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Biomedical subjects

J F Dunn

Publications and source records attributed to J F Dunn.

At least 73 records · Page 4Linked to original sources
PubMed1990

Alteration of vitamin D metabolism in Mexican-Americans.

Studies were performed to investigate vitamin D metabolism in Mexican-Americans. Groups of 15 whites and 16 Mexican-Americans ranging in age from 18 to 41 years were evaluated. All of them were within 25% of their ideal body weight. Each of them was admitted to the Clinical Research Center of the University of Texas Health Science Center and placed on a daily diet estimated to contain 400 mg calcium and 900 mg phosphate. It was found that whereas serum vitamin D (1.8 +/- 0.5 versus 7.6 +/- 1.3 ng/ml, P less than 0.001) and serum 25-hydroxyvitamin D (9 +/- 1 versus 17 +/- 2 ng/ml, P less than 0.01) were significantly lower and serum 1,25-dihydroxyvitamin D (37 +/- 2 versus 28 +/- 2 pg/ml, P less than 0.001) was significantly higher in the Mexican-Americans than in the whites, serum calcium (9.1 +/- 0.1 versus 9.2 +/- 0.1 mg/dl), magnesium (1.84 +/- 0.07 versus 1.80 +/- 0.07 mEq/liter), and Gla protein (19 +/- 3 versus 21 +/- 2 ng/ml) were not different in the two groups. Urinary calcium (144 +/- 14 versus 124 +/- 16 mg/day), phosphate (672 +/- 51 versus 683 +/- 44 mg/day), sodium (110 +/- 8 versus 99 +/- 9 mEq/day), potassium (43 +/- 4 versus 49 +/- 3 mEq/day), and magnesium (7.3 +/- 0.7 versus 7.7 +/- 0.5 mEq/day) and creatinine clearance (173 +/- 14 versus 154 +/- 7 liters/day) were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Increased testosterone in type I diabetic subjects with severe retinopathy.

Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured serum testosterone, estradiol, DHEA-S, and sex hormone binding globulin levels in 26 men and 22 women with type I diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic complications. The mean age was 23 years and the mean duration of diabetes was 14 years. Subjects with proliferative or preproliferative retinopathy (greater than or equal to retinopathy level 51-80) were matched by duration of diabetes (+/- 2 years) and sex to subjects with minimal or no retinopathy (less than or equal to retinopathy level 21). Seven stereoscopic retinal photographs of each eye were obtained and photographs were read by the University of Wisconsin Reading Center. Serum testosterone concentrations were significantly higher in male diabetic subjects with proliferative retinopathy (648 +/- 36 ng/dl) than in male diabetic subjects with minimal or no retinopathy (512 +/- 43 ng/dl) (P = 0.017). No other statistically significant differences in sex hormones between subjects with and without proliferative retinopathy were observed. Although these results should be regarded as preliminary because of the small number of subjects, they support the hypothesis that testosterone concentrations may be associated with the development of retinopathy in type I diabetic patients.

Adolescent↗
PubMed1990

The relationship of insulin sensitivity and metabolic clearance of insulin to adiposity and sex hormone binding globulin.

Previous studies have shown that sex hormone binding globulin (SHBG) is negatively associated with insulin concentrations in premenopausal women. We determined insulin sensitivity (SI) and clearance (KI) in 8 non-obese men and 13 nonobese premenopausal women using the minimal model of Bergman and colleagues. Insulin clearance and insulin sensitivity were strongly correlated (p less than 0.05). SHBG was positively correlated with SI (i.e., individuals with high levels of SHBG had greater insulin sensitivity) in both men (r = .738, p less than 0.05) and women (r = .577, p less than 0.06). Insulin clearance was also positively correlated with SHBG in men (r = .619) and in women (r = .476) (0.05 less than p less than 0.10). Since obese subjects have both lower SHBG concentrations and decreased insulin sensitivity, we examined the effect of correcting for adiposity by partial correlation analyses. SHBG was not associated with KI after adjustment for BMI. SHBG was still positively correlated with SI in both men (r = .708) (p less than 0.06) and women (r = 0.541) (p less than 0.06), suggesting that the relationship between SHBG and insulin sensitivity is not confounded by obesity. Thus, the relationship of androgenicity with insulin sensitivity (but not insulin clearance) was independent of adiposity.

Adipose Tissue↗
PubMed1990

Increased production of tumor necrosis factor by normal immune cells in a model of the humoral hypercalcemia of malignancy.

