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Biomedical subjects

B E Tuch

Publications and source records attributed to B E Tuch.

97 records · Page 6Linked to original sources
PubMed1979

Male pseudohermaphrodite reared as a female.

A 31-year-old male pseudohermaphrodite has been brought up as a female. The parents had told their child not to discuss the problem of ambiguous genitalia with anyone. As a teenager masculinization had occurred. Chromosome analysis of both peripheral blood and gonadal tissue was 46XY. The internal gonads were testes surrounded by a rim of ovarian stroma. A rudimentary cervix opened into a small vagina, as did the urethra in a valve-like fashion. The phallus was amputated during surgical reconstruction of the external genitalia to create a phenotypic female and the vagina was enlarged. Oestrogen therapy resulted in breast development.

Child Rearing↗
PubMedDate not supplied

Long-term organ culture of large numbers of human fetal pancreata: analysis of their insulin secretion.

Cultured human fetal pancreas has been transplanted into diabetic man in an attempt to cure the metabolic disorder. However, the capacity of large numbers of these organs to secrete insulin in organ culture has not been reported previously. This report sets out the characteristics of 321 human fetal pancreases of gestational age 12-20 weeks obtained over a period of 34 months, 295 of these being maintained in organ culture. Average insulin secretion was constant at 2.22 +/- 0.35 mU/plate/day over a 90-day period, the maximal duration of culture possible. Explants were lost because of infection or reduced insulin secretion. Practical guidelines for obtaining and maintaining viable explants in culture were established as follows: Insulin secretion had to be greater than 0.1 mU/plate/day. Secretory rates of this order were associated with a positive insulinogenic response to theophylline. Prostaglandin induction, suction curettage, and hysterotomy were equally suitable as methods of termination of pregnancy. The pancreas had to be obtained within 4 hours of termination of pregnancy. The tissue had to be diced into explants within a further 4 hours.

Fetus↗
PubMedDate not supplied

Development of fetal sheep pancreas after transplantation into athymic mice.

The capacity of the fetal sheep pancreas to grow and function when transplanted into athymic mice was examined to determine whether this source of tissue might be of potential use in reversing diabetes. For this purpose fetal sheep pancreases were obtained in the period between 50 days of gestation and fullterm (148 days). Explants (1 mm3) in organ culture secreted insulin for at least 7 days, but in steadily diminishing amounts. Acute exposure to arginine (10 mM) and theophylline (10 mM), but not glucose (20 mM), calcium chloride (10 mM), and sodium butyrate (10 mM), caused acute secretion of insulin. Explants survived for many months when grafted beneath the renal capsule of athymic mice, but their growth was less, the epithelial-like component smaller, and the percentage of endocrine cells (31 +/- 5%) fewer than the case of transplanted fetal human pancreas. The beta cell was the predominant endocrine cell in the ungrafted fetal sheep pancreas. In the transplanted fetal sheep pancreas this was not so, the alpha and PP cells being dominant--beta:alpha:delta:PP = 3:14:3:11. This pattern was unchanged when the recipient mice were hyperglycaemic--beta:alpha:delta:PP = 4:13:4:28, with no reduction of blood glucose levels being observed for up to 4 mo after transplantation. Altering the site of transplantation to the spleen or liver did not improve survival of the endocrine cells. Fetal sheep pancreatic explants when transplanted into athymic rats failed to survive. Thus, although the unusual pattern of endocrine differentiation in fetal sheep pancreas transplanted into athymic mice makes it an interesting model for further studies of fetal development, it is not of benefit in normalizing the blood glucose levels of the recipients.

Animals↗
PubMedDate not supplied

Production and characterization of fetal sheep pancreatic islet-like cell clusters.

Explants of fetal sheep pancreas transplanted into diabetic athymic mice survive for many months but there is only partial differentiation of the endocrine cells. As an alternative form of graft we examined the possibility of creating islet-like cell clusters (ICCs) by collagenase digestion of the fetal sheep pancreas, as has been described for human and porcine fetal pancreas. Such ICCs did form at the rate of 6-23 per 10 mg pancreas; their size varied between 65 and 474 microns (median 232 microns) and their insulin content was 1.6 +/- 0.2 mU per 20 ICCs. Laser scanning confocal analysis showed that 4.6 +/- 0.7% of the cells contained insulin. Insulin was secreted from ICCs maintained in culture at the daily rate of 2.5 mU per 30 ICCs. Arginine but not glucose or theophylline enhanced acute insulin secretion in vitro. Transplantation of up to 1000 ICCs into athymic and acid mice resulted in sparse growth of the epithelial-like cells in the graft and only partial differentiation of the endocrine cells. Hyperglycaemia in diabetic recipients was not normalized. Thus, while functioning ICCs can be created from fetal sheep pancreas, they do not appear to be appropriate for transplantation to reverse diabetes in mice.

Animals↗
PubMedDate not supplied

Outcome of xenografted fetal porcine pancreatic tissue is superior in inbred scid (C.B-17/Icr-scid/scid) compared to outbred nude (CD-1-nu/nu) mice.

Nude mice are used as recipients of foreign tissue because of their inability to reject these grafts. Our experience has been that there is variable rejection of fetal porcine insulin-producing tissue transplanted into CD-1 (athymic) outbred nude mice. To examine the suitability of this line of nude mouse as a recipient of the tissue, fetal porcine pancreas was grafted either into these outbred animals or into an inbred mutant strain of mice, the more immunocompromised severe combined immunodeficient (scid) mouse. Eight weeks after transplantation grafts were recovered from recipients and assayed for insulin content. Mean insulin levels were not significantly different between the two groups of mice, but a wider range of values was obtained from grafts recovered from nude (CD-1-nu/nu) mice. Reversal of diabetes in hyperglycemic recipients was achieved in 4 of 8 nude mice and 8 of 8 scid (C.B-17/lcr-scid/scid) mice. The time taken to achieve this was longer in the nudes than the scid mice, 121 +/- 12 vs. 44 +/- 2 days, the grafts increasing in size at a slower rate in the nude mice. Time taken for the weight of the grafts to double in size was 94 +/- 17 vs. 32 +/- 1 days, respectively. Histologically the grafts in the scid mice contained mostly epithelial cell clusters, a majority of which were insulin containing. In the nude mice that achieved normoglycemia, a similar pattern was observed and, as well, there was a localized lymphoid infiltrate. In those nude mice that remained diabetic fibrous tissue predominated together with a lymphoid infiltrate. In summary, fetal porcine pancreatic tissue grows and develops more efficiently when xenografted into scid rather than outbred nude mice.

Animals↗