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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 721 records · Page 40Linked to original sources
PubMed1998

Association of high-altitude pulmonary edema with the major histocompatibility complex.

BACKGROUND: A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. METHODS AND RESULTS: The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6-positive subjects with HAPE was significantly higher than that of the HLA-DR6-negative subjects with HAPE. CONCLUSIONS: There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Adolescent↗
PubMed1998

Does passive smoking impair endothelium-dependent coronary artery dilation in women?

OBJECTIVES: This study sought to examine whether passive smoking is associated with endothelial dysfunction in the coronary arteries. BACKGROUND: Long-term exposure to cigarette smoking has been reported to suppress endothelium-dependent arterial dilation in humans. Endothelial dysfunction is an early feature of atherogenesis, and the impairment of acetylcholine (ACh)-induced coronary artery dilation indicates coronary endothelial dysfunction. METHODS: We studied 38 women (40 to 60 years old) who had no known risk factors for coronary artery disease other than tobacco smoking: 11 nonsmokers who had never smoked and had never been regularly exposed to environmental tobacco smoke; 19 passive smokers with self-reported histories of exposure to environmental tobacco smoke of > or = 1 h/day for > or = 10 years; and 8 active smokers. We examined the response of the epicardial coronary artery diameters (proximal and distal segments of the left anterior descending [LAD] and left circumflex [LCx] coronary arteries) to the intracoronary injection of ACh into the left coronary artery by means of quantitative coronary angiography. RESULTS: ACh significantly dilated the distal segment in nonsmokers (percent change from baseline diameter: LAD 13.7+/-3.4%, p < 0.05; LCx 18.8+/-2.9%, p < 0.01) but not the proximal segment (LAD 7.4+/-3.5%; LCx 3.1+/-5.0%). ACh significantly constricted all segments of the left coronary artery in passive smokers (LAD: proximal -20.3+/-3.7%, p < 0.05; distal -22.3+/-4.1%, p < 0.01; LCx: proximal -20.8+/-3.1%, p < 0.05; distal -17.3+/-2.9%, p < 0.01) and active smokers (LAD: proximal -14.8+/-3.4%, p < 0.05; distal -27.2+/-6.0%, p < 0.01; LCx: proximal -14.5+/-6.6%, p < 0.05; distal -22.4+/-4.0%, p < 0.01). Thus, ACh constricted most coronary arteries in both passive and active smokers and dilated the coronary arteries in nonsmokers. CONCLUSIONS: Impairment of ACh-induced coronary artery dilation, indicating coronary endothelial dysfunction, may occur diffusely in passive smokers as well as in active smokers.

Acetylcholine↗
PubMed1998

The primary site of CD4- 8- B220+ alphabeta T cells in lpr mice: the appendix in normal mice.

There have been no reports on an abundance of CD4- 8- B220+ alphabeta T cells, seen in autoimmune mice carrying the lpr gene (abnormal Fas gene), in any immune organs of normal mice. We herein report, however, that such alphabeta T cells were abundant at intraepithelial sites of the appendix in normal mice. They lacked the expression of NK1.1 Ags (C57BL/6 mice), but had the morphology of granular lymphocytes and contained forbidden T cell clones in the minor lymphocyte-stimulating antigen (Mls) system (C3H/He mice with Mls-1b2a). In other words, many properties of intraepithelial T cells in the appendix resembled those ascribed to abnormal alphabeta T cells, which expand in the lymph nodes and spleen of lpr mice. In the case of lpr mice, CD4- 8- B220+ alphabeta T cells first expanded in the appendix and then extended to other organs. CD4- 8- B220+ alphabeta T cells seemed to originate in situ from c-kit+ stem cells in the appendix. These results suggest that the appendix is one of the primary sites in which CD4- 8- B220+ alphabeta T cells exist, and that these cells carry many primordial properties as prototype T cells.

Animals↗
PubMed1998

Randomized, double-blind, placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure.

