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Biomedical subjects

S Katsuki

Publications and source records attributed to S Katsuki.

At least 19 recordsLinked to original sources

Systemic lupus erythematosus with a giant rectal ulcer and perforation.

A 41-year-old man with systemic lupus erythematosus (SLE) who developed pelvic inflammation due to perforation of a giant rectal ulcer is described. The patient presented with persistent diarrhea, abdominal pain and fever without development of disease activity of SLE. Endoscopic and radiological examinations revealed a perforated giant ulcer on the posterior wall at the rectum below the peritoneal evagination. The ulcerated area was decreased after a colostomy was performed at the transverse colon to preserve anal function. The patient is currently being monitored on an outpatient basis. It should be noted that life-threatening complications such as perforated ulcer of the intestinal tract could occur without SLE disease activity.

Adult↗

[Geobotanical studies on the island of Tanegashima (affinity of world property island Yakushima)].

A list was drawn up of wild plants growing on Tanegashiama island that were identified in our field work, and the list was compared with the flora of the rest of Japan and the flora of Taiwan. There were 166 families and 1,218 species consisting of 23 families and 159 species of Pteridophyta, 4 families and 7 species of Gymnosperma, 113 families and 700 species of the dicotyledous Angiosperma, and 26 families and 353 species of monocotyledous Angiosperma. There are 229 families and 5,500 species of plants in Japan, 196 families and 3,019 species in Kyushu, and 228 families and 3,477 species in Taiwan. There are 11 species of endemic plants on Tanegashima and Yakushima, and the best known of them is Pinus armandii Francht. var. amamiana Hatsushima. There are 181 species of flora of flora limited to the northern element, including several important medicinal plants, such as Akebia quinata Decaisne and Zanthoxylum piperitum DC. The 69 species of flora limited to the southern element include several important tropical plants, such as Messerschmidia argentea Johnston and Clerodendrum inerme Gaertn. Most of these plants are distributed on both island, but some of are distributed only Tanegashima. We concluded that one of the temperate borderlines of Japanese flora in the temperate zone is the islands of Tokara. The flora of Tanegashima and Yakushima are having a closely affinity of plant species and having the rich plant species.

Botany↗

Aberrant crypt foci of the colon as precursors of adenoma and cancer.

BACKGROUND: Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer. METHODS: Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line. RESULTS: We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between the number of aberrant crypt foci, the presence of dysplastic foci, the size of the foci, and the number of adenomas. After sulindac therapy, the number of foci decreased, disappearing in 7 of 11 subjects. In the untreated control group, the number of foci was unchanged in eight subjects and slightly increased in one (P<0.001 for the difference between the groups). CONCLUSIONS: Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.

Adenoma↗

[Aberrant crypt foci as biomarkers in chemoprevention for colorectal cancer].

Aberrant crypt foci (ACF) are small lesions identifiable in whole-mount preparations of normal-appearing human colonic mucosa with the aid of methyleneblue staining under stereoscopic microscope. Highly frequent mutations of K-ras genes were found, and increased proliferative activities were also observed. Therefore, K-ras gene mutation may have some role in formation of ACF. Using rat experimental model, formation of ACF was shown to be enhanced by cancer promoters (such as secondary bile acids), and to be suppressed by chemopreventive agents (deoxycholic acid and aspirin). Based on these findings, ACF are considered to be precursors of colon cancer. We demonstrated that ACF are the precursors of adenoma-carcinoma sequence. Moreover, we showed that ACF may be suitable biomarkers of chemopreventive agents for colon cancers.

Animals↗

Analysis of CA repeats in first intron of class I ADH gene in Long-Evans Cinnamon rats developing fatal intoxication after ethanol intake.