The rat Leydig cell tumor is a well characterized model of the humoral hypercalcemia of malignancy. The studies reported here were provoked by the observation that tumor-bearing rats become extremely cachectic and develop hypertriglyceridemia as they become hypercalcemic. Since the bone resorbing cytokine tumor necrosis factor (TNF)/cachectin is associated with cachexia and hypertriglyceridemia, we examined hypercalcemic tumor-bearing rats for evidence of increased TNF production using a TNF radioimmunoassay. We found that immunoreactive TNF was increased in the plasma of tumor-bearing rats. The increase in plasma TNF was comparable to that previously shown in hypercalcemic nude mice bearing Chinese hamster ovarian cell tumors transfected with the human TNF gene. There was no detectable TNF activity in tumor culture media which suggested that the tumor itself was not the source of excess TNF production. However, we found that tumor cell conditioned media enhanced the production of TNF activity by normal macrophages in vitro, indicating that increased TNF production in vivo may result from a tumor factor(s) which stimulates TNF production by normal immune cells. When TNF was added together with tumor products to organ cultures of fetal rat long bones, osteoclastic bone resorption was potentiated. These data are consistent with the concept that in this model of the humoral hypercalcemia of malignancy, increased TNF production by normal immune cells is increased, has systemic effects as suggested by cachexia and hypertriglyceridemia, and may work in concert with factors produced directly by tumor cells to overwhelm normal calcium homeostasis.

Animals↗
PubMed1990

Osgood-Schlatter disease.

Osgood-Schlatter disease is a generally benign, self-limited knee condition most commonly found in rapidly growing and athletically active adolescents. Diagnosis is based on clinical and radiographic examination. Although the etiology of this disorder is controversial, chronic microtrauma to the tibial tuberosity secondary to overuse of the quadriceps muscle is suspected. Management strategies usually include analgesics and restrictions on physical activities involving the knee. Surgical treatment may be required in recurrent, disabling cases or for removal of a cosmetic deformity.

Adolescent↗
PubMed1989

Induction of tumour hypoxia by a vasoactive agent. A combined NMR and radiobiological study.

The effect of hydralazine treatment on 3 murine tumours (RIF-1, KHT and 16/C) was monitored using 31P-NMR. Changes in the 31P-NMR spectrum are compared with measurements of radiobiological hypoxic fraction (RHF) in the RIF-1 and KHT. Hydralazine is known to reduce temporarily blood flow in experimental tumours, and thus cause a transient increase in the RHF to 100% (in RIF-1 and KHT). This correlates with a decline in energy status as measured by 31P-NMR (i.e. there was an increase in Pi in all three tumours). Time-course data from the RIF-1 and KHT tumours show that maintenance of anaesthesia prolongs the hypoxia induced by hydralazine.

Animals↗
PubMed1989

Common bile duct healing. Do different absorbable sutures affect stricture formation and tensile strength?

Few basic investigations have addressed the problem of common bile duct strictures. We systematically investigated the healing canine end-to-end choledochal anastomosis and tested the hypothesis that common bile duct anastomoses sutured with monofilament polyglyconate absorbable suture would heal with less stricture formation and greater tensile strength than those sutured with braided polyglactin 910 and chromic catgut sutures. Seventy-six canines, randomized to control vs sutured groups, underwent either mobilization (controls) or transection of the mid-common bile duct and were allowed to heal 5, 10, 15, or 50 days postoperatively before sacrifice. The type of absorbable suture used to construct a common bile duct anastomosis was found to have no major effect on anastomotic strictures nor on anastomotic breaking strength. Polyglyconate suture caused significantly less perianastomotic inflammation than did chromic suture, with polyglactin 910 sutures evoking an intermediate inflammatory response. Surgeons may safely choose sutures for biliary procedures based on the clinical circumstances and personal preference.

Anastomosis, Surgical↗
PubMed1989

Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population.

Previous data have indicated that decreased sex hormone binding globulin (SHBG) is associated with increased overall and upper body adiposity and higher levels of glucose, insulin and triglyceride (TG) and decreased levels of high-density lipoprotein (HDL) cholesterol. Since Mexican Americans have greater overall and upper body adiposity, higher rates of non-insulin-dependent diabetes mellitus, higher TG and lower HDL levels than non-Hispanic whites, we postulated that they would also have lower levels of SHBG. We measured total testosterone and total estradiol using a commercial radioimmunoassy and SHBG using a dextran-coated charcoal technique in premenopausal women (61 Mexican American and 39 non-Hispanic white) as part of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. There were no significant ethnic differences in total testosterone or total estradiol. SHBG, however, was lower in Mexican American (0.285 micrograms/dl) than in non-Hispanic white women (0.429 micrograms/dl) (P = 0.009). After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfolds (centrality index), SHBG remained lower in Mexican Americans (0.307 micrograms/dl) than in non-Hispanic whites (0.396 micrograms/dl), although this difference was no longer statistically significant (P = 0.083). BMI, WHR and centrality index were all negatively associated with SHBG (P less than 0.01). The lower levels of SHBG in premenopausal Mexican American women compared to non-Hispanic white women may reflect greater in-vivo androgenicity and may be related to a variety of metabolic abnormalities seen in this ethnic group.

Adipose Tissue↗
PubMed1988

The relationship of sex hormones to hyperinsulinemia and hyperglycemia.

Mexican-Americans, a high-risk population for non-insulin-dependent diabetes mellitus (NIDDM), have been previously reported to have decreased levels of sex-hormone-binding globulin (SHBG). We measured total testosterone, total estradiol and SHBG, glucose and insulin in premenopausal women (58 Mexican-Americans and 38 non-Hispanic whites) as part of the San Antonio Heart Study, a population-based study of cardiovascular risk factors. Although total estradiol and total testosterone were, in general, not correlated with metabolic variables, SHBG was negatively correlated with glucose and insulin. After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfold (Centrality Index), SHBG was still significantly correlated with insulin concentrations (P less than .001). Since Mexican-Americans were previously reported to be more hyperinsulinemic than non-Hispanic whites, we examined the effect of adjusting for SHBG on insulin levels in this small population. While unadjusted insulin concentrations in Mexican-Americans were higher than in non-Hispanic whites (354 microU/mL v 236 microU/mL, respectively, P = .009), adjustment for BMI, WHR, and centrality index reduced the ethnic difference in insulin levels considerably (P = .014). However, only after adjusting for SHBG as well, did the ethnic difference in insulin levels became nonsignificant. Our data suggest that alterations in sex hormones and SHBG in particular may be related to the hyperinsulinemia and the high rates of NIDDM in Mexican-Americans.

Adult↗
PubMed1988

Pseudofolliculitis barbae.

Pseudofolliculitis barbae is a chronic, distressing and potentially disfiguring dermatologic disorder that occurs predominantly in black men. The condition is caused by hairs curling back into the skin and is characterized by papules, pustules and, occasionally, keloidal scars over the beard region. Management includes cessation of shaving, the use of depilatories or topical antibiotics and modification of shaving techniques.

Facial Dermatoses↗
PubMed1988

The effect of ketoconazole on steroidogenesis. II. Adrenocortical enzyme activity in vitro.

The activity of five adrenocortical steroidogenic enzymes, 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase) 17,20 desmolase (17,20D), 21-hydroxylase (21-OHase) and 11-hydroxylase (11-OHase), were measured in vitro in purified mitochondria or microsomes from rhesus monkey (Macaca mulata) and human adrenal tissue in the presence and absence of graded concentrations of ketoconazole. Rhesus 3 beta-HSD activity was unaffected by ketoconazole at concentrations up to 5000 microM. However, human adrenal 3 beta-HSD was inhibited by approximately 40% (p less than .01) at concentrations of 500 microM and by 80% at 100 microM. 17-OHase and 17,20D were significantly inhibited in the human at 5 microM (p less than .001) and in the rhesus monkey at 50 microM (p less than .001). A similar inhibitory effect was found on microsomal 21-OHase, with significant inhibition at 5 microM ketoconazole in the human and rhesus monkey (p less than 0.001). Mitochondrial 11-OHase was also significantly inhibited by ketoconazole in both the human (p less than .005) and rhesus (p less than .001) at 2.0 microM. These results represent documentation of the specific adrenal steroidogenic steps affected by ketoconazole and confirm the observations that this imidazole derivative is a powerful inhibitor of enzymes in the glucocorticoid pathway.

3-Hydroxysteroid Dehydrogenases↗
PubMed1988

The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.

The in vitro inhibition of Leydig cell microsomal steroidogenesis by ketoconazole, a potent P-450 dependent enzyme blocker, was evaluated in the human, stallion and pig. Purified Leydig cells were isolated by mechanical dispersion of teased, decapsulated whole testes and sieving through a 0.25 mm stainless steel mesh. The activity of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase), 17,20-desmolase (17,20D), 17-ketosteroid reductase (17-KSR) and aromatase were measured using a constant amount (50 microM) of 14C-labelled substrates in the presence of varying concentrations of pure ketoconazole. Products were isolated by thin layer chromatography and verified by derivative formation. 17-OHase and 17,20D activities were significantly inhibited (p less than .001) by ketoconazole at concentrations as low as 5 microM. 3 beta-HSD, 17-KSR and aromatase activities were only significantly inhibited by ketoconazole at concentrations of 500 and 5000 microM. These data describe the specific loci of inhibition of ketoconazole on testicular steroidogenesis and confirm the observations that ketoconazole is an effective inhibitor of androgen biosynthesis in several species.