BACKGROUND: Reduced cGMP production caused by increased superoxide has been proposed as a mechanism of nitrate tolerance during continuous nitrate therapy. This study was designed to evaluate the effects of ascorbate, an antioxidant, on the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure. METHODS AND RESULTS: Twenty patients with congestive heart failure were randomized to receive intravenous infusion of nitroglycerin concomitantly with placebo (placebo group, n=10) or intravenous ascorbate (vitamin C group, n=10). After baseline measurements were obtained, dose titration was started by the infusion of nitroglycerin at a rate of 0.5 microg/kg per minute (titration period). Measurements of hemodynamic parameters and blood sampling were performed serially at 0, 6, 12, 18, and 24 hours after the titration period. At baseline, mean pulmonary artery pressure (MPAP, mm Hg), mean pulmonary capillary wedge pressure (PCWP, mm Hg), plasma vitamin E level (micromol/L), and platelet cGMP level (pmol/10[9] platelets) were comparable in the two groups (placebo group: MPAP, 48+/-6; PCWP, 24+/-4; cGMP, 0.76+/-0.12; vitamin E, 18.2+/-1.2; vitamin C: MPAP, 49+/-7; PCWP, 24+/-4; cGMP, 0.71+/-0.16; vitamin E, 18.6+/-1.3). In both groups, at 6 hours after the titration period, MPAP and PCWP were significantly decreased (placebo group: MPAP, 26+/-5; PCWP, 15+/-4; vitamin C: MPAP, 26+/-4; PCWP, 16+/-4), and platelet cGMP was significantly increased (placebo group: 2.42+/-0.24; vitamin C: 2.26+/-0.26). However, at 18 hours after titration, in the placebo group, MPAP (44+/-5) and PCWP (23+/-4) were increased, and platelet cGMP (0.85+/-0.20) and plasma vitamin E levels (12.4+/-1.4) were significantly decreased. In contrast, in the vitamin C group, MPAP (31+/-6), PCWP (17+/-5), platelet cGMP (2.49+/-0.23), and plasma vitamin E levels (17.6+/-1.4) were maintained for 18 hours after the titration period. CONCLUSIONS: These findings indicate that ascorbate, an antioxidant, may prevent the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure.

Aged↗
PubMed1998

ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair.

DNA mismatch repair ensures genomic stability by correcting biosynthetic errors and by blocking homologous recombination. MutS-like and MutL-like proteins play important roles in these processes. In Escherichia coli and yeast these two types of proteins form a repair initiation complex that binds to mismatched DNA. However, whether human MutS and MutL homologs interact to form a complex has not been elucidated. Using immunoprecipitation and Western blot analysis we show here that human MSH2, MLH1, PMS2 and proliferating cell nuclear antigen (PCNA) can be co-immunoprecipitated, suggesting formation of a repair initiation complex among these proteins. Formation of the initiation complex is dependent on ATP hydrolysis and at least functional MSH2 and MLH1 proteins, because the complex could not be detected in tumor cells that produce truncated MLH1 or MSH2 protein. We also demonstrate that PCNA is required in human mismatch repair not only at the step of repair initiation, but also at the step of repair DNA re-synthesis.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen.

Proper control of the mammalian cell cycle requires the function of cyclin-dependent kinase (CDK) inhibitors. The p21 family currently includes three distinct genes, p21, p27(Kip1), and p57(Kip2), that share a common N-terminal domain for binding to and inhibiting the kinase activity of CDK-cyclin complexes. The p21 protein also binds to proliferating cell nuclear antigen (PCNA) through a separate C-terminal domain affecting DNA replication and repair. The p27 and p57 proteins also each contain unique C-terminal domains whose functions are unknown. Here we show that the human p57 protein, like p21, contains a PCNA-binding domain within its C terminus that, when separated from its N-terminal CDK-cyclin binding domain, can prevent DNA replication in vitro and S phase entry in vivo. Disruption of either CDK/cyclin or PCNA binding partially reduced p57's ability to suppress myc/RAS-mediated transformation in primary cells, while loss of both inhibitory functions completely eliminated p57's suppressive activity. Thus, control of cell cycle and suppression of cell transformation by p57 require both CDK and PCNA inhibitory activity, and disruption of either or both functions may lead to uncontrolled cell growth.

