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T Maki

Publications and source records attributed to T Maki.

At least 181 records · Page 10Linked to original sources

Age-related changes in glucocorticoid and androgen receptors of cultured human pubic skin fibroblasts.

In order to evaluate age-related changes in glucocorticoid receptor and androgen receptor of cultured human pubic skin fibroblasts in young and aged men, we determined both [3H]dexamethasone binding and [3H]methyltrienolone (R1881, potent androgenic steroid) binding, using dispersed whole cell assay. Scatchard analyses of specific [3H]dexamethasone binding to the fibroblasts of young and aged men showed a single class of high-affinity binding sites with a mean (+/- SD) binding site concentration (Bmax) of 12.69 +/- 2.36 X 10(4) and 12.87 +/- 12.21 X 10(4) sites/cell, respectively, and mean (+/- SD) dissociation constant (Kd) of 5.60 +/- 0.41 and 7.36 +/- 2.17 nM, respectively. Scatchard analyses of specific [3H]R1881 binding to the same cultured skin fibroblasts of young and aged men showed a single class of high-affinity binding sites with a mean Bmax of 5.77 +/- 1.02 X 10(3) and 2.82 +/- 0.97 X 10(3) sites/cell, respectively, and a mean Kd of 0.56 +/- 0.23 and 0.50 +/- 0.28 nM, respectively. These findings indicate that there were no significant age-related changes in binding site and affinity of glucocorticoid receptor in cultured human pubic skin fibroblasts, whereas binding sites of androgen receptor significantly decreased in those of aged men as compared to young men, without significant change in affinity.

Adult↗

Studies in small bowel transplantation. Prevention of graft-versus-host disease with preservation of allograft function by donor pretreatment with antilymphocyte serum.

Donor pretreatment with antilymphocyte serum (ALS) effectively prevents graft-versus-host disease (GVHD) in a unidirectional (parent-to-F1 hybrid) rat small bowel transplantation model. ALS must be administered prior to or at the time of transplantation, and the intraperitoneal route is more effective than subcutaneous administration. Donor pretreatment with ALS uniformly prevents GVHD without impairing subsequent allograft function as measured by absorption of dietary energy and nitrogen, weight gain, and bowel morphology. These rodent studies suggest that ALS treatment of donors as well as recipients in small bowel transplantation may be a highly effective, simple, and easily applicable method to prevent or ameliorate GVHD in human small bowel transplantation.

Animals↗

Multiple donor allotransplantation. A new approach to pancreatic islet transplantation.

Currently it is not feasible to isolate sufficient numbers of islets from a single pancreas for clinical transplantation. We examined whether small numbers of islets obtained from multiple donors could be used for transplantation. Islets were isolated from four inbred strains of mice (DBA/2, DBA/1, C3H, and A.SW) by a stationary collagenase digestion and Ficoll separation and transplanted into the renal subcapsular space of streptozotocin-induced diabetic B6AF1 mice. At least 200 handpicked islets were required to produce normoglycemia in syngeneic and allogeneic diabetic recipient mice. None of the mice given 50 islets became normoglycemic within 2 weeks postgrafting. When various numbers of purified islets from a single donor were transplanted, the survival was significantly better for 200-islet allografts than for 800-islet and 400-islet allografts. When a 200-islet composite graft was prepared from four donors (50 fresh handpicked islets from each donor), the survival of the composite graft as measured by sustained normoglycemia in nonimmunosuppressed recipients was dramatic, with 17 of 18 recipients maintaining normoglycemia indefinitely (greater than 200 days). Similarly, when islets isolated from four donors and cultured for various periods were mixed and transplanted (200 islets/recipient) all recipient mice (n = 8) enjoyed indefinite graft survival. Use of higher numbers of purified islets or crude islets in a composite multiple-donor islet allograft was less effective in achieving indefinite graft survival. Thus, transplantation of a composite graft made up with subtherapeutic numbers of islets from multiple histoincompatible donors to provide adequate therapeutic numbers is a practical solution to the lack of islet availability. In addition, composite islet grafts appear to possess immunological advantages, with significantly prolonged survival over that produced by single-donor islet grafts.