Aldehyde-Lyases↗
PubMed1987

Adrenal response to corticotropin during therapy with itraconazole.

Itraconazole is a triazole with a mechanism of action similar to that of ketoconazole. Endocrine side effects of ketoconazole, including impaired cortisol synthesis, have been well documented (A. Pont, J. R. Graybill, P. C. Craven, J. N. Galgiani, W. E. Dismukes, R. E. Reitz, and D. A. Stevens, Arch. Intern. Med. 144:2150-2153, 1984). We examined the adrenal response to corticotropin in 10 patients being treated with itraconazole. No impairment of cortisol synthesis could be demonstrated.

Adrenal Cortex↗
PubMed1986

Living related kidney donors. A 14-year experience.

Living related donor (LRD) nephrectomies are controversial due to the risks to the donor and improved cadaveric graft survival using cyclosporine A. Between December 22, 1970, and December 31, 1984, 1096 renal transplants were performed at a single institution, 314 (28.6%) from LRD. The average age was 34.3 years (range: 18-67); none had preoperative hypertension. All nephrectomies were performed transabdominally. Major perioperative complications occurred in 22 (7.0%). These include wound infections (3.5%), pancreatitis (1.0%), injuries to spleen (1.0%) or adrenal gland (0.3%) requiring removal, pneumonitis (0.6%), ulnar nerve palsy (0.6%), femoral artery thrombosis after arteriogram (0.3%), pulmonary embolus (0.3%), and upper pole infarct of contralateral kidney (0.3%). There are six known deaths in this series, none of which were related to the operation. Major late complications were seen in 50 (20.0%) of 250 patients followed for 6 to 175 months (mean 53.1 months). These included definite hypertension (5.6%), suture granuloma (4.4%), incisional hernia (3.6%), proteinuria (2.4%), bowel obstruction (2.0%), nephrolithiasis (1.2%), wound infection (0.4%), scrotal hydrocele (0.4%), and chronic pancreatitis (0.4%). While the risk of hypertension appears to increase as the interval from donation increases, no cases of renal failure after donation have been noted, and negligible proteinuria among those followed long-term has been seen in this series. It is felt that living related kidney donation is justified when the relative is sincerely motivated and well informed prior to donation.

Adolescent↗
PubMed1986

Consistency and change in mothers' behavior toward young siblings.

Siblings differ markedly in behavioral development, and it has been suggested that differential maternal treatment may contribute significantly to these differences. The question of how consistently mothers treat their different children was examined in a study of 45 sibling pairs from the Colorado Adoption Project, in which each child at 24 months of age was videotaped at home with the mother. The results showed mothers to be consistent in affection and verbal responsiveness but to differ in their controlling behavior toward the 2 siblings. Comparison of the same mother's behavior to the 2 siblings at 12 months and at 24 months showed little stability in maternal behavior to the same child over this age period.

Adoption↗
PubMed1986

Production of 1,25-dihydroxyvitamin D3 by human T cell lymphotrophic virus-I-transformed lymphocytes.

The human T cell lymphotrophic virus type I (HTLV-I) has recently been identified in a T cell lymphoma associated with hypercalcemia and increased bone turnover. Since increased serum concentrations of 1,25-dihydroxyvitamin D have been reported in this disease, we have examined the capacity of HTLV-I-infected cord blood lymphocytes to metabolize 25-hydroxyvitamin D3. Our results demonstrate that HTLV-I-infected cells have the capacity to metabolize 25-hydroxyvitamin D3 to a substance that co-migrates with 1,25-dihydroxyvitamin D3 by high performance liquid chromatography over a silica column using either 12% isopropanol in hexane or 5% isopropanol in dichloromethane. The metabolite binds to the 1,25-dihydroxyvitamin D3 receptor in rat osteosarcoma cells and stimulates bone resorption in cultures of fetal rat long bones. Mass spectrometric analysis of the metabolite confirmed the presence of 1,25-dihydroxyvitamin D3. Production of 1,25-dihydroxyvitamin D by lymphoma cells may contribute to the pathogenesis of the hypercalcemia seen in patients with HTLV-I-associated T cell lymphomas.

Animals↗
PubMed1986

Vitiligo.

Vitiligo is characterized by depigmentation in large or small areas of the skin. There is a complete lack of melanin production in the hypopigmented areas, due to the destruction of previously active melanocytes. This is in contrast to albinism, in which melanocytes are present but there is little or no pigmentation because of defective or absent tyrosinase. Although the etiology of vitiligo remains unknown, an autoimmune theory is gaining acceptance.

Adolescent↗