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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 37 records · Page 2Linked to original sources
PubMed2002

Lung impairment following cardiac surgery in patients with pulmonary hypertension.

BACKGROUND: Postoperative respiratory management following cardiac surgery is sometimes troublesome in patients with pulmonary hypertension. We retrospectively studied the relationship between the etiology of preoperative pulmonary hypertension and the postoperative decline of blood oxygenation capacity by focusing on the postoperative intravascular fluid volume. METHODS: Sixteen adult patients with an atrial septal defect (preload group) and 17 patients with solitary mitral valve disease (afterload group) were studied. The mean age of the patients in the preload and afterload group was 51 and 52 years old, respectively. RESULTS: Preoperative pulmonary-systemic pressure ratio and pulmonary artery resistance index were significantly higher in the preload group than in the afterload group. The respiratory index (RI) and the pulmonary shunt ratio (Qs/Qt) measured immediately after the operation was larger in the afterload group than in the preload group. Postoperative RI and Qs/Qt remained high until postoperative day 3 in both groups. In the preload group RI on postoperative day 1 had a reverse correlation with the central venous pressure (CVP). Meanwhile, the RI in the afterload group on postoperative day 1 was slightly larger in patients with a high CVP and pulmonary capillary wedged pressure. Similar relationships were seen in the relations between pulmonary capillary wedged pressure and RI in the afterload group. CONCLUSIONS In conclusion, a preoperative pulmonary vascular change and a postoperative precipitous decrease of pulmonary blood flow may have caused postoperative lung oxygenation impairment in the preload group. An extended period of extracorporeal circulation associated with cardiac arrest and postoperative volume overload may have caused lung impairment in the afterload group. In aspect of postoperative management, low CVP is beneficial to the patients in the afterload group, however, hypovolemia should be avoided in patients of the preload group.

Blood Gas Analysis↗
PubMed2002

[Congenital tracheoesophageal fistula; report of an adult case].

We experienced an adult case of congenital tracheoesophageal fistula which was successfully treated by surgical intervention. A 69-year-old female was admitted with complaint of coughing and fever. The patient previously had had several episodes of pneumonia. Esophagography and thoracic CT demonstrated a tracheoesophageal fistula in the upper of the thoracic esophagus. Following the resection of the fistula, the trachea was closed with one layer suture and the esophagus was closed with two layer sutures. A pedicled fifth intercostal muscle was interposed between the tracheal and esophageal suture lines. There was mild inflammatory change in surrounding tissues of the fistula. Pathological examination revealed that the fistula was covered with the squamous epithelium, and had the muscularis mucosa. Her postoperative course was uneventful.

Aged↗
PubMed2002

Chemoprevention of large bowel carcinogenesis; the role of control of cell proliferation and significance of beta-catenin-accumulated crypts as a new biomarker.

Control of cell proliferation is important for cancer prevention since cell proliferation has essential roles in carcinogenesis in the processes of both initiation and promotion. In large bowel carcinogenesis, carcinogens produce hyperproliferation of cells in the target sites and the cell proliferation persists even after the cessation of carcinogen exposure. Chemopreventive agents principally control the increased cell proliferation when given in the initiation as well as post-initiation phases. Aberrant crypt foci (ACF) which appear soon after carcinogen exposure in large bowel carcinogenesis in rodents have been used as a reliable biomarker for screening of potential chemopreventive agents. Recently, our group demonstrated the presence of probable premalignant lesions with frequent beta-catenin gene mutations and accumulation of the corresponding protein in the colonic epithelium of rats given a large bowel carcinogen. Such early-appearing lesions lack the morphological appearance of ACF. Expression of these beta-catenin-accumulated crypts (BCAC) is markedly suppressed by a chemopreventive cyclooxygenase-2 inhibitor, celecoxib. BCAC are suggested to be more reliable biomarkers than ACF for screening effective chemopreventive agents for colorectal cancer and for investigating the mode of action of the agents.

Animals↗
PubMed2001

Cell proliferation in cancer prevention; effects of preventive agents on estrogen-related endometrial carcinogenesis model and on an in vitro model in human colorectal cells.

Proto-oncogenes such as c-fos, c-jun and c-myc are known to relate to cell proliferation and differentiation. Some oriental herbal medicines like Glycyrrhizae radix or Juzen-taiho-to were found to suppress estradiol-17 beta (E2)-induced expression of c-fos/jun in uterine corpus and inhibited N-methyl-N-nitrosourea and E2-induced endometrial carcinogenesis in mice. It is suggested that the effects of such oriental drugs are exerted probably through suppression of estrogen-induced c-fos/jun expression and they are promising preventing agents for endometrial cancers. In the combined in vitro assay for cell proliferation (MTS assay) and apoptosis (DNA fragmentation) in human colorectal cancer cells (Colo 320), a number of naturally occurring chemopreventive agents such as curcumin, quercetin, auraptene, 1'-acetoxychavicol acetate (ACA) and indole-3-carbinol were shown to generate apoptosis as well as to inhibit cell proliferation. The results suggest a mode of action of these chemopreventive agents and also imply that such in vitro short term assay is useful for detection of new agents for cancer prevention.

Adenocarcinoma↗
PubMed2001

Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.

Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.

Acyltransferases↗
PubMed2001

Adenomatous polyposis coli (APC) gene promoter hypermethylation in primary breast cancers.

Similar to findings in colorectal cancers, it has been suggested that disruption of the adenomatous polyposis coli (APC)/beta-catenin pathway may be involved in breast carcinogenesis. However, somatic mutations of APC and beta- catenin are infrequently reported in breast cancers, in contrast to findings in colorectal cancers. To further explore the role of the APC/beta-catenin pathway in breast carcinogenesis, we investigated the status of APC gene promoter methylation in primary breast cancers and in their non-cancerous breast tissue counterparts, as well as mutations of the APC and beta- catenin genes. Hypermethylation of the APC promoter CpG island was detected in 18 of 50 (36%) primary breast cancers and in none of 21 non-cancerous breast tissue samples, although no mutations of the APC and beta- catenin were found. No significant associations between APC promoter hypermethylation and patient age, lymph node metastasis, oestrogen and progesterone receptor status, size, stage or histological type of tumour were observed. These results indicate that APC promoter CpG island hypermethylation is a cancer-specific change and may be a more common mechanism of inactivation of this tumour suppressor gene in primary breast cancers than previously suspected.

Adult↗
PubMed2001

Relation of ST-segment changes in inferior leads during anterior wall acute myocardial infarction to length and occlusion site of the left anterior descending coronary artery.

We investigated the relation between left anterior descending (LAD) coronary artery morphology and inferior lead ST-segment changes to elucidate the clinical significance of such changes in 159 patients with anterior wall acute myocardial infarction (AMI). Patients with 1-vessel LAD artery lesions were divided into an ST depression group (n = 40), an ST elevation group (n = 25), and a no-ST-change group (n = 94) based on ST-segment changes in the inferior leads. The relation between each group and the infarct-related lesion and the presence of a wrapped LAD artery was then investigated. The percentage of patients with the infarct-related lesion in the proximal LAD artery was significantly higher in the ST depression group and significantly lower in the ST elevation group. The percentage of patients with a wrapped LAD artery was significantly higher in the ST elevation group and significantly lower in the ST depression group. The wall motion index determined echocardiographically was significantly higher in the ST depression group and the no-ST-change group than in the ST elevation group. Our findings suggest that inferior lead ST-segment changes during anterior wall AMI arise as a result of competition between reciprocal changes caused by high lateral wall AMI due to lesions of the proximal LAD artery, which depress the ST segment, and inferoapical wall AMI due to a wrapped LAD artery, which elevates the ST segment. In patients with no ST-segment changes, echocardiography was useful for distinguishing the amount of affected LAD artery territory.

Adult↗
PubMed2001

Cloning of a lymphatic peptide/histidine transporter.

Although peptide transport across the plasma membrane has been characterized well in the kidney and the intestine, the functional relevance of this transport in other organs has not been addressed. Here we report the cloning of a cDNA for a novel peptide/histidine transporter found in the rat (rPHT2), whose mRNA is expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino acids and showed 49% identity with the brain PHT (PHT1) [Yamashita, Shimada, Guo, Sato, Kohmura, Hayakawa, Takagi and Tohyama (1997) J. Biol. Chem. 272, 10205-10211]. rPHT2 mRNA was abundant in lung, spleen and thymus, and detected faintly in brain, liver, adrenal gland and heart by Northern-blot analysis and reverse transcriptase PCR (RT-PCR). Intense signals for the gene were found in immunocytes using in situ hybridization. Ectopic expression of rPHT2 protein in HEK-293T cells and BHK cells was not found on the cell surface, but was found on the lysosomal membrane using light- and electron-microscopic analysis. Recombinant rPHT2 protein reconstituted into liposomes showed proton-dependent transport activity with histidine and histidyl-leucine. These findings suggest that rPHT2 is involved in the protein catabolic pathway in the lymphatic system.

Amino Acid Sequence↗
PubMed2001

Selective interaction of triazole derivatives with DWF4, a cytochrome P450 monooxygenase of the brassinosteroid biosynthetic pathway, correlates with brassinosteroid deficiency in planta.

Brassinazole, a synthetic chemical developed in our laboratory, is a triazole-type brassinosteroid biosynthesis inhibitor that induces dwarfism in various plant species. The target sites of brassinazole were investigated by chemical analyses of endogenous brassinosteroids (BRs) in brassinazole-treated Catharanthus roseus cells. The levels of castasterone and brassinolide in brassinazole-treated plant cells were less than 6% of the levels in untreated cells. In contrast, campestanol and 6-oxocampestanol levels were increased, and levels of BR intermediates with hydroxy groups on the side chains were reduced, suggesting that brassinazole treatment reduced BR levels by inhibiting the hydroxylation of the C-22 position. DWF4, which is an Arabidopsis thaliana cytochrome P450 isolated as a putative steroid 22-hydroxylase, was expressed in Escherichia coli, and the binding affinity of brassinazole and its derivatives to the recombinant DWF4 were analyzed. Among several triazole derivatives, brassinazole had both the highest binding affinity to DWF4 and the highest growth inhibitory activity. The binding affinity and the activity for inhibiting hypocotyl growth were well correlated among the derivatives. In brassinazole-treated A. thaliana, the CPD gene involved in BR biosynthesis was induced within 3 h, most likely because of feedback activation caused by the reduced levels of active BRs. These results indicate that brassinazole inhibits the hydroxylation of the C-22 position of the side chain in BRs by direct binding to DWF4 and that DWF4 catalyzes this hydroxylation reaction.

Arabidopsis Proteins↗
PubMed2001

Nuclear BAG-1 localization and the risk of recurrence after radiation therapy in laryngeal carcinomas.

BAG-1 is a multifunctional chaperone modulator may contribute to p53-mediated cell cycle arrest. We attempted to investigate whether BAG-1 expression is correlated with prognosis of laryngeal carcinoma patients after radiotherapy. Immunohistochemical analyses revealed BAG-1 expression was present in all laryngeal carcinomas examined, and its expression pattern varied, i.e. cytoplasmic, nuclear and both these staining types. Patients whose tumors predominantly express nuclear BAG-1 have a significantly poor failure-free survival rate after radiotherapy. We thus propose that nuclear BAG-1 localization is a prediction of unfavorable outcome should radiation therapy be undertaken for laryngeal carcinoma patients.

Biomarkers, Tumor↗
PubMed2001

Polyamine cytotoxicity in the presence of bovine serum amine oxidase.

The toxicity of extracellular spermine, determined in the presence of fetal calf serum, was studied using three cell lines: FM3A, L1210, and NIH3T3 cells. Amine oxidase in fetal calf serum produces aminodialdehyde generating acrolein spontaneously, H(2)O(2), and ammonia from spermine. Spermine toxicity was prevented by aldehyde dehydrogenase, but not by catalase. Similar concentrations of spermine and acrolein were needed to produce toxicity. Other aldehydes (formaldehyde, acetaldehyde, and propionaldehyde) and hydrogen peroxide were less toxic than acrolein. Spermidine and 3-aminopropanal, which produces acrolein, also exhibited severe cytotoxicity. The degree of cytotoxicity of spermine, spermidine, and 3-aminopropanal was nearly parallel with the amount of acrolein produced from each compound. Thus, it was deduced that acrolein is a major toxic compound produced from polyamines (spermine and spermidine) by amine oxidase.

3T3 Cells↗
PubMed2001

Myocardial damage and left ventricular dysfunction in patients with and without persistent negative T waves after Q-wave anterior myocardial infarction.