Amino Acid Sequence↗
PubMed1998

Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K-ras mutation.

BACKGROUND: The authors sought to elucidate the histogenesis of pancreatic ductal carcinoma by correlating K-ras mutation with mucus type in normal epithelium, mucous cell hyperplasia (MCH), and carcinoma. METHODS: Seventy-four solid-type carcinomas (SCs), 23 ductectatic-type carcinomas (DCs), and specimens of 24 normal pancreata were studied. By histochemical staining, normal duct epithelia, areas of MCH, and carcinomas were classified as having sulfo-type or sialo-type mucus. Foci from normal, DC, SC, sulfo-type, or sialo-type specimens were assessed for K-ras mutation at codon 12 by nested polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Of the SCs, 9 were sulfo-type and 65 were sialo-type; all DC specimens were sialo-type, and all normal epithelia were sulfo-type. All foci of sulfo-type, nonneoplastic epithelia were negative for K-ras mutation. In contrast, 124 of 313 sialo-type MCH foci (40%) had a K-ras mutation. Of 74 SCs, only 3 of 9 sulfo-type tumors (33%) were positive for the mutation. Sixty of 65 sialo-type SCs (92%) had a K-ras mutation, whereas 15 of 23 sialo-type DCs (65%) had a mutation. K-ras mutant carcinomas (including both SCs and DCs) were associated with K-ras mutant MCH in 109 of 198 MCHs (55%), whereas carcinomas without a K-ras mutation had mutations in 6 of 68 MCHs (9%). MCH in normal pancreata revealed K-ras mutations in 9 of 51 foci (18%). In addition, in K-ras mutant carcinomas, frequency of K-ras mutation in MCH increased from 27% (11 of 41 foci) of nonpapillary MCHs to 62% (98 of 157 foci) of papillary MCHs; but in K-ras wild-type carcinoma, the mutation rate in MCH was unchanged from 12% (3 of 26 foci) to 7% (3 of 42 foci) in nonpapillary and papillary foci, respectively. CONCLUSIONS: These results suggest a strong relationship between the risk of pancreatic carcinoma and the presence of combinations of K-ras gene mutation, papillary growth, and expression of sialomucin in foci of MCH.

Adult↗
PubMed1998

Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma.

BACKGROUND: In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries. METHODS: Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS: For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important. CONCLUSIONS: In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries.

Adenoma↗
PubMed1998

Benzene exposure, glutathione S-transferase theta homozygous deletion, and sister chromatid exchanges.

Recent studies have shown a strong positive correlation between chromosomal aberrations and future cancer risk. Sister chromatid exchange (SCE) has been widely applied in monitoring early biological effects to assess human genetic risk of cancer at the population level. We studied 45 Chinese workers (23 in the painting workshop of a glass factory with occupational exposure to benzene, and 22 fitters and planers in the punching and planing machine workshops of a nearby shipyard without such an exposure) to examine the association between occupational exposure to benzene and SCE frequency in peripheral blood lymphocytes. We also sought to investigate whether the glutathione S-transferase class theta gene (GSTT1) affects individual susceptibility to cytogenetic damage induced by in vivo exposure to benzene or in vitro exposure to diepoxybutane. The time-weighted average concentrations of benzene were 0.71 ppm in the exposed group and 0.03 ppm in the non-exposed group. Controlling for age, gender and educational level, cigarette smoking was significantly associated with increased SCE frequencies (P < 0.05), while GSTT1 genotype was significantly associated with DEB-induced SCEs (P < 0.01). There was no relationship between benzene exposure and baseline or DEB-induced SCEs. After stratification by smoking status, the GSTT1 deletion was a significant predictor of DEB-induced SCEs for both smokers (P < 0.05) and nonsmokers (P < 0.01). A significant benzene-GSTT1 interaction was found in nonsmokers (P < 0.05). Our study suggests that GSTT1 is an important determinant of heterogeneity in individual susceptibility to chromosomal damage associated with exposure to benzene.

