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Biomedical subjects

K Kawahara

Publications and source records attributed to K Kawahara.

At least 19 recordsLinked to original sources
PubMed2000

Down-regulation of drs mRNA in human colon adenocarcinomas.

We have previously reported that the drs gene, whose mRNA expression is down-regulated by retroviral oncogenes such as v-src and v-K-ras, has the ability to suppress transformation by v-src and v-K-ras in the rat cell line F2408. We have also isolated a human homolog of this gene (h-drs) and shown that expression of h-drs mRNA is markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down-regulation of the drs gene and malignant tumor formation in human cancer tissues, we examined expression of drs mRNA in human normal tissues, colon adenoma, and adenocarcinoma tissues by in situ hybridization. Expression of drs mRNA was detected in most normal tissues tested, including those of the colon, bladder, and ovary. However, drs mRNA was hardly expressed in any of the colon adenocarcinoma tissues examined. Northern blot analyses confirmed these results. Neither gross deletion nor re-arrangement of the drs genome was detected by Southern blot hybridization in these adenocarcinoma tissues. drs mRNA was significantly expressed in colon adenoma with mild atypia but down-regulated in adenomas with moderate atypia and focal carcinoma. Our results indicate that down-regulation of drs mRNA is closely correlated with development of colon adenocarcinoma, suggesting a tumor-suppressor function of the drs gene in human cancers.

Adenocarcinoma↗
PubMed2000

Down-regulation of beta-catenin by the colorectal tumor suppressor APC requires association with Axin and beta-catenin.

The tumor suppressor adenomatous polyposis coli (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. APC forms a complex with beta-catenin, Axin, and glycogen synthase kinase-3beta and induces the degradation of beta-catenin. In the present study, we examined whether APC association with Axin is required for degradation of beta-catenin. We found that a fragment of APC that induces beta-catenin degradation was rendered inactive by disruption of its Axin-binding sites. Also, overexpression of an Axin fragment spanning the regulator of the G-protein signaling domain inhibited APC-mediated beta-catenin degradation. An APC fragment with mutated beta-catenin-binding sites but intact Axin-binding sites also failed to induce degradation of beta-catenin. These results suggest that APC requires interaction with Axin and beta-catenin to down-regulate beta-catenin.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Evaluation of the malignant grade of thymic epithelial tumors according to the epithelial subclassification.

We investigated the clinicopathological correlations among 49 surgically resected thymic epithelial tumors (TET), which were subclassified according to the six subtypes established by the Marino, Kirchner, and Müller-Hermelink system, which were renamed as follows: spindle cell type (medullary thymoma), mixed spindle and polygonal cell type (mixed medullary and cortical thymoma), small polygonal cell type (predominantly cortical thymoma), large polygonal cell type (cortical thymoma), atypical type (well differentiated thymic carcinoma), and cytologically malignant type (high-grade thymic carcinoma). The related categories were grouped for statistical analysis as follows: group 1, spindle cell type and mixed type; group 2, small polygonal cell type and large polygonal cell type; group 3, atypical type; group 4, cytologically malignant type. The association of each group with the presence of myasthenia gravis, tumor stage, and the length of survival was studied. Myasthenia gravis was significantly present in patients with small polygonal type, large polygonal type, and atypical type tumors (groups 2 and 3) (P = 0.003). The tumors in group 1 showed the lowest tumor stage while those of group 4 had the most advanced tumor stage (P = 0.002). The patients in group 4 had the worst prognosis, followed by those in group 3, 2, and 1, in that order. The differences among these groups were statistically significant (P = 0.0003). From our results, we determined that TET can be separated into an extremely low-grade malignancy group (group 1), a low-grade malignancy group (group 2), an intermediate malignancy group (group 3), and a high-grade malignancy group (group 4).

Epithelial Cells↗
PubMed2000

Structural analysis of two glycosphingolipids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata.

