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Biomedical subjects

K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 325 records · Page 18Linked to original sources
PubMed1994

OK432 inhibits experimental hepatic metastasis of colon adenocarcinoma ACL-15 in F344 rats.

The effect of OK432 on hepatic metastasis, induced by inoculating 1 x 10(6) ACL-15 cells from a rat colon adenocarcinoma cell line into the ileocolic vein of male F344 rats, was investigated in this study. Metastases were detected 14 days after inoculation in the control rats, however, pretreatment 3 days prior to the tumor cell inoculation with an anti-asialoGM1 antibody, which eliminates natural killer (NK) cell activity in vitro, increased the number of hepatic metastases, shortened the survival time, and decreased the NK activity of the nonparenchymal liver cells (NPC). In contrast, pretreatment with OK432 2 days prior to tumor inoculation significantly decreased the number of hepatic metastases, prolonged the survival time, and augmented the NK activity of the NPC, although treatment with OK432 3 or 7 days after inoculation did not decrease the number of hepatic metastases. Moreover, NPC from the OK432-pretreated rats had a marked antitumor effect against ACL-15 cells in the Winn's neutralization test. The results of this study indicate that pretreatment with OK432 before tumor cell inoculation inhibits hepatic metastasis in this experimental model, possibly by augmentating liver-associated NK activity.

Adenocarcinoma↗
PubMed1994

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs.

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E1 (PGE1) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE1 at 0.2 micrograms/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE1 was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE1 is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.

Alprostadil↗
PubMed1994

Inhibitory effects of prostacyclin analogue, TFC-132, on aortic neointimal thickening in vivo and smooth muscle cell proliferation in vitro.

Effects of a new prostacyclin analogue, TFC-132, on neointimal thickening following intimal mechanical injury and on the proliferation of cultured aortic smooth muscle cells (SMCs) were studied. The intimal injury was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 days after drawing out the tubing. TFC-132 (0.6 mg/kg or 1.2 mg/kg) was given orally at 8-h intervals through the experiment. The serum concentrations of the analogue rose significantly 1 and 2 h after administration. The mean intimal thickening in the TFC-132 treated groups was significantly thinner than in the control one. Human aortic SMCs were cultured and 3H-thymidine incorporation into DNA (DNA synthesis) was measured at the varying concentrations of TFC-132. The analogue inhibited DNA synthesis of cultured SMCs at 10(-6) and 10(-5) M. These data indicate that a new prostacyclin analogue, TFC-132, has an inhibitory effect on the neointimal thickening after intimal injury and on the aortic SMC proliferation.

Animals↗
PubMed1994

Clinical implications of cervical lymph node metastasis patterns in thoracic esophageal cancer.

OBJECTIVE: The authors attempt to clarify the clinical implications of cervical lymph node metastases from thoracic esophageal cancers. SUMMARY BACKGROUND DATA: Cervical lymph node metastases from thoracic esophageal cancer have been considered to be incompatible with curative resection. However, recent studies have demonstrated that cure is achievable in patients with such metastases. METHODS: Patterns of esophageal cancer metastasis to the cervical nodes and long-term results after tumor resection were investigated in 23 patients undergoing bilateral cervical lymphadenectomy for treatment of thoracic esophageal cancer. RESULTS: The number of positive nodes per patient was significantly greater (p < 0.05) in lower esophageal cancers (median: 15) than in upper or mid esophageal cancers (median: 2.5). Simultaneous metastases to three nodal regions (the neck, mediastinum, and abdomen) were significantly more common (p < 0.001) in lower esophageal tumors (88.9%) than in upper and mid esophageal lesions (7.1%). Although the overall 5-year survival rate was 16.5%, long-term survival was achieved only in patients with upper or mid esophageal cancer.

Adult↗
PubMed1994

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.

Adult↗
PubMed1994

Tetrahydrobiopterin synthesis and inducible nitric oxide production in pulmonary artery smooth muscle.

We recently reported (Am. J. Respir. Cell Mol. Biol. 7: 471-476, 1992) that a mixture of lipopolysaccharide (LPS) and cytokines produced a time-dependent increase in mRNA and protein expression of inducible nitric oxide synthase (iNOS) in cultured rat pulmonary artery smooth muscle cells (RPASM). In the current study we extend observations on regulation of iNOS in RPASM by showing that de novo synthesis of tetrahydrobiopterin (BH4) is critical for LPS and cytokine-induced NO production. A mixture of LPS and the cytokines gamma-interferon, interleukin-1 beta, and tumor necrosis factor-alpha increased steady-state levels of mRNA of GTP-cyclohydrolase-I (GTP-CH), the rate-limiting enzyme in BH4 biosynthesis. Levels of mRNA to GTP-CH became detectable by 4 h, with further increases at 24 h by Northern blot analysis and reverse-transcriptase polymerase chain reaction. Total intracellular biopterin levels, undetectable under basal conditions, increased after 24 h exposure to LPS and cytokines (to 32.3 +/- 0.8 pmol/mg protein). LPS and cytokine-induced NO production, determined by nitrite concentrations in the medium, was decreased in a concentration-dependent manner by the GTP-CH inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP) at 24 h. DAHP also inhibited completely the LPS- and cytokine-induced accumulation of intracellular biopterins. Sepiapterin, which supplies BH4 through a salvage pathway independent of GTP-CH, reversed the effect of DAHP on LPS and cytokine-induced NO production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Pharmacokinetic and clinical evaluation of cefozopran in the pediatric field].

