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Biomedical subjects

H B Bosmann

Publications and source records attributed to H B Bosmann.

At least 19 recordsLinked to original sources
PubMed2000

Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein.

Immune activation results in the activation of adrenal steroidogenesis and inhibition of gonadal steroidogenesis. Previous studies indicated that these effects were caused primarily by activation and suppression of the secretion of ACTH and LH, respectively. However, other evidence indicated a direct effect of the immune system on the gonads. In this study, serum testosterone, quantitated by RIA after lipopolysaccharide injection, showed a significant decrease within 2 h. Parallel measurement of serum LH showed no change. There were no differences in LH receptor or cAMP produced in Leydig cells between vehicle- and lipopolysaccharide-injected mice. The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner. No change in StAR protein messenger RNA (mRNA) was detected by Northern analysis during this time, nor were any changes found in the levels of mRNA for the steroidogenic enzymes P450scc, 3beta-hydroxysteroid dehydrogenase delta4-delta5-isomerase, or P450c17. In the adrenal, StAR protein was increased, as was StAR protein mRNA. No changes were observed in the levels of mRNA for P450scc, 3beta-hydroxysteroid dehydrogenase delta4-delta5-isomerase, or P450c21. Thus, although the mechanisms of regulation differ, changes in the levels of StAR protein are a sensitive indicator of the steroidogenic capacity of these two tissues.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Sepsis produces depression of testosterone and steroidogenic acute regulatory (StAR) protein.

The hypothesis that induction of chronic peritoneal sepsis would produce depression of serum testosterone due to a decrease in Leydig cell steroidogenic acute regulatory (StAR) protein or P450c17 steroidogenic enzyme was tested. Male Sprague-Dawley rats (350-400 g) were randomized to septic and nonseptic groups. Sepsis was induced with a cecal slurry (200 mg/kg in 5 mL of 5% dextrose in water (D5W); intraperitoneal) while nonseptic rats received only sterile D5W. Animals (n = 6, in each group) were killed by CO2 asphyxiation and blood samples were collected by direct cardiac puncture at 24 h after induction of sepsis/sham sepsis. The serum concentration of corticosterone, progesterone, estradiol, and testosterone was determined using radioimmunoassay. Western blot analysis was utilized to quantify Leydig cell StAR protein and P450c17 enzyme. Sepsis produced a significant decrease in the serum concentration of testosterone, a down-regulation of StAR protein, and an increase in serum estradiol 24 h after induction of sepsis (as compared with the nonseptic group). Protein levels of P450c17 in Leydig cells and serum concentrations of progesterone and corticosterone 24 h after induction of sham sepsis or sepsis were not different. It is concluded that the decreases in serum testosterone after 24 h of chronic peritoneal sepsis correlated with reductions in StAR protein.

Animals↗
PubMed1998

Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and serum steroid hormones during sepsis.

Production of nitric oxide (NO) via NO synthase (NOS) has been implicated in the regulation of steroidogenesis in normal physiology and septic pathophysiology. The hypothesis that blockade of NOS by NG-nitro-L-arginine methyl ester (L-NAME) would affect testicular blood flow and circulating levels of steroid reproductive hormones was tested. Male Sprague-Dawley rats (350-450 g) were randomized to septic and nonseptic groups. Sepsis was induced with an intraperitoneal (i.p.) injection of a cecal slurry (200 mg/kg in 5 mL 5% dextrose in water (D5W)) in rats, while nonseptic rats received only sterile D5W. The rats (n = 6 per group) were catheterized in the jugular vein, left ventricle (via right carotid artery), and tail artery to determine blood flow and systemic hemodynamics and to collect blood at 24 h after induction of sepsis/sham sepsis. After baseline (24 h post-cecal slurry challenge) measurement, L-NAME (.50 mg/ kg x min) was infused through the jugular vein for 10 min, blood flow was determined using a radioactive microsphere technique, and blood samples were collected. The serum concentrations of corticosterone, progesterone, and testosterone were determined using radioimmunoassay. Plasma concentrations of NO byproducts (NOx) were determined using the Greiss reaction. After 24 h, heart rate, testicular blood flow, and NOx levels were significantly increased, whereas the serum concentration of testosterone was significantly decreased in the septic group as compared with the nonseptic group. However, serum concentrations of progesterone and corticosterone at 24 h after induction of sham-sepsis or sepsis were not statistically different. Infusion of L-NAME significantly reduced the testicular blood flow and serum NOx levels in septic rats as compared with their baseline values. The administration of L-NAME significantly increased the concentration of testosterone in nonseptic and septic rats as compared with their respective basal values. However, testosterone levels in septic rats were still significantly lower than in nonseptic rats. The results of this study indicate that the synthesis of NO through NO synthase may play a role in the regulation of testicular blood flow and the serum levels of testosterone, associated with chronic peritoneal sepsis in the rat.

