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Biomedical subjects

H Iguchi

Publications and source records attributed to H Iguchi.

At least 199 records · Page 11Linked to original sources

Increased lysyl oxidase activity in culture medium of nonparenchymal cells from fibrotic livers.

Lysyl oxidase, which plays an important role in collagen deposition in chronic liver diseases, was studied in nonparenchymal cell cultures from fibrotic human livers. Liver biopsy specimens were obtained from control patients without apparent hepatic disease, and from patients with chronic persistent hepatitis, chronic active hepatitis, or liver cirrhosis. Nonparenchymal cells from biopsy specimens were cultured. At the third passage of the culture, lysyl oxidase activity was measured in the culture medium and cell layer. Most of the activity in the culture medium of cirrhotic liver cells was significantly higher than that in the medium of liver cells from controls or from patients with chronic hepatitis, whereas no significant difference in activity was noted between chronic persistent hepatitis and chronic active hepatitis cells. In patients with chronic hepatitis, lysyl oxidase activity in the culture medium from liver cells of alcoholics was significantly higher than that in the medium from liver cells of nonalcoholics. Thus, increased lysyl oxidase activity was found in the medium of nonparenchymal cell cultures from patients with cirrhosis and from alcoholics with chronic hepatitis. This increased activity may be related to fibrotic processes in the liver.

Adolescent↗

Cadmium- or zinc-binding to bone lysyl oxidase and copper replacement.

Lysyl oxidase was purified to about 3,000- to 5,000-fold from epiphyseal cartilages of chick embryos. Purification was accomplished by sequential column chromatographies of collagen-sepharose, DEAE-Cellulose and Sephacryl S-200. The molecular weight of the most purified enzyme from 4 different isomers as determined by gel-filtration technique using Sephacryl S-200 column was 32,000 and the purified enzyme contained one copper atom per mole. When the enzyme (copper content: 1.12 g-atom per mole) was incubated with 1 X 10(-4)M cadmium, followed by gel-filtration, 0.12 g-atom of cadmium was incorporated into the enzyme per mole and consequently 0.23 g-atom of prosthetic copper was released from the enzyme (loss of 21%) with a substantial decrease of the enzyme activity by 22.8%, but 50% loss of copper caused by treatment with 1 X 10(-3)M cadmium did not further decrease the activity. When the enzyme was incubated with 1 X 10(-4)M zinc, 0.38 g-atom of zinc bound to the enzyme and 65% copper was lost, resulting in 34% loss of the activity. Loss of 84% copper (experiment with 1 X 10(-3)M zinc), however, led to 47% inhibition. These findings indicate the existence of metal-metal interaction in the enzyme that can significantly influence the activity, though inhibition of the enzyme was not strictly proportional to either the amount of copper released or the amount of cadmium or zinc bound to the enzyme.

Amino Acid Oxidoreductases↗

Tissue distribution and molecular forms of a novel pituitary protein in the rat.

A sensitive and specific radioimmunoassay (RIA) was developed for a novel pituitary protein that we recently isolated from human and porcine pituitary gland and designated 7B2. By employing this RIA, we were able to detect and assay this novel protein in different rat tissue extracts. The concentrations of 7B2 in rat anterior pituitary lobe, neurointermediate lobe, hypothalamus, adrenal medulla and thyroid gland were 10,400 +/- 804; 6,190 +/- 908; 773 +/- 50; 697 +/- 83 and 1,368 +/- 116 pg/mg tissue (wet weight, n = 10, mean +/- SEM), respectively. However, the concentrations of 7B2 were lower than 30 pg/mg tissue in extracts of pancreas, ileum and colon, and were below the sensitivity of the RIA in extracts of liver, kidney, spleen, lung, adrenal cortex and testis. Gel permeation chromatography of extracts of anterior pituitary lobe, neurointermediate lobe, hypothalamus, adrenal medulla and thyroid gland on Sephadex G-100 revealed that most of the immunoreactive (Ir)-7B2 has an apparent molecular weight of 45,000-50,000. Subsequent dissociation of this Ir-7B2 by polyacrylamide gel electrophoresis containing sodium dodecyl sulfate (SDS) yielded an Ir-7B2 with an apparent molecular weight of around 19,000. In addition, high K+ concentration (50 mM) induced the release of Ir-7B2 from cultured cells of both rat anterior pituitary and neurointermediate lobe. Finally, Ir-7B2 was detected in the neurosecretory granule fraction prepared from porcine neurointermediate lobe. These results indicate that 7B2 may be a novel secretory protein in the pituitary gland.

Amino Acid Sequence↗

Synergistical effects of ovine corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on the release of pro-opiomelanocortin (POMC) related peptides by pituitary adenoma of a patient with Nelson's syndrome in vitro.

