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Biomedical subjects

J A Jackson

Publications and source records attributed to J A Jackson.

At least 19 recordsLinked to original sources

Platelet-derived growth factor regulation of fos stability correlates with growth induction.

A brief exposure of quiescent, density-arrested Balb/c 3T3 fibroblasts to platelet-derived growth factor (PDGF) results in expression of the proto-oncogene c-fos; furthermore, the translation product of c-fos, p55fos, was shown to have increased stability in cells upon continued exposure to PDGF. The induction of competence or growth initiation requires a longer exposure to PDGF than that necessary for the induction of the immediate-early, growth-related genes. The need for the continued presence of PDGF for growth initiation beyond the time required for the induction of immediate-early gene expression may be due, in part, to PDGF-dependent post-translational stabilizations of gene products. We speculate that a PDGF-mediated event increases p55fos stability, resulting in a continued elevated level of Fos protein, which in turn allows a continued Fos-mediated activity required by Balb/c 3T3 cells to become competent to enter the cell cycle.

3T3 Cells

Testosterone deficiency as a risk factor for hip fractures in men: a case-control study.

The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men. The study was a matched case-control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center. The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period, 11 men with a history of hip fractures in the preceding 25 months, and 28 randomly selected age-, race-, and living status-matched control subjects (mean age 73 years). Serum pooled total testosterone (9.2 +/- 5.5 nmol/L vs. 12.8 +/- 5.4 nmol/L; p less than 0.02) and free testosterone (37.9 +/- 18.8 pmol/L vs. 48.4 +/- 20.6 pmol/L; p less than 0.03) were significantly lower in hip fracture vs. control patients. Testosterone deficiency was found in 20 (71%) hip fracture men vs. 9 (32%) of the controls (p = 0.003; odds ratio 5.3). Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results. Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men (p less than 0.001). The conclusion is that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men. Prevention of hip fractures in men may involve early recognition and treatment of testosterone deficiency.

Aged

Inhibition of bovine retinal microvascular pericyte proliferation in vitro by adenosine.

Adenosine acts on bovine retinal microvascular pericytes through one or more adenosine receptor subtypes present on the cell surface. Retinal pericytes cultured in medium containing adenosine at concentrations from 10(-6) to 10(-4) M showed significant reduction in proliferation following several days in vitro compared with control cultures. The effects of adenosine were mimicked by polyadenylic acid and inhibited by 8-phenyltheophylline, indicating involvement of a cell surface receptor. Metabolites of adenosine had no effect on pericyte proliferation. An A2 adenosine receptor-specific analogue also inhibited pericyte growth, suggesting that inhibition by adenosine is mediated by A2-receptors and might involve a transient increase in adenosine 3',5'-cyclic monophosphate levels. The results of the present study demonstrate that in addition to demonstrated stimulatory effects on capillary endothelial cells, adenosine also has a direct inhibitory effect on retinal pericytes. We hypothesize a dual function of adenosine within the capillary wall resulting in loss of inhibition of endothelial cells and suggest a role for this nucleoside in pathological neovascularization processes such as proliferative diabetic retinopathy.

Adenosine

Influence of cation-anion balance on feed intake, body weight gain, and humoral response of dairy calves.

The objective of this study was to examine the influence of diets with varying cation-anion balance on performance and humoral responses in young, growing dairy calves. Twenty-eight Holstein and 4 Jersey female calves were blocked at 56 to 70 d after birth according to breed and age and assigned randomly to dietary treatments of 0, 21, 37, and 52 meq(Na + K) - Cl/100 g of dietary DM. Diets were based on cracked corn, dried brewers grains, and oats and were fed for 8 wk. Feed intake and average daily gain tended to increase quadratically, being highest for calves fed the +37-meq diet and lowest for those fed the 0-meq diet. Blood and urine pH increased linearly with increasing dietary cation-anion balance. Plasma Ca increased linearly, and Mg and Cl decreased linearly with increasing cation-anion balance. Plasma Na and P were unaffected by dietary treatments. Urinary Ca, Mg, and Cl excretions decreased linearly; urinary P, Na, and K excretion increased linearly with increasing dietary cation-anion balance. Blood pH increased linearly with increasing dietary cation-anion balance. Blood partial pressure of CO2 and HCO3 increased concurrently with increasing dietary cation-anion balance. Results indicate that altering cation-anion balance may impact DMI and average daily gain in the young ruminant.

