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Biomedical subjects

Y Kato

Publications and source records attributed to Y Kato.

At least 19 recordsLinked to original sources

[A case of Cushing's disease associated with a non-functioning adrenal tumor].

A 52-year-old woman was admitted to our hospital for further examination of central obesity, hypertension and hirsutism suggesting Cushing's syndrome. Hirsutism had been remarkable for two years, and muscle weakness of the lower extremities gradually developed during the past year. CT scan revealed a tumor in the left adrenal gland which was 1 cm in diameter, round, well-circumscribed, homogeneous and not enhanced. Endocrine data disclosed increased urinary 17-OHCS (11.5-16.4 mg/day) and elevated plasma ACTH (125 pg/ml) and cortisol (19 micrograms/dl) with a lack of diurnal rhythm. Administration of the single-dose dexamethasone (1mg) did not suppress plasma cortisol. However, consecutive administration of either 2mg or 8mg of dexamethasone for 2 days suppressed both plasma cortisol and urinary 17-OHCS. Administration of metyrapone raised both urinary 17-OHCS and plasma ACTH levels. Rapid ACTH test resulted in a hyperresponse of plasma cortisol. CRF injection raised plasma ACTH and cortisol. Bilateral adrenal glands were well demonstrated by 19-iodocholesterol (I-131) scintigraphy during the administration of dexamethasone. MRI with Gd-contrast revealed a microadenoma in the sella turcica. With the diagnosis of Cushing's disease, the microadenoma was removed by the transsphenoidal approach and adrenal function was normalized. However, the left adrenal tumor remained on CT scan but was not demonstrated by scintigraphy. These findings indicate that this is a very rare case of Cushing's disease which was associated with an unilateral non-functioning adrenal tumor.

Adenoma

Induction of 103-kDa gelatinase/type IV collagenase by acidic culture conditions in mouse metastatic melanoma cell lines.

Gelatinases/type IV collagenases have been shown to be involved in tumor invasion and metastasis. In this study, we examined the effect of culture medium pH on the secretion of the gelatinases from mouse B16 melanoma cell lines and human tumor cell lines using zymography analysis. The highly metastatic clone F10 of B16 melanoma did not secrete any gelatinase in neutral culture media (pH 7.1-7.3), whereas it secreted a high level of a 103-kDa gelatinase in an initial pH range of 5.4-6.1. The addition of an excess amount of glucose into a neutral culture medium also induced the gelatinase secretion from the cells by decreasing the medium pH during incubation. The extent of the acid-induced gelatinase secretion by the B16 melanoma cell lines was in the order of BL6 greater than F10 greater than F1 much greater than the parent B16 line, in good agreement with the order of their metastatic potentials. Two human cell lines (A549 and HT1080) secreted a higher level of a 90-kDa gelatinase at pH 6.8 compared with pH 7.3. The acid-induced gelatinase secretion from B16-F10 cells was blocked by cycloheximide, indicating that the enzyme induction was due to de novo synthesis. When in vitro tumor cell invasion was assayed in Boyden chambers, B16-F10 cells incubated in an acidic medium exerted a more active migration through type IV collagen gel than those in a neutral medium. These results suggest that the acidic environment formed around tumor tissues may be an important factor in invasion and metastasis of some types of tumors.

Animals

The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer.

Although gastric cancer is the most common cancer in the world, genetic changes during its carcinogenesis are not well understood. Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer. Based on this idea, DNAs isolated from gastric cancers were examined by means of a RNase protection analysis coupled with polymerase chain reaction followed by sequencing of the polymerase chain reaction products. By screening nearly one-half of the coding region of the APC gene in 44 tumors, somatic mutations were detected in three tumors: a missense mutation, a nonsense mutation, and a 5-base pair deletion resulting in a frame shift which causes truncation of the gene product. These results suggest that the mutation of the APC gene also plays an important role during the carcinogenesis of at least some gastric cancers.

Adenocarcinoma

Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity.

The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.

Carcinoma, Hepatocellular

Clonal Ig-gene rearrangement in some cases of gastric RLH detected by PCR method.

Clonal immunoglobulin (Ig) heavy chain gene rearrangement in gastric reactive lymphoid hyperplasia (RLH) cases was investigated by means of the 'double' polymerase chain reaction (PCR) using formalin-fixed and paraffin-embedded tissue. Rearranged DNA sequences, formed by combinations of variable (VH) and joining (JH) regions, were amplified with oligomeric primers. One microgram of DNA extracted from formalin-fixed and paraffin-embedded tissue was applied as the 'first PCR' template and one ten-thousandth of the first PCR product was used as the 'second PCR' template. As a control study for the double PCR method, DNA isolated from frank B cell gastric malignant lymphomas was assessed. Clear single bands between 100 and 150 base pair markers in length were evident on agarose gel electrophoresis in 10 out of 13 cases (76.9%) of malignant lymphomas while 2 out of 22 cases (9%) of RLHs revealed clear single bands of the same length, suggesting malignant lymphomas; however, no histologic features of malignant lymphomas were present. It is concluded that even gastric RLH cases satisfying histopathologic criteria for benign lymphoid hyperplasia may contain occult monoclonal B cell populations suggesting a continuous and progressive spectrum of lesions contributing to B cell neoplasia.

