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Biomedical subjects

V Grill

Publications and source records attributed to V Grill.

At least 145 records · Page 8Linked to original sources
PubMed1990

Immunohistochemical localization of parathyroid hormone-related protein in parathyroid adenoma and hyperplasia.

Parathyroid hormone-related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohistochemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1-34) and PTHrP(50-69). Primary hyperplastic glands are negative. No staining with anti-PTHrP(106-141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia.

Adenoma↗
PubMed1990

Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high insulin responders.

We compared the effects of dexamethasone-induced insulin resistance on B-cell secretory performance in 12 low insulin responders (LIR) and in eight high insulin responders (HIR). A hyperglycemic clamp (120 minutes) was performed before and after the subjects had ingested dexamethasone 3 mg x 2 for 2 1/2 days. Fasting levels of blood glucose increased from 4.60 +/- 0.13 to 5.74 +/- 0.23 mmol/L after dexamethasone in LIR and from 4.37 +/- 0.18 to 5.26 +/- 0.13 mmol/L in HIR. Dexamethasone treatment increased fasting levels of total immunoreactive insulin (IRI), C-peptide, and proinsulin, as well as the proinsulin to IRI ratio to a similar degree in LIR and HIR. The amount of glucose infused to uphold hyperglycemia during the clamp decreased by 54% after dexamethasone in LIR and by 46% in HIR. Mean level of stimulated IRI during the clamp increased after dexamethasone by 43% in LIR and by 53% in HIR. Mean level of stimulated C-peptide increased by 11% (not significant) in LIR and by 24% in HIR. Mean level of stimulated proinsulin increased by 86% in LIR and by 93% in HIR. The effects of dexamethasone on insulin secretion varied among individuals, since steroid treatment failed to affect IRI responses to glucose in two LIR and two HIR. The magnitude of dexamethasone effects on secretion was not correlated to pre-dexamethasone insulin sensitivity as assessed by a somatostatin-insulin-glucose infusion test (SIGIT) or by M/I (glucose infused/insulin level) ratios of the control clamp.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Abnormal regulation by glucose of somatostatin secretion in the perfused pancreas of NIDDM rats.

We have investigated the influence of non-insulin-dependent diabetes on the regulation of somatostatin secretion from the pancreatic D cell. These results were compared with the concomittantly measured secretory responses from A and B cells. Rats were rendered non-insulin-dependent diabetic by neonatal injection of streptozotocin (STZ). Secretion was studied in perfused pancreas at 6-10 weeks of age. At this age, STZ rats were mildly hyperglycemic, their nonfasting blood glucose being 9.0 +/- 0.8 vs. 5.6 +/- 0.2 mM in control rats. In perfused pancreas from the latter rats, high glucose, i.e., 16.7 mM, stimulated somatostatin secretion but completely failed to do so in STZ rats. Arginine (in the presence of low glucose, i.e., 3.3 mM) moderately stimulated somatostatin secretion in controls but fourfold more in STZ rats. Preperfusion with high glucose markedly potentiated subsequent arginine-induced somatostatin secretion in controls but failed to do so in STZ rats. Basal glucagon release was inhibited by ambient high glucose in control and STZ rats alike. Arginine-induced glucagon release was profoundly inhibited both by ambient and previous exposure to glucose in controls but only slightly and nonsignificantly in STZ rats. The insulin response to high glucose in controls was reduced by 90% in STZ. The insulin response to arginine (in the presence of low glucose) was 3.3-fold enhanced in STZ. Ambient and previous high glucose markedly enhanced arginine-induced insulin secretion in controls but only moderately so in STZ rats. We conclude that already mild hyperglycemia is associated with marked D-cell insensitivity to glucose that is qualitatively similar to A- and B-cell insensitivity.

Animals↗
PubMed1990

The cytoplasmic Ca2+ response to glucose as an indicator of impairment of the pancreatic beta-cell function.

The effects of glucose on the cytoplasmic Ca2+ concentration (Ca2+i) regulating insulin release were investigated using pancreatic beta-cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca2+i followed by a rise, often manifested as high amplitude oscillations. The Ca2+i-lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the beta-cells were already depolarized by tolbutamide. Glucose-induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin- and noninsulin-dependent diabetes mellitus. Brief exposure of beta-cells to 2.2 mmol l-1 streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca2+i. The results indicate that glucose-induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defects in diabetes mellitus.

Animals↗
PubMed1990

D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects.

