[Significance of the gonads in the young rodents (pre-pubertal period)--biosynthesis of 5 alpha-reduced C19-steroids].
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Biomedical subjects
Publications and source records attributed to T Tsujimura.
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Testicular homogenates from white rabbits of 0.4, 1, 3, 4, 5, 8, 18, and 24 months of age were incubated with [3H]progesterone and NADPH. At 12 days of age, major C21-17-OH-and C19- steroids formed from progesterone were 17alpha-hydroxyprogesterone and testosterone. However, at 4-24 months of age, 17alpha-hydroxyprogesterone, 3beta,17alpha-dihydroxy-5alpha-pregnan-20-one, and 5alpha-reduced C19-steroids such as 17beta-hydroxy-5alpha-androstan-3-one, 3beta-hydroxy-5alpha-androstan-17-one, and 5alpha-androstane-3beta,17beta-diol were the major products. The formation of significant quantities of 5alpha-reduced C19-steroids, which had been demonstrated previously only in prepubertal testes of rats and mice, was present in prepubertal as well as adult testes of rabbits. These findings clearly indicate that the metabolic patterns of progesterone in the adult rabbit differ from those in the adult rat and mouse. The major C19-steroids formed by testes are testosterone in the adult rat and mouse, but 5alpha-reduced C19-steroids in the adult rabbit.
Testicular homogenates from mice of 23 and 70 days of age were incubated for 3-120 min with either 3-H-progesterone, 14-C-progesterone, 3-H-5alpha-pregnane-3,20-dione or 14-C-progesterone plus 3H-5alpha-pregnane-3,20-dione in the presence of NADPH. After incubation, radioactive products were purified and identified by column and paper chromatography, with derivative formation and recrystallization to constant specific activity. In immature mouse testes, the results indicate two biosynthetic pathways leading to C19 steroids from progesterone, one from progesterone via 17-hydroxyprogesterone and androstenedione to testosterone and a second via 5alpha-reduced C21 steroids to 5alpha-reduced C19 steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol. In adult mouse testes, very few 5alpha-reduced metabolites of all the delta-4-3-ketosteroids are shown to be produced from progesterone, while evident 17alpha-hydroxylation of 5alpha-pregnane-3,20-dione followed by C17-20 lyase reaction is demonstrated.
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A patient with hepatocellular carcinoma, associated segmental portal vein thrombosis, and accompanying pneumobilia, developed a liver abscess and sepsis following transcatheter chemoembolization (TCE). It was believed that the combination of bile duct necrosis after arterial occlusion and pneumobilia led to ascending enteric infection and seeding of the necrotic tumor, which ultimately led to fatal outcome. We conclude that TCE is contraindicated in such cases.
It has been reported that ovarian fibromas display low signal intensity on both T1- and T2-weighted magnetic resonance images. We report an ovarian fibroma exhibiting low signal intensity on a T1-weighted image and high signal intensity on a T2-weighted image. Microscopically pronounced myxomatous changes were shown in the fibroma. The signal intensity of ovarian fibromas differs with the degree of myxomatous change.
BACKGROUND: The radiological appearance of peritoneal serous papillary carcinoma (PSPC) is described. METHODS: Three cases of PSPC were analyzed retrospectively with regard to the radiological appearance and histopathological features. RESULTS: All three patients were women, aged 44-71 years. Massive ascites and a greater omentum tumor were observed on computed tomography in all patients. Double-contrast enema performed in one patient showed irregularity on the upper aspect of the transverse colon. Radiological examinations excluded primary tumors in both gastrointestinal and genital organs in all patients. Histological diagnosis was made from the surgical specimen in two patients and from an autopsy specimen in one patient. All patients had a large omental tumor involving the transverse colon, but the ovaries were not involved or only minimally involved on the surface. Serum CA125 was markedly elevated, and immunohistochemical staining for CA125 was positive within the tumor cell cytoplasm in all three patients. CONCLUSION: PSPC cannot be diagnosed from radiological findings alone because of its similarity to metastatic peritoneal carcinomatosis and peritoneal mesothelioma. Marked elevation of serum CA125 may help with PSPC diagnosis. Response to treatment is promising, and exploratory laparotomy is thus justified when a patient shows characteristic radiological findings and high CA125 level.
17 human cell lines that differ significantly in level of O6-alkylguanine-DNA alkyltransferase (AGT) activity were identified by comparing their sensitivity to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and determining the level of AGT activity in cell extracts from the various lines by measuring the decrease in radiolabeled O6-methylguanine from DNA, using high-performance liquid chromatography. 9 lines exhibited high levels of AGT activity, 2 showed an intermediate level (25-50% of the mean of those with the higher levels), and 6 exhibited very low or virtually undetectable levels of AGT. Included were several lines that are very deficient in capacity for nucleotide excision repair. When representatives from the 3 categories of cell lines defined by the level of AGT activity were compared for sensitivity to the cytotoxic and mutagenic effect of MNNG, they showed an inverse correlation between the degree of cell killing and frequency of mutants induced and the level of AGT activity. The cells' capacity for nucleotide excision repair did not affect these results. Exposure of cells with a high level of AGT activity to O6-methylguanine in the medium reduced the AGT activity 60-80%. These pre-treated cells exhibited a significantly higher frequency of MNNG-induced mutants than did cells that were not pre-treated, suggesting that the O6-methylguanine lesion in DNA is responsible for a significant proportion of the mutations induced. Cell strains containing substrates for assaying intrachromosomal homologous recombination were constructed using parental cell lines from each of the 3 categories of AGT activity. These strains showed an inverse correlation between the level of AGT activity and the frequency of MNNG-induced recombination. When various cell lines representing the 3 categories of AGT activity were compared for sensitivity to ethylnitrosourea, the results were consistent with AGT and nucleotide excision repair playing a role in preventing cell killing and mutation induction by this agent.
Testicular and plasma testosterone levels were found to be decreased markedly in streptozotocin diabetic rats compared with those of controls. Treatment with 6 units NPH insulin daily for one week almost normalized plasma testosterone levels parallel to the increase in body and liver weights in diabetic rats, while testosterone levels in testicles were not significantly changed. Plasma prolactin and LH levels were unchanged among control, diabetic and diabetic insulin-treated rats. Thus, testosterone reduction in the testis might play a role in diabetic impotence.
Interleukin-12 (IL-12) treatment is effective in the CSA1M but not in the Meth A and CSA1M-variant tumor models. The authors investigated the cause by which IL-12 treatment fails to induce tumor regression in these two tumor models. T cells from CSA1M-bearing mice have high levels of IL-12 responsiveness, whereas cells from Meth A-bearing mice display marginal levels of responsiveness. Because IL-12 responsiveness in T cells is induced after T-cell receptor stimulation, the lack of IL-12 responsiveness suggests that T cells in Meth A-bearing mice are not sensitized to Meth A tumor antigen. Immunization of normal mice with attenuated Meth A tumor cells resulted in a protective immunity, as shown by the rejection of challenged viable Meth A cells. Such an immunization, when performed in Meth A-bearing mice, induced potent IL-12 responsiveness in T cells. Nevertheless, IL-12 treatment in these mice did not inhibit tumor growth. In another IL-12-incurable (CSA1M-variant) model, IL-12 responsiveness was observed before tumor cell immunization. However, IL-12 treatment was ineffective regardless of whether tumor cell immunization was performed. In these two models, the failure of IL-12 treatment to induce tumor regression was associated with the lack of T-cell migration to tumor sites. These results indicate that the sensitization of T cells to tumor antigens and generation of IL-12 responsiveness are insufficient to induce tumor regression when these sensitized T cells are not allowed to migrate to tumor sites.
Signaling through the c-kit receptor tyrosine kinase (Kit) is essential for development and survival of mast cells but not of basophils. Moreover, we recently found an activation mutation of Kit in several tumor mast cell lines.