Adult↗
PubMed1998

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic mutations, V133E and C456F, in Japanese siblings.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT; EC 2.8.3.5; locus symbol OXCT) is the key enzyme of ketone body utilization. Hereditary SCOT deficiency (MIM 245050) causes episodes of severe ketoacidosis. We developed a transient expression system for mutant SCOT cDNAs, using immortalized SCOT-deficient fibroblasts. This paper describes and characterizes three missense mutations in two SCOT-deficient siblings from Japan. They are genetic compounds who inherited the mutation C456F (c1367 G-->T) from their mother. Their paternal allele contains two mutations in cis, T58M (c173 C-->T) and V133E (c398T-->A). Expression of SCOT cDNAs containing either V133E or C456F produces no detectable SCOT activity, whereas T58M is functionally neutral. T58M is a rare sequence variant not detected in 100 control Japanese alleles. In fibroblasts from the proband (GS02), in whom immunoblot demonstrated no detectable SCOT peptide, we measured an apparent residual SCOT activity of 20-35%. We hypothesize that the high residual SCOT activity in homogenates may be an artifact caused by use of the substrate, acetoacetyl-CoA by other enzymes. Expression of mutant SCOT cDNAs more accurately reflects the residual activity of SCOT than do currently available assays in cell or tissue homogenates.

Cell Line, Transformed↗
PubMed1998

Disrupted expression of matrix genes in the growth plate of the mouse cartilage matrix deficiency (cmd) mutant.

Chondrodysplasia in the autosomal recessive cartilage matrix deficiency (cmd) mutant is caused by lack of the proteoglycan aggrecan arising from a mutation in the gene. Homozygous cmd/cmd mice are characterized by disorganisation of chondrocytes in the growth plate, disproportionate dwarfism, cleft palate, and perinatal lethality. We have studied the impact of the aggrecan deficiency on the expression of other matrix genes during the differentiation of chondrocytes in the growth plate of cmd/cmd 18.5 day fetuses. Compared with the wild-type, there are significant differences in the growth plates of cmd mutants in the combinations of co-expression of genes encoding the glycoprotein link protein, proteoglycan syndecan 3, collagens alpha 1 (X) [Col10a1], alpha 2(XI) [Col11a2], and the alternative transcripts of alpha 1 (II) [Col2a1 type IIA form], and alpha 1 (IX) [Col9a1 long and short forms]. The discordance of gene expression in cmd chondrocytes may be additional factors contributing to the disrupted cellular architecture of the growth plate resulting from the primary absence of aggrecan.

Aggrecans↗
PubMed1998

Low level of mixing of partner cells seen in extrathymic T cells in the liver and intestine of parabiotic mice: its biological implication.

c-kit+ stem cells have recently been found in the liver and intestine of adult mice. We examined whether such stem cells give rise to extrathymic T cells in these organs in situ. To this end, we used parabiotic B6.Ly5.1 and B6.Ly5.2 mice, i.e. mice sharing the circulation. The origin of lymphocytes was identified by anti-Ly5.1 and anti-Ly5.2 monoclonal antibodies in conjunction with immunofluorescence assays. Lymphocytes in the blood, spleen, lymph nodes and liver had become a half-and-half mixture of Ly5.1+ and Ly5.2+ cells in both individuals by day 14. However, this level of mixing decreased in extrathymic T cells in the liver (i.e. NK T cells) and intestine by day 14 and thereafter. The same was observed in T cells of the thymus. The data from immunohistochemical staining supported the results of immunofluorescence assays for suspension cells. The present results raise the possibility that extrathymic T cells in the liver and intestine may arise from their own pre-existing precursor cells, possibly from their own stem cells. Another important finding was that the composition pattern of lymphocyte subsets in one individual was quite similar to that in its partner at various sites. This result was interpreted to mean that only selected partner cells migrate to specific sites in the other partner individual.

