Biomedical subjects
Publications and source records attributed to H Nishida.
The structure of glisoprenins A and B, novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors, was determined by spectroscopic analyses, mainly 1H and 13C NMR and MS. Glisoprenin A was deduced to be a tetrahydroxynonaprenol and glisoprenin B to be an oxidative modification of glisoprenin A.
The effects of arachidonic acid and arachidonoyl CoA on the catabolism of prostaglandin E2 in a 105000 x g supernatant fraction from rabbit kidney cortex were examined. Arachidonic acid reduced the 15-hydroxy prostaglandin dehydrogenase activity by 50% at 20 microM, while arachidonoyl CoA showed weak inhibition for the enzyme activity (15% at 20 microM). However, arachidonoyl CoA strongly inhibited the prostaglandin delta 13 reductase activity, the concentration required for 50% inhibition being about 3 microM. The dehydrogenase inhibition by arachidonic acid was non-competitive with regard to NAD+ and prostaglandin E2, respectively. Arachidonoyl CoA was also a non-competitive inhibitor for the reductase with regard to NADH and 15-keto prostaglandin E2, respectively. These results suggest that arachidonic acid and arachidonoyl CoA can be important modulating factors in prostaglandin catabolism by the kidney cortex.
A 36-year-old woman was hospitalized because of nephrotic syndrome. On admission, laboratory studies revealed total protein 5.9g/dl, total cholesterol 381mg/dl, urine protein 2-4g/day, C3 68mg/dl(90-185mg/dl) and the immunological tests showed that antinuclear factor, anti-DNA antibodies and the LE cell phenomenon were positive. Renal function was within normal range. After admission, renal biopsy was done. Light microscopic finding showed diffuse membranous glomerulonephritis, and vacuolization of epithelial cells. Immunofluorescent microscopic finding showed a granular specific staining for IgG, IgM, C3 and C1q along the capillary loops. Electron microscopic finding showed subepithelial and subendothelial dense deposits, and visceral epithelial cell cytoplasm containing osmiophilic multilamellar lipoid bodies. In the studies of the enzyme activities, the patient's fibroblast extract demonstrated a partial deficiency of alpha-galactosidase, and urine ceramide trihexoside was positive. But the patient's leukocyte extract did not demonstrate a deficiency of alpha-galactosidase. So Fabry's disease associated with lupus nephritis was diagnosed. It seems that the case of Fabry's disease which is an X-linked disorder caused by deficiency of the lysosomal enzyme alpha-galactosidase, associated with lupus nephritis, is extremely rare.
Seventeen patients with hepatocellular carcinoma were treated by intraarterial injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/- SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg, respectively. The therapy was given once in 10 patients, twice in 6 and 4 times in one. Over 50 per cent reduction in tumor size was obtained in 5 patients (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was observed in 3 of 7 patients (43%) with the initial serum AFP level of more than 200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases. However, they disappeared within 2 weeks after therapy was completed. No severe complications were encountered except one case of a liver abscess which healed by administration of antibiotics. No severe changes in laboratory data were observed. This study suggests that a new method of intraarterial injection must be developed to enhance the therapeutic effect even more, in addition to an increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP in LPD.
To analyze and compare the effects of saphenous vein grafts (SVG) and arterial grafts (AG) on the long-term results of the coronary artery bypass grafting (CABG), retrospective nonrandomized studies were performed in 1,400 consecutive patients with CABG in terms of reoperation, postoperative transluminal coronary angioplasty (PTCA) to the grafts, actuarial survival rate, and cumulative event free rate. AG was used frequently in recent cases in which more diffuse and multiple vessel disease were encountered. No statistically significant differences were noted in any of the reoperation free rate, actuarial survival rate, success rate of the PTCA, and cumulative event free rate between SVG and AG, because the long-term results of the SVG was apparently better than reported Caucasian's long-term results, while those of the AG were as good as Caucasian's. Reoperation and PTCA for the AG were performed less than one year after the CABG in most cases and restenosis after the PTCA was rare. In contrast, those for the SVG were mainly done late postoperative period, and the incidence of the restenosis after the PTCA was very high. These results indicated that the main cause of the graft failure in the AG was technic-related, and that of the SVG was graft's atherosclerosis. We conclude from this study that AG should be indicated more extensively than SVG, but proper indication and application of the AG in various situations and technical improvement to avoid stenosis at anastomosis are important to improve the long-term results of the CABG.
We carried out sequential coronary bypass grafting using the gastroepiploic artery (GEA) as an in situ graft in seven patients. Four patients had sequential graft from the right coronary to the circumflex. Three patients were anastomosed to two or three peripheral branches of the right coronary artery. There were no early deaths. Postoperative angiograms revealed that the patency rate was 92.3% (12/13 anastomoses). Sequential GEA grafting is available to anastomose the peripheral branches of the right coronary and the circumflex where the in situ internal thoracic artery is difficult to access. Therefore, this procedure will be indicated for multiple coronary artery bypass grafting.
