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Biomedical subjects

M Hoenig

Publications and source records attributed to M Hoenig.

At least 55 records · Page 3Linked to original sources
PubMed1992

Hematologic and serum biochemical effects of long-term administration of anti-inflammatory doses of prednisone in dogs.

Results of routine hematologic and serum biochemical analyses from 12 healthy adult male dogs that were given prednisone (0.55 mg/kg of body weight, PO, q 12 h) for 35 days were compared with those of a control group of 6 dogs that were given gelatin capsules. Analyses were performed at 2-week intervals during and after prednisone administration. Lymphocyte and eosinophil counts were significantly (P less than 0.005) decreased after 2 and 4 weeks of prednisone treatment, compared with controls. Two weeks after treatment, eosinophil counts in prednisone-treated dogs were similar to those of control dogs, whereas lymphocyte counts remained low 4 weeks after treatment in treated dogs (1,869 +/- 145 cells/microliters), compared with that in control dogs (3,662 +/- 548 cells/microliters). Neutrophil and monocyte counts did not significantly change during glucocorticoid administration. Mean platelet volume significantly (P less than 0.001) decreased after 4 weeks of prednisone treatment, but returned to pretreatment values by 2 weeks after treatment. Four weeks of prednisone treatment did not cause significant increased activity in serum alanine transaminase, total alkaline phosphatase or the steroid-induced isoenzyme of alkaline phosphatase. Significant increases in serum albumin (P less than 0.001) and total protein (P less than 0.05) concentrations were detected after 4 weeks of treatment, but mean values were not significantly different from those of controls 2 weeks after treatment ended. Results of our study indicate that eosinophil and lymphocyte counts are the most sensitive indicators of long-term glucocorticoid administration at anti-inflammatory dosages of 1.1 mg/kg daily.

Alkaline Phosphatase↗
PubMed1991

Calcium transport by plasma membranes from a glucose-responsive rat insulinoma.

Inside-out plasma membrane vesicles from a glucose-responsive rat insulinoma showed an ATP- and Mg2(+)-dependent uptake of Ca2+. The Km (concentration giving half-maximal activity) for Ca2+ was 60 nM. In the presence of 0.4 microM free Ca2+, the Km for ATP was 15 microM, and the Km for Mg2+ was 4 microM. Glucose (30 mM) decreased Ca2+ uptake by 50%, while other insulin secretagogues had no effect, except for glyceraldehyde, which stimulated Ca2+ uptake. Calmodulin increased the uptake of Ca2+, while trifluoperazine and vanadate inhibited the uptake. The Ca2(+)- and Mg2(+)-dependent ATPase from this tumor has a 10- to 20-fold higher requirement for Ca2+, which suggests that this enzyme is not responsible for Ca2+ transport, rather, Ca2+ transport activity represents only a small fraction of the total Ca2(+)-ATPase activity. The physiological importance of Ca2+ transport in insulin secretion is evident from the inhibition of Ca2+ uptake by glucose, which leads to a decrease in Ca2+ efflux from the cell. This inhibition would lead to an increase in intracellular free Ca2+ and insulin release.

Animals↗
PubMed1990

Megaesophagus in two cats.

Megaesophagus was diagnosed in 2 cats. Both had a history of regurgitation, and one was dyspneic. Radiography of the thorax and abdomen revealed generalized megaesophagus and gastric distention with gas. There was no esophageal motility during fluoroscopic observation. The prognosis for cats with megaesophagus is guarded. Although they may be satisfactory pets, cats with this condition should not be used for breeding because the condition is believed to be inherited through recessive genes.

Animals↗
PubMed1990

Glucose inhibits the high-affinity (Ca2+ + Mg2+)-ATPase in the plasma membrane of a glucose-responsive insulinoma.

