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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 685 records · Page 38Linked to original sources

Dose- and stage-related sex difference in the incidence of cytosine arabinoside induced digit anomalies in the mouse fetus.

Pregnant mice of the Jc1:ICR strain were injected intraperitoneally with a single dose of 2.5, 5, or 10 mg/kg of cytosine arabinoside (Ara-C) on day 9.5 or 10.5 of gestation (dg). Mice were killed on 18.4 dg, and the incidences of digit anomalies were compared between male and female fetuses. In the group treated with 10 mg of Ara-C on 9.5 dg, oligodactyly of the hindlimbs was produced more frequently in male fetuses. In the group treated with 5 mg of Ara-C on 10.5 dg, oligodactyly of the forelimbs tended to occur more frequently in male fetuses. Also, in this group, oligodactyly of the hindlimbs occurred more frequently in male fetuses, whereas polydactyly occurred more frequently in female fetuses. The observed difference in the incidences of digit anomalies between male and female fetuses may be explained either in terms of the sex-related time lag in the critical period for digit development or by a probable sex difference in embryonic susceptibility to Ara-C.

Abnormalities, Drug-Induced↗

Effects of tumor necrosis factor (TNF) on transplanted tumors induced by methylcholanthrene in mice. A histopathologic study.

The effects of a highly purified tumor necrosis factor (TNF) on transplanted methylcholanthrene (Meth A)-induced murine tumors were compared with those of lipopolysaccharide (LPS). TNF caused immediate subepidermal edema and hyperemia followed 2 h later by fibrin thrombi in tumor blood vessels. Finally hemorrhagic necrosis with dispersal of tumor cells occurred. LPS produced similar hemorrhagic necrotizing changes. However, the necrotic action of LPS was delayed and complete tumor regression was not achieved with LPS. These findings suggest that tumor necrosis induced by TNF is due to circulatory disturbance associated with a microvascular injury in the tumor manifested by hyperemia and multiple fibrin thrombi.

Animals↗

Necrotizing activity of tumor necrosis factor: histopathological investigation using Meth A sarcoma and granulation tissue.

The action of tumor necrosis factor (TNF) was investigated histopathologically in mice using methylcholanthrene A (Meth A)-induced sarcomas and granulation tissue induced by autotransplantation of fragments of liver and spleen. Highly purified murine TNF caused hemorrhagic necrosis of both the tumors and the granulation tissue. Proliferation of tumor capillaries, demonstrated microangiographically, occurred 2 h after TNF administration and hyperemia of tumor vessels was obvious after 3-6 h. Hyperemia and capillary leakage were also observed in the granulation tissue 6 h after TNF injection and hemorrhage was noted in the epidermis after 12 h. These results strongly suggest that the in vivo necrotizing action of TNF is mainly related to capillary injury.

Animals↗

Development of capillary networks from rat microvascular fragments in vitro: the role of myofibroblastic cells.

A new model useful for studying capillary growth in vitro is described. When the microvessel fragments and accompanying single cells (myofibroblastic cells) from rat epididymal fat pads were co-cultivated, the myofibroblastic cells initially began to grow and reached confluence. A few days later, endothelial cells started to sprout from the vessel fragments, forming cellular cord networks on and in the multilayered myofibroblastic cells. Ultrastructurally, the lumina, surrounded by the endothelial cells having intercellular junctions, were observed at cross-sectioned cellular cords. The growth of cellular cords from the fragments always occurred after the myofibroblastic cells had reached confluence. The medium conditioned to isolated rat myofibroblastic cells stimulated not only the proliferation of the endothelial cells from the bovine capillary and human vein but also the migration of bovine capillary endothelial cells in vitro. Moreover, the extracellular matrix produced by rat myofibroblastic cells modulated the morphology of bovine capillary endothelial cells to a cordlike shape. These observations strongly suggest that the formation of the capillary in vitro is induced by myofibroblastic cells.

Animals↗

Solitary hemangioblastoma within the third ventricle.

