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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 379 records · Page 21Linked to original sources
PubMed1995

Fission yeast sta mutations that stabilize an unstable minichromosome are novel cdc2-interacting suppressors and are involved in regulation of spindle dynamics.

Cytological observations have shown that the presence of unstable minichromosomes can delay progression through the early stages of mitosis in fission yeast (Schizosaccharomyces pombe), suggesting that such minichromosomes may provide a useful tool for examining the system that regulates the coordinated segregation of chromosomes. One such unstable minichromosome is a large circular minichromosome. We previously showed that the mitotic instability of this minichromosome is probably due to the frequent occurrence of catenated forms of DNA after replication. To identify genes involved in the regulation of chromosome behavior in mitosis, we isolated mutants which stabilized this minichromosome. Three loci (sta1, sta2, and sta3) were identified. Two of them were found to be suppressors of temperature-sensitive mutations in cdc2, which encodes the catalytic subunit of muturation promoting factor (MPF). They show no linkage to, and are thus different from, suc1, and cdc13, previously identified as genes that interact with cdc2. The other mutation mapped to a gene previously identified as being required for the correct formation of the mitotic spindle. Data provided in this study suggest that the sta genes are involved in the regulation of spindle dynamics to ensure proper chromosome segregation during mitosis.

CDC2 Protein Kinase↗
PubMed1995

Inhibitory effects of green tea infusion on in vitro invasion and in vivo metastasis of mouse lung carcinoma cells.

The peroral administration of green tea infusion reduced the number of lung colonies of mouse Lewis lung carcinoma cells in a spontaneous metastasis system. The experiments with artificially reconstituted basement membrane suggested that this reduction could be understood by the inhibitory effects of the green tea infusion and its constituent catechins on the penetration of the cells through the basement membrane.

Animals↗
PubMed1995

Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis.

We have identified a novel membrane-type matrix metalloproteinase (MT-MMP) expressed on the cell surface and inducing activation of pro-gelatinase A in vitro. In this study, we further examined the possibility that MT-MMP is the activator of pro-gelatinase A in tumors as well as in vitro. Expression of MT-MMP mRNA was analyzed by Northern blotting in 58 cases of human lung carcinomas. MT-MMP mRNA expression was increased in tumor tissues compared with adjacent normal tissues. The ratio of MT-MMP mRNA levels in tumor/normal tissues (T/N ratio) was 3.19 +/- 1.62 in 29 cases of adenocarcinoma, 3.09 +/- 1.44 in 24 cases of squamous cell carcinoma, 4.40 +/- 0.47 in 3 cases of large cell carcinoma and 3.63 +/- 2.11 in 2 cases of small cell carcinoma, respectively. Activated gelatinase A, as detected by gelatin zymography, was also predominant in tumors compared with normal tissue counterparts, though the difference in mRNA levels was not significant. The activation ratio of gelatinase A in tumor vs. normal tissues correlated well with that of MT-MMP mRNA expression and with lymph node metastases. Our findings suggest that MT-MMP is indeed the tumor-specific activator of pro-gelatinase A in lung carcinomas and is important to initiate invasion of basement membranes.

DNA, Complementary↗
PubMed1995

Production of interleukin 8 in adult T-cell leukemia cells: possible transactivation of the interleukin 8 gene by human T-cell leukemia virus type I tax.

Interleukin 8 (IL-8) mRNA was detected in peripheral leukemic cells obtained from adult T-cell leukemia patients, as well as in cultured human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines (HUT-102, MT-1, SALT-3, and SKT-1B). With the use of ELISA, IL-8 protein was also detected in the culture medium of these cells and in the extracellular fluids of patients. Furthermore, we demonstrated that the HTLV-I-derived transactivator protein, tax, could stimulate endogenous IL-8 gene expression in an uninfected T-cell line (Jurkat) and in a rheumatoid synovial cell line (E-11). Induction of IL-8 by tax at protein level was also demonstrated in transfected cells. We found that the IL-8 NF-kappa B-binding site specifically formed a complex with NF-kappa B-containing nuclear extracts from HTLV-I-infected T-cell lines and freshly isolated leukemic cells from adult T-cell leukemia patients. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results suggest that the HTLV-I tax gene may transactivate the IL-8 gene through the kappa B site in HTLV-I-infected cells and that constitutive expression of the IL-8 gene may play a role in HTLV-I-associated pathogenesis.