Animals↗
PubMed1998

Soluble CD16 in the treatment of murine lupus nephritis.

To determine if soluble CD16 (sCD16) could alter the expression of lupus-like disease, groups of 10 female NZB/NZW mice (age 16-20 weeks) were given sCD16 three times a week for 5 weeks (control; 100 microg; 200 microg/dose) after onset of proteinuria. Results of this study indicate that the administration of sCD16 after onset of disease lowered anti-DNA levels, delayed the development of proteinuria, and significantly prolonged survival while the mice were on treatment. These results indicate that sCD16 alters the expression of autoantibodies and the progression of renal disease in NZB/NZW mice, suggesting that therapies directed at Fc receptors may be useful in the treatment of SLE.

Animals↗
PubMed1998

In vivo 3D localized 13C spectroscopy using modified INEPT and DEPT.

The 3D localized 13C spectroscopy methods LINEPT and LODEPT, which are modifications of INEPT and DEPT, are proposed. As long as a 13C inversion pulse (180-degree pulse) is applied at 1/(4J) before the proton echo time in LINEPT and a 13C excitation pulse (90-degree pulse) is applied at 1/(2J) before the proton echo time in LODEPT, the proton echo time can be set to any value longer than 1/(2J) in LINEPT and longer than 1/J in LODEPT. As a result, the proton and the 13C pulses can be applied separately and these proton pulses can be made slice-selective pulses. These localization features of LINEPT and LODEPT were evaluated using a phantom consisting of a cylinder filled with ethanol placed inside another cylinder filled with oil, and localized ethanol spectra could be obtained. In vivo 3D localized 13C spectra from the brain of a monkey could be obtained using decoupled LINEPT, and glutamate C-4 appeared directly after the administration of glucose C-1, followed by the appearance of glutamate C-2, C-3 and glutamine C-2, C-3, C-4.

Animals↗
PubMed1998

Genetic and immunological analyses of Vls (VMP-like sequences) of Borrelia burgdorferi.

DNA fragments containing the VMP-like sequence (Vls) were cloned from Borrelia burgdorferi strain 297. Analyses by PCR, PFGE, and Southern hybridization revealed that the Vls sequences existed in multi-copies on the 20-kb borrelial plasmid, but not on chromosomes or other plasmids. One Vls unit of the strain 297 was about 669 bases, and predicted peptides length was 223 amino acids. Homologues of the Vls fragment were detected in three B. burgdorferi strains, a B. garinii strain 20047, and a B. afzelii strain P/Gau. A recombinant VlsII protein prepared in Escherichia coli strain JM109 reacted with antibodies that existed in three of five patients, by immunoblotting. These results suggested that the Vls of B. burgdorferi is expressed in Lyme disease patients.

Amino Acid Sequence↗
PubMed1998

System B0,(+)-mediated regulation of lysine transport in Caco-2 human intestinal cells.

We investigated whether lysine transport would be subject to adaptive regulation in Caco-2 human intestinal cells. The activity of Lys transport in Caco-2 cells decreased with increasing incubation time with 10 mM Lys. Among the two systems involved in Lys transport, the system b0,+ component was greatly decreased by incubating cells with 10 mM Lys, whereas the system y+ component did not change. These results suggest that system b0,+ mainly contributes to the adaptive regulation of Lys transport in Caco-2 cells.

Amino Acid Transport Systems↗
PubMed1998

Noninvasive measurement of aortic pressure waveform by ultrasound.

At present, the aortic pressure (Pa) waveform can only be measured invasively. In this paper, we describe a new noninvasive method of measuring Pa. The aortic diameter (Da) pulse waveform was measured noninvasively from the suprasternal fossa using an echo-tracking system that was applied to the anterior and posterior aortic wall echoes. To eliminate viscoelastