not in WBC. Adduct patterns of WBC DNA were qualitatively similar to those of internal organs, but adduct amounts varied. BP, a systemic carcinogen, bound nearly as much to WBC DNA as to target-tissue DNA samples; whereas the liver carcinogens, DBC and safrole, bound to WBC DNA considerably less (22- and 51-fold, respectively) compared with liver DNA. The number of adducts in 10(7) nucleotides of WBC, liver, lung, kidney and spleen DNA, respectively, were: 2, 5, 3, 2 and 3 with BP; 6, 131, 6, 14 and 4 with DBC; 5, 238, 3, 5 and 0.6 with safrole. For CSC, these values were 0, 1 and 0.02 in WBC, lung and spleen, respectively. Our results show that carcinogen binding to WBC DNA does not reflect binding to target-tissue DNA in a quantitative sense for the carcinogens studied except for BP, and that WBC are not suitable surrogates for monitoring CSC exposure by DNA-adduct measurement after topical application. The CSC data in mice was consistent with the previous findings in humans that smokers' tissues but not WBC show smoking-related bulky/aromatic DNA adducts, as measured by 32P-postlabeling.

Transvection and long-distance gene regulation.

Abstract: Numerous genes contain regulatory elements located many tens of kilobases away from the promoter they control. Specific mechanisms must be required to ensure that such distant elements can find and interact with their proper targets but not with extraneous genes. This review explores the connections between transvection phenomena, the activation of domains of homeotic gene expression, position effect variegation and silencers. These various examples of long-distance effects suggest that, in all cases, related forms of chromatin packaging may be involved.

Atelosteogenesis type III : a distinct skeletal dysplasia with features overlapping atelosteogenesis and oto-palato-digital syndrome type II

Abstract: We present 5 cases of a short-limb dwarfism syndrome whose manifestations overlap those of atelosteogenesis and oto-palato-digital syndrome Type II. Clinical, radiographic, genetic, and histologic data are presented which demonstrate differences between our patients and previously reported cases of these other conditions. We conclude that the disorder seen in these children represents a distinct chondrodysplasia for which we propose the name atelosteogenesis Type III.

Experimental development of a fixed volume, gravity draining, prosthetic urinary bladder.

Abstract: A fixed volume, semi-rigid, gravity draining prosthetic urinary bladder has been developed in experimental animals. The conceptual model demands: 1) an encrustation resistant lumenal surface; 2) successful urothelial-prosthesis and bowel-prosthesis anastomoses; 3) a transcutaneous abdominal wall prosthesis that bonds with skin, muscle, bladder, and peritoneum which resists external and intraluminal bacterial challenge; and 4) an air permeable, fluid impermeable filter which allows passive filling and gravity evacuation of urine. The principles involved have been successfully tested in rodents, rabbits, swine, and dogs. To date two total alloplastic prosthetic bladders fabricated from Biolor II and Proplast have been inserted in mini-swine for 4 weeks.

32P-assay of DNA adducts in white blood cells and placentas of pregnant women: lack of residential wood combustion-related adducts but presence of tissue-specific endogenous adducts.

Abstract: Residential wood combustion (RWC), which has been increasingly used as a heating source, is of health concern because emissions from RWC contain carcinogenic polycyclic aromatic hydrocarbons (PAH). To assess health risk, the possible formation of PAH-DNA adducts in white blood cells (WBC) and placentas of nonsmoking women exposed to RWC smoke during pregnancy was measured by a nuclease P1-enhanced 32P-postlabeling assay having a sensitivity limit of one lesion per 10(9-10) DNA nucleotides. DNA samples isolated from 12 exposed specimens (8 WBC, 4 placentas) and 13 unexposed control specimens (8 WBC, 5 placentas) were hydrolyzed to mononucleotides, which were then 32P-labeled and separated by high-resolution thin-layer chromatography. Comparison of autoradiograms of exposed DNA samples with those of controls failed to show exposure-related adducts. All placental DNA maps exhibited one major (47 +/- 10%) and 12 minor extra spots, however, that were not seen on WBC-DNA maps. These derivatives corresponded to an average of 12 (+/- 6) modifications in 10(9) nucleotides. Similarly, WBC DNA showed four spots that were absent in placental DNA and were not quantified because of their low levels. Neither placental nor WBC DNA adducts coincided chromatographically with the product formed by the reaction of benzo(a)pyrene diol epoxide I with N2 of guanine in DNA. Although these results suggest that RWC smoke does not elicit detectable levels of aromatic DNA adducts in humans, lack of evaluation of RWC exposure levels leaves some uncertainty in this conclusion. The results, however, clearly show that placental and WBC DNA contain covalent modifications that are unrelated to RWC exposure. These DNA derivatives may be caused by ingestion and/or inhalation of, or skin contact with, low levels of environmental genotoxicants or may arise from endogenous electrophiles of as yet unknown origin.

Clinical evaluation of an automated chemical inhibition assay for lactate dehydrogenase isoenzyme 1.

Abstract: We evaluated an automated assay for lactate dehydrogenase (LD; EC 1.1.1.27) isoenzymes, supplied by Boehringer Mannheim Diagnostics (BMD) and based on selective chemical inhibition of non-LD-1 isoenzymes by guanidine thiocyanate. Results were compared with the Roche Isomune LD-1 method. The Hitachi 717 analyzer was used to measure enzyme activity for both procedures in 229 serum samples. One hundred specimens were also analyzed by the Helena rapid electrophoresis (REP) method. We determined the limit of linearity of the BMD method to be about 1200 U of LD-1 per liter. The analytical correlation of BMD (y) with Isomune (x) yielded y = 1.0x + 0.5 U/L, r = 0.997, Sy/x = 16.9 (range 20-1397 U/L). The regression equation for BMD vs REP was y = 1.1x + 7.2% (r = 0.800, Sy/x = 7.4, range 14-83%). Average values for within-run precision for low (38 U/L), medium (180 U/L), and high (865 U/L) controls were 4.1%, 1.0%, and 0.5%, respectively (16 trials of six each). The average values for run-to-run precision were 4.1%, 1.7%, and 1.1%, respectively, for these controls (n = 16). We used receiver-operating characteristic curves to determine optimum decision limits. Using an LD-1 cutoff of 40% of total LD, we obtained a clinical sensitivity of 97-100% and a specificity of 95% when blood was collected during the optimum interval, 24-48 h after the onset of chest pain. We conclude that the BMD LD-1 assay is equivalent to the immunochemical and electrophoretic assays for measuring the LD-1 isoenzyme.

The role of religions in the analysis of the ethical issues of human gene therapy.

Abstract: Beginning with critical writings of certain theological ethicists in 1965, religious bodies increasingly have been fostering studies of emerging issues implied by genetic technology. While...

A health sciences library liaison project to support biotechnology research.

Abstract: Suite a l'initiative de creation d'un centre national d'information en biotechnologie de la Bibliotheque Nationale de Medecine (NLM-National Library of Medecine), le HAM-TMC (Houston Academy of Medecine-Texas Medical Center) a decide d'apporter un soutien et un developpement special a la biotechnologie en ouvrant un poste de bibliothecaire assurant un service d'information aupres de clients effectuant des recherches en biotechologie. Les raisons du developpement de l'industrie biotechnologique a Houston sont exposees et les activites de liaison et les nouveaux clients du HAM-TMC sont presentes

Influence of lovastatin on the pharmacokinetics, toxicity and immunologic response of cyclosporine in the obese Zucker rat.

Abstract: The combined use of lovastatin, a hypolipidemic agent effective in the reduction of cholesterol levels, and the lipophilic immunosuppressant, cyclosporine, was studied in the obese rat model. Pharmacokinetics, immunosuppressive activity, lipid levels, and creatinine clearances were compared between groups administered drug-free vehicle, lovastatin or cyclosporine alone, or concomitant cyclosporine and lovastatin. All groups were pre-treated with either oral lovastatin 2.5 mg kg-1 day-1 or propylene glycol vehicle for 1 week. Although no differences in renal function were observed in rat groups administered cyclosporine or lovastatin alone, there was a significant reduction in baseline creatinine clearance following combination therapy compared to placebo controls (70 +/- 18 vs 121 +/- 16 per cent of baseline; p less than 0.05). No differences in trough cyclosporine concentrations were observed between groups. Similarly, mean areas under the whole blood concentration-time profiles were not significantly different with or without concomitant lovastatin (61823 +/- 27295 vs 41470 +/- 10312 ng h ml-1; p = 0.13). No differences in systemic clearance or volume of distribution of parent cyclosporine were observed with combination therapy. Furthermore, lipid levels and T-lymphocyte activity were unchanged with the addition of lovastatin. Per cent increases in creatine kinase were significantly correlated with percentage drop in baseline renal function, suggesting the development of rhabdomyolysis. The present data support the interaction between cyclosporine and lovastatin observed clinically, resulting in acute renal dysfunction. Caution should be exercised in their combined use.

Application of Physics in Medicine

Abstract: DOI: http://dx.doi.org/10.5915/22-2-13560 The application of physics principles to medical practice has made an outstanding contribution in the diagnosis and treatment of cancer. Further amalgamation of research, application, cooperation and understanding of physics and medicine will enhance new perspectives on the benefits of ionizing and nonionizing radiations for medical diagnosis and therapy. In this paper, a general survey has been made of physics applications in medicine.