We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects.

Adult↗
PubMed1990

Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects.

We compared regional cerebral blood flow (rCBF) and arteriojugular vein differences of glucose, ketones, glycerol, lactate, pyruvate, and O2 in eight subjects with well-controlled insulin-dependent diabetes mellitus (IDDM) and in six healthy volunteers. Duration of diabetes was 19.4 +/- 2.1 yr. Measurements were performed before and after 120 min of insulin infusion and concomitant Biostator-controlled normoglycemia. Net uptake of ketones was seen in IDDM subjects before but not after insulin. Net uptake of glucose did not differ significantly between groups. During normoglycemia the molar ratio of O2 to glucose uptake was lower in IDDM than in nondiabetic subjects (4.68 vs. 5.50; P less than 0.05; Wilcoxon test). Small but significant release of lactate and pyruvate was seen in IDDM but not in nondiabetic subjects. The rCBF was measured by 11CH3F and position emission tomography. Global mean CBF was higher in IDDM subjects (64.9 +/- 5.9 vs. 49.3 +/- 2.7 ml.100 g-1.min-1, means +/- SE in nondiabetic subjects, P less than 0.05). rCBF was enhanced in many cortical and subcortical areas, whereas it was decreased in the head of the caudate nucleus. Neuropsychological testing did not reveal obvious cognitive dysfunction. The results imply that a larger fraction of glucose is nonoxidatively metabolized in the IDDM subjects and furthermore indicate an abnormal rCBF pattern in these subjects.

Acetoacetates↗
PubMed1990

Parathyroid hormone-related protein and calcium homeostasis in lactating mice.

Parathyroid hormone (PTH)-related protein has been shown to be a factor responsible for hypercalcemia of malignancy. Recent studies have shown the presence of mRNA for PTH-related protein in lactating breast tissue, suggesting a physiological role for this peptide during lactation. In the present study, we evaluated the effect of neutralization of PTH-related protein activity in lactating mice (by passive immunization) on various parameters of maternal and neonatal calcium homeostasis. PTH-related protein bioactivity, as tested in the adenylate cyclase assay, was present in mouse milk, and this activity was completely neutralized by the antisera used in the present study. In lactating mice, the effects of injection of PTH-related protein antisera on maternal serum calcium concentrations, milk calcium and phosphorus concentration, pup growth, dam femur calcium content, and pup calcium content were similar to those of the injection of normal rabbit serum. Therefore, maternal PTH-related protein does not appear to have a role in calcium homeostasis during lactation.

Animals↗
PubMed1990

Tumor resection and antibodies to parathyroid hormone-related protein cause similar changes on bone histomorphometry in hypercalcemia of cancer.

Bone resorption is increased in both humoral hypercalcemia of malignancy (HHM) and primary hyperparathyroidism. On the other hand, bone formation parameters are increased in primary hyperparathyroidism and decreased in HHM. Recently, a PTH-related protein (PTHrP) has been shown to be responsible for the hypercalcemia in the syndrome of HHM. In the present study we evaluated the effects of a neutralizing antiserum to PTHrP on bone histomorphometric parameters in hypercalcemic athymic mice bearing a human squamous cell lung cancer. These effects were compared to those of tumor resection. Similar to the effects of tumor resection, the antiserum to PTHrP resulted in a decrease in serum Ca levels, a decrease in bone resorption, and an increase in bone formation parameters. The studies, therefore, indicate that PTHrP is the major factor responsible for all of the features, including the decreased bone formation seen in HHM.

Animals↗
PubMed1990

A comparison of brain glucose metabolism in diabetes as measured by positron emission tomography or by arteriovenous techniques.

[U-11-C]-glucose and positron emission tomography was used to evaluate transport and oxidative metabolism of glucose in the brain of non-diabetic and insulin dependent diabetic (IDDM) subjects. These results were compared with results obtained by the Fick principle. Blood glucose was regulated by a Biostator controlled glucose infusion during a constant insulin infusion. [U-11-C]-glucose was injected during normoglycemia as well as during moderate hypoglycemia. The tracer data were analysed using a three compartment model with a fixed correction for [11-C]-CO2 egress. During normoglycemia the influx rate constant (k1) and blood brain glucose flux of the two groups were similar. During hypoglycemia k1 increased significantly and to the same extent in both groups. During normoglycemia the tracer calculated metabolism of glucose was higher in the brain of non-diabetic than of diabetic subjects. When measured by the Fick principle the net uptake of glucose was broadly the same for the groups. During normoglycemia the molar ratio of O2 to glucose uptake was, however, lower in IDDM than in non-diabetic subjects (4.67 vs 5.50, P less than 0.05, Wilcoxon test). A significant release of lactate and pyruvate was seen in IDDM but not in non-diabetic subjects. The results imply that a larger fraction of glucose is non-oxidatively metabolized in IDDM than in non-diabetic subjects.