Persistent T-wave inversions during the chronic stage of Q-wave myocardial infarction (MI) indicate the presence of a transmural infarction with a fibrotic layer pathologically. The aim of the present study was to examine the relation between left ventricular (LV) damage and changes in polarity of the T waves from the acute to chronic phase in patients with Q-wave anterior wall MI. We studied 140 patients with persistent T-wave inversions in leads with Q waves (negative T-wave group) and 158 patients with positive T waves (positive T-wave group) at 12 months after anterior MI. In the positive T-wave group, the precordial T waves reverted from a negative to a positive morphology < 3 months after MI in 21 patients (3 M-positive T-wave subgroup), 3 to 6 months in 52 patients (6 M-positive T-wave subgroup), and 6 to 12 months in 75 patients (12 M-positive T-wave subgroup). Ten patients had persistent positive T waves without initial T-wave inversion (persistent positive T-wave group). Wall motion index and LV dimension were higher and the wall thickness for the infarct area and LV ejection fraction were lower in the negative T-wave than in the positive T-wave groups, except the persistent positive T-wave group in the chronic stage (p < 0.0001). Wall motion in the infarcted area improved over the course of 1 year in the 3 M-, 6 M-, and 12 M-positive T-wave subgroups (p < 0.0001), but not in the persistent positive T-wave group. Among the patients with T-wave inversions after admission, those who had persistent negative T waves after 12 months had worse LV function. In patients with initial T-wave inversion, earlier normalization of the precordial T waves was associated with greater improvement in LV function. Patients with persistent positive T waves without initial negative T waves had poorer recovery of LV function than patients with persistent negative T waves. We conclude that the presence of inverted T waves in leads with abnormal Q waves 12 months after MI and the time required for T-wave normalization can be used to assess the degree of LV dysfunction.

Aged↗
PubMed2001

Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.

Our previous study (Cancer Res., 60: 3323-3327, 2000) showed that frequent beta-catenin gene mutations are present in beta-catenin-accumulated crypts, which occur early in rodent colonic carcinogenesis, with a lack of the appearance of aberrant crypt foci (ACF). To clarify the nature of such lesions, we performed a sequential analysis of the morphological and biological properties of beta-catenin-accumulated crypts. Azoxymethane was administered s.c. to male F344 rats (15 mg/kg body weight) once a week for 3 weeks, and the animals were sacrificed at 5, 10, and 20 weeks after the carcinogen treatment. Both the number of crypts/lesion and the diameter of beta-catenin-accumulated crypts were significantly increased with time courses of 5, 10, and 20 weeks from carcinogen exposure (P < 0.01). Likewise, the histological abnormality in those crypts, assessed by semiquantitative analyses, was also increased with time (P < 0.01). Conversely, ACF did not show any increase in histological abnormality during the time course and maintained a monotonous histology throughout the experiment. The histological abnormality score for beta-catenin-accumulated crypts was significantly higher than for ACF at every time point (P < 0.001). The number of AgNOR/nucleus in beta-catenin-accumulated crypts was significantly higher than in ACF (P < 0.001). Beta-catenin-accumulated crypts were accompanied frequently by Paneth cells and had decreased hexosaminidase activity. Such data, together with the results in our previous report, strongly suggest that beta-catenin-accumulated crypts, which are independent of ACF, are truly premalignant lesions for colon cancer.

Animals↗
PubMed2001

Calcium inhibits willardiine-induced responses in kainate receptor GluR6(Q)/KA-2.

A number of studies have demonstrated that willardiine [(S)-1-(2-amino-2-carboxyethyl) pyrimidine-2,4-dione] is a useful agonist for the activation of AMPA/kainate receptors. Here we examine the effect of extracellular calcium on currents evoked by willardiine in HEK 293 cells expressing the GluR6(Q)/KA-2 kainate receptor subunits. At a concentration of 1.8 mM, Ca2+ inhibited the currents induced by 100 microM willardiine by approximately 50%. When extracellular Na+ ions were replaced with Ca2+ ions there were no measurable inward currents. We conclude that Ca2+ inhibition of the willardiine-induced response is concentration dependent.

Alanine↗
PubMed2001

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues.

BACKGROUND: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbs1 play a critical role in DNA DSB repair. METHODS: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbs1 in 134 specimens from various normal and tumor tissues with different radiosensitivity. RESULTS AND CONCLUSION: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbs1 was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbs1, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues.

Antigens, Nuclear↗