The effects of synthetic ovine corticotropin-releasing factor (oCRF), arginine vasopressin (AVP), alpha-melanocortin (alpha MSH), and dexamethasone on the release of pro-opiomelanocortin (POMC)-related peptides were studied on a pituitary adenoma of a patient with Nelson's syndrome. CRF, at doses up to 100 ng/ml, has no effect on IR-ACTH, IR-hNT or IR-beta LPH secretion by the pituitary adenoma cells within the first week of monolayer culture. During the second week of in vitro conditions, however, the cells responded to oCRF (1-100 ng/ml) with a significant increase in all three POMC-related peptides. AVP (10 and 100 ng/ml) was effective in stimulating secretion of the three POMC-related peptides on day 6 in vitro; in addition, during the second week in culture, AVP (1 ng/ml) acted synergistically with 1-100 ng/ml of oCRF to release IR-ACTH, IR-hNT and IR-beta LPH at least 3-4 fold higher than CRF alone. alpha MSH (10 micrograms/ml) and dexamethasone (10(-6)M) did not alter the release of any of the three peptides. These results demonstrate that CRF and AVP can act synergistically on human pituitary tissue in vitro to promote the release of POMC-related peptides and also in vivo as shown by others.

Adenoma↗

[Case of hyperthyroidism with pancytopenia].

A case of hyperthyroidism associated with pancytopenia has been reported. A 51-year-old woman was hospitalized for the investigation of struma, peripheral edema and fatigue. Hormonal studies revealed hyperfunction of the thyroid gland. Hematological examinations showed normocytic normochromic anemia, leukopenia and thrombocytopenia with hyperplastic bone marrow and increased serum iron levels. Elevations of the anti-thyroidal antibody and anti-microsomal antibody, and a decrease in CH50 titer were observed. A Coombs' test and anti-leukocytic antibody and anti-thrombocytic antibody tests were negative. The numbers of erythrocyte and thrombocyte were normalized after the administration of methimazole for three months as were the findings of the bone marrow and the serum iron level. However, leukopenia was maintained due to the effect of methimazole. It should be suggested that the etiology of pancytopenia might be due to hyperthyroidism. Although the mechanism of pancytopenia in a patient with hyperthyroidism is unclear, it might be related to the reduced life-span of whole blood components and/or partially to the autoimmune mechanism.

Female↗

A high performance liquid chromatographic method of analysis of 4'-O-tetrahydropyranyladriamycin and their metabolites in biological samples.

A method for measuring 4'-O-tetrahydropyranyladriamycin (THP) and its metabolites in biological samples are described. By reversed-phase high performance liquid chromatography using fluorescence detection, THP and its metabolites were all separated on a single chromatogram within 18 minutes. A linear calibration curve was obtained up to 2,000 ng/ml of THP in plasma. The recovery of THP in the analysis was more than 95% above 5 ng/ml and 87.1% even at 1.25 ng/ml. Thus the lower limit was 1.25 ng/ml in biological samples. Blood levels and urinary excretion in mice and dogs were satisfactory measured by this analytical method.

Animals↗

Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis.

To evaluate the influence of changes in liver function on serum levels of melatonin, we measured serum levels and MCR of the hormone in patients with liver cirrhosis and in healthy control subjects. Daytime (0900-1100 h) serum levels of melatonin in patients with liver cirrhosis were significantly elevated compared to those in healthy subjects. Significant positive correlations of the daytime serum levels of melatonin with the serum retention rate of indocyanine green dye and serum levels of total bilirubin were noted. The clearance of melatonin from blood showed a biphasic first-order kinetic pattern. The half-life of each phase was significantly prolonged in patients with cirrhosis compared to healthy subjects. Our data indicate that the elevated daytime serum levels of melatonin in patients with liver cirrhosis are due to decreased clearance, probably related to decreased liver blood flow, lowered activity of 6 beta-hydroxylase, and competition with bilirubin in the intrahepatic transport system.

Adult↗

Pharmacological studies on carbapenem antibiotics. I. Metabolism of PS-5 in animal tissues.

After injection into mice and dogs, PS-5 showed a very rapid decrease in its blood concentration, compared with cefazolin. Using in vitro experiments with tissue homogenates and acetone powder preparations, the kidney was found to be the primary site of PS-5-inactivation, although the extent of the inactivation varied depending on the species of animals. The comparative stability data of PS-5, NS-5 (deacetylated PS-5), thienamycin and N-formimidoylthienamycin in kidney homogenates of mouse, rabbit, dog and man are presented. Bilateral nephrectomy and the injection of ethylenediaminetetraacetate seemed to prolong the survival time of PS-5 in rats and mice respectively.

Animals↗