Animals↗
PubMed1997

Sepsis alters myocardial and plasma concentrations of endothelin and nitric oxide in rats.

Cardiovascular derangements during sepsis may arise from a mismatch between endothelin (ET) and nitric oxide (NO). We hypothesized that progression of chronic peritoneal sepsis would affect cardiac performance and would modulate the concentrations of NO and ET in the heart and plasma. Male Sprague-Dawley rats (340-390 g) were catheterized and made septic with a cecal slurry (200 mg/kg: i.p.). Heart rate, mean arterial pressure, and plasma ET and nitrite/nitrate (NOX) were determined at 0, 4, 8, 12, 24, and 48 h after induction of sepsis. Septic rats were found to have tachycardia at 48 h following induction of sepsis. Mean arterial pressure and pulse pressure were not altered in septic and non-septic rats. In a separate series of experiments, the function of isolated hearts from septic and non-septic rats was assessed at preload pressures of 2, 5, and 10 mmHg. Sepsis produced a significant decrease in rates of pressure development and relaxation (+/-dP/dt) at 24 and 48 h as compared to the hearts of non-septic rats. In septic rats, plasma concentrations of ET were significantly increased at t = 4, 8, 12 h as compared to basal values, and at 12 h as compared to non-septic rats, and returned to basal levels at 24 and 48 h. In contrast, circulating NO levels did not become elevated until t = 8 h and remained elevated throughout the remaining times. In the left ventricle, the concentration of ET was found to be significantly increased both in septic and non-septic rats at 4 and 8 h as compared to t = 0 h. In the left ventricles of non-septic rats, ET levels returned to baseline values at 12 h, while in septic rats, the concentration of ET remained significantly elevated until 12 h. In septic rats, left ventricular NO levels were found to be significantly increased at t = 12 h. It appeared that induction of sepsis contributed to an imbalance in the plasma concentration of ET and NO 12 h after the induction of sepsis. However, a similar imbalance was not observed in the left ventricle. It is concluded from these observations that peritoneal sepsis in a chronic rat model produced a divergence of plasma NO and ET levels. This suggests a homeostatic imbalance between vasoactive mediators, i.e. ET and NO, could contribute to the cardiovascular derangements that occur during sepsis.

Animals↗
PubMed1996

Steroid hormone alterations following induction of chronic intraperitoneal sepsis in male rats.

The influence of sepsis on male reproductive function in chronic animal models has not been extensively investigated. On the basis of earlier clinical studies, it was hypothesized that chronic intraperitoneal (i.p.) sepsis in rats would modulate the circulating levels of steroid reproductive hormones. Male Sprague-Dawley rats (300-375 g) were randomized to septic and nonseptic groups. Sepsis was induced with cecal slurry (200 mg/kg/5 mL 5% dextrose in water (D5W); i.p.) in septic rats, while nonseptic rats received only sterile D5W. The rats (n = 8-12) were catheterized to measure systemic hemodynamics and to collect blood at 0, 12, 24, and 48 h after induction of sepsis/sham sepsis. A separate group of normal rats was included to serve as an unoperated control group. The plasma concentration of corticosterone, progesterone, and testosterone in serum was determined using radioimmunoassay. The heart rate was significantly increased at t = 12, 24, and 48 h following induction of sepsis. However, septic rats did not display any significant alterations in the mean arterial pressure and pulse pressure. Basal circulating concentrations of serum corticosterone, progesterone, and testosterone were 356 +/- 124 ng/mL, 2.37 +/- 1.03 ng/mL, and 1.88 +/- .29 ng/mL, respectively, in the unoperated rats. At t = 0 h there was a significant increase in the levels of corticosterone in septic rats and in the levels of progesterone in both septic and nonseptic rats. The elevations in the concentrations of corticosterone and progesterone returned to basal values after 24 and 48 h. The septic animals had significantly decreased levels of testosterone at t = 24 and 48 h as compared with basal values and nonseptic groups. Our model of sepsis produced a time-dependent decrease in levels of testosterone, an end product of male steroidogenesis. This, along with unchanged levels of corticosterone and progesterone at 24 and 48 h following sepsis, indicates that separate mechanisms for steroidogenesis regulating synthesis of these steroid hormones (progesterone and testosterone) occur with sepsis. It is concluded that in our chronic septic rat model, induction of i.p. sepsis produced dysfunction in steroidogenesis, which selectively affected the synthesis of testosterone.

Animals↗
PubMed1996

Acute in vivo inhibition of testosterone by endotoxin parallels loss of steroidogenic acute regulatory (StAR) protein in Leydig cells.

In an experimental endotoxemia model utilizing mice, serum testosterone was found to be decreased 90% two h post ip injection of 200 micrograms of lipopolysaccharide (LPS). This decrease was sustained for 9 days. The early depression of serum testosterone was shown to be associated with a decrease in Steroidogenic Acute Regulatory (StAR) protein levels while the prolonged decrease corresponded to decreased protein and transcript levels of steroidogenic enzymes in Leydig cells. This acute and prolonged depression of testosterone production could lead to impaired spermatogenesis, accessory duct failure, and contribute to decreased male fertility following acute inflammation.

Animals↗
PubMed1989

Superoxide dismutase activity in Alzheimer's disease: possible mechanism for paired helical filament formation.

Activity of the free radical scavenging enzyme, superoxide dismutase (SOD-1), was determined in fibroblast cell lines derived from familial Alzheimer's patients, trisomy 21 patients and normal controls. In the present study, SOD-1 activity was significantly elevated by 30% in Alzheimer's cell lines when compared to normal euploid cell lines. As SOD-1 activity is known to be elevated about 50% in trisomy 21 patients, these cell lines were included as a control for tissue culture and assay conditions. In the present study, SOD-1 activity was significantly increased by 42 +/- 11% in trisomy 21 patients. The elevation in SOD-1 activity observed in the familial Alzheimer's patients supports the theory that paired helical filaments are synthesized in Alzheimer's disease by free radical hydroxylation of proline residues in paired helical filament precursor protein(s).

Adolescent↗
PubMed1987

Growth hormone response to edrophonium in Alzheimer's disease.

Neuropathologic data from patients with Alzheimer's disease indicate the presence of neurofibrillary tangles in hypothalamic regions associated with regulation of pituitary hormone release. The authors explored the hypothesis that cholinergic projections to hypothalamic nuclei controlling pituitary growth hormone (GH) release degenerate in Alzheimer's disease. Integrity of cholinergic regulation was tested by assaying the GH response to a presynaptic cholinergic challenge. After administration of the choline esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients. The magnitude of GH blunting was correlated with cognitive and functional deficits. Possible implications of these data for enhanced accuracy in the diagnosis of dementia are discussed.

Aged↗
PubMed1986

Properties of a local anesthetic receptor in rat brain.

Saturable binding of local anesthetics in rat brain homogenates was demonstrated using (14C)-lidocaine and (3H)-bupivacaine. Saturation analyses revealed a single class of binding sites for lidocaine and bupivacaine. A series of drugs with local anesthetic properties inhibited this binding, while drugs without local anesthetic activity did not affect the specific binding. Specific binding of lidocaine and bupivacaine was maximal from pH 8 to 10; the pH versus binding profile was similar to that reported for local anesthetic blocking of peripheral nerve conduction. These characteristics suggest that binding of local anesthetics to this or similar sites mediates their pharmacological activity.

Anesthetics, Local↗
PubMed1985

Human platelet reactivity with intact segments of rabbit aorta and selected regions of rabbit, rat and human aorta.

