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Biomedical subjects

C L Han

Publications and source records attributed to C L Han.

11 recordsLinked to original sources

Neointimal formation by circulating bone marrow cells.

The origin of smooth muscle cells involved in vascular healing was examined. Eighteen C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 106 bone nucleated marrow cells from congenic (Ly 5.1) male donors. Successful repopulation by donor marrow was demonstrated after 4 weeks by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal antibody. The iliac artery of six of the chimeric mice was scratch-injured by five passes of a probe, causing severe medial damage. After 4 weeks the arterial lumen was obliterated by a cell-rich neointima, with alpha-smooth muscle actin-containing cells present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y chromosome-specific probe. An organized arterial thrombus was formed in the remaining 12 chimeric mice by inserting an 8-0 silk suture into the left common carotid artery. Donor cells staining with alpha-smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage. Our results suggest that bone marrow-derived cells are recruited in vascular healing as a complementary source of smooth muscle-like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair.

Arteriosclerosis↗

Blood vessels from bone marrow.

Lengths of silastic tubing were inserted into the peritoneal cavity of rats or rabbits. By two weeks the free-floating implants had become covered by a capsule consisting of several layers of "macrophage"-derived myofibroblasts and collagen matrix overlaid by a single layer of mesothelial cells. The tubing was removed from the harvested implant and the tissue everted. This now resembled an artery with an inner lining of mesothelial cells (the "intima"), a "media" of myofibroblasts, and an outer collagenous "adventitia." The tube of living tissue was grafted by end-to-end anastomoses into the transected carotid artery or abdominal aorta of the same animal in which the tissue had been grown, where it remained patent for four months and developed structures resembling elastic lamellae. The myofibroblasts developed a high volume fraction of myofilaments and became responsive to contractile and relaxing agents similar to smooth muscle cells of the adjacent artery wall.

Anastomosis, Surgical↗

Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family--implications for etiology of fetal alcohol syndrome and alcohol-related diseases.

The alcohol dehydrogenase (ADH) family is involved in the metabolism of both ethanol and retinoids. To quantitatively assess the potential contributions to first-pass metabolism of ethanol and the ethanol interference with retinoid homeostasis, saturation kinetics for ethanol oxidation as well as inhibition kinetics by ethanol for all-trans-retinol oxidation of human class I alpha alpha, beta1beta1, beta2beta2, gamma1gamma1, class II pi pi, class III chi chi, and class IV mu mu were evaluated and compared. Class I and class II ADHs exhibited substrate inhibition with inhibition constants ranging over 250-720 mM (except gamma1gamma1) ethanol. Class IV ADH displayed no appreciable inhibition up to 1 M ethanol. Activity of the class III enzyme (190 nM subunit) was undetectable at 250 mM ethanol. The kinetic simulations indicate that the hepatic pi pi and the gastric mu mu can most effectively contribute to first-pass metabolism of alcohol. The Michaelis constant (Km), turnover number (k(cat)), and catalytic efficiency (k(cat)/Km) for retinol oxidation relative to that for ethanol oxidation in class I, class II, and class IV ADHs ranged over 0.00022-1.3, 0.071-0.48, and 0.24-650, respectively. Ethanol was a competitive inhibitor against retinol for class I, II, and IV ADHs with apparent inhibition constants ranging over 0.037-11 mM, indicating that retinoic acid synthesis through the ADH pathways can be tremendously blocked during social/heavy drinking. These findings support the notion that first-pass metabolism of alcohol may occur mainly in the liver through class II pi pi and that cellular retinoid signaling may be perturbed by ethanol via ADH pathways.

Alcohol Dehydrogenase↗

Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: results from a seroepidemiological case-control study.

OBJECTIVE: To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas. METHODS: We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression. RESULTS: Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stronger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95% CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive tumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76, 18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.35, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-16. The risk associated with HPV-16 seropositivity was higher among smokers (OR 8.5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13). CONCLUSION: Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of some vulvar tumors and that smoking may be an important cofactor involved in the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the role of smoking and other cofactors in this disease process are warranted.

Adult↗

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Enzyme-Linked Immunosorbent Assay↗

Effects of the calcium antagonist isradipine on 24-hour ambulatory blood pressure, platelet aggregation, and neutrophil oxygen free radicals in hypertension.

The effects of isradipine on ambulatory blood pressure, platelet aggregation, and oxygen free radicals were assessed in 30 patients with hypertension in a non-comparative 16-week study. After 4 weeks of placebo run-in, patients received isradipine at 2.5 mg twice daily for 12 weeks. The average supine systolic/diastolic blood pressure (155 +/- 17/101 +/- 11 mm Hg) was significantly reduced at the end of treatment (144 +/- 13/95 +/- 9 mm Hg; p less than 0.01). The heart rate was not significantly altered. Isradipine had no adverse effects on red or white blood cells or on plasma viscosity. The thromboxane B2 level and epinephrine-induced platelet aggregation were significantly (p less than 0.05) reduced. High-density lipoprotein cholesterol was significantly (p less than 0.01) increased after vs. before treatment; total cholesterol was significantly (p less than 0.05) increased at midstudy, but this was not significant at the end of the study. Other biochemical parameters were unchanged. Studies of neutrophil oxygen free radicals by serum opsonized zymosan and phorbol myristate acetate were not affected by isradipine. In conclusion, isradipine is an effective antihypertensive agent that also has beneficial effects on platelet aggregation and lipids while having no effects on neutrophil oxygen free radicals or most of the biochemical variables tested, making it an ideal agent for hypertension.

Aged↗