We conducted pharmacokinetic and clinical studies on cefozopran (CZOP, SCE-2787), an aminothiadiazolmethoxyiminoacetamido cephalosporin, and obtained the following results. 1. Concentrations in serum/excretion in urine We studied pharmacokinetic in children upon intravenous bolus injection and 30-minute intravenous drip infusion in single doses of 10 and 20 mg/kg. Upon intravenous bolus injection, mean serum concentrations 30 minutes after administration of 10 and 20 mg/kg were 27.8 and 52.3 micrograms/ml, respectively, and half-lives were 2.01 and 2.02 hours, respectively. Upon 30-minute intravenous drip infusion, mean serum concentrations on completion of the drip infusions of 10 and 20 mg/kg were 36.8 and 70.3 micrograms/ml, respectively, and half-lives were 1.74 and 4.11 hours, respectively. Their urinary recovery rates in the first 8 hours after administration were higher than 67.0% in the former regimen and between 23.2 to 98.0% in the latter. 2. Clinical results 54 patients were treated with CZOP for 32 cases of pneumonia, 11 cases of bronchitis, 3 cases of cervical lymphadenitis, 1 case of purulent tonsillitis, 2 cases of phlegmon, 2 cases of enterogastritis and 3 cases of urinary tract infections. CZOP gave "excellent" or "good" responses in 53 cases. 1 case of urinary tract infection showed fair response. Diarrhea was observed in 1 case. Abnormal laboratory test results were noted in 9 patients including elevations of eosinophils, GOT and GPT. In no cases the treatment had to be discontinued.

Adolescent↗
PubMed1994

Two cases of Holstein calves with bovine leukocyte adhesion deficiency (BLAD) (case report).

Two Holstein calves showing clinical signs such as ulcerative stomatitis, severe gingivitis, periodontitis, loss of teeth and stunted growth, associated with marked neutrophilia, were evaluated by clinicopathologic analysis, neutrophil functions and flow cytometric analysis of CD18 expression on neutrophils. Decreased CL response, chemotaxis, yeast phagocytosis, and deficient CD18 expression of neutrophils from affected animals were demonstrated. Pathological findings involved were ulcerative gingivitis, severe periodontitis, laryngitis, and multiple ulcers in forestomach. This study demonstrates that neutrophil functions are closely associated with impaired iC3b receptor, and these affected animals were diagnosed as bovine leukocyte adhesion deficiency (BLAD).

Animals↗
PubMed1994

The association between extrahepatic biliary carcinoma and the junction of the cystic duct and the biliary tree.

OBJECTIVE: To establish accurately the sites of primary extrahepatic biliary carcinomas, so that optimal treatment may be given. DESIGN: Retrospective study. SETTING: University department of surgery. SUBJECTS: 120 patients with 121 primary extrahepatic biliary carcinomas. MAIN OUTCOME MEASURES: Site of tumour (primary site being geometric centre of tumour) and distance from junction of cystic duct and the biliary tree on histological examination of the resected specimen. RESULTS: 64 of the tumours (53%) were within 5 mm of the junction; 14 were proximal to the junction, 32 distal, and 18 within the cystic duct itself. CONCLUSIONS: Over half the primary extrahepatic biliary tumours were within 5 mm of the junction of the cystic duct and the rest of the biliary tree. Further investigations are required to find out if any particular aetiological factor can be identified.

Adenocarcinoma↗
PubMed1994

[Research on the correlation between DNA recombinational mutation and cancer malignancy in human colon cancers].