Two glycosphingolipids, GSL-1 and GSL-3, were isolated from Sphingomonas capsulata and studied by methylation analysis, laser desorption mass spectrometry, and 1H and 13C NMR spectroscopy, including two-dimensional 1H,1H COSY and heteronuclear 13C,1H COSY experiments. GSL-1 and GSL-3 differ in their carbohydrate part, their structures being alpha-D-GlcpA-(1-->1)-Cer and alpha-D-Galp-(1-->6)-alpha-D-GlcpN-(1-->4)-alpha-D-GlcpA(1-- >1)Cer, respectively. Variations occur in the ceramide of GSL-1 and GSL-3, both having the same long-chain bases, erythro-2-amino-1, 3-octadecanediol (sphinganine), (13Z)-erythro-2-amino-13-eicosene-1, 3-diol and (13Z)-erythro-2-amino-13,14-methylene-1,3-eicosanediol, in the ratios 2.6 : 1 : 3.5 in GSL-1 and 1 : 1.2 : 1.5 in GSL-3. All bases are quantitatively substituted by amide-linked (S)-2-hydroxymyristic acid.

Carbohydrate Conformation↗
PubMed2000

Discrimination among three species of medicinal Scutellaria plants using RAPD markers.

An analysis of random amplified polymorphic DNA (RAPD) was performed using nine accessions of three species of medicinal plants in the genus Scutellaria (S. galericulata, S. lateriflora and S. baicalensis; known collectively as skullcap) in an effort to distinguish between members of these three species. Dried aerial parts of the two species S. galericulata and S. lateriflora are difficult to distinguish morphologically. Ten arbitrary primers produced 92 fragments, and eight of the primers yielded 23 species-specific fragments among the three species. Six fragments were specific for S. galericulata, seven for S. lateriflora and ten for S. baicalensis. When primers A02 and A06 were used in the polymerase chain reaction, RAPD fragments that were specific for each of the three species were generated simultaneously. Primer A02 produced five species-specific fragments: one was specific for S. galericulata; two for S. lateriflora; and two for S. baicalensis. Primer A06 produced three species-specific fragments: one for S. galericulata; one for S. lateriflora; and one for S. baicalensis. The RAPD markers that were generated with these two primers should rapidly identify members of the three species of Scutellaria. The consistency of the identifications made with these species-specific RAPD markers was demonstrated by the observation that each respective marker was generated from three accessions of each species, all with different origins. Furthermore, cluster analysis using the 92 RAPD fragments produced a dendrogram of genetic relatedness that was in good agreement with the taxonomic designations of the three species. Thus, the RAPD markers should be useful for the future identification of members of the three species of medicinal Scutellaria plants.

Plants, Medicinal↗
PubMed2000

Effects of abstinence from cigarette smoking on the cardiorespiratory capacity.

PURPOSE: The purpose of this study was to determine the effect of 6 or 7 d of abstinence from cigarette smoking on the cardiorespiratory capacity of young men. METHODS: The subjects were 11 male volunteers, mean age 20.5 yr. Their mean smoking duration and cigarettes smoked per day were about 3.5 yr and 20.5 cigarettes, respectively. On the first day of the study, the subjects' physical characteristics, pulmonary functions, and maximal oxygen debt predicted by bicycle ergometer exercise were measured. The subjects' heart rate at rest (HRrest), blood pressure, venous blood analysis and maximal oxygen intake (VO2max) in a treadmill exercise test were measured on the second day. From the time of the second-day measurements, the subjects abstained from cigarette smoking. On the eighth and ninth days of the study, the same measurements were taken as the measurements of the first and second days, respectively. RESULTS: The changes between before and after abstinence from smoking were as follows. The plasma cotinine had almost disappeared after the 7 d of abstinence from smoking. Pulmonary functions did not show a significant improvement. Although there were no significant changes in the HRrest or systolic or diastolic blood pressure, the pulse pressure was significantly increased (P < 0.05). Although the blood components were not changed significantly, the PO2, O2 saturation, HCO3, and CO2 concentration were significantly increased. The predicted maximal oxygen debt was not significantly decreased. Although the VO2max and maximal ventilation volume were not changed, the exercise time was significantly prolonged (P < 0.001). The heart rate during the treadmill exercise at almost all stages decreased significantly; however, the maximal heart rate did not change. CONCLUSION: In conclusion, exercise performance was improved by the 7 d of abstinence from smoking.

