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Biomedical subjects

A Hayek

Publications and source records attributed to A Hayek.

At least 19 recordsLinked to original sources
PubMed1992

Intrapancreatic islet transplantation in experimental diabetes in the rat.

Pancreatic islets have been transplanted successfully to a variety of organs except the pancreas. Since this organ is the most physiologic recipient for islets in rodents with chemically induced diabetes, we have placed neonatal islets intrapancreatically in highly inbred Lewis rats with streptozotocin (ST) diabetes. Transplantation of 2,000 neonatal islets into the pancreas of diabetic rats reversed diabetes within 2 weeks in all of the treated rats (seven of seven). The same success rate was obtained using the same number of islets placed under the kidney capsule in 11 recipients. Although cured of their diabetes, rats in both groups with inadequate islet-cell mass were not able to produce glucose tolerance tests equal to those observed in normal animals. Higher insulin levels were measured in the rats receiving islets under the kidney capsule, as compared with those placed intrapancreatically. In summary, syngeneic islet transplants to the pancreas of ST-diabetic rats are successful in reversing the diabetic state. This model may be useful to the study of islet function after islet transplants into their natural environment.

Animals↗
PubMed1992

Reversal of experimental diabetes by injection of syngeneic islets into peripheral veins.

This study was undertaken to evaluate the safety and effectiveness of intravenous (i.v.) injection of islets, via a peripheral vein, in the treatment of experimental diabetes in highly inbred Lewis rats. Rats were made diabetic by the i.v. injection of streptozocin, and donor islets were isolated from neonatal rats. Two wk after the induction of diabetes, rats with glucose concentrations > 19 mM were divided into two groups: one group of six rats was injected with 2000 neonatal islets into the external jugular vein; the second group of rats, acting as control, was injected in the same vein with medium alone. Within 2 wk of the islet transplant, 100% (6/6) of the rats were cured of the diabetes. None of the control rats experienced any improvement. As expected, pancreatic islets so administered embolized to the lungs. Glucose tolerance tests in the rats receiving the islet transplant were indistinguishable from normal rats. These results could be important to clinical transplantation if the procedure is as successful in larger animals using autotransplanted islets or allografts protected from immune rejection.

Animals↗
PubMed1992

Subcutaneous growth hormone-releasing hormone therapy in growth hormone-deficient children: first year of therapy.

The purpose of this study was to determine the efficacy and safety of GH-releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty previously untreated prepubertal children with GHRH deficiency were treated for 1 yr in a multicenter, open label, company-sponsored study with at least 20 micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main effects were enhancement of linear growth, advancement in bone age, and alteration in general blood chemistries and hormonal values. The mean velocity of the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at 1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/- 2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for the second 6 months. The high dose group increased their mean linear growth velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/- 1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year of therapy. No adverse changes in general biochemical, hormonal, or pituitary radiographic analyses were noted. No change in fasting glucose or insulin concentrations, or excessive generation of insulin-like growth factor-I concentrations occurred. We conclude that GHRH in a daily dose of 20-40 micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH-responsive GH-deficient patients. It was well tolerated without side-effects. Glucose intolerance was not noted.

Adolescent↗
PubMed1992

[Fibroma of the tunica albuginea. Apropos of a case].

Fibroma of the tunica albuginea is a rare, benign lesion. Only twenty cases have been published. We have observed one case a solitary testis of a 40 years old patient. The treatment performed was enucleation. The interest of this case consists in the rarity of the case and the operative solution proposed. After a review of the literature, we summarise the characteristics of this disease.

Adult↗
PubMed1991

The use of digital image processing to quantitate angiogenesis induced by basic fibroblast growth factor and transplanted pancreatic islets.

We have used digital image processing as a technique to quantify the formation of blood vessels in situ in response to the application of either an angiogenic peptide, basic fibroblast growth factor, or isolated pancreatic islets. The peptide or the islets were placed under the rat kidney capsule. For in vivo microscopy fluorescein-labeled dextran was injected intravenously and video images were made as deemed appropriate. Images to be analyzed were selected manually, digitized, and stored in a computer for processing. The calculation of the total vessel length per area was called the microvascular index. Three weeks after the transplantation of 200 islets, the microvascular index was fairly constant and did not change significantly when the same measurements were performed 1 week later. In another experiment, pellets containing 0.5 micrograms of basic fibroblast growth factor produced an angiogenic response no different from that of a control pellet. At a dose of 1 microgram, however, the response was statistically significant after 1 week. These data indicate that digital image processing may be a useful method to quantitate the angiogenesis induced by local administration of angiogenic stimulants.

Animals↗
PubMed1991

Functional impact of attachment and purification in the short term culture of human pancreatic islets.

We have evaluated the effects on islet function of several manipulations of the substrate and tissue culture conditions in the short term culture of human islets. Specifically, we have studied the influence of several matrices, additions to the medium, and the use of basic fibroblast growth factor (FGF)-saporin mitotoxins to eliminate fibroblastoid cells from the cultures. The human islets were obtained from the Human Islet Transplant Center at Washington University Medical Center (St. Louis, MO). Substrates used to facilitate islet attachment were poly-L-lysine, gelatin, Matrigel, collagen, and bovine corneal endothelial cell matrix. RPMI-1640 medium was supplemented with either 22.2 mM glucose or 10 micrograms/mL human insulin. FGF-saporin mitotoxin was used at a concentration of 10 nM. The greatest improvement in islet cell function in either static or stimulated situations was obtained when we used bovine corneal endothelial cell matrix as the matrix, supplemented the medium with a high concentration of glucose or insulin, and eliminated fibroblast-like cells by exposing the cultures to basic FGF-saporin mitotoxin. The conditions described in this report could greatly improve the culture of human islets for use in clinical and laboratory research.

Cell Adhesion↗
PubMed1990

Effects of prolactin and glycosylated prolactin on (pro)insulin synthesis and insulin release from cultured rat pancreatic islets.

In order to study the possible differential effects of the nonglycosylated and glycosylated forms of prolactin on insulin content and secretion in pancreatic islets, neonatal rat pancreatic islets were exposed for 6 days in vitro to 2 micrograms/ml of nonglycosylated ovine prolactin (oPRL), or to 2 micrograms/ml of glycosylated oPRL (G-oPRL). oPRL stimulated a significant increase (p less than 0.01) in the total amount of insulin released into the medium over the 6 day culture period; however, G-oPRL had no effect. Islets cultured for 6 days in the presence of oPRL showed no increase in the amount of DNA per islet. However, there was a significant (p less than 0.007) increase in the amount of total protein synthesized by the islets exposed to oPRL. These findings suggest that the effect of oPRL on neonatal rat pancreatic islet cells is a nonspecific effect. The nonglycosylated form of PRL may play a role in B-cell function by promoting protein synthesis, which results in augmented insulin synthesis.

Animals↗
PubMed1990

Angiogenic peptides in pancreatic islet transplantation to diabetic rats.

To overcome the deleterious effects of hyperglycemia on islet transplantation, we have used recombinant basic fibroblast growth factor (FGF), an angiogenic peptide, concurrently with the intrasplenic placement of neonatal islets in severely diabetic rats. In both experimental and control rats, a minipump, secured to the spleen with a small indwelling catheter, delivered either the basic FGF at 10 ng/hr, or only the diluent. The rate of cure in the animals receiving the islets plus the peptide was significantly higher (70%) than in control rats (20%). This difference (P less than 0.05), could not be attributed to direct effects of the peptide on islet function or to increased islet cell replication. We believe that these results may be best explained as an enhancement by basic FGF of the angiogenic process in the transplant islets.

Administration, Topical↗
PubMed1990

Selective elimination of fibroblasts from pancreatic islet monolayers by basic fibroblast growth factor-saporin mitotoxin.

Fibroblast proliferation regularly impedes the initiation and maintenance of pancreatic islet monolayers in culture. We recently characterized a specific cytotoxin to cells expressing the basic fibroblast growth factor receptor by conjugating the growth factor to saporin-6, a ribosome-inactivating protein. In contrast to untreated islets, isolated adult rat islets grown on a substrate prepared from bovine corneal endothelial cells and incubated with the mitotoxin at 10-nM concentration for 96 h were free of contaminating fibroblasts. Histological and functional studies revealed there was no damage to the islets. The results suggest that treatment of this cell type with basic fibroblast growth factor mitotoxins may be an important tool for culture of pure islets for physiological and clinical studies.

Animals↗
PubMed1989

Biological actions of 53 kDa nerve growth factor as studied by a blot and culture technique.

A blot and culture technique has been utilized to examine the biological actions of 53,000 Dalton (53 kDa) nerve growth factor (NGF) present in the submaxillary gland (SMG) of adult male and female mice. SMG-proteins were first resolved by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (PAGE) under reducing conditions and then transferred to a nitrocellulose (NTC) sheet by electroblotting. Specific areas corresponding to 53 kDa NGF were cut and cultured with the rat pheochromocytoma cell line, PC-12. NTC strips bearing the 53 kDa NGF band stimulated cell flattening and neurite formation in serum containing growth medium and augmented cell survival in serum-free growth medium. Similar results were obtained with NTC strips bearing the 13 kDa NGF band. The results suggest that 53 kDa NGF, like 13 kDa NGF, exerts both tropic and trophic actions on its target neurons.

Adrenal Gland Neoplasms↗
PubMed1989

Enhancement of pancreatic islet cell monolayer growth by endothelial cell matrix and insulin.

The roles of glucose and insulin in the promotion of DNA synthesis in pancreatic islet cell monolayers were assessed using a variety of in vitro conditions. Several substrates including collagen, poly-l-lysine, Matrigel, and the extracellular matrix produced by cultured bovine endothelial cells (BCEM) were compared for their ability to promote monolayer growth. Islets grown on BCEM in combination with medium RPMI 1640 supplemented with 22.2 mM glucose or 10 micrograms/ml insulin gave the best results as determined by new DNA synthesis. The new-form monolayers were free of contaminating fibroblasts. These results suggest that insulin is critical to pancreatic islet growth when the cells are attached to biocompatible matrices.

Animals↗
PubMed1988

Decrease in the number of neonatal islets required for successful transplantation by strict metabolic control of diabetic rats.

We have investigated the influence of glycemic control on the number of transplanted neonatal islets needed to cure streptozotocin (STZ)-diabetic rats. Intrasplenic transplantation of 1000 neonatal islets to a group of STZ-diabetic rats with poor glycemic control cured only 30% of the rats. In a second group, insulin at doses of 10-15 U/day given for 5 days after transplantation improved the cure rate to 72%. Normalization of blood glucose by a previous transplant to the kidney capsule produced cure in 100% of the rats. The above results were obtained despite the fact that isolated adult islets, when compared with neonatal islets, were larger, contained more protein and DNA--and, in response to glucose stimulation, released more insulin than neonatal islets. These experiments show that neonatal islets are an excellent source of endocrine replacement tissue when transplanted intrasplenically, and that the number of islets needed to cure experimental diabetes is significantly reduced by normalization of the metabolic milieu in the recipient.

Animals↗
PubMed1987

An in vivo model for study of the angiogenic effects of basic fibroblast growth factor.

We have investigated the angiogenic effects of basic fibroblast growth factor following its implantation in slow release beads under the kidney capsule. The presence of basic fibroblast growth factor in the subcapsular space induced a marked angiogenic response maximal at 1 microgram dose per kidney. Histological examination at the site of treatment failed to reveal evidence of an inflammatory response, thus supporting the observation that basic fibroblast growth factor alone can stimulate in vivo neovascularization. Beads pretreated with saline or with human growth hormone had no angiogenic effect. Because of the readily accessible location in the retroperitoneal space, the ease of drug delivery, and the marked vascular proliferation seen in response to FGF, our results suggest that the kidney capsule is an excellent model for study of the physiological role played by FGF and related peptides in promoting angiogenesis in vivo.

Animals↗
PubMed1986

Hormone release, islet yield, and transplantation of fetal and neonatal rat dorsal and ventral pancreatic islets.

Fetal (20-21 day gestation) and neonatal (less than 5-day-old) rat islets were isolated from the glucagon-rich (dorsal) and glucagon-poor (ventral) pancreatic regions. After 1 or 2 wk in culture, groups of islets from each region were transferred to culture dishes containing Krebs-Ringer bicarbonate buffer with low (2.4 mM) and high (16.7 mM) glucose plus aminophylline. After 2 wk in culture, insulin released into medium was higher than after 1 wk, and more so if the islets originated from dorsal tissue (P less than .01). Glucagon release in response to alanine (10 mM) stimulation was also significantly higher in dorsal than in ventral islets (6.38 +/- 1.98 vs. 1.49 +/- 0.89 pg X islet-1 X h-1, respectively; P less than .02). Coincident with higher insulin and glucagon release, islet yield was greater in tissue from the dorsal neonatal pancreas than from that obtained in the fetal and neonatal ventral pancreas [range: dorsal, 131-180 (median, 153), vs. ventral, 53-127 (median, 84), islets obtained on day 5 of culture]. Neonatal islets of dorsal origin were transplanted intrasplenically (500-3000 islets) to streptozocin-induced diabetic inbred Lewis rats. Only rats receiving greater than 2500 islets were cured by transplantation. These experiments show that dorsal fetal islets secrete more insulin than do ventral islets and that islet yield is higher when islets are isolated from dorsal rather than from ventral perinatal pancreatic tissue. Despite their in vitro behavior, more neonatal dorsal islets are required to cure experimental diabetes than are reported with adult islets.

Animals↗
PubMed1985

Fetal rat islet insulin deficiency following maternal administration of streptozotocin.

Pancreatic islets were isolated from the fetuses of normal rats and rats made diabetic by the iv administration of streptozotocin (STZ) on either Day 3 or 5 of pregnancy. Of the rats made diabetic on Day 3, one group also received insulin injections at the appearance of glucosuria. Maternal blood glucose on Day 20 of gestation was significantly different in the diabetic rats (405 +/- 27 mg/dl) from the normal (97 +/- 1 mg/dl) and insulin-treated diabetic rats (69 +/- 9 mg/dl). While fetal weight was significantly decreased in the STZ-treated rats (2.64 +/- 0.13 g vs 3.52 +/- 0.05 g for the control group, P less than 0.005), fetal glucose was significantly higher in the STZ-treated than in normal pups (342 +/- 11 vs 35 +/- 1 mg/dl, P less than 0.005). Both fetal weight and glucose were normalized by insulin treatment: 3.16 +/- 0.18 g and 31 +/- 7 mg/dl, respectively. Insulin release from fetal islets of diabetic dams was blunted after a week in culture both in basal and stimulated conditions. After 2 weeks in culture, there was partial recovery in the insulin response to glucose but it did not equal to that measured in fetal islets from the normal and insulin-treated diabetic rats. These data suggest maternal hyperglycemia severely impairs fetal weight and insulin release from fetal rat islets in vitro, and correction of the hyperglycemia by insulin treatment not only improves fetal weight and glucose concentrations, but it also normalizes insulin release from fetal rat islets in vitro.

Animals↗
PubMed1979

Reverse tri-iodothyronine to tri-iodothyronine ratio and gestational age.

The biologic significance of reverse tri-iodothyronine is not yet identified. Cord blood values reflect the fetal thyroid state, with rT3 excess and tri-iodothyronine deficiency. In an attempt to correlate thyroid function and gestational age, T3 and rT3 concentrations were measured by radioimmunoassay on 64 cord blood samples. Infant gestational ages ranged from 29 to 42 weeks; birth weights from 650 to 3,870 gm. The results show a significant positive correlation between gestational age and T3 and a significant negative correlation between gestational age and rT3. The rT3/T3 offers the best correlation.

Female↗