Acute Disease↗
PubMed1995

Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity.

Agents that inhibit hepatic cholesterol biosynthesis reduce circulating cholesterol levels in experimental animals and humans, and may be of pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS-21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1. It also lowered plasma cholesterol levels in hamsters fed a high saturated fat and cholesterol diet. RS-21607 inhibited hepatic microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity in hamsters in a dose-dependent manner (ED50 = 31 mg/kg), and this was highly correlated with serum cholesterol lowering (r = 0.97). Cholesterol lowering by azalanstat and cholestyramine was additive, and the increase in HMG-CoA reductase brought about by cholestyramine was attenuated significantly by azalanstat. In vitro studies with HepG2 cells indicated that this modulation of reductase activity was indirect, occurring at a post-transcriptional step, and it is proposed that a regulatory oxysterol derived from dihydrolanosterol (or lanosterol) may be responsible for this regulation. Azalanstat does not appear to lower circulating cholesterol in the hamster by up-regulation of the hepatic LDL receptor, suggesting that other mechanisms are involved. Orally administered azalanstat (50-75 mg/kg) stimulated hepatic microsomal cholesterol 7 alpha-hydroxylase activity by 50-400% in hamsters, and it is postulated that this may result from modified cholesterol absorption and bile acid synthesis.

Acetates↗
PubMed1995

Peritoneal macrophages from stroke-prone spontaneously hypertensive rats accumulate more cholesteryl ester than do macrophages from Wistar-Kyoto rats.

The intracellular cholesterol metabolism of peritoneal macrophages from stroke-prone spontaneously hypertensive rats (SHRSP) was compared to that of normotensive Wistar-Kyoto rats (WKY) in order to examine the role of macrophages in the development of arterial fat deposits in the SHRSP. Scavenger receptor activity and intracellular acyl CoA:cholesterol acyltransferase (ACAT) activity were significantly higher in macrophages from SHRSP compared to findings in WKY, in the presence of modified low-density lipoprotein (LDL), acetylated-LDL (Ac-LDL). Moreover, macrophages from the SHRSP accumulated more cholesteryl ester than seen in WKY in response to Ac-LDL. ACAT activity and cholesteryl ester accumulation were inhibited by specific ACAT inhibitor, HL-004, to a similar extent, in macrophages from WKY and SHRSP. These findings suggest the susceptibility of SHRSP to arterial fat deposits.

Animals↗
PubMed1995

A large circular minichromosome of Schizosaccharomyces pombe requires a high dose of type II DNA topoisomerase for its stabilization.

We have constructed circular minichromosomes, ranging in size from 36 to 110 kb, containing the centromeric repeats of Schizosaccharomyces pombe cen3. Comparison of their mitotic stability showed that the circular minichromosomes became more unstable with increasing in size, however, a linear cen3 minichromosome, which is almost the same size as the largest circular one tested, does not show such instability. High levels of expression of the top2+ (type II DNA topoisomerase; topo II) but not top1+ gene (type I DNA topoisomerase) suppressed the instability of the largest circular minichromosome, whereas partial inactivation of topo II dramatically destabilized the minichromosome. A mutant topo II, defective in nuclear localization but still retaining its in vitro relaxation activity, did not stabilize the circular minichromosome. These results indicate that endogenous type II DNA topoisomerase is insufficient for accurate segregation of the circular minichromosome. In addition, the replication of the minichromosomal DNA appears to proceed normally, because the presence of the unstable minichromosome did not cause G2 delay. A likely cause of the instability is intertwining of the minichromosome DNA possibly occurring after DNA replication. An interaction between topo II and the centromeric repeats is implied by the finding that multiple copies of the centromeric repeat, dg-dh, affect stability of the minichromosome similarly to top2+ gene dosage.

Chromosomes, Fungal↗
PubMed1995

Human RPB5, a subunit shared by eukaryotic nuclear RNA polymerases, binds human hepatitis B virus X protein and may play a role in X transactivation.

The X gene of human hepatitis B virus encodes the polypeptide HBx which transactivates viral and host genes through a variety of cis-acting enhancer elements present in RNA polymerases I, II and III promoters. To better understand the mechanism of X transactivation, we cloned cDNAs of proteins that bind HBx. Here we demonstrate that one of these cDNAs is a full-length cDNA of human RPB5, a subunit shared by RNA polymerases. The HBx transactivation domain and the central region of human RPB5 were necessary for the specific binding of the two proteins as shown by: (i) in vitro assays using deletion mutants of fusion proteins; (ii) in vivo assays which detect associated proteins by co-immunoprecipitation of the non-fused proteins from transfected HepG2 cells. Over-expressed HBx seemed to associate with assembled forms of endogenous human RPB5 in HBx-transfected cells, since the endogenous RPB5 co-immunoprecipitated with HBx. The HBx binding region of human RPB5 by itself stimulated chloramphenicol acetyltransferase activities from several different reporters having X-responsive element(s). Our results support the idea that the interaction of HBx and human RPB5 can facilitate HBx transactivation and that human RPB5 has a domain which can communicate with transcriptional regulators.

Amino Acid Sequence↗
PubMed1995

Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells.

cDNA cloning revealed the presence of two related but distinct types of human interleukin-8 (IL-8) receptors, type I (type A) and type II (type B). By immunizing rabbits with glutathione-S-transferase fused with the NH2-terminal domain of each type of IL-8 receptor, we prepared polyclonal antibodies that specifically recognized the NH2-terminal domain of each type of IL-8 receptor. Immunofluorescence analysis of human peripheral blood leukocytes demonstrated that mature granulocytes except eosinophils express both types of IL-8 receptors. A majority of monocytes and CD16+ natural killer (NK) cells in peripheral blood were stained with both antibodies, whereas CD3+ T or CD20+ B lymphocytes in peripheral blood or CD34+ cells in cord blood were not stained with either antibody. These results suggest that both types of human IL-8 receptors were coordinately and selectively expressed in mature granulocytes, monocytes, and CD16+ NK cells.

Amino Acid Sequence↗
PubMed1995

Clinicopathological study of primary malignant tumors of the lung: an analysis of 993 tumors resected at the Kanazawa University Hospital between 1979-1993.

A retrospective study was conducted of 993 malignant tumors of the lung in 977 patients. The male-female sex ratio was 2.6:1. The age distribution of the males did not differ from that of the females and the overall mean age was 64.3 +/- 9.5 years (range, 13-85 years). Forty-three percent of the patients were in their seventh decade. The location was peripheral in 81% of the tumors and central in 19%. Of the central tumors, 85% were squamous cell (epidermoid) carcinoma (SCC), while 58% of the peripheral tumors were adenocarcinoma (ADENO). In males, 49% of all tumors were SCC and 36% ADENO, while in females 76% were ADENO. The incidence of positive lymph node metastasis increased in parallel with the pT status in both central and peripheral carcinomas. However, it was noted that, of peripheral lung carcinomas, no SCC with a diameter of 15 mm or less had lymph node metastasis, whereas 18.9% of the ADENO of this size were positive for lymph node metastasis. These results indicate that lymph node metastasis can occur even in small-sized peripheral ADENO less than 15 mm. Thus, early detection and surgery together with mediastinal lymph node dissection are necessary even for small-sized tumors to improve the prognosis in patients with peripheral ADENO of the lung.

Adolescent↗
PubMed1995

Results of surgical treatment of pulmonary metastases.

From 1970 to 1993, 155 thoracotomies for metastatic lung tumors were performed on 113 patients in the Department of Surgery, Kanazawa University School of Medicine. Overall 30-day mortality amounted to 0.9% (1/113). The cumulative 3- and 5-year survival rates were 39.4% and 29.1%, respectively. The overall median survival was 24 months. The 5-year survival rate for carcinoma was 37.2% and for sarcoma it was 14.5% (P < 0.01). The other significant predictors of better long-term survival with metastatic lung tumors were solitary lesions, disease-free interval (DFI) > 24 months, and tumor size < or = 20 mm in diameter. There was no significant difference in survival based on the method of pulmonary resection. Repeat thoracotomy for recurrent metastases was performed in 27 patients, whose 5-year survival rate after the first lung resection was 35.5%. For bilateral pulmonary metastases, we recently performed simultaneous bilateral thoracotomy via median sternotomy on 25 patients and transsternal simultaneous bilateral thoracotomy on 8 patients. The latter procedure provides a wide operative field and better survival. We conclude that resection of metastatic lung tumors is safe and effective, and that repeat thoracotomy is warranted in selected patients with recurrent pulmonary metastases.

Adolescent↗
PubMed1995

Hypolipidemic and antiatherosclerotic effects of a novel ACAT inhibitor, HL-004, in stroke-prone spontaneously hypertensive rats.

The hypolipidemic and antiatherosclerotic effects of a novel acyl CoA:cholesterol acyltransferase (ACAT) inhibitor, HL-004, were studied in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were administered 0.01-0.09% HL-004 mixed in a hypercholesterolemic (HC) diet for 50 days. HL-004 reduced the cholesterol and triglyceride levels in serum, as well as those in the liver, small intestine, and aorta, in a dose-dependent manner. HC diet-induced severe fat deposition in the mesenteric arteries, which is characteristic of SHRSP, was also decreased by HL-004. The ACAT activity of the small intestine and liver was decreased by HL-004. In particular, liver ACAT activity was significantly low in SHRSP given 0.09% HL-004, compared to that of normal animals. These results suggest that HL-004 is a systemic ACAT inhibitor and that the ACAT inhibition in the intestine, liver, and aorta is involved in the hypolipidemic and antiatherosclerotic effects of HL-004.

Acetanilides↗
PubMed1995

Serum-soluble interleukin-2 receptor levels before and after surgical treatment for Graves' disease.

Serum-soluble interleukin-2 receptor (ssIL-2R) is released from its specific affinity membrane receptor on activated T lymphocytes and is detected as a form of the alpha-chain of IL-2R in the peripheral blood. We measured the ssIL-2R levels by enzyme-linked immunosorbent assay in 29 healthy subjects and 39 patients with Graves' disease who were given antithyroid drugs to prepare them for surgical treatment. The preoperative ssIL-2R levels in Graves' patients were significantly higher than those in the healthy controls (681 +/- 387 vs 369 +/- 149 U/ml); in particular, the preoperative levels in hyperthyroid patients were significantly higher than those in euthyroid patients. On the 5th day after thyroid resection, their ssIL-2R levels (560 +/- 296 U/ml) were significantly lower than the preoperative levels. There were no correlations between the preoperative ssIL-2R levels and the immunological parameters such as thyroglobulin antibody, microsomal antibody, and thyroid-stimulating hormone receptor antibody. Thus, we conclude that ssIL-2R levels can be decreased by surgical resection of goiter in Graves' patients whose hyperthyroid status does not respond to the administration of antithyroid drugs, and this may be a useful indicator of immunological status after surgical treatment of Graves' disease.

Adult↗
PubMed1995

Multiple endocrine neoplasia type 1 presenting as insulinoma, gastrinoma, and postbulbar duodenal ulcers: report of a case.

We report herein the unusual case of a 55-year-old man with multiple endocrine neoplasia type 1 presenting as hyperparathyroidism, hyperpituitarism, insulinoma, and gastrinoma with postbulbar duodenal ulcers. The patient was referred to our hospital for further investigations of nephrolithiasis, acromegaly, and hematemesis. Laboratory studies showed high serum levels of calcium, parathyroid hormone, growth hormone, insulin, gastrin, and prolactin. Computed tomography of the cranial cavity demonstrated an enlargement of the serra turcica and swelling of two parathyroid glands in the neck. Computed tomography and angiography of the abdomen also showed a mass in the head of the pancreas. Endoscopy demonstrated reflux esophagitis, erosive gastritis, and multiple postbulbar duodenal ulcers. We diagnosed this patient as having multiple endocrine neoplasia type 1, with concomitant lesions of the pituitary gland, parathyroid glands, and islet cells of the pancreas. Following excision of the two enlarged parathyroid glands, his serum calcium and parathyroid hormone levels fell to within the normal range. Thereafter, a total gastrectomy was performed to alleviate the frequent bleeding from the upper gastrointestinal tract. However, resection of the pancreatic mass could not be performed owing to severe inflammation around the duodenum, probably induced by the postbulbar duodenal ulcers.

Adenoma↗
PubMed1995

Alteration in gastric nerve fibers containing gastrin-releasing peptide in relation to the gastrin-producing cell population after truncal vagotomy in a rat model.

The fine structural alteration in the gastric nerve fibers containing gastrin-releasing peptide (GRP) was studied in relation to the dynamics of gastrin-producing cells (G-cells) after truncal vagotomy in a rat model. The circulating gastrin levels were markedly elevated from the 1st day after vagotomy and the number of G-cells with positive immunoreaction for G17 and G34(1-15) was significantly increased in the vagotomized group. On the 3rd day after vagotomy, the G-cells showed conspicuous ultrastructural changes characterized by hypertrophy of the Golgi complexes and increased numbers of secretory granules. The GRP-positive nerve fibers formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa close to the blood vessels and showing varicosities composed of either small clear or GRP-positive large vesicles containing an electron-dense core. In the oxyntic mucosa of the vagotomized rats, axonal swelling of the nerves occurred on the 3rd day, and a depletion of GRP immunoreactivity was evidenced by a markedly decreased number of large-cored vesicles on the 7th day, when the serum GRP levels were also found to be markedly elevated. These findings indicate that the alteration in gastric nerve fibers containing GRP after truncal vagotomy may be related to hypergastrinemia and antral G-cell hyperplasia in the rat gastric mucosa.

Animals↗
PubMed1995

Significance of superoxide dismutase (SOD) in human colorectal cancer tissue: correlation with malignant intensity.

The significance of superoxide dismutase (SOD) activity in colorectal cancer tissue was determined from the aspect of the antioxidant defense system. SOD activity and thiobarbituric acid reactive substance were measured in the tumor, in tissues adjacent to the tumor, and in regions that appeared normal, and the results were analyzed in terms of various histopathological factors (stage of disease, depth of invasion, venous invasion, etc.). DNA ploidy pattern and cell proliferation in cancer tissue were also measured, and the results analyzed in relation to SOD activity. SOD activity in cancer tissue was higher than in the other two regions. SOD activity in cancer tissue increased with the progression of stage, and changed with the depth of invasion. There was a significant difference in SOD activity between patients with venous invasion and those in whom this was absent. Stepwise regression analysis suggested that venous invasion was the most significant factor influencing SOD activity. The proliferation index was high in cancer tissue with low SOD activity. The incidence of aneuploidy was high in cancer with high SOD activity, whereas the incidence of diploidy was high in cancer with low SOD activity. These results suggest that elucidation of the antioxidant system in cancer tissue can provide us with a better strategy for cancer treatment.

Aged↗
PubMed1995

Treatment of multiple primary squamous cell carcinomas of the lung.

BACKGROUND: The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy. MATERIALS: We treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3% of all squamous cell carcinoma patients undergoing resection. RESULTS: Two patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation. CONCLUSIONS: The surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.

Aged↗