(Ca2+ + Mg2+)-ATPase enzyme activity of a purified plasma membrane preparation from a glucose responsive rat insulinoma, was characterized as Ca2(+)-dependent dephosphorylation of [gamma-32P]ATP. A high-affinity enzyme with a Km(ATP) ranging from 20 to 30 microM and a Km(Ca2+) of 1 microM was identified. Glucose inhibited this high-affinity enzyme in a dose-dependent manner, with no significant inhibition at a concentration between 0 and 5 mM, 50% inhibition at 13.3 mM and 94.5% inhibition at 30 mM. The inhibitory effect of glucose was immediate and rapidly reversible. The effect was stereospecific for the alpha-anomer. These findings support the concept that glucose acts directly at the beta-cell plasma membrane and is involved in the maintenance of elevated intracellular free calcium concentrations associated with insulin release by directly or indirectly inhibiting energy-dependent calcium efflux. Glyceraldehyde (20 mM) increased enzyme activity 3-fold, while other metabolic fuels had no effect. This suggests that inhibition of the enzyme is not an obligatory requirement for insulin release. Calmodulin stimulated the enzyme activity in calmodulin-depleted but not in undepleted membranes. Trifluoperazine (30-100 microM) inhibited (Ca2+ + Mg2+)-ATPase in a dose-dependent manner (14-61% activity) and the activity was also inhibited by vanadate (0.1-1.0 mM) and NaCl (150 mM).

Adenoma, Islet Cell↗
PubMed1989

Effect of estradiol on low density lipoprotein uptake by bovine aortic endothelial cells.

The means by which estrogen retards atherosclerosis cannot be explained solely by changes in circulating lipoprotein levels. We studied the effects of 17 beta-estradiol on the binding, incorporation, and degradation of low density lipoprotein (LDL) by cultured bovine aortic endothelial cells (BAEC). Estrogen receptors in the cytoplasm and nucleus of BAEC could be demonstrated by immunofluorescent staining. Estradiol was found not to affect surface binding of LDL to BAEC. However, at physiologic concentrations (50 pg/ml), estradiol did enhance LDL uptake by the BAEC (P less than 0.005). This enhancement was present but somewhat reduced at higher concentrations of estrogen (P less than 0.05). Only approximately 10% of incorporated LDL was trichloroacetic acid soluble, indicating a low rate of LDL degradation. The relative rate of LDL breakdown within the BAEC was not altered by estrogen. These results, showing estrogen stimulation of LDL uptake by the BAEC, do not clarify the protective effect of this hormone. It is speculated that estrogen may augment the cellular clearance of LDL.

Animals↗
PubMed1989

Characterization of calcium channels of a glucose-responsive rat insulinoma.

Voltage-dependent calcium channels are important in the control of calcium influx into excitable cells. With the use of cells isolated from a glucose-responsive rat insulinoma, the effect of the calcium-channel blocker nitrendipine on insulin release was examined. When 50 nM nitrendipine was added with a stimulatory glucose concentration (30 mM), first-phase insulin release was preserved, whereas the second phase was inhibited by 39.4 +/- 5.3%. When 50 nM nitrendipine was also present during basal and stimulated insulin release, the insulin release from fresh cells was significantly less during both phases compared with cells not exposed to nitrendipine (P less than 0.05). In cells cultured for 1 day in 30 mM glucose, a diminished insulin response was seen on stimulation with 30 mM glucose. Nitrendipine (50 nM) did not lead to a further decrease in insulin release. Saturable binding sites in homogenate, whole cells, and purified plasma membranes prepared from the insulinoma were characterized using [3H]nitrendipine. The Kd (in pM) for homogenate from uncultured cells was 225 +/- 34 (n = 11), whereas the Bmax (in fmol/mg protein) was 52 +/- 5. The number of apparent binding sites for [3H]nitrendipine was reduced by approximately 50% in cultured cells (Bmax = 30 +/- 5 fmol/mg protein). The reduction in insulin release from cultured cells correlated well with the reduction in nitrendipine binding. It is concluded that the decrease in the number of apparent binding sites for nitrendipine after culture represents a reduction in functional calcium channels associated with influx of calcium and insulin release.

Adenoma, Islet Cell↗
PubMed1989

Impairment of glucose tolerance in hyperthyroid cats.

Intravenous glucose tolerance tests were performed in eight adult cats before and after a 4-week treatment with thyroxine. The untreated cats had a mean fasting blood glucose concentration of 7.7 +/- 0.3 mmol/l and a mean fasting insulin concentration of 88 +/- 31 pmol/l which were not significantly different from mean fasting glucose and insulin concentrations after 4 weeks of thyroxine administration (6.9 +/- 0.2 mmol/l and 101 +/- 28 pmol/l respectively). At 120 min after glucose injection, the glucose concentration in untreated cats returned to baseline concentrations as did the insulin concentration. However, in the hyperthyroid cats both glucose and insulin concentrations were significantly (P less than 0.001) higher (13.6 +/- 0.8 mmol/l and 245 +/- 17 pmol/l respectively) in comparison with the baseline and untreated cats. The t1/2 for glucose disappearance was significantly higher in the cats rendered hyperthyroid, and the glucose disposal rate constant (K) was significantly lower in this group. It is concluded that hyperthyroidism in cats leads to impairment of glucose tolerance possibly due to peripheral insulin resistance.

Animals↗
PubMed1989

The effect of estrogen on low-density lipoprotein binding kinetics in aortic endothelial cells.

The inhibition of atherosclerosis by estrogen has been shown clinically and experimentally, but the mechanism by which this occurs is unknown. Previous studies have shown that estrogen enhances the uptake of low-density lipoprotein (LDL) by bovine aortic endothelial cells (BAEC) while not altering membrane binding at saturating levels of LDL. In this study the effect of estrogen on LDL binding kinetics has been investigated. Computer-assisted Scatchard analysis of binding data suggests a single-site binding model. Estrogen-treated BAEC showed a lower binding affinity (Ka = 2.47 +/- 0.74 E7 M-1) than control cells (1.95 +/- 0.21 E7 M-1) (p = 0.0012). Estrogen-treated cells, however, had a greater binding capacity (Bmax = 1.26 +/- 0.07 E-10M) than control cells (Bmax = 8.49 +/- 0.44 E-11M) (p = 0.0004). The latter was due primarily to a difference in LDL binding at higher concentrations of LDL (greater than 40 micrograms/ml). These findings are consistent with an estrogen-stimulated increase in low-affinity binding of LDL to BAEC, which may not be directly receptor mediated and which appears to enhance the uptake of LDL at higher lipoprotein concentrations. Such alterations in LDL uptake by endothelial cells could influence the formation of atherosclerotic plaque.

Animals↗
PubMed1987

Multiple myeloma associated with the heavy chains of immunoglobulin A in a dog.

On the basis of microscopic evaluation of bone marrow aspirate, multiple myeloma and secondary marrow hypoplasia was diagnosed in a 7-year-old female Doberman Pinscher. Electrophoresis, radial gel diffusion, and immunoaffinity chromatography indicated that serum and urine specimens contained alpha immunoglobulins without kappa or lambda light chains. Whole immunoglobulins (Ig) A, IgG, or IgM were not found. The dog was treated with prednisolone and melphalan for 11 weeks, after which time the owner refused examination and treatment of the dog.

Animals↗
PubMed1987

HPLC analysis of nucleotide profiles in glucose-stimulated perifused rat islets.

Nucleotide concentrations were measured in isolated pancreatic islets from rats using HPLC. This method was used to study the role of nucleotides in islets, which were perifused for several hours with different substrates and exhibited signs of exhaustion. Using islet tissue extracts, it was possible to determine 11 nucleotides. It was hoped that alterations in islet nucleotide concentrations would provide clues for the biochemical basis for the exhaustion phenomenon; however, changes in nucleotide concentrations that were observed in exhausted islet tissue did not correlate with corresponding changes in insulin release. Therefore, they are unlikely to be directly related to islet exhaustion.

Animals↗
PubMed1986

Determination of selenium and arsenic in animal tissues with platform furnace atomic absorption spectrometry and deuterium background correction.

Determination of selenium and arsenic in animal tissues is disturbed mainly by spectral interferences, uncorrectable with the dueterium arc. These interferences are produced by the calcium and magnesium phosphates always present in these matrixes. In animal tissue solution this disturbance may be avoided by addition of 20 micrograms of Ni (nitrate) for a 10 microliter sample. A lower amount of nickel does not allow a correct development of analyte absorbance signals whereas an excess induces a loss of sensitivity for the two elements studied. Measurement of peak-height proved to be most suitable, integrated absorbance being partially influenced by the matrix. The slope constants of working curves obtained with different animal matrixes are very close and direct calibration becomes possible. This was confirmed by analysis of several reference materials.

Animals↗
PubMed1986

In vitro exhaustion of pancreatic beta-cells.