Adult↗
PubMed2000

Emendation of the description of Blastomonas natatoria (Sly 1985) Sly and Cahill 1997 as an aerobic photosynthetic bacterium and reclassification of Erythromonas ursincola Yurkov et al. 1997 as Blastomonas ursincola comb. nov.

Photosynthetic properties of Blastomonas natatoria (Sly 1985) Sly and Cahill 1997, which had been recognized as being non-photosynthetic, were examined and compared with those of its close relative, the aerobic photosynthetic bacterium, Erythromonas ursincola Yurkov et al. 1997. HPLC experiments demonstrated that bacteriochlorophyll a was present in a detectable amount in the lipid extract from B. natatoria DSM 3183T as well as that from E. ursincola DSM 9006T. The puf genes, encoding the proteins of the photosynthetic reaction centre and core light-harvesting complexes, were detected by PCR from both the organisms. 16S rDNA sequence comparisons and DNA-DNA hybridization studies confirmed that B. natatoria and E. ursincola were closely related genetically in a single genus. On the basis of phenotypic, chemotaxonomic and phylogenetic data, it is proposed that the description of B. natatoria is emended as a species of aerobic photosynthetic bacteria and that E. ursincola is reclassified as Blastomonas ursincola comb. nov.

Alphaproteobacteria↗
PubMed2000

Study of the smoking behavior of medical doctors in Fukui, Japan and their antismoking measures.

We conducted a survey on smoking among all members of the medical association in Fukui Prefecture, using a questionnaire to be filled in by the subjects. The survey was conducted from December of 1996 to February of 1997, and the return rate was 90.8%. The main results of this survey were as follows: the prevalence of current smoking among medical doctors was 26.0% (male: 27.8%, female: 5.2%), which was lower than that of adults in the general population. The prevalence of past smoking among doctors 20 to 34 years old by age cohort was highest and that among doctors 35 years old and higher declines as age cohort increased. Doctors' participation in activities for the prevention of smoking in the general society was also found to be at a low level.

Adult↗
PubMed2000

[Clinical evaluation of VATS lobectomy for lung cancer].

Thoracoscopic lobectomy is now recognized as a possible less invasive surgical option for stage I primary non-small cell lung cancer. We have widely used thoracoscopic procedure for surgical diagnosis of lung nodules especially in lung peripheral region as well as resection of primary lung cancer. Results of 47 thoracoscopic lobectomy during last 5 years were compared with 24 standard lobectomy under postero-lateral thoracotomy. There were no significant differences in the duration of surgery, post-operative hospital stay, intraoperative blood loss and post-operative survival. All but three patients who were diagnosed as n 2 disease or tumor with extrapulmonary extension post-operatively are surviving at the time of survey. We conclude that thoracoscopic lobectomy is safe and less invasive procedure compared to standard thoracotomy. We believe it can provide sufficient outcome for stage I non-small cell lung cancer.

Aged↗
PubMed2000

[Thymidylate synthase activity after preoperative administration of 5-FU in patients with gastric or colorectal cancer].

Continuous intravenous injection of 5-FU was given at 300 mg/m2 to patients with gastric or colorectal cancer for consecutive 3 days preoperatively, and the relationships between the time until collection of samples (from final administration of 5-FU to excision of tissue samples) and total thymidylate synthase (TS total) activity, free thymidylate synthase (TS free) activity, thymidylate synthase inhibition rate (TSIR), thimidine kinase (TK) activity, and tissue 5-FU and FdUMP concentrations investigated. TS total was shown to gradually reduce with time, but the relationship between time and the other assay items could not be identified due to large variability in the data. TS total and TK also proved to be affected also by the sites at which the samples were collected, and exhibited significantly higher enzyme activity in tumor tissue than that in normal tissue.