Animals↗

Immunologic and metabolic effects of caval versus portal venous drainage in small-bowel transplantation.

We compared the immunologic and metabolic effects of systemic (i.e., caval) versus portal venous drainage of small-intestinal allografts in rats. Survival times in either unidirectional rejection or graft-versus-host disease models were not significantly altered by the route of venous drainage. Portoportal and portacaval isografts and controls were then pair-fed after transplantation. After 6 weeks of pair-feeding, weight gain, plasma amino acid concentration, and the histologic appearance of the liver were similar among the three groups. Hepatic protein synthesis was greater in pair-fed rats with portoportal isografts, although this difference disappeared in the fasted state. Our data suggest that there is little immunologic or metabolic advantage of portal versus systemic venous drainage of small-intestinal allografts in rats. Because the latter is technically simpler, it may be preferable in small-bowel transplantation.

Animals↗

31P NMR spectroscopy of the stomach by zig-zag coil.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic investigations of the rat stomach were performed utilizing a 1-cm2, three-turn, zig-zag coil. A zig-zag coil of this dimension produced an effective B1 field that extends only within a 4-mm distance from the plane of the surface coil, rendering it possible to obtain high-resolution 31P spectra localized to the stomach without contamination from surrounding tissues. Normal stomach showed a characteristic spectral pattern with resonances reflecting inorganic phosphate (Pi), phosphocreatine (PCr), and the alpha-, beta-, and gamma-phosphates of adenosine triphosphate (ATP). Ischemia-induced changes in Pi, PCr, and ATP resonances were readily followed in vivo with a time resolution of 2.13 min. Indomethacin-induced ulcer revealed a low intracellular pH and a decrease in the PCr to Pi ratio indicating the partially ischemic conditions of ulcerative lesions of the stomach as has been previously suggested. The present studies indicate that 31P NMR spectroscopy utilizing a zig-zag coil is a powerful tool to study local pathology of the gastrointestinal (GI) tract. Since zig-zag coils suitable for fiberscopic devices are easily constructed, clinical applications of the present technique are apparent.

Animals↗

Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection.

Pancreatic distension with collagenase solution followed by stationary in vitro digestion yields large numbers of intact islets. We compared in rats two routes of collagenase injection, pancreatic ductal (PD) and portal venous (PV), for islet yield, in vitro insulin secretory capacities, and in vivo functional viability. The islet yield in the PD method (n = 11) was greater than that in the PV method (n = 8) (682 +/- 27 vs. 417 +/- 39 per pancreas, P less than 0.025). The insulin release from the PD islets in response to 16.7 mM glucose increased gradually following culture, 3.2 +/- 0.8 ng/10 islets/30 min (fresh) to 12.3 +/- 2.1 (24-hr culture). In contrast, insulin release from the PV islets increased during the first 6 hr of culture, but decreased after 24 hr in culture. Under electronmicroscopic examination, the PD islets revealed a well preserved structure with healthy endocrine cells, while the PV islets showed a dilated capillary network and distorted endocrine cell continuity. When 100 PD islets were transplanted into streptozotocin-induced diabetic B6AF1 mice (n = 8), all the recipient mice restored normoglycemia (less than 200 mg/dl) within 1-4 days following transplantation and maintained it until rejection. However, the recipient mice given 100 PV islets showed a significant delay in restoring normoglycemia, and 3 of 8 mice given 100 PV islets were still hyperglycemic on day 4 postgrafting. In summary, pancreatic ductal collagenase injection followed by stationary in vitro digestion reproducibly yields higher numbers of intact and viable islets when compared with portal venous collagenase injection, indicating the superiority of this method to portal venous injection.

Animals↗