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Biomedical subjects

A Hayek

Publications and source records attributed to A Hayek.

90 records · Page 5Linked to original sources
PubMed1975

Neonatal hyperthyroidism following intrauterine hypothyroidism.

An infant, whose mother was treated for thyrotoxicosis during pregnancy, appeared normal at birth, but laboratory data were indicative of hypothyroidism. On the sixth day of life the infant had clinical and laboratory evidence of hyperthyroidism. A plan of management is proposed for infants born to thyrotoxic mothers.

Adult↗
PubMed1975

Dicentric Y chromosome in mixed gonadal dysgenesis.

A 15-year-old girl was investigated because of ambiguous genitalia. Her chromosome studies showed a 45, X/45, Xdic(Yq) mosaicism. The identity of the dicentric Y chromosome was demonstrated by its typical fluorescent banding patterns. Histological evidence of mixed gonadal dysgenesis with intragonadal tumour was observed, confirming the occurrence of gonadoblastoma associated with mosaicism in which at least one cell bears a Y chromosome.

Adolescent↗
PubMed1973

Endocrine studies in anencephaly.

Endocrine function has been investigated in four anencephalic neonates to determine the influence of absence of cortical and hypothalamic tissue and of hypoplasia of the pituitary. Intravenous glucose administration resulted in higher peak values for blood sugar and more rapid glucose disposal rates than reported in normals. Intravenous insulin tolerance tests on two of the infants failed to evoke elevations in plasma growth hormone, and the infants showed a remarkable resistance to the hypoglycemic effect of insulin. Administration of lysine-vasopressin caused an active growth hormone release. Similarly, there was a large increase in serum thyrotropin after administration of synthetic thyrotropin-releasing hormone. Basal levels of both thyrotropin and growth hormone were low as compared with values reported for normal newborns. Prolactin values obtained on three of the infants were in the normal range. The results strongly suggest that anterior pituitary function mediated by the hypothalamus and its releasing factors is deficient in anencephaly. However, the anterior pituitary can release growth hormone and thyrotropin when stimulated directly and, in the case of thyrotropin release, may function autonomously. The normal prolactin values presumably reflect the absence of the hypothalamic prolactin inhibitory factor.

Anencephaly↗
PubMedDate not supplied

Protection from cell death in cultured human fetal pancreatic cells.

Endocrine cells from the human fetal pancreas will proliferate in vitro on extracellular matrix but lose hormone expression, and redifferentiation requires removal of the expanded cells from the matrix and reaggregation into cell aggregates. However, extensive cell death occurs during manipulation and culture. The mechanism of cell death was examined at each stage throughout the process under different experimental conditions to determine optimal protocols to increase cell viability. During shipment, the addition of trehalose to the media to prevent necrosis increased yield 17-fold, while during culture as islet-like cell clusters the apoptosis inhibitor Z-VAD increased yield 1.8-fold. Following disruption of cell matrix interactions and reaggregation, there was marked evidence of apoptotic bodies by the TUNEL assay. Addition of nicotinamide or Z-VAD, or removal of arginine from the media during reaggregation, reduced the number of apoptotic bodies and the effect was additive. However, a combination of treatments was necessary to significantly increase the yield of viable cells. We conclude that cell death of human fetal pancreatic tissue in culture results from both necrosis and apoptosis and that understanding the mechanisms at the cellular level will lead to protocols that will improve cell viability and promote beta-cell growth.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

Islet cell mass and the longevity of islet grafts in diabetic rats.

In an attempt to demonstrate that a limited beta-cell mass is able to maintain normoglycemia in streptozocin-diabetic rats, two groups of inbred rats received transplants of 500 or 1000 neonatal islets (corresponding to 10 and 20% of total islet cell mass, respectively) into the spleen. A close correlation was found between the functional longevity of the islet graft, and the total beta-cell mass transplanted into the diabetic animals. Although euglycemia was maintained for 4-12 mo, the islet transplants were insufficient to produce glucose tolerance tests equal to those observed in normal rats. Relapse of diabetes correlated with histological findings of distorted islet architecture containing vacuolated beta-cells in the grafts. This condition was not reversed after a month of normoglycemia. Spontaneous recovery of beta-cell function in native islets was documented in 50% of the diabetic rats with prolonged normoglycemia following islet transplantation. This report shows that transplantation of as few as 500 neonatal islets, the equivalent of 10% of total islet cell mass, is sufficient to maintain normoglycemia in diabetic rats, albeit temporarily. A close correlation was found between the transplanted islet cell mass and the functional longevity of the islet graft.

Animals↗
PubMedDate not supplied

Differential integrin expression facilitates isolation of human fetal pancreatic epithelial cells.

We have studied the expression of the beta 1 family of integrins in fetal and adult human pancreas. Immunohistochemical staining with a monoclonal anti-beta 1 antibody revealed that the epithelial cells of the human fetal pancreas express high amounts of beta 1 integrin, while the pancreatic stromal cells express substantially lower amounts. Islets of Langerhans from human adult pancreas also expressed high amounts of beta 1 integrin. Taking advantage of the extremely high affinity binding between the invasin protein of Yersinia pseudotuberculosis and many beta 1 integrins, we have been able to isolate highly enriched populations of fetal pancreatic epithelial cells. Epithelial-enriched cell populations retain the ability to differentiate into mature endocrine cells following transplantation into nude mice.

Adhesins, Bacterial↗
PubMedDate not supplied

Morphology and function of cultured human fetal pancreatic cells transplanted into athymic mice: a longitudinal study.

Islet-like cell clusters generated from human fetal pancreases between 18-24 wk gestation were able to grow and mature both morphologically and functionally after transplantation under the kidney capsule of athymic nude mice. Grafted tissue, predominantly ductal in appearance was unresponsive to glucose 2 wk after grafting. The tissue assumed the trabecular column-like architecture of adult islets by 3 mo, with a concomitant 3-4-fold increase in serum human C-peptide concentration after glucose challenge. Moreover, at that time the surface area of insulin containing cells in the graft increased 20-fold over the starting material. Exocrine components, identified by their characteristic eosinophilic secretory granules were also identified at this time. Transplanted cell clusters were capable of releasing C-peptide for at least 12 mo, when the experiment was terminated. At this time, 1 yr posttransplantation, although the proportion of insulin containing cells in the graft remained unchanged from that measured at 4 mo, a reduction in the magnitude of the C-peptide response to glucose was observed; this finding coincided with a significant mononuclear infiltrate in some areas of the transplanted tissue. In summary, human fetal pancreatic cells grown in tissue culture as cell aggregates, after transplantation under the kidney capsule, remain functionally viable for virtually the life span of immunocompromised rodents. Because of their long-term viability, the use of islet-like cell clusters is a potentially useful method to expand transplantable cells.

Animals↗
PubMedDate not supplied

Isolation and characterization of a cell line from the epithelial cells of the human fetal pancreas.

Pancreatic cell lines are useful for basic studies of pancreatic biology and for possible application to cell transplantation therapies for diabetes. A retroviral vector expressing simian virus 40 (SV40) T antigen and H-rasval12 was used to infect a monolayer culture of epithelial cells from an 18-wk human fetal pancreas. Infected cells gave rise to a clonal epithelial cell line, designated TRM-1. This cell line expresses epithelial markers as well as gult2 and small amounts of insulin and glucagon. TRM-1 is the first cell line to be generated from the human fetal pancreas and also the first cell line derived directly from the fetal pancreas of any species. The approach that we have used to develop TRM-1 should be applicable to isolating cell lines from other stages of human pancreatic development.

Animals↗