The effects of a new chalcone derivative, xanthoangelol E, isolated from Angelica keiskei Koidzumi, on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit were examined. When gastric antral mucosal slices were incubated with xanthoangelol E (0.05-1.0 mM), there was no significant effect on the production of prostaglandin (PG) E2, PGF2 alpha and their metabolites. On the other hand, this compound inhibited effectively the production of thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid from exogenous arachidonic acid in platelets, and the concentration required for 50% inhibition (IC50) was approximately 5 microM. The formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid was also reduced by this drug (IC50, 50 microM). These results suggest that xanthoangelol E has the potential to modulate arachidonic acid metabolism in platelets and that this action may participate in some pharmacological effect of the plant.
Effects of exercise and differing calcium intakes on bone hardness and bone constituents were examined using mice (40 weeks old) in successive stages of senescence to contribute to our understanding of preventive measures against osteoporosis. In the present study, the mice were divided into four groups, combinations of stock diet (Ca: 1.25 g/100 g) or low Ca diet (Ca: 0.15 g/100 g), with or without physical exercise (forced exercise, 40 min/day at a velocity of 12 m/min) and maintained in their respective conditions for 16 weeks. Autopsies were performed or representative mice every four weeks (44, 48, 52, 56 weeks old). The obtained results are summarized as follows: 1) In female mice highest values for femoral bone weight were observed after 48 weeks in the mice exposed to forced exercise and on a stock diet and had a significant difference from the other groups. No difference was observed in male mice. 2) Bone hardness had a tendency to be reduced with age in all groups. The velocity of diminution was small in the mice kept on stock diet as compared to those on a low Ca diet. The highest bone hardness was observed in the mice kept in forced exercise and stock diet group at every stage. 3) Bone constituents, Ca, P and hydroxyproline, showed no differences in concentration per weight of bone. But higher total content in the femur was obtained in the mice kept on a stock diet. 4) No differences in concentration of serum calcitonin and parathormone were seen in every group of male mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid extract of mature sperm of the toad, Bufo japonicus, exclusively comprised sperm-specific basic proteins which moved faster than somatic histones on acid/urea/Triton X-100 polyacrylamide gel electrophoresis. When these proteins were purified by reversed-phase high-performance liquid chromatography they were found to consist of three components; one of these was a phosphorylated form of another, so that there were only two distinct components (P1 and P2). Amino acid sequence analyses indicated that the components both contained 39 amino acid residues, with 43.6% Arg, and differed only in the 28th amino acid residue (P1, Asp; P2, Glu). They had molecular masses of 5092 Da (P1) and 5106 Da (P2). The nucleotide sequences of cDNA clones encoding P1 (245 bases) and P2 (305 bases) showed that the difference in the amino acid residue between P1 and P2 was due to the difference of a nucleotide at position +87. Both cDNAs possessed a canonical signal (AATAAA) for polyadenylation and/or cleavage of transcript at the 3' untranslational region. Statistical analyses of amino acid sequence similarities suggested that the Bufo protamines are homologous with the protamines of fishes rather than with those of avian/mammalians.
Distribution of Lipiodol within hepatic tumor was evaluated using serial computed tomography. Imagistic Lipiodol transition into the tumor via hepatic artery was slower than that of water soluble contrast medium, spreading to central part first and turn to peripheral part of the tumor. This method was thought to be useful to clarify Lipiodol distribution in hepatic tumor and to decide the method or necessity of additional trans-arterial therapy.
Liver glycogen content decreased in golden hamsters experimentally infected with plerocercoids of Spirometra erinacei. The activity of glycogen synthase a decreased significantly in infected animals, whereas that of glycogen phosphorylase a was not significantly affected. These observations suggest that changes in glycogen content were not attributable to increased glycogenolysis, but rather resulted from suppressed glycogenesis. Plasma immunoreactive insulin (IRI) concentrations in infected animals were slightly lower than those in controls, but the differences were not statistically significant. Plasma glucagon concentrations were significantly higher in infected animals. These results suggest that the suppression of glycogen synthase activity in S. erinacei-infected hamsters was attributable to enhanced levels of glucagon and that enhanced secretion of glucagon was caused by parasite-induced hypoglycemia.
Metastatic colon carcinoma of the heart is a rare diagnosis, and an uncommon finding at autopsy. This report describes a patient with a huge intracavitary colonic metastasis of the right atrium causing both a superior vena cava syndrome and an obstruction of the tricuspid valve. To our knowledge, no similar case has been previously reported.
The gastric pedicle is commonly used for reconstruction following resection of esophageal cancer. However, we recently experienced a case in which two gastric tube ulcers occurred three months postoperatively; one penetrating into the pericardial cavity and the other into the left brachiocephalic vein. To our knowledge, no other such a case has ever been reported and we therefore report and discuss its etiology and management.
It has recently come to be thought that cases of juvenile polyposis have a natural tendency to develop adenoma and/or carcinoma. Here we present a case of juvenile polyposis coli with adenomatous change in a 21-year-old male, with a review of 34 cases of juvenile polyposis in the Japanese literature, and discuss the pathogenetic development of the polyps and their malignant potential. In this case, focal or entire adenomatous areas were found in large part of the polyps in the resected sigmoid colon and rectum, though these findings had not been recognized in 23 polypectomy specimens from the rectum 10 months prior to the operation. It was suggested that adenomatous change developed quickly in a very short time.
A cDNA library was prepared in lambda gt 11 from poly(A)+ mRNA isolated from a pure population of Xenopus round spermatids and screened with an antibody against SP3-5 (sperm-specific proteins) of Xenopus sperm. Positive clones were sequenced and an arginine-rich clone, designated pXSP531, was obtained. The 473-nucleotide sequence of pXSP531 contained an open reading frame of 237 nucleotides which was preceded by a 5' untranslated region of 67 nucleotides. The 3' untranslated region contained 149 nucleotides, including a consensus polyadenylation signal (AAATAAAA). Twenty nucleotides of a poly(A) tail was contained in the pXSP531. SP3-5 were separated from each other by reverse-phase chromatography and sequenced. The amino acid sequence of the peptide fragments which were obtained by digestion of SP4 with V8 protease and separated by reverse-phase chromatography was identical to the sequence of the N-terminal 43 and C-terminal 15 amino acids deduced from the nucleotide sequence of pXSP531. This result demonstrates that pXSP531 encodes SP4. Northern hybridization of RNA extracted from primary spermatocytes and round spermatids on Days 0 and 6 with SP4 cDNA probe (pXSP531) showed that SP4 mRNA is present both in primary spermatocytes and in round spermatids as is protamine mRNA in the rainbow trout. The size of the SP4 mRNA in round spermatids on Day 0 was longer by 60 nucleotides compared to that in primary spermatocytes and that in spermatids on Day 6 was shorter by 30 nucleotides compared to that on Day 0. These size differences were due to differences in the length of the poly(A) tracts because digestion of poly(A) with ribonuclease H resulted in the shortening of mRNA to the same size for three stages.
Three monoclonal antibodies (MAbs1A2, 3C5, and 4C2) for human aldolase A [EC 4.1.2.13] were established. MAbs1A2, 3C5, and 4C2 were shown to belong to subclasses IgM, IgG1, and IgG2a, respectively. None of the MAbs inhibits aldolase A activity. Their epitopes were mapped in detail on the molecule by examining the reactivities of the MAbs to chimeric proteins between aldolases A and B [Kitajima et al. (1990) J. Biol. Chem. 265, 17493-17498] in ELISA and to the CNBr-cleaved fragments of aldolase A in immuno-blotting. MAbs1A2 and 3C5 reacted with sites located within amino acid residues 306-363 at the C-terminal region of the enzyme. MAb4C2 recognized an epitope of the enzyme present within amino acid residues 34-108 at the N-terminal region. In a competitive binding assay, MAbs1A2 and 3C5 competed with each other for binding to the antigen and also interfered with the binding of MAb4C2, whereas MAb4C2 failed to inhibit the binding of MAbs1A2 and 3C5 to the antigen. MAb3C5 showed a species-specificity in the reaction with the antigen; it reacted with human and rabbit aldolase A with similar reactivity but not at all with the rat and mouse enzymes, which differ from the human and rabbit enzymes in two amino acid residues at positions 328 and 348. Reactivities of MAbs to aldolase A were further examined with engineered enzymes containing an amino acid substitution.(ABSTRACT TRUNCATED AT 250 WORDS)
Along with the recent progress in controlling the diabetic state during pregnancy, the number of diabetic pregnancies in our country has been increasing. It is not appropriate to apply White's classification to Japanese pregnant women, because more than two-thirds are NIDDM and it is not easy to clarify their duration of illness. Neonatal complications were analyzed in 160 infants of diabetic mothers (IDMs) who were admitted to Tokyo Women's Medical College over the past five years. All were inborn except four. Neonatal outcomes of IDDM and NIDDM were not statistically different. The overall incidence of neonatal complications in IDMs was 66%, and there were no neonatal deaths. Offspring whose mothers had been suffering from retinopathy were likely to be premature and light-for-date infants. A planned pregnancy in diabetic women is likely to decrease neonatal complications. The cooperative total care of diabetic mothers and their offspring by respective specialists, namely endocrinologists, obstetricians and neonatologists is essential for the better prognosis of infants of diabetic mothers.
Penicillium purpurogenum FO-608, a soil isolate, was found to produce a series of new inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Three active compounds, designated purpactins, A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. Purpactins inhibit ACAT activity in an enzyme assay system using rat liver microsomes with IC50 values of 121 approximately 126 microM. Purpactin A also inhibited cholesterol ester formation in J 774 macrophages, indicating the inhibition of ACAT activity in the living cells by purpactin A.