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Biomedical subjects

N Maloney

Publications and source records attributed to N Maloney.

7 recordsLinked to original sources

Exposure to the anti-TNF-alpha drug thalidomide induces apoptotic cell death in human T leukemic cells.

TNF-alpha is a pro-inflammatory cytokine that plays a key role in disorders due to HIV-1 infection and replication such as Kaposi sarcoma, wasting, aphthous ulcerations and progression to AIDS. The controversial drug thalidomide is anti-inflammatory, anti-angiogenic and a selective inhibitor of TNF-alpha that is being studied as a treatment for HIV-1-related disorders, immune disorders and cancer. The cellular and molecular mechanism of thalidomide is unclear despite renewed clinical interest in the drug. Previous data from this laboratory indicate that thalidomide decreases cell growth and cell-cell interactions of human T leukemic cells. The specific aim of the present study is to determine whether thalidomide administration induces cell death via apoptosis. Low dose thalidomide treatment of human T leukemic cells exhibited rapid increases in caspase-3 activity, annexin V-FITC binding and DNA disintegration that is characteristic of apoptosis. These data indicate that low doses of thalidomide signal human T leukemic cells to die by apoptosis, which is a possible method of altering inflammatory cells and inflammatory activities.

Caspase 3↗

CYP17 genotype and breast cancer risk.

The MspAI polymorphism in the 5' untranslated region of CYP17 has been evaluated as a breast cancer risk factor in a hospital-based case-control study in New York City. The study population consisted of 363 women [123 breast cancer patients and 240 patient controls (123 benign breast disease without atypical hyperplasia, 117 women without breast disease)]. There were 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls) and 84 Hispanics (27 cases, 57 controls); 142 premenopausal women and 221 postmenopausal women. Consistent with a previous report (Feigelson et al., Cancer Res., 57: 1063-1065, 1997) we found no evidence to implicate the minor variant (restriction site present allele, designated A2) as a breast cancer risk factor. Furthermore, we sought evidence to implicate the minor variant of CYP17 in the development of more aggressive breast cancers (n = 38/121) as had been reported previously. Although confidence intervals (CI) overlap, the data presented here do not provide support for previously reported findings (odds ratio, 0.9; 95% CI, 0.4-2.0; n = 38 versus odds ratio, 2.5; 95% CI, 1.1-5.2; n = 40). Clearly this question needs to be resolved in a larger study. No evidence was found to support the contention that inheritance of the minor variant is a predictor of early age at menarche. Allelic frequencies between different ethnic groups were not found to be different with the exception of Hispanic controls, in which the genotypic distribution was not consistent with the Hardy-Weinberg equilibrium.

Black People↗

Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system.

To understand the potential early responses of human bone and the calcium endocrine system to spaceflight, we studied 8 healthy men, aged 35-44 years before, during, and after bed rest in a -6 degrees head-down tilt model for microgravity. Based on a novel single-dose labeling schedule, average rates of bone formation in the iliac crest were reduced in 6, unchanged in 1, and increased in 1 following the bed rest period. The decrease was greatest for subjects whose daily walking miles were highest (r = -0.762, p less than 0.05, n = 7). Before a measurable increase in ionized serum calcium the sixth bed rest day, there was increased excretion of urinary calcium and sodium, evident the first 2 bed-rest days and parallel for the entire week (r = 0.92, p less than 0.001). Reduced excretion of phosphorus and 3', 5' cyclic adenosine monophosphate on the first and second bed rest days was followed by an increase in serum phosphorus by the sixth bed rest day. Depressed serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were manifest by the sixth and seventh bed rest days. The similarity of the response of bone and the calcium endocrine system of healthy men after only 7 days to results of longer term bed rest studies emphasizes the responsiveness of the adult human skeleton to biomechanical stimuli induced by changes in activity and/or position.

Adult↗

Bone biopsy to diagnose hyperoxaluria in patients with renal failure.

Primary hyperoxaluria is a rare congenital disorder characterized by large quantities of urinary oxalate with resultant nephrocalcinosis and nephrolithiasis and by deposits of calcium oxalate in other organs. Renal failure occurs early in life. Reports of unsuccessful renal transplantation attempts in this disorder underscore the need for antemortem diagnosis. Percutaneous bone biopsy is a relatively new procedure that is easily done at bedside, safe, and of potentially high yield in the demonstration of tissue oxalate. Three cases presented here show the characteristic histologic picture seen in this disease. In one case, the diagnosis was established by bone biopsy.

Adolescent↗