Animal Feed

The cardiovascular capacities of adults with Down syndrome: a comparative study.

The purpose of this study was to compare the cardiovascular capacities of individuals with Down syndrome (DS) to individuals without Down syndrome who are mentally retarded. Sixteen young adults with DS and 16 individuals without DS (12 males and 4 females, respectively), all with mild/moderate mental retardation, participated in this study. Peak VO2 (absolute and relative), VE (1.min-1), heart rate (HR, b.min-1), and RER (VCO2/VO2) were determined by exercise tests utilizing a treadmill (TM) and Schwinn Air-Dyne ergometer (SAE). The best test result was chosen from the TM and SAE tests and used for statistical comparisons. Cardiac output (Q, 1.min-1) was measured while standing quietly and while walking at 3 mph, 0% grade, using the CO2 rebreathing method for 11 (9 males and 2 females) subjects from each group. Arteriovenous oxygen differences (a-v O2), cardiac index (QI), and stroke volume (SV) were calculated from VO2, Q, HR, and body surface area. Peripheral vascular resistance (PVR), left ventricular work index (LVWI), and left ventricular stroke work index (LVSWI) were calculated from mean arterial pressure, Q, QI, and stroke volume index. Results showed that individuals without DS had statistically significant (P less than 0.01) higher mean peak VO2 (35.6 vs 24.6 ml.kg-1.min-1; 2567 vs 1683 ml.min-1), VE (89.3 vs 59.2 1/min-1), and HR (179 vs 159 b.min-1) than individuals with DS, respectively. No differences in RER were seen between the groups. No differences were seen in cardiovascular parameters measured while quietly standing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Renin-secreting juxtaglomerular tumor causing severe hypertension: diagnosis by computerized tomography-directed needle biopsy.

Renin-secreting tumors are a rare cause of severe hypertension accompanied by hypokalemia. Typically, these tumors have been difficult to diagnose preoperatively by standard radiographic and hormonal studies. We describe a 44-year-old man who was hospitalized for paroxysmal hypertension and who had a 2.3 cm. mid upper pole renal mass on sonography. Computerized tomography-directed needle biopsy revealed a juxtaglomerular tumor and surgical excision of the tumor was curative. We discuss the unique diagnostic aspects of this case.

Adult

Preovulatory changes in glycosaminoglycans and collagen content in the stigma region of the follicle of the domestic hen.

The present study determined the amount and types of glycosaminoglycans and collagen concentrations in follicles of the domestic hen. The stigma (S; the area of follicular rupture) and nonstigma (NS) regions of the theca layer were isolated from the preovulatory follicle (F1) and an immature follicle (F2) that were to ovulate 30 min and 26 h later, respectively. Glycosaminoglycan density, which was estimated by measuring follicular uronic acid concentration (micrograms/mg dry wt), was lower (p less than 0.01) in F1S (2.6 +/- 0.1) compared to F1NS (3.4 +/- 0.2), F2S (3.4 +/- 0.1), and F2NS (3.4 +/- 0.1). Theca glycosaminoglycans consisted of approximately 58% dermatan sulfate, 20% heparan sulfate, and 22% hyaluronic acid. The F1S contained lower (p less than 0.05) amounts of dermatan sulfate and hyaluronic acid compared to F1NS, F2S, and F2NS. There was no significant difference in amounts of heparan sulfate in the F1S, F1NS, F2S, and F2NS. Collagen density, which was estimated by measuring follicular hydroxyproline concentrations (micrograms/mg dry wt), were lower (p less than 0.01) in F1S (20.3 +/- 1.4) and F2S (19.8 +/- 1.4) compared to F1NS (28.9 +/- 1.9) and F2NS (29.9 +/- 2.7). However, there was not a further decrease in collagen concentration in the F1S compared to F2S. We suggest that glycosaminoglycans may be degraded specifically in the stigma region of the preovulatory follicle prior to ovulation. The lower amount of collagen in the stigma region may decrease the tensile strength in the stigma compared to the nonstigma region regardless of maturational stage.

Animals

Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells.

The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day (mean +/- SEM; n = 5) after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by [35S]methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium. The immunoreactive IGFBP-1 isolated from culture medium was found to be identical, by a number of criteria, with IGFBP-1 derived from decidual tissue. These results were consistent with a primary role of progestin exposure, whether in vivo or in vitro, in converting endometrial stromal cells to cells potentially able to exhibit the high rates of IGFBP-1 production typical of the decidualized endometrium of pregnancy.