A case of solitary hemangioblastoma within the third ventricle is presented. This case was not associated with von Hippel-Lindau disease. Only two other cases of hemangioblastoma arising in the third ventricle have been previously reported.

Adult↗

Pituitary enlargement associated with Addison's disease.

We report a case of Addison's disease with pituitary enlargement which could easily have been misinterpreted as a pituitary adenoma or other pituitary disease. Serial computed tomography following replacement therapy was essential to confirm the diagnosis.

Addison Disease↗

Inhibition of tumor-induced migration of bovine capillary endothelial cells by mouse and rabbit tumor necrosis factor.

The effect of tumor necrosis factor (TNF) on the tumor-induced endothelial migration was evaluated with the use of a phagokinetic track assay. TNF from both ddy mice and Japanese albino rabbits (sp act, 3-5 X 10(5) U/mg, respectively) was found to inhibit the migration of bovine capillary endothelial (BCE) cells stimulated by factors from tumor cells, such as the medium conditioned with mouse sarcoma 180 cells or human meningioma extract. These TNF preparations, however, did not affect the spontaneous migration of the BCE cells. When mouse TNF was further fractionated by polyacrylamide gel electrophoresis, only TNF-positive fractions showed an inhibitory activity on the tumor-induced endothelial motility. Moreover, monoclonal antibody against rabbit TNF completely neutralized its migration-inhibitory activity. These findings indicate that the observed inhibitory effect of TNF preparations on the endothelial motility evoked by tumor is exclusively ascribed to the function of TNF. This activity presumably is involved in the suppression of tumor angiogenesis in vivo.

Animals↗

Studies of the effects of FK506 on renal allografting in the beagle dog.

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

Administration, Oral↗

Elimination of viruses (human immunodeficiency, hepatitis B, vesicular stomatitis and Sindbis viruses) from an intravenous immunoglobulin preparation.

More than 10(4) plaque-forming units (pfu)/ml of HIV are inactivated during the alcohol fractionation step from plasma to fraction (Fr)-II+III, greater than 10(4) pfu/ml is inactivated from Fr-II+III to Fr-II and greater than 10(4) pfu/ml is inactivated during the polyethylene glycol (PEG) fractionation process from Fr-II+III to intravenous IgG (IVIG). The total inactivation rate from plasma to IVIG via Fr-II+III or Fr-II was calculated to be greater than 10(8) or 10(12), respectively. The PEG fractionation method produces an intact and unmodified IVIG. In addition, the PEG fractionation method at a low ionic strength was found to be effective for the elimination of greater than 10(5) units of other viruses, including hepatitis B, vesicular stomatitis and Sindbis viruses.

Chemical Fractionation↗

Ga-67 myocardial scintigraphy in patients with acute myocarditis.

Four patients with acute myocarditis were examined by Ga-67 myocardial scintigraphy. Two cases showed positive scintigram. In one of these cases, the first scintigram showed positive one month after onset of acute myocarditis, and three and four months after its onset, Ga accumulation slightly decreased intermittently. However, six months after its onset, the scintigram showed strongly positive again. Endomyocardial biopsy of this case six months from its onset showed some mononuclear cell infiltration in the myocardial interstitium. From these changes of scintigram during the course of the disease and biopsy findings, this case appeared to be one of "smoldering" or "chronic recurrent" myocarditis. Another case showed weakly positive one month after onset of disease, in spite of a negative CRP. In the remaining two cases, Ga-67 scintigram showed negative, although CRP was + and 5+, respectively. The sensitivity of the Ga-67 myocardial scintigram may not be very high. But when it continues to show positive, acute myocarditis seems to be "smoldering" and transferring to DCM. Ga scintigram is a noninvasive examination for myocarditis and is a useful screening test for identifying myocarditis, and serial scans may eliminate the need for frequent biopsies in suspected myocarditis cases.

Acute Disease↗

FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.

FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin.

Animals↗

FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.

Animals↗