Adult↗
PubMed1999

Hypernuclear acetylation in atherosclerotic lesions and activated vascular smooth muscle cells.

Recent studies have implicated acetylation of several nuclear proteins such as histones and p53 on their epsilon-portion of lysine residues in eukaryotic transcription. Here we raised a specific polyclonal antibody against epsilon-acetylated lysine. Using the antibody, we detected hypernuclear acetylation (HNA) in atherosclerotic vascular smooth muscle cells (VSMCs). Thrombin, a humoral factor known to cause activation and proliferation of VSMCs, strongly potentiated HNA in cultured VSMCs. MAP kinase pathway and a signal coactivator CREB binding protein (CBP) were involved in thrombin-induced HNA of VSMCs. Our results suggest that coactivators cooperating with signal-dependent transcription activators play an important role in atherosclerogenesis via HNA in VSMCs.

Acetylation↗
PubMed1999

Localization of the ATP-sensitive potassium channel subunit (Kir6. 1/uK(ATP)-1) in rat brain.

The Kir6.1/uK(ATP)-1, subunit of ATP-sensitive K(+) channels (K(ATP)), was localized in adult rat brain by in situ hybridization and immunohistochemistry. The mRNA of this subunit was ubiquitously expressed in various neurons and nuclei of the adult rat brain. Interestingly, Kir6.1/uK(ATP)-1 mRNA was also expressed in glial cells. Kir6.1/uK(ATP)-1 protein staining gave a dispersed array of fine dots throughout all neurons and glial cells examined. Under electron microscope, the immunoreactive products were specifically restricted to the mitochondria. The present study indicates that this K(ATP) subunit is localized in the mitochondria and may play a fundamental role in vital brain function.

Adenosine Triphosphate↗
PubMed1999

Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase.

A novel inwardly rectifying K+ channel, Kir7.1, with unique pore properties, was cloned recently. Working in the field of osmoregulation, we have also identified the same human and rat channel and found that the channel is unique not only in its pore sequence but also in its dense localization in the follicular cells of the thyroid gland. Northern blot analysis revealed that the channel message was abundantly expressed in the thyroid gland and small intestine, and moderately in the kidney, stomach, spinal cord and brain. Immunohistochemistry of the rat thyroid, intestine and choroid plexus demonstrated the expression of the channel protein in the follicular cells and epithelial cells, suggesting a role in the regulation of the ion-transporting functions of these specialized cells. The unique pore properties of Kir7.1 make it a strong candidate for the hypothetical low-conductance K+ channel that is functionally coupled with Na+,K(+)-ATPase by recycling K+. We therefore further examined the co-localization of Kir7.1 and Na+,K(+)-ATPase and found that both are localized in the basolateral membrane of the thyroid follicular cell; in the choroid plexus, which is known to be unique in having Na+,K(+)-ATPase in the apical side of the epithelial cells, Kir7.1 was found in the apical membrane, implying a close functional coupling between the channel and Na+,K(+)-ATPase.

Amino Acid Sequence↗
PubMed1999

Complement activation by bacterial surface glycolipids: a study with planar bilayer membranes.