To learn more about possible limited beta-cell secretory capacity and factors essential for insulin release, a perifusion system was applied that allowed the in vitro study of insulin secretion from isolated pancreatic islets for more than 6 h. Islets isolated from rats were stimulated with various glucose concentrations (7.5, 16.7, and 30 mM), alpha-ketoisocaproate (30 mM), and 30 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine for several hours in Krebs-Ringer-bicarbonate buffer (KRB) or RPMI 1640. Islets showed "exhaustion" with all stimulatory conditions used when KRB was the perifusion medium. This was not prevented by addition of amino acids, phosphate, myo-inositol or arachidonic acid. With RPMI 1640 as the basal medium, exhaustion was not seen at 7.5 mM but was readily approached at higher glucose concentrations. It is possible that the exhaustion phenomenon observed here is due to a depletion of a readily releasable insulin pool.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Glucose induces insulin release and a rise in cytosolic calcium concentration in a transplantable rat insulinoma.

An important role for calcium in the cellular events leading to insulin secretion is supported by many studies. However, simultaneous measurements of changes in intracellular free Ca2+ concentrations [( Ca2+]i) and insulin release in response to secretagogues have not been performed. Using cells isolated from a glucose-responsive insulinoma, changes in [Ca2+]i were measured with the fluorescent calcium probe quin2. With the nutrient secretagogues glucose (30 mM) and D,L-glyceraldehyde (GA; 20 mM), [Ca2+]i increased slowly, reaching a peak approximately 15 min after addition of the stimulus, while KCl (25 mM) and carbachol (2 mM) led to a rapid but transient increase in [Ca2+]i. Glucose increased [Ca2+]i from 104 +/- 6 (mean +/- SEM) to 248 +/- 31 mM (n = 13), and GA caused a rise in [Ca2+]i from 96 +/- 6 to 280 +/- 39 nM (n = 4). KCl and carbachol caused a rise from 107 +/- 6 to 184 +/- 5 nM and from 98 +/- 5 to 157 +/- 5 nM, respectively (n = 5 each). When insulin release was measured simultaneously with changes in [Ca2+]i and compared to unstimulated cells, the following results were obtained. During the first 5 min of stimulation, high glucose caused a 90 +/- 12% increase in insulin release and a 72 +/- 11% rise in [Ca2+]i (n = 5). GA evoked a 122 +/- 30% increase in insulin secretion, with a 82 +/- 17% rise in [Ca2+]i (n = 3). Both KCl and carbachol caused a 58 +/- 9% increase in insulin release, with 7 +/- 4% and 50 +/- 2% rises in [Ca2+]i, respectively (n = 4 each). Insulin release was also measured in a perifusion system. It was shown that glucose (30 mM), GA (20 mM), and alpha-ketoisocaproate (30 mM) caused a biphasic release of insulin, while KCl (25 mM) and carbachol (2 mM) caused a monophasic release. The results show that [Ca2+]i increases during the stimulation of insulin secretion when measured simultaneously on the same beta-cells. However, while these changes coincide, a simple direct quantitative relationship between insulin release and the rise in [Ca2+]i could not be demonstrated.

Adenoma, Islet Cell↗
PubMed1985

Triiodothyronine production by the perfused rat kidney is reduced by diabetes mellitus but not by fasting.

The effects of fasting and streptozotocin-induced diabetes on renal T3 production were studied in the isolated perfused rat kidney. Kidneys were perfused for 1 h at 37 C and pH 7.4 with two perfusion media, containing different oncotic agents (BSA and a modified collagen product, Haemaccel) and with widely varying free T4 concentrations [15.6 ng/dl (200 pM) in BSA, 132 ng/dl (1703 pM) in Haemaccel]. Basal kidney T3 concentrations fell by 65.3 +/- (SE) 5.2 and 56.4 +/- 3.4% of control in fasted and diabetic rats, respectively, in parallel with similar decreases in serum T3 concentrations. Fasting did not alter T3 production, T4 uptake, or the conversion of T4 to T3 in the perfused kidney. In contrast, diabetes decreased renal T3 production by 43.7 +/- 5.4% (P less than 0.001) and 31.2 +/- 3.5% (P less than 0.005) from control when perfused with BSA and Haemaccel, respectively. This decline in T3 production was the result of an insulin-reversible decrease in the conversion of T4 to T3, whereas T4 uptake was unchanged. Kidneys from diabetic rats retained more of the T3 produced than did kidneys from control rats, and this was also reversed with insulin treatment. These studies demonstrate significant differences in the metabolism of T4 and disposition of the T3 generated in the kidneys of fasting and diabetic rats. In both fasting and diabetes, T4 metabolism in the kidney was qualitatively and quantitatively different than that previously observed in the perfused liver. We postulate that decreased sensitivity or exposure to intraportal hormones and/or metabolites may explain these differences.

Animals↗
PubMed1984

Pharmacological modifications of insulin release in vitro from fuel-responsive transplantable insulinomas.

The response of insulinoma tissue to glucose, alpha-ketoisocaproate, and the modifiers of insulin release, tolbutamide, isoproterenol, and acetylcholine, was studied. Tumor tissue was transplanted under the kidney capsule of 14 rats, and the tumor-bearing kidneys were perfused in vitro about 8 weeks later. The plasma glucose concentration of these animals was 85.0 +/- 7.0 mg/dl, while the plasma insulin concentration was 13.8 +/- 1.5 ng/ml (normal, 180.5 +/- 7.0 mg/dl and 2.6 +/- 0.5 ng/ml, respectively; n = 26). Glucose (30 mM) evoked a 3- to 5-fold increase in insulin secretion, similar to the increase seen when either 100 micrograms/ml tolbutamide or 0.5 micrograms/ml isoproterenol were added to the perfusion medium containing 5 mM glucose. Propranolol at 50 micrograms/ml, but not at 20 micrograms/ml, inhibited insulin release stimulated by isoproterenol. Acetylcholine (10 or 100 microM) did not stimulate insulin secretion. alpha-Ketoisocaproate caused the highest insulin release of all stimuli studied. Glucagon or somatostatin release was not seen in any of the experiments. These results show that the tumor tissue transplanted under the kidney capsule responds not only to model fuels, but also to the sulfonylurea class of drugs and to adrenergic agents.

Acetylcholine↗
PubMed1984

Fuel-induced insulin release in vitro from insulinomas transplanted into the rat kidney.

We studied the release of insulin, glucagon, and somatostatin in response to glucose, glyceraldehyde (GA), and alpha-ketoisocaproate (KIC) from rat kidneys containing transplanted insulinomas. Kidneys were perfused about 11 wk after transplantation when the plasma glucose concentration of the fed animals had decreased from 180 +/- 7 to 95.1 +/- 9.9 mg/dl and plasma insulin concentrations had increased from 2.6 +/- 0.5 to 14.2 +/- 2.0 ng/ml. The insulin content of the tumor-containing kidney ranged from 40 to 679 micrograms; the glucagon and somatostatin concentrations ranged from undetectable levels to 3.7 micrograms and 248 ng, respectively. The average response to 30 mM glucose and 10 mM GA was a four- to fivefold increase in insulin secretion, whereas 30 mM KIC caused a 16- to 28-fold increase. In vitro stimulation of the insulinoma with 30 mM glucose primed the beta-cell response to a second stimulus following a short rest period. Cytochalasin B did not enhance this primed glucose response. Diazoxide inhibited glucose, GA, and KIC-stimulated insulin release. Glucose, GA, and KIC stimulated glucagon release in 2 of 17 insulinomas studied here. Somatostatin release was not seen in any of the experiments. These findings show that this islet cell tumor transplanted under the kidney capsule releases insulin in response to physiologic and model fuel substances. Thus, this particular transplantable tumor offers an opportunity to study the biochemistry and biophysics that underlie fuel-stimulated insulin release.

Adenoma, Islet Cell↗
PubMed1983

Identification and significance of glucokinase in transplantable insulinomas.

Glucose 6-phosphotransferases were investigated in two transplantable rat insulinoma tumor lines. Homogenates of tumors contained glucose phosphorylating activities of both high (e.g. supernatant Km = 0.060 mM and pellet Km = 0.077 mM) and low (Km = 7.6 mM) affinities for glucose. Chromatography of supernatants (105,000 X g) of insulinomas on DEAE-Cibacron Blue F3GA agarose evidenced glucose 6-phosphotransferase activity which eluted similarly to glucokinase from rat liver. Kinetic studies of insulinoma glucokinase also indicated similarity with liver glucokinase, i.e. cooperative rate dependence on glucose concentration and comparable Km values for glucose, and it did not phosphorylate N-acetylglucosamine. These characteristics of glucose 6-phosphotransferase in insulinomas are similar to those of the enzyme found in islets of Langerhans. Since glucokinase is thought to serve as glucose sensor of insulin secretory pancreatic beta-cells, these transplantable insulinomas offer great promise for biochemical and biophysical studies of the nature of glucose-induced insulin release.

Adenoma, Islet Cell↗