Search PubMed⌕ Search

Biomedical subjects

K Sakakibara

Publications and source records attributed to K Sakakibara.

At least 37 records · Page 2Linked to original sources
PubMed1995

Synthesis and antitumor activity of novel dolastatin 10 analogs.

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.

Animals↗
PubMed1994

Serum hepatitis C virus RNA level as a predictor of subsequent response to interferon-alpha therapy in Japanese patients with chronic hepatitis C.

Serum hepatitis C virus (HCV) RNA level has been shown to be a good predictor of subsequent response to interferon-alpha (IFN) therapy in US patients in whom genotype 1a/1b are both predominant. To determine whether serum HCV RNA level is a predictor of subsequent response to IFN in Japanese patients or not, appropriately collected pre-IFN therapy serum samples from 35 Japanese patients with chronic HCV infection were studied. Serum HCV RNA level and HCV genotype were determined and correlated with the subsequent response to IFN. Response to IFN was defined by serum alanine transaminase level: complete and sustained response (n = 15), complete response followed by relapse (n = 10), and no response (n = 10). Patients with complete and sustained response had lower pre-IFN serum HCV RNA level (median: RT-PCR+, bDNA-) compared to the complete response to relapse group (median: 5.25 x 10(6) genome equivalent/ml [eq/ml], P < 0.001) and the no response group (median: 10.63 x 10(6) eq/ml, P < 0.001). Seven (46.7%) of the complete and sustained response patients had HCV genotype 2a and three patients had a mixture of genotypes 1b and 2a. In contrast, all 10 patients in the complete response to relapse group had genotype 1b whereas 8 of 10 patients in the non-response group had genotype 1b and 2 had genotype 2b. The patients with HCV genotype 2a had lower serum HCV RNA level than those with 1b (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[A case of Cabrol's procedure in which selective cerebral perfusion was necessitated].

A 69-year-old man underwent Cabrol's procedure for annuloaortic ectasia and complicated multiple cerebral infarction. Preoperative CT scan showed atherosclerotic changes from the aortic arch to descending aorta. During extracorporeal circulation, arterial cannulation was made through left subclavian artery to prevent cerebral infarction due to detouched atheroma from the descending aorta. Intraoperatively, the ascending aorta was also atheromatous and ulcerative. In this case, cerebral infarction was most likely due to detouched atheroma from the aortic arch in retrograde blood flow during extracorporeal circulation. To prevent this complication, selective cerebral perfusion during extracorporeal circulation should have been selected.

Aged↗
PubMed1993

Correlation between serotonergic measures in cerebrospinal fluid and blood of subhuman primate.

The relationship between the concentration of serotonin (5-hydroxytryptamine; 5-HT), its precursor; tryptophan (Trp) and the main metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and blood of monkey have been studied. 5-HT, Trp and 5-HIAA underwent circadian changes in both CSF and blood. Significant correlations were found between 5-HT, 5-HIAA and Trp in CSF and blood. The significance of these findings and their relationship to the use of peripheral serotonergic system as a functional model of the central nervous system are discussed.

Animals↗
PubMed1993

Characterization of OM-B monoclonal antibody-defined antigen associated with mucinous type human ovarian tumor.

Partial characterization of the OM-B antigen associated with mucinous-type ovarian tumors was conducted. This antigen was defined by OM-B monoclonal antibody, which was raised against a mucinous-type ovarian tumor, and was present in all the mucinous-type tumors tested, but only a fraction of serous-type tumors. The OM-B crude antigen preparation fractionated from cystic fluids had a density of 1.40-1.43 g/ml, with a high neutral sugar content. Molecular mass (M(r)) estimated by gel filtration was more than 2,000,000. Trypsinization of the antigen preparation under appropriate conditions resulted in two major bands and one minor band with molecular sizes of less than M(r) 250,000, as detected by immunoblotting. Immunoaffinity chromatography was then conducted and the amino acid composition of the purified product was determined; the high contents of serine, threonine and proline are characteristic of a mucin. Binding inhibition enzyme-linked immunosorbent assay was developed to measure OM-B antigen activity in cystic fluids and sera from patients with mucinous-type tumors. The antigen was easily detected in most cystic fluids, but not in sera, suggesting that improvement in the sensitivity of this assay is necessary before its utilization for serum diagnosis will be feasible.

Antibodies, Monoclonal↗
PubMed1993

Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma.

In order to elucidate the influence of the risk factors of coronary heart disease on the fibrinolytic activity, relationships between blood pressure, body mass index (BMI), plasma lipoprotein (a) (Lp(a)) level and the plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in the subjects with mild hypertension. Systolic blood pressure showed a positive correlation with total PAI-1 and free PAI-1. Diastolic blood pressure showed no correlation with these proteins involved in the fibrinolytic system. BMI had a positive correlation with total PAI-1, free PAI-1 and euglobulin clot lysis time (ECLT). Plasma Lp(a) level showed correlation with neither blood pressure nor fibrinolytic parameters, but it showed weak negative correlation with body mass index (BMI). These results suggest that high blood pressure and obesity tend to increase free PAI-1 which reduces fibrinolytic activity. Lp(a), however, seems not to influence directly the fibrinolytic system but may work to decrease fibrinolytic activity only in conjunction with other risk factors. The effects of daily drinking of alcohol and smoking on the fibrinolytic system were also investigated in the present study and we obtained the results that habitual drinking increased plasma levels of both tPA and PAI-1 whereas smoking did not affect fibrinolytic activity. These results suggest that risk factors for coronary heart disease such as hypertension and obesity are closely related to the impaired fibrinolysis.