Planar asymmetric glycolipid/phospholipid bilayer membranes were used as a reconstitution model of the lipid matrix of the outer membrane of Gram-negative bacteria to study complement (C) activation by various bacterial surface glycolipids with the aim of defining the C activation pathway. As glycolipids the lipopolysaccharides of Salmonella enterica serovar Minnesota R mutant strains R595 (Re LPS) and R4 (Rd2 LPS), pentaacyl lipid A from the LPS of the Escherichia coli Re mutant F515, and glycosphingolipid GSL-1 of Sphingomonas paucimobilis IAM 12576 were used. Methylester and carboxyl-reduced derivatives of GSL-1 were used to elucidate the role of the carboxyl group as common functional group of LPS and GSL-1 for C activation. The formation of lytic pores was monitored via the measurement of changes in membrane current. For all glycolipids we observed a considerable increase in membrane current soon after addition of whole human serum due to the formation of lytic pores in the membranes. Pore formation was dependent on the presence of C9, indicating that the observed current changes were due to C activation. We found that in our reconstitution system of the outer membrane lipid A, Re LPS, and Rd2 LPS activated the classical pathway, the activation being independent of specific anti-LPS antibodies. In contrast, GSL-1 and the methylester derivative of GSL-1 activated the alternative pathway even at the low serum concentrations used in this study (about 0.2% v/v). Interestingly, the carboxyl reduced GSL-1 activated the classical pathway.

Antibodies↗
PubMed1999

p53 mutations predict non-small cell lung carcinoma response to radiotherapy.

In vitro and animal studies, the effect of loss of p53 function on radiosensitivity is controversial. p21Waf1/Cip1 is a potent inhibitor of cyclin-dependent kinases and p21 gene polymorphisms are associated with some human cancers. We sought to determine whether p53 mutations or p21 polymorphisms affect response to radiotherapy in patients with recurrent non-small cell lung carcinoma (NSCLC). Thirty-four patients with NSCLC who underwent radiotherapy for recurrent tumors after potentially curative resection were studied. Gene alterations or polymorphisms were analyzed in DNA from the primary tumor tissue, and the response to radiotherapy was based on the metastatic lesion. Mutations in exons 5-8 of the p53 gene were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. p21 gene polymorphisms were identified by restriction digestion (BsmAI or PstI) of PCR products. Mutations in p53 were found in 13 of 34 patients (38.2%). The response rates (complete plus partial) were 15.4% for patients with tumors having p53 mutations and 61.9% for patients with wild-type p53 (P = 0.013). There was no significant difference between p21 polymorphisms and response to radiation. p53 gene mutations predict response to radiotherapy in NSCLC. Our results provide clinical support for the in vitro model that loss of p53 function decreases radiosensitivity.

Adult↗
PubMed1999

Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit model of atherosclerosis: possible mechanisms.

BACKGROUND: The increased severity of the myocardial injury produced by coronary occlusion-reperfusion in models of atherosclerosis is associated with an increase in leukocyte accumulation in the ischemic myocardium. Expression of P-selectin, an adhesion molecule involved in the interaction between leukocytes and endothelium, is increased in atherosclerotic vessels. Long-term angiotensin-converting enzyme (ACE) inhibition has been shown to reduce atherosclerotic vascular change in experimental models. METHODS AND RESULTS: We examined changes in the size of the infarct resulting from coronary occlusion/reperfusion in normally fed and cholesterol-fed rabbits that were chronically treated with quinapril. Infarct size was significantly larger in the cholesterol-fed versus normally fed rabbits. ACE activity in the ischemic and nonischemic myocardium was significantly reduced by quinapril. Chronic quinapril administration significantly ameliorated the increased myocardial injury in cholesterol-fed rabbits. Quinapril administration markedly increased the myocardial cGMP content and reduced the myeloperoxidase activity in the border region of the ischemic myocardium in cholesterol-fed rabbits. The enhanced expression of P-selectin in myocardial tissue of cholesterol-fed rabbits was also effectively reduced by quinapril treatment. The above effects of quinapril were eliminated by blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis. CONCLUSIONS: Chronic quinapril treatment ameliorated the severity of myocardial injury produced by coronary occlusion/reperfusion in cholesterol-fed rabbits, possibly because of reversal of the enhanced interaction between leukocytes and endothelium in the ischemic myocardium via a bradykinin-related pathway.

Angiotensin-Converting Enzyme Inhibitors↗