Blood Glucose↗
PubMed1990

[Anatomo-functional study of penile innervation in the rat].

The Wistar rat represents a very useful model in experimental surgery and in scientific research. The anatomic structures are very similar to those encountered in man. Moreover the cost for their purchase, breeding and nourishment is very low and it's possible to perform surgical maneuvers without sterility. Nevertheless the penis has an extremely small dimension and its anatomic structure is quite different from that of man because corpora cavernosa are almost completely occupied by an osteo-cartilagenous formation: the os penis. For this reason it's very difficult to perform a physiopathological study of erection on the rat. On the other hand the nervous fibres are very similar for course and localization to those encountered in man and monkeys. Their electrical stimulation causes an erection which is adequate in duration and intensity to be evident.

Animals↗
PubMed1990

Histological alterations by a diet containing seeds of Garcinia kola: effect on liver, kidney, and intestine in the rat.

Histological examination of liver, kidney, and duodenum of rats fed a diet containing 10% (w/w) dry powdered seeds of Garcinia kola for 6 weeks revealed cellular changes that were not observed in pair-fed control animals. The main cellular changes observed in the rats fed on Garcinia kola diet included vacuolation of duodenal villous epithelial cells, numerous intracytoplasmic vacuoles in hepatocytes, and mild hydropic degeneration in cells of the renal proximal tubular epithelium. These changes are probably due to the flavonoids contained in G. kola seeds.

Animals↗
PubMed1989

Purification and characterization of recombinant human parathyroid hormone-related protein.

Full-length human parathyroid hormone-related protein (PTHrP-(1-141] as well as a carboxyl-terminal shortened form (PTHrP-(1-108] have been expressed from recombinant DNA-derived clones. These proteins were expressed in Escherichia coli as fusion proteins so that cyanogen bromide cleavage yields the desired product. Both proteins were purified and then characterized by sodium dodecyl sulfate gel electrophoresis, amino-terminal amino acid sequencing, peptide mapping, and mass spectral analysis. Recombinant PTHrP-(1-141), PTHrP-(1-108), synthetic PTHrP-(1-34), and naturally derived PTHrP are all equipotent in the stimulation of cyclic AMP levels in the osteoblast-like cell line UMR 106-01. However, PTHrP-(1-141) and -(1-108) are two to four times more active than PTHrP-(1-34) in the stimulation of plasminogen activator activity from this cell line. PTHrP-(1-141) reacts equipotently with PTHrP-(1-34) in a radioimmunoassay using an antiserum prepared against PTHrP-(1-34). PTHrP-(1-141), -(1-108), and -(1-84) were used as PTHrP-specific mobility standards on sodium dodecyl sulfate gel electrophoresis to determine the approximate length of two forms of naturally derived PTHrP. The data show that PTHrP purified from the lung tumor cell line BEN contains a major form of about 108 amino acids and another form of about 141 amino acids.

Amino Acid Sequence↗
PubMed1989

Amelioration of 4'-epidoxorubicin-induced cardiotoxicity by sodium cromoglycate.

Epirubicin induces an important noncytotoxic release of histamine from rat peritoneal cells in vitro. This exocytotic response is inhibited by sodium cromoglycate, similarly to that elicited by the classic mast cell secretagogue, compound 48/80. Mast cells obtained from the peritoneal cavities of rats treated with epirubicin in vivo were extensively degranulated; in contrast, samples obtained from rats pretreated with sodium cromoglycate showed normal appearing mast cells. When injected i.p., immediately before the antineoplastic agent, cromolyn significantly improved the survival time and the microscopic appearance of myocardial tissues of epirubicin-treated mice. The results indicate that histamine release could play an important role in the pathogenesis of anthracycline-induced cardiotoxicity.

Animals↗
PubMed1989

Studies on sex dependency of B-cell susceptibility to streptozotocin in a rat model of type II diabetes mellitus.