Adult↗
PubMed1993

[Right thoracotomy to approach mitral or tricuspid valve in reoperation].

Four patients underwent mitral valve re-replacement, and required tricuspid annuloplasty in two, through a right thoracotomy. There was no major postoperative morbidity and recovery was full and uneventful. The indications for selection of this approach were isolated mitral valve disease or combined tricuspid and mitral valve disease, severe adhesion between heart and sternum on CT scan, intact aortic valve and no severe reduction of respiratory function. We recommend right thoracotomy to approach atrioventricular valves in selected situations in patients for reoperations.

Aged↗
PubMed1993

[Cavernous lymphangioma of mediastinum--a case report].

A 2-year-old girl with mediastinal cavernous lymphangioma was successfully treated in 1991. She had a cough and an abnormal shadow in the right mediastinum was shown on her chest X-ray. The tumor, which spread from the right upper mediastinum to the pre-aorta, was demonstrated on CT and MRI. On August 8, 1991, the operation was performed through the right thoracotomy. The tumor was located in the right-upper and middle mediastinum and involved N. phrenics and vagus, but didn't invade and was completely resected. It was 4.2 x 3.4 x 3.2 cm in size and the cut surface of the tumor had an appearance consisting of the soft solid tissue, but containing partial cystic spaces. Histological diagnosis was cavernous lymphangioma. The mediastinal cavernous lymphangioma has been reported in only 6 cases in the Japanese medical literature.

Child, Preschool↗
PubMed1992

Simultaneous expression of type I procollagen mRNA and albumin in cirrhotic human liver.

The gene expression of human type I procollagen was investigated in cirrhotic human liver by using in situ hybridization with nonradioactive DNA probes. Using in situ hybridization can provide direct evidence for the cell type capable for type I collagen synthesis in tissues. T-T dimerized DNA probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibodies against T-T dimer. The data demonstrated that type I collagen is synthesized in hepatocytes and stellate cells in pseudolobules and in fibroblasts in Glissons capsules in cirrhotic human livers. We indicated hepatocytes morphologically and functionally by using immunohistochemical localization of albumin, which was used as a marker of hepatocyte, since albumin is synthesized exclusively by hepatocytes.

Adult↗
PubMed1992

Both 17 beta-estradiol and tamoxifen induce c-fos messenger ribonucleic acid expression in human endometrial carcinoma grown in nude mice.

We previously demonstrated the estrogen-like effects of tamoxifen on the acceleration of growth and increased progesterone receptor concentrations of human endometrial carcinomas grown in the nude mouse experimental model. In our current study the modulation of protooncogene expression by 17 beta-estradiol and tamoxifen in human endometrial carcinomas was investigated. The protooncogenes investigated in this study were c-fos, c-jun, c-myc, N-myc, HER-2/neu, c-erbB, c-fms, and c-Ha-ras. Among those we found that c-fos expression was induced by 17 beta-estradiol in the following 17 beta-estradiol-sensitive tumors: EnCa-101 and EnCa-X. The induction was apparent within 1 hour, reached peak level at 2 hours (16-fold), and remained constant up to 4 hours. The c-fos messenger ribonucleic acid returned to prestimulation level by 12 hours. Tamoxifen also stimulated c-fos expression, the expression pattern being similar to that of 17 beta-estradiol albeit of a lesser degree. The messenger ribonucleic acid transcripts for other protooncogenes tested did not show significant changes during hormonal manipulation. The induction of c-fos expression by tamoxifen is consistent with its estrogen-like effect on endometrial carcinoma growth.

Animals↗
PubMed1991

[Early diagnosis of acute mesenteric artery occlusion--clinical and experimental study].

This study was undertaken for the purpose of making early diagnosis of acute superior mesenteric artery occlusion (SMAO). (Clinical Study) This study included 16 patients with SMAO. The early diagnoses by clinical, laboratory, echographic and radiologic findings which were commonly obtained in the cases of abdominal emergency, were difficult. Angiography was useful method for its diagnosis. But in its early stage, we could hardly determine which patient was subject to angiography, therefore non-invasive and simple screening modelity is needed for its early diagnosis. (Experimental Study) Portal blood flow (PVF) is considered to decrease when superior mesenteric artery (SMA) is occluded, because SMA is a main feeder of portal vein. If SMAO has specific portal hemodynamics, its early diagnosis will be possible by non-invasive PVF measurement using an ultrasonic duplex system (PD). We investigated the portal hemodynamic changes in experimental SMAO, peritonitis and ileus using 24 mongrel dogs. Our results showed that PVF to cardiac output ratios (PCR) of SMAO models were under 10% and in contrast, those of others were over 10%. So SMAO models were distinguishable from others. These suggested that PCR measured by PD and echocardiography was an useful indicator of early diagnosis of SMAO.

Acute Disease↗