Adult

Role of sulfur and chloride in the dietary cation-anion balance equation for lactating dairy cattle.

Ten Holstein cows averaging 120 d in lactation were arranged in replicated 5 x 5 Latin squares with 3-wk periods to evaluate the role of sulfur (S) in the dietary cation-anion balance equation. Diets were based on corn silage in Exp. 1 and sorghum silage in Exp. 2. Supplemental S and chloride (Cl) from the double sulfate of potassium and magnesium and CaCl2 were used to manipulate dietary cation-anion balance from 0 to +30 meq when expressed as meq [(Na + K)-(Cl + S)]/100 g diet DM and from +19 to +49 meq when expressed as meq [(Na + K)-Cl]/100 g diet DM. Blood pH was not affected by cation-anion balance, although both S and Cl supplementation tended to lower pH. Blood HCO3- and urine pH decreased and plasma calcium (Ca) and urinary Ca excretion increased as anion was added to the diet. Milk fat production tended to be increased by the low S supplementation. Dietary Cl and S had similar effects on acid-base status. Therefore, we suggest that S be included with Cl in the dietary cation-anion balance equation for lactating dairy cows as follows: meq [(Na + K)-(Cl + S)]/100 g diet DM. Although response of acid-base status to S and Cl was similar, as more data comparing the acidogenicity of S vs Cl become available, it may be necessary to include a modifying coefficient for S in the equation to adjust for differences between S and Cl in acid-generating potential. This coefficient may be further dependent on the dietary source of S.

Acid-Base Equilibrium

Endotoxin mastitis in cows milked four times daily.

As part of a project to identify the pathophysiological cause or causes of mastitic hypogalactia, midlactation cows were infused in two homolateral quarters with 10 micrograms of endotoxin while being milked four times daily to resolve better the temporal changes in mammary synthetic activity during endotoxin mastitis. Milk fat was decreased by the first milking (5 h) postinfusion and then recovered rapidly. In contrast, milk yield and the yields of protein and lactose were not significantly inhibited until the second milking, and these yields recovered slowly thereafter. The decline in milk yield by infused quarters was only 20% greater than the decline by uninfused quarters in this experiment. Mammary inflammation developed rapidly in infused quarters as milk serum albumin concentration was maximal at the first milking. Milk SCC and NAGase were also elevated at this time, and maximal levels occurred at milkings 2 to 4. Increased temperature, increased cortisol, and a mild anorexia were apparent at the first milking only. Endotoxin treatment had no effect on serum prolactin or glucose. These data suggest that the delayed hypogalactia is consequent to the mammary inflammation and systemic responses following endotoxin infusion. The results indicate that different pathophysiological events may inhibit synthesis of the different milk components.

Animals

Influence of dietary sodium bicarbonate on the potassium metabolism of growing dairy calves.

We evaluated the influence of supplemental dietary NaHCO3 on K metabolism of young dairy calves. Thirty-two Holstein and Jersey male and female calves were blocked at 56 to 70 d after birth according to breed, sex, and age and assigned randomly to a 2 x 2 factorial arrangement of dietary treatments for 8 wk: .4% K with 0% NaHCO3, .4% K with 2% NaHCO3, .6% K with 0% NaHCO3, and .6% K with 2% NaHCO3. Feed intake was not affected by dietary KCl or NaHCO3 supplementation, but average daily gain increased with increased K and tended to be reduced by dietary NaHCO3. Plasma K was elevated by increased dietary K but generally was unaffected by NaHCO3. Urinary Ca excretion appeared to be reduced by NaHCO3; urine pH increased with supplemental NaHCO3. Results indicate 1) the K requirement of the growing calf is between .40 and .55% of diet DM, 2) because urinary K excretion was elevated by dietary NaHCO3, the K requirement may be increased when the diet is supplemented with NaHCO3, and 3) average daily gain and plasma K are sensitive indicators of dietary K in the growing calf.

Animals

Effects of copper sources and dietary cation-anion balance on copper availability and acid-base status in dairy calves.

Twenty-four Holstein and Jersey calves (14 Holstein), 4 to 11 d of age, were assigned randomly to six treatments in a 2 x 3 factorial arrangement to examine the effects of Cu sources and dietary cation-anion balance on Cu availability and acid-base balance. Treatments were cationic basal diet (20 meq of dietary cation-anion balance on a DM basis), cationic basal diet supplemented with CuO, cationic basal diet supplemented with CuSO4, anionic basal diet (-10 meq), anionic basal diet supplemented with CuO, and anionic basal diet supplemented with CuSO4. Copper sources did not show any effect on growth of calves. The cationic diet increased calf growth compared with the anionic diet at wk 12 of the experiment. Blood pH was increased by the cationic diet in comparison with the anionic diet at wk 8 and 12. Blood pH also was increased by CuSO4 compared with CuO treatment in the early period of the treatment. Blood bicarbonate concentration was decreased by CuO and the anionic diet. Interactions between Cu sources and cation-anion balance were found for blood pH and bicarbonate concentration. Liver Cu concentration was increased by CuSO4 but not by CuO supplementation compared with control. Therefore, CuSO4 was found to be highly available, whereas CuO was a very poorly available source of Cu for young calves.

Acid-Base Equilibrium

Reduced lactational performance following intravenous endotoxin administration to dairy cows.

Nonpregnant lactating cows were given 100 micrograms of endotoxin via the jugular vein to determine effects of intravenous endotoxin administration on mammary inflammation and lactational performance. At the first milking (11 h) posttreatment, milk yield was reduced 33%. Milk fat percentage was elevated at this time, but lactose concentration was decreased. Milk yield and composition returned to pretreatment levels within 2 d. Clinical mastitis was not induced by endotoxin treatment, but milk SCC, NAGase, serum albumin, and lactoferrin were increased by 50%. This increase was small compared with increases during mastitis and may have resulted from lower milk volume. These results support the hypothesis that part of the reduced lactational performance during endotoxin mastitis is mediated by systemic pathophysiological responses and indicate that intravenous endotoxin administration may be a useful model to study adverse effects of infectious disease on lactational performance.

Animals

Suppression of milk production during endotoxin-induced mastitis.

Healthy, midlactation cows were given intramammary infusions of 10 micrograms of endotoxin in two homolateral quarters. Productive, inflammatory, and systemic responses were studied to investigate the pathophysiological effects of mastitis on lactational performance. Endotoxin suppressed milk yield in all quarters of treated cows. A more severe and prolonged suppression occurred in infused quarters compared with uninfused quarters. The fat percentage of milk from all quarters was increased with a greater increase occurring in infused quarters. The protein composition of milk was elevated, and the lactose concentration was depressed in infused quarters. Mammary inflammation--as measured by milk SCC, NAGase, serum albumin, and lactoferrin--was limited to infused quarters. Changes in milk NAGase closely paralleled changes in milk SCC. Daily feed intake was unaffected, and serum glucose levels did not decline following infusion. The lactose concentration of urine increased rapidly after infusion. Reduction in milk yield in all quarters, but varying changes in milk composition in infused versus uninfused quarters suggest that mastitic hypogalactia is mediated by multiple pathophysiological events and is not solely due to inflammatory damage to the mammary epithelium. Part of the reduced lactational performance may result from escape of milk components from the udder into the circulation.

Acetylglucosaminidase

Hyperandrogenemia and virilization with simultaneous pituitary and adrenal adenomas.

We describe a postmenopausal woman who presented with virilizing hyperandrogenemia and was found to have an intrasellar tumor and a large left adrenal mass. Pathologic studies showed on undifferentiated hypophyseal adenoma with immunostaining for chromogranin only and a benign adrenocortical adenoma. In light of current understanding of the regulation of adrenal androgen secretion and adrenocortical mitogenesis, we postulate that this case may be explained by secretion of adrenal androgen-stimulating and mitogenic factors by the pituitary tumor.

Adenoma

Disseminated histoplasmosis with bilateral adrenal enlargement: diagnosis by computed tomography-directed needle biopsy.

Disseminated histoplasmosis is a rare and potentially fatal disease caused by the dimorphic soil fungus Histoplasma capsulatum. We describe a 67-year-old man with diabetes who presented with a 6-month history of fever, weight loss, and mental deterioration; using computed tomography (CT), we found hepatosplenomegaly and bilateral adrenal masses. CT-directed adrenal biopsy showed yeast forms consistent with H capsulatum. Therapy with ketoconazole was accompanied by adrenal insufficiency (treated successfully with prednisone and fludrocortisone) and produced an excellent therapeutic response. We address the differential diagnosis of bilateral adrenal enlargement, and we discuss the clinical features, diagnosis, and treatment of disseminated histoplasmosis, a disease that includes parts of the Southwestern United States in its endemic region.

Adrenal Glands