A technique measuring platelet reactivity with vessel wall subendothelium has been modified to examine platelet reactivity with vessel pieces in place of intact segments of aorta of a specific diameter. This modification of Baumgartner's original technique (1) allows measurement of blood platelet reactivity with vessel pieces, 5 X 10 mm in size, mounted on perfusion chambers with "twist bands." Adhesion and aggregation of human platelets to deendothelialized surfaces of intact segments of rabbit aorta and pieces of rabbit, rat and human aorta, were equivalent. This modification will expand the use of Baumgartner's technique to investigations of platelet vessel wall interactions using blood platelets and vessels from numerous experimental animal models and humans. It will also facilitate examination of possible differences in thrombogenocity of selected areas of vessels such as those exhibiting stages of atherosclerotic plaque formation.

Animals↗
PubMed1982

Modulation of antitumoral antibody-dependent cellular cytotoxicity and natural killer activity by Adriamycin and daunorubicin.

Mouse effector cells isolated from various anatomical sources failed to mediate antibody-dependent cellular cytotoxicity (ADCC) against alloantiserum-coated L1210 murine leukemia cell targets, whereas rat spleen cells appeared to be potent mediators of this activity. Following suppression of effector cell function 3 days after a single drug injection, the nylon wool non-adherent population of rat spleen cells from daunorubicin (DM)-treated rats demonstrated an increased ability to mediate ADCC compared to controls. Alternatively, although suppression occurred at day 7, no rebound enhancement was demonstrated by the same cell population isolated from Adriamycin (AM)-treated animals for as long as 12 days post-injection. Natural killer (NK) activity, measured as the ability of the nylon wool non-adherent rat spleen cell population to lyse uncoated L1210 cells, was modulated by drug treatment in a similar manner at each time point although the changes were not significant. In contrast to NK cells for which a substantial amount of activity remained adherent to nylon wool, all K cell activity was found in the non-adherent spleen cell population. The effector cell, in both cases, was not susceptible to antithymocyte serum plus complement treatment; however, NK activity appeared trypsin-sensitive whereas K cell activity did not. Therefore, AM and DM demonstrated different activities with regard to in vivo modulation of antitumoral ADCC.

Animals↗
PubMed1982

Recurrent decreases of erythrocyte electrophoretic mobility in rats exposed to 1.0 R whole-body x-radiation.

Circulating erythrocytes from rats were examined up to 30 weeks post whole-body exposures of 1.0 R for alterations in the expression of net negative surface charge as measured by whole-cell microelectrophoresis in saline sorbitol. Erythrocyte electrophoretic mobility was determined in an apparatus composed of a horizontal transilluminated cylindrical chamber, equipped with a reversible, blacked platinum electrode, immersed in a water bath maintained at 25.0 +/- 1.0 degree C (Rank Brothers). In two separate experiments, recurrent decreases in the expression of net negative surface charge occurred at 10, 17, and 30 weeks post-irradiation. At these times distributional analyses of recorded erythrocyte electrophoretic mobility (EEPM) values revealed a skewing of the normally distributed EEPM population values to lower EEPM. Total sialic acid content released from hydrolyzed erythrocyte membrane preparations revealed no significant differences between erythrocytes from sham and irradiated animals. In vivo post-irradiation labeling of erythrocytes with diisopropyl-[32P] phosphorofluoridate at 4 and 33 weeks (separate experiments) indicated only a minor abbreviated erythrocyte life span at 33 weeks. Therefore, effects from low dose (1.0 R) whole-body irradiation would appear to include a recurrent defect in the expression of the net negative surface charge.

Animals↗
PubMed1982

Modulation of antibody-dependent cellular cytotoxicity against chicken erythrocyte targets by adriamycin and daunorubicin.

Peritoneal exudate cells isolated from Adriamycin (AM) or daunorubicin (DM)-treated mice demonstrated an increased ability to mediate antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated chicken red blood cell targets. Following initial suppression of this cell-mediated function 3 days after a single injection, increased effector cell efficiency occurred to an equal degree in both groups of drug treated mice by day 10 compared to controls. This increase in ADCC activity occurred in parallel with a decrease in the total number of peritoneal cells recovered. It is hypothesized that the drugs acted to modulate ADCC in two ways: 1) suppression by induction of suppressor cell activity, and 2) enhancement by elimination of suppressor cells which resulted in increased effector activity of the remaining cells.

Animals↗