Base Sequence

Effects of lisinopril and low-dose trichlormethiazide on lipoprotein metabolism in patients with mild to moderate hypertension.

Fifty-six hypertensive patients were recruited to participate in a 12 week, randomised, multicentre trial to compare the effects of lisinopril (n = 31) and low-dose trichlormethiazide (n = 25) administration on blood pressure and lipoprotein metabolism. Both systolic and diastolic BPs decreased significantly after administration of lisinopril (5-40mg/day, mean dose 11 mg/day) and trichlormethiazide (2.0-4.0 mg/day, mean dose 2.2 mg/day). There were no significant changes in lipids, lipoproteins or apolipoproteins with either drug for 12 weeks and no significant differences between the two drugs for these parameters. It is concluded that lisinopril and low-dose trichlormethiazide administration are effective antihypertensive measures without any adverse effects after 12 weeks on lipoprotein metabolism in patients with mild to moderate essential hypertension.

Adult

A sustained occupancy in vivo of cardiovascular calcium antagonist receptors by mepirodipine and its relation to pharmacodynamic effect in spontaneously hypertensive rats.

The occupancy in vivo of cardiovascular and cortical Ca++ antagonist receptors by mepirodipine in spontaneously hypertensive rats (SHR) was investigated. At 0.5, 3 and 6 hr after an oral administration of mepirodipine (3 mg/kg) in SHR, there was a significant (69, 51 and 41%, respectively) decrease in the number of cardiac (+)-[3H]PN 200-110 binding sites (Bmax) compared to control values. At 12 hr later, the Bmax value returned to the control value. On the other hand, the mepirodipine administration had little effect on the dissociation constant (Kd) for cardiac (+)-[3H]PN 200-110 binding except at 0.5 hr, when there was a significant increase in the value, suggesting a change in the density rather than affinity of Ca++ antagonist receptors. In the cerebral cortex of these rats, there was a significant (34%) decrease in Bmax values for (+)-[3H]PN 200-110 binding only at 0.5 hr after mepirodipine administration. In contrast, nifedipine administration had a significant increase in Kd values for cardiac (+)-[3H]PN 200-110 binding without a change in Bmax values. The occupancy of cardiac Ca++ antagonist receptors by mepirodipine correlated significantly with its hypotensive effect in SHR. There was approximately a 39 mm Hg reduction of blood pressure by occupying 50% of these receptors. After an i.v. injection of (+)-[3H]PN 200-110 (15 microCi) to SHR, there was specific binding of the ligand in particulate fractions of heart, aorta, ileum and cerebral cortex, but not liver and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[TRH test].

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Adult

Enzymic cis-trans isomerization of nitrofuran derivatives: isomerizing activity of xanthine oxidase, lipoyl dehydrogenase, DT-diaphorase and liver microsomes.

Xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) supplemented with an electron donor could catalyze the cis-trans isomerization of 3-(5-nitro-2-furyl)-2-(2-furyl)acrylamide, 3-(5-nitro-2-furyl)-2-phenylacrylamide and 3-(5-nitro-2-furyl)-2-(2-furyl)acrylonitrile. The direction of isomerization (cis leads to trans, cis in equilibrium trans or trans leads to cis) is dependent on the chemical structure of these nitrofuran derivatives. Lipoyl dehydrogenase (NADH:lipoamide oxidereductase, EC 1.6.4.3), DT-diaphorase (NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2) and liver microsomes could also catalyze the conversion of cis-3-(5-nitro-2-furyl)-2-(2-furyl)acrylamide to its trans isomer in the presence of an appropriate electron donor. Such isomerizing activity of these enzymes is much higher than their nitro-reducing activity. In addition, the cis-trans isomerization of some nitrofuran derivatives was demonstrated with the liver slices and the small intestines of rats. A new cis-trans isomerization mechanism which is based on transfer of a single electron by an enzyme system to a nitrofuran derivative to give the radical-anion was proposed. This postulated mechanism was supported by the preliminary experiments using pulse radiolysis technique.

Animals

Peripheral lymphocyte culture in the diagnosis of drug induced liver injury.

In order to evaluate the usefulness of the peripheral lymphocyte culture method for the diagnosis of drug-induced liver injury, a study was carried out on 21 cases of drug-induced liver injury (Group A). Nine cases in Group A showed a positive lymphocyte stimulation test. Out of 9 cases which showed positive stimulation six cases were cholestatic type of liver injury, and the remaining three were of hepatitic type. The results suggest that peripheral lymphocyte culture method is a useful method for diagnosis of drug-induced liver injury.

Adult