The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats that displays spontaneous hepatitis and liver cancer. We previously demonstrated that LEC rats died of acute ethanol intoxication after being fed a liquid diet containing 5% ethanol. Furthermore, we found that both alcohol dehydrogenase (ADH) and aldehyde dehydrogenase activities were remarkably suppressed in the liver of LEC rat, compared with Wistar rats. In the present study, we further investigated ethanol metabolism in the non-ADH pathway and what caused the decrease of liver ADH activity in LEC rats. Blood ethanol concentration 5 hr after intraperitoneal administration of ethanol in LEC rats was higher than in the Wistar rats, indicating that ethanol oxidation was impaired in LEC rats. The expression of liver cytochrome P-450IIE1 in the LEC rat was as much as that in Wistar rats. Regarding decreased ADH activity in the liver of LEC rats, we examined an alternating purine-pyrimidine (CA) repeat-length polymorphism in the first intron of a class I ADH gene that would play a role in altering ADH activity. A polymerase chain reaction method was used to amplify the CA repeat in the first intron of this class I ADH gene, a nine CA repeat insertion and a point mutation were detected in LEC rats. These results suggest that this alternating sequence would modify transcription of the class I ADH gene in LEC rats. Thus, LEC rats have abnormal ethanol metabolism in the ADH pathway.

Alcohol Dehydrogenase↗

Detection of activity in the conditioned medium of ethanol-treated HepG2 cells which stimulates collagen synthesis in IMR-90 cells.

Hepatic fibrosis often occurs in alcoholic liver diseases without accompanying tissue necrosis or inflammation. However, the precise mechanism of this fibrosis has not been fully clarified. In the present study, using the hepatoblastoma cell line HepG2 as a model for hepatocytes, we identified a factor that stimulates collagen synthesis of fibroblasts in a conditioned medium of HepG2 cells after treatment with ethanol. Type 1 procollagen peptide (PIC) in a culture of human fibroblast IMR-90 markedly increased after incubation with the conditioned medium of ethanol-treated HepG2 cells. The stimulating activity on the production of PIC by IMR-90 remained after the dialysis and evaporation of the conditioned medium of HepG2 cells, indicating this factor was not as volatile from low molecular substances such as acetaldehyde, acetate, or lactate. The activity of this factor diminished with heat or trypsin treatment. A gel chromatographic analysis disclosed that the molecular weight of this factor was approximately 8000 Da. These results suggest that a polypeptide factor secreted from HepG2 cells by treatment with ethanol stimulates collagen synthesis of fibroblasts.

Carcinoma, Hepatocellular↗

Autoantibody against a 78 kDa membrane protein of HepG2 cell in the sera of patients with alcoholic liver diseases.

Sera from 14 normal control subjects, 30 patients with alcoholic liver diseases (fatty liver, n = 8; hepatitis, n = 13; liver cirrhosis, n = 9), 7 controls with chronic hepatitis B, and 8 controls with chronic hepatitis C were masured for their concentrations of antibodies against HepG2 membrane protein by a binding assay utilizing 125I-labeled protein A. When the cut-off level was set as the mean value plus 2 SD of normal control subjects, the incidence of positivity was 75%, 69.2%, and 77.8% in patients with alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, respectively. Both the mean serum antibody values and the positive incidence were significantly higher in patients with alcoholic liver diseases than in either the normal controls or in the control patients with chronic hepatitis. Sodium dodecylsulfate polyacrylamide gel electrophoresis of 125I-labeled HepG2 membrane protein precipitated with IgG from patients with alcoholic liver diseases revealed an immunoreactive band at a molecular weight of 78,000 daltons (gp78). The antibody activity remained after immunoabsorption by human liver-specific lipoprotein (LSP) but decreased when HepG2 cells were pre-treated with trypsin or neuraminidase. Consequently, gp78 appears to be a glycoprotein distinct from LSP, and is specifically recognized by IgG from patients with alcoholic liver diseases. This assay may provide a new system to measure autoantibody to hepatocytes in alcoholic liver diseases.

Autoantibodies↗

Ethanol inhibits asialoglycoprotein receptor synthesis but augments its mRNA expression in a human hepatoma cell line.

The effect of ethanol on the expression of asialoglycoprotein receptor protein and its mRNA was studied in a human hepatoma cell line, HepG2. The number of asialoglycoprotein receptors on the cell surface was decreased to 60% of the control level, without a loss in affinity, by incubating the cells with 100 mM ethanol. The decrease in cell surface asialoglycoprotein receptors was paralleled by a decrease in total receptor numbers, including intracellular and surface receptors. The internalization of asialoglycoprotein was also diminished, to 44% of that in control cells. The decreases in cell surface receptors and total receptor numbers were partially restored by 2 mM 4-methylpyrazole, suggesting that ethanol metabolites participated in the diminution of asialoglycoprotein receptor expression. However, the steady-state expression of asialoglycoprotein receptor mRNA was increased in ethanol-treated cells and further augmented by a longer ethanol exposure. These paradoxical results, i.e., the decrease of asialoglycoprotein receptor protein and the increase of its mRNA expression, suggest that the reduction in the asialoglycoprotein receptor protein is a post-transcriptional event and that a possible feedback regulatory mechanism may control asialoglycoprotein receptor gene transcription and/or impair the degradation of its mRNA.

Alcohol Dehydrogenase↗

Abnormal ethanol metabolism in Long-Evans Cinnamon rats, a mutant strain developing spontaneous hepatoma.

The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma (HCC). We first tried to examine effects of ethanol consumption on the development of HCC, and fed a Lieber's liquid diet containing 5% ethanol to LEC rats. However the rats died within 2 weeks because of acute alcohol intoxication. In LEC rats, the concentration of ethanol and acetaldehyde in blood was significantly higher, and liver alcohol dehydrogenase activity was slightly lower and acetaldehyde dehydrogenase activities were remarkably suppressed compared to those of Wistar rats. These results suggest that LEC rats have hereditary deficiencies of ethanol and acetaldehyde metabolizing enzymes.

Acetaldehyde↗

Abnormal hepatic iron accumulation in LEC rats.

The LEC (Long-Evans cinnamon) rat is a mutant strain displaying hereditary hepatitis and spontaneous hepatocellular carcinoma, and shows abnormal hepatic copper accumulation similar to that occurring in Wilson's disease. We evaluated the iron metabolism of LEC rats compared to LEA (Long-Evans agouti) rats. Hepatic iron and ferritin concentrations were remarkably increased depending on age in LEC rats but not in LEA rats. Increased hepatic iron is normally associated with decreased serum transferrin and total iron binding capacity in hepatic iron overload. In LEC rats, however, both serum transferrin and total iron binding capacity increased with increasing hepatic iron. This increase of serum transferrin and hepatic iron may be an additional important factor contributing to liver injury in LEC rats.

Age Factors↗

Morphological and functional changes of islets of Langerhans in FK506-treated rats.

FK506, a new immunosuppressant, caused glucose intolerance in rats given daily oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia under normal feeding. Besides the glucose intolerance, insulin secretion was impaired and insulin levels in the pancreas were lowered. Histopathologically, there was vacuolation of the Langerhans islets in the animals given 10 mg/kg. After withdrawal of the drug, these changes in pancreatic function and morphology returned to normal within 2 weeks. The findings indicate that FK506 caused dose-dependent but reversible islet toxicity in rats.

Animals↗

The clinical pharmacokinetics of two different preparations of intrarectal ketoprofen following spinal or local anesthesia for anal surgery.

Two different preparations of commercially available suppositories containing Ketoprofen (KP) were administered to 49 patients immediately following anal surgery. The KP was prepared as either fatty suppositories (FS) or gelatin capsulated suppositories (GCS) and surgery was performed under either spinal (n = 37) or local anesthesia (n = 12). Similar results were observed in the kinetics of KP after both FS and GCS administration. The extent of bioavailability of the two dosage forms in the patient groups and control subjects (n = 10) were essentially equal. When the pharmacokinetic parameters of KP were compared between patient groups under spinal and local anesthesia, significant differences were found in the values of the peak level (C max), peak time (T max), and terminal phase half-life (t 1/2). The C max decreased by one-half, while the T max and t 1/2 increased twice and four times, respectively, in patient operated on under spinal anesthesia compared to those operated on under local anesthesia. The absorption rate constant (Ka) following spinal anesthesia was significantly less than that following local anesthesia or that of the healthy subjects (p less than 0.01). A "flip-flop" phenomena could be seen in the time profiles of plasma KP concentration following spinal anesthesia.

Administration, Rectal↗

Enzyme immunoassay of human protein C by using monoclonal antibodies.

An enzyme-linked immunosorbent assay (ELISA) for measuring human protein C by using two monoclonal antibodies directed toward the heavy chain of protein C is reported. This assay enabled the determination of protein C in concentrations of 10 to 400 ng/ml in less than 3 hours with a single antigen-antibody reaction. Within-run and between-run coefficients of variation were less than 8%. The mean concentrations of protein C in plasma of 42 normal subjects, 24 patients with liver disease, 27 with DIC, 48 with warfarin therapy and 15 with congenital protein C deficiency, were 4.2, 3.0, 2.3, 2.1 and 1.9 micrograms/ml, respectively. The results obtained with the present ELISA correlated well with those of radioimmunoassay (r = 0.935, n = 81) as well as those of Laurell's Rocket method (r = 0.910, n = 81) by using rabbit anti-human protein C serum. The present method was sensitive and specific for measurement of protein C and also PIVKA-protein C in plasma.

Antibodies, Monoclonal↗

Clinicopathological study of the heart and coronary arteries of autopsied cases from the community of Hisayama during a 10-year period. Part V. Comparison of autopsy findings with electrocardiograms--Q.QS items of the Minnesota Code.

In a longitudinal study of a general population in Hisayama, Japan, 339 persons aged 40 years or over at death were autopsied during the period November 1, 1961-October 31, 1971. In 308 of these people, electrocardiograms taken at the periodic examinations were available, and Q.QS items of the Minnesota Code were recorded in 49 persons. The sensitivity of item 1-1 to autopsy-proven old myocardial infarction was 0.32 and the specificity was 0.95. Using the estimated prevalence of old myocardial infarction in this community--77 per 100,000--the proportion of persons without old myocardial infarction among those with item 1-1 in the general population (PF+) was 0.9954 and the proportion of persons with old myocardial infarction among those without item 1-1 (PF-) was 0.0005. The sensitivity of items 1-1 and 1-2 to old myocardial infarction was 0.43 and the specificity was 0.94. PF+ of items 1-1 and 1-2 was 0.9949 and PF- was 0.0005. These large values of PF+ mean that more than 99 per cent of persons with these items are probably false positives if these items are used as a screening test for this disease in the general population of this community, i.e., that these items cannot be defined as a definite myocardial infarction.

Aged↗

The central anti-serotonin activity of zotepine, a new neuroleptic, in rats.

2-Chloro-11-(2-dimethyl-aminoethoxy) dibenzo [b, f] thiepin (zotepine) is a new neuroleptic drug which is structurally different from known neuroleptics. Zotepine, chlorpromazine, propericiazine, and cyproheptadine inhibited hyperthermia induced by dosing with fenfluramine in rats in a warm environment (26-28 degrees C). Fenfluramine is known to induce hyperthermia by mediation of central serotonin. Zotepine had a 10 times or greater potency than chlorpromazine, propericiazine and cyproheptadine in inhibiting the hyperthermia. Thioridazine did not inhibit the hyperthermia, whereas haloperidol accelerated the hyperthermia. Zotepine was also the most potent inhibitor of 3H-serotonin binding to rat cortical synaptosomes in vitro. However, cyproheptadine had the strongest anti-serotonin activity in rat fundus preparations, while zotepine and other neuroleptics showed the same order of potency. These results showed that zotepine is a unique neuroleptic with potent central anti-serotonin activity. The central anti-serotonin activity of zotepine is discussed in connection with its lesser extrapyramidal side effects in humans.

Animals↗