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D Handelsman

Publications and source records attributed to D Handelsman.

10 recordsLinked to original sources
PubMed2001

Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array.

BACKGROUND: To understand the molecular mechanisms underlying prostate cancer, we have utilized the gene expression array to search for genes whose expression is altered in this disease. METHODS: RNA quality from manual microdissected tissue was compared with that from microselected tissue by electrophoresis. For array analysis, malignant and normal prostate epithelium was enriched using microselection technique from prostate cancer and the peripheral zone of a normal prostate. Identical array membrane was hybridized to labeled cancer and normal cDNA, respectively. The differentially expressed gene was further evaluated by RT-PCR. RESULTS: Microdissection, but not microselection, causes visible degradation to RNA. Of the 588 genes on the membrane, 87 genes yielded significant signals. Based on a three fold difference relative to normal prostate tissue, 1 gene was overexpressed and 12 genes underexpressed in prostate cancer. Of them, five showed statistically significant reduction in mRNA levels in six prostate cancer specimens compared with seven normal prostate specimens. These five genes are glutathione S-transferase M1 (GSTM1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha receptor-1 (TNFR-1), transforming growth factor beta3 (TGF-beta3), and inhibitor of DNA binding-1 (ID-1). CONCLUSIONS: GST-based metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some helix-loop-helix nuclear proteins could be potentially important in organ-confined prostate cancer and deserve further investigation.

Adult↗
PubMed2000

Androgen deficiency and bone mineral density in men with rheumatoid arthritis.

OBJECTIVE: To investigate the prevalence of osteopenia/osteoporosis in a group of men with rheumatoid arthritis (RA); and to analyze the relationship between sex hormone status and bone mineral density (BMD), taking into account disease activity, disease duration, and corticosteroid intake. METHODS: Clinical and demographic details were collected on 50 consecutive men with RA. BMD at the lumbar spine and femoral neck were measured, together with plasma concentrations of testosterone, sex hormone binding globulin, and luteinizing hormone. RESULTS: The median age of patients was 67 years, with median disease duration 20 years. Fourteen patients had never been treated with oral corticosteroids, the remaining 36 received a range of prednisone doses over prolonged periods. Plasma testosterone concentration was moderately reduced in 40% (< 10 nmol/l) and severely reduced in 6% of men (< 8 nmol/l), but androgen deficiency was not related to bone density or fractures. Spinal and femoral neck BMD was reduced in 38 and 71% of the men, respectively. Femoral neck BMD was related to age, weight, disability status, and specific disease activity scores. The only predictors of spinal BMD were pack-years of smoking and physician global assessment. CONCLUSION: Reduced BMD is common among men with RA. The predictors for spine and femoral neck BMD bear little direct relationship to blood testosterone concentrations despite the relatively high prevalence of low testosterone concentrations in this population. These findings are more consistent with the possibility that low testosterone concentrations in men with RA are a bystander effect of systemic inflammatory disease.

Adrenal Cortex Hormones↗
PubMed1998

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Adult↗
PubMed1988

A twin study of the psychiatric side effects of oral contraceptives.

Oral contraceptive (ORC)-related depression and irritability are among the most commonly reported drug-induced psychiatric symptoms. To investigate the etiological role of genetic factors in ORC-related symptoms, we studied questionnaire responses in 715 monozygotic and 416 dizygotic volunteer twin pairs concordant for ORC usage. Biometrical genetic analysis indicated that the liability to ORC-related depression was clearly influenced by genetic but not familial-environmental factors. Similar, but less definitive, results were found for ORC-related irritability. Multivariate genetic analysis indicated that both the genetic and the individual-specific environmental factors that influenced the liability to ORC-related depression and irritability were largely distinct from those that influence baseline levels of psychiatric symptoms. Genes play an important etiological role in ORC-related psychiatric side effects. The genes that influence liability to these side effects appear to differ from those that are etiologically important in baseline psychiatric symptomatology.

Affect↗
PubMed1987

Effect of phorbol and glucose on insulin secretion from the human fetal pancreas.

It has been reported previously that 12-0-tetradecanoylphorbol-13-acetate is capable of stimulating the release of insulin from adult and neonatal pancreatic tissue. The data from this study show that this agent at a concentration of 1.3 uM, in the presence of 2.8 mM glucose, was unable to cause significant secretion of insulin from cultured human fetal pancreatic explants. By contrast 20 mM glucose was able to cause a small but significant immediate increase in secretion of insulin, but was unable to maintain this response beyond ten minutes. When the two agents were combined, a synergistic effect was seen throughout the entire 50 minute period of stimulation. The reason for this synergism is unclear since, whilst both secretagogues were able to cause a rise in the levels of diacylglycerol, together no extra effect was observed.

Arachidonic Acid↗
PubMed1984

Pituitary-ovarian function in mothers who have had two sets of dizygotic twins.

Serum gonadotropin and estradiol levels were measured in 14 women with regular menses during the early and midfollicular phases. Early follicular follicle-stimulating hormone and, to a lesser extent, luteinizing hormone levels were significantly higher in a group of eight women who had had at least one set of dizygotic twins (six of whom had had two sets) than in a control group of six women with no dizygotic twins. Estradiol levels also tended to be higher in mothers of twins, particularly in the midfollicular phase. The two groups of women did not differ in age, height, weight, or parity.

Adolescent↗