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Biomedical subjects

J D Pearson

Publications and source records attributed to J D Pearson.

246 records · Page 14Linked to original sources
PubMedDate not supplied

Mixed-effects regression models for studying the natural history of prostate disease.

Although prostate cancer and benign prostatic hyperplasia are major health problems in U.S. men, little is known about the early stages of the natural history of prostate disease. A molecular biomarker called prostate specific antigen (PSA), together with a unique longitudinal bank of frozen serum, now allows a historic prospective study of changes in PSA levels for decades prior to the diagnosis of prostate disease. Linear mixed-effects regression models were used to test whether rates of change in PSA were different in men with and without prostate disease. In addition, since the prostate cancer cases developed their tumours at different (and unknown) times during their periods of follow-up, a piece-wise non-linear mixed-effects regression model was used to estimate the time when rapid increases in PSA were first observable beyond the background level of PSA change. These methods have a wide range of applications in biomedical research utilizing repeated measures data such as pharmacokinetic studies, crossover trials, growth and development studies, aging studies, and disease detection.

Aged↗
PubMedDate not supplied

Lipid metabolism in cultured aortic smooth muscle cells and comparison with other cell types. Part 2. Reversibility of lipid accumulation caused by hyperlipemic serum.

The lipid compositions of cultured rabbit aortic smooth muscle cells and skin fibroblasts were determined for cells grown in media containing either normolipemic or hyperlipemic sera. Both cell types accumulated cholesteryl esters and triglycerides after treatment with hyperlipemic serum. Within 4 days of returning cells that had accumulated these neutral lipids to medium containing a low percentage of normolipemic serum, their concentrations in both cell types had returned to levels similar to those found in cells cultured in standard growth medium. Thus the accumulation of cholesteryl esters and triglycerides in smooth muscle cells, as in fibroblasts, may be completely reversed in vitro.

Animals↗
PubMedDate not supplied

Lipid metabolism in cultured aortic smooth muscle cells and comparison with other cell types. Part I. Composition of cells grown in hyperlipemic serum.

The lipid compositions of cultured rabbit aortic smooth muscle cells, adventitial fibroblasts and skin fibroblasts were determined for cells grown in media containing either normolipemic or hyperlipemic serum. No significant changes were found in cell phospholipid composition. Each of the threee cell types responded similarly to hyperlipemic serum, accumulating esterified cholesterol and triglyerides.

Animals↗
PubMedDate not supplied

Altered transcriptional regulation of human interstitial collagenase in cultured skin fibroblasts from older donors.

Primary human dermal fibroblasts isolated from the medial aspect of the proximal forearm of young and old donors were compared for the expression of interstitial collagenase, 72 kDa type IV collagenase, the tissue inhibitor of metalloproteinase type 1, and pro-alpha 2 (I) collagen mRNA at basal levels and after stimulation with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate. Higher basal and induced steady-state mRNA levels of interstitial collagenase were found in the cells from older donors. Ratios of basal and induced steady-state mRNA levels of interstitial collagenase to pro-alpha 2 (I) collagen, and interstitial collagenase to the tissue inhibitor of metalloproteinases type 1 were also higher in the cells from older donors. Seventy-two kiloDalton type IV collagenase and pro-alpha 2 (I) collagen mRNA showed similar levels of expression in the cells from young and old donors and were not altered by treatment with 12-O-tetradecanoyl-phorbol-13-acetate. Transient transfection assays with the interstitial collagenase promoter linked to a reporter gene showed increased activity of the reporter in cell strains with high interstitial collagenase mRNA levels. Mobility shift assays demonstrated increased binding activity to the specific 12-O-tetradecanoyl-phorbol-13-acetate response element in nuclear extracts from the cell strains with higher induced collagenase mRNA levels and higher reporter gene activity. These findings are consistent with the observed phenotype of interstitial collagenase and its specific tissue inhibitor in the senescent fibroblast aging model.

Adolescent↗
PubMedDate not supplied

Selective migration from Samoa: a longitudinal study of pre-migration differences in social and psychological characteristics.

In 1981 extensive questionnaire and interview data were collected on some 100 young Samoan adults. Five years later in 1986 we determined their whereabouts and divided the data in accordance with migration status. The answers of the 35 who had migrated in the intervening period were contrasted to those 65 who remained in Samoa. The migrants differed in several distinct areas. Migrants reported a higher degree of peer-reliance as a personal adaptive strategy. Migrants also reported larger numbers of individuals in social support networks, a higher quality of support and more community involvement. They also report less expressive display of anger. Those who did not migrate reported a slightly better view of life in Samoa and abroad, as well as better relations with their friends and neighbors. These findings support a hypothesis that migrants are pre-selected to fit into migrant communities and do not appear to be misfits who are unhappy with life in Samoa.

Adaptation, Psychological↗
PubMedDate not supplied

The influence of hypoglycaemic agents on the growth and metabolism of human endothelial cells.

Using human umbilical vein endothelial cells, and human microvascular endothelial cells from omental and subcutaneous fat obtained at laparotomy, we studied the effects of sulphonylureas and the biguanide metformin on endothelial cell proliferation, prostacyclin production, ecto-5'-nucleotidase activity, and von Willebrand factor release. Each drug produced a concentration-dependent proliferation of umbilical vein but not of microvascular endothelial cells. The stimulation of umbilical vein endothelial cell proliferation by sulphonylureas, but not by metformin, was serum- and insulin-dependent. Sulphonylureas and metformin had no effect on the proliferation of human dermal fibroblasts, smooth muscle cells derived from the umbilical artery, or 3T3 cells, until concentrations greater than 100 fold those found in vivo were reached, when there was inhibition of proliferation. These agents had no effect on prostacyclin or von Willebrand factor production, or on ecto-5'-nucleotidase activity, until high concentrations were used, at levels which also inhibited proliferation. The results suggest that the sulphonylureas and metformin, may, at concentrations found in vivo, induce changes in the turnover of endothelial cells from large vessels, but not of microvascular endothelial cells.

3T3 Cells↗
PubMedDate not supplied

Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.

OBJECTIVE: To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease. DESIGN: Case-control study of men with and without prostate disease who were participants in a prospective aging study. SETTING: Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging. PATIENTS: Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer. OUTCOME MEASURES: Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease. RESULTS: Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively. CONCLUSIONS: The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.

Aged↗
PubMedDate not supplied

Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens.

Anti-neutrophil cytoplasm antibodies (ANCA) are strongly associated with the development of systemic vasculitis. Myeloperoxidase and proteinase-3 have been identified as targets for P-ANCA and C-ANCA, respectively. Both enzymes are released from neutrophil azurophil granules following neutrophil activation and both are highly cationic. Purified myeloperoxidase is demonstrated to bind non-convalently to endothelial cell membranes, to retain its enzymic function following binding, and to retain its antigenicity for P-ANCA. Endothelial cell-bound myeloperoxidase enhances complement-dependent cytotoxicity of some P-ANCA sere that also contain anti-endothelial cell antibodies. Studies using purified proteinase-3 show that it also can bind to endothelial cells and be recognized by C-ANCA. The interactions of myeloperoxidase and proteinase-3 with endothelial cells and ANCA may thus contribute to the development of vascular injury in patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