Non-insulin-dependent (Type 2) diabetes in the rat can be induced by a neonatal injection of streptozotocin (STZ). At adult age male rats are more severely affected than female rats. Such difference could be due to a sex-related dissimilarity in susceptibility to STZ; this possibility was investigated in the present study. Incubation of isolated islets from male and female rats with STZ for 30 min, followed by tissue culture for 24 h, induced a dose-dependent decrease in insulin content that was similar in islets of both sexes. STZ in vivo, injected i.p on the second day of life, markedly enhanced blood glucose levels and reduced pancreatic insulin content when measured 2-12 days after the STZ injection. The parameters of B-cell damage did not differ, however, between male and female pups. Testosterone treatment, when started two days after the STZ injection, significantly accentuated hyperglycemia in both sexes during the second week of life. Body weight and pancreatic insulin content were not affected by the testosterone treatment. In conclusion, B-cell susceptibility to STZ in vitro or in vivo, during the neonatal period, is not influenced by gender. The hyperglycemic effect of testosterone indicates that the rise in androgens, starting with puberty, is at least partially responsible for a more severe diabetic state in male than in female rats at adult age.

Androgens↗
PubMed1989

Impaired somatostatin response to orally administered glucose in type II diabetes entails both somatostatin-28 and -14 and is associated with deranged metabolic control.

UNLABELLED: We have investigated the effects of hyperglycemia in Type II diabetic patients on the somatostatin response to oral glucose. In these patients hyperglycemia prevailed (11.8 +/- 1.4 mmol/l) and was markedly increased to a maximum of 18.9 +/- 1.0 mmol/l following the ingestion of 75 g of glucose. The rise in blood glucose following glucose ingestion failed to induce a rise in plasma levels of somatostatin-like immunoreactivity. Biostator-regulated insulin infusion normalized fasting levels of blood glucose and reduced the hyperglycemia following glucose ingestion, i.e. blood glucose now rose from 4.6 +/- 0.1 to a maximum of 7.3 +/- 0.8 mmol/l. This moderate rise in blood glucose was accompanied by a significant (p less than 0.05) rise in somatostatin-like immunoreactivity. Somatostatin-28 and somatostatin-14 were separated using a Sephadex G-50 fine column. Biostator treatment suppressed plasma levels of both peptides during fasting conditions. Treatment was also accompanied by a rise in both peptides during the first hour following glucose ingestion; this rise did not occur in the untreated state. IN CONCLUSION: lack of somatostatin response to glucose in non-insulin-dependent diabetes mellitus is associated with deranged metabolic control. Unresponsiveness to glucose entails the secretion of both somatostatin-28 and -14.

C-Peptide↗
PubMed1989

Fasting for 72 h decreases the responses of counterregulatory hormones to insulin-induced hypoglycaemia in normal man.

We have evaluated the influence of fasting on the response of counterregulatory hormones to insulin-induced hypoglycaemia. Eight healthy, non-obese volunteers were studied after an overnight fast and again after a 72-h fast period. Levels of blood glucose were higher after overnight fasting (4.59 +/- 0.10 mmol/l) than after 72 h of fasting (3.38 +/- 0.12 mmol/l). Hypoglycaemia was induced by a constant insulin infusion (2.4 mU/kg/min) and clamped between 2.1 and 2.3 mmol/l of glucose by a variable glucose infusion. Hypoglycaemia evoked stimulation of glucagon release after the overnight fast but did not alter release after 72 h of fasting. The response of other counterregulatory hormones were also influenced by the longer fasting period: the normal rise in adrenaline levels during hypoglycaemia was delayed and attenuated and the normal rise in cortisol levels was absent; paradoxically, cortisol levels decreased during hypoglycaemia. Seventy-two hours of fasting, therefore, profoundly alters hormonal responses to hypoglycaemia.

Adult↗
PubMed1989

Visualization of the Langerhans cells in the human vaginal epithelium by the L-dopa histofluorescence method.

In this study we used the technique of L-DOPA histofluorescence for visualizing Langerhans cells in the human vaginal epithelium. Biopsy specimens were incubated with L-DOPA and sectioned by cryostat. The sections were exposed to formaldehyde vapour; during this passage, chemical conversion of L-DOPA into a strongly fluorescent compound occurred. Langerhans cells were clearly visualized in the vaginal epithelium; cell bodies and dendritic processes fluoresced sharply. The method is rapid and specific: it represents an useful tool for demonstrating Langerhans cells in the stratified squamous epithelium of vagina.

Adult↗