The mutagenicity of quercetin, a flavonoid, was examined by means of DNA fingerprint analysis using the Pc-1 and Pc-2 minisatellite probes that efficiently detect mutations due to recombination. Treatment of FM3A and BMT-11 tumor cells with 55 microM quercetin resulted in gain and loss of bands in the fingerprints in both cell lines. The frequencies of the clones having undergone mutation were 9/26 and 2/11, using Pc-1 probe, respectively, in the two lines. These results seem to provide a molecular basis for the phenotypic variations of BMT-11 tumor cells induced by quercetin, giving direct evidence of genetic instability of the tumor cells. Moreover, we examined for a possible correlation between frequencies of DNA recombinational mutations and cancer malignancy in human colon cancers. DNA of four human colon cancer tissues and corresponding peripheral blood cells were prepared, respectively, and examined by DNA fingerprint analysis using hPc-1 polymorphic minisatellite probe. These four specimens exhibited no extra-bands resulting from recombination and/or DNA slippage at present. We would explain how the prognosis of cancer patients is related to frequencies of DNA recombinational mutation.

Aged↗
PubMed1993

cDNA cloning, expression in Escherichia coli and purification of human 6-pyruvoyl-tetrahydropterin synthase.

cDNA clones for human 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the biosynthetic pathway of tetrahydrobiopterin, were isolated from a human Molt-4 cell cDNA library by cross-hybridization with a rat cDNA. One cDNA clone contained the entire coding sequence of 435 base pairs. The cDNA was expressed in Escherichia coli using the expression vector pMAL as a fusion protein with maltose-binding protein. After affinity purification through its maltose-binding protein domain, the fusion protein was digested by factor Xa at a specific cleavage site inserted between the domains. The main product was a protein species with a native molecular mass of 90 kDa and a subunit molecular mass of 17 kDa, and the molecular masses and its kinetic properties were similar to those of the human enzyme purified from the liver.

ATP-Binding Cassette Transporters↗
PubMed1993

Feedback regulation mechanisms for the control of GTP cyclohydrolase I activity.

Guanosine triphosphate (GTP) cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), is subject to feedback inhibition by BH4, a cofactor for phenylalanine hydroxylase. Inhibition was found to depend specifically on BH4 and the presence of another protein (p35). The inhibition occurred through BH4-dependent complex formation between p35 protein and GTP cyclohydrolase I. Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. These findings also provide a molecular basis for high plasma BH4 concentrations observed in patients with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency.

Animals↗
PubMed1993

Enzymatic synthesis of 6R-[U-14C]tetrahydrobiopterin from [U-14C]GTP.

An enzymatic method for preparing 6R-[U-14C]-tetrahydrobiopterin from [U-14C]GTP is presented. This method utilizes purified preparations of three biosynthetic enzymes for 6R-tetrahydrobiopterin, i.e., Escherichia coli GTP cyclohydrolase I, rat 6-pyruvoyl-tetrahydropterin synthase, and rat sepiapterin reductase. Based on the catalytic properties of these enzymes, the reaction conditions were optimized to complete the entire conversion reaction from GTP to 6R-tetrahydrobiopterin in a single reaction solution without the need to isolate unstable intermediates after each enzymatic reaction. The reaction conditions thereby established yielded [U-14C]biopterin in an amount equivalent to 75%, on a molar basis, of the initial amount of [U-14C]GTP. The product was subsequently isolated by high-performance liquid chromatography. The method produced labeled 6R-tetrahydrobiopterin with a specific activity of 450 Ci/mol and an overall yield of more than 60%.

Alcohol Oxidoreductases↗
PubMed1993

Cloning of a cDNA encoding rat intestinal 15 kDa protein and its tissue distribution.

A cDNA encoding rat intestinal 15 kDa protein was isolated and sequenced from a rat ileum-specific cDNA library. This cDNA was found to contain an open reading frame of 384 nucleotides as well as 5' (27 nucleotides) and 3' (46 nucleotides) non-coding regions. The deduced sequence of 127 amino acids was identical to that of rat I-15P which was purified from rat intestinal epithelium. The nucleotide sequence of the open reading frame exhibited 79% identity to that of the porcine gastrotropin. Northern blot analysis indicated that the same size of transcript as that of the ileum was detected in the ovary, suggesting that I-15P or a homologous protein might be involved in the metabolism of steroids in steroid hormone-producing tissues.

Amino Acid Sequence↗
PubMed1993

Percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis.

The effectiveness and long-term results of percutaneous cholecystostomy for acute acalculous cholecystitis are evaluated. Fifteen patients with acute acalculous cholecystitis were treated prospectively by this procedure, using a pigtail catheter successfully placed under ultrasonographic and fluoroscopic guidance. Prompt relief of the signs and symptoms of cholecystitis was achieved in 14 patients. One required emergency cholecystectomy for uncontrolled bleeding after drainage. Another patient underwent prophylactic cholecystectomy before further chemotherapy for leukaemia. The remaining 13 patients required no further surgery. Morbidity and mortality rates were 13 per cent and nil respectively. Long-term follow-up showed no recurrence of cholecystitis after removal of the catheter. Percutaneous cholecystostomy is a safe, effective and usually definitive procedure for the treatment of acute acalculous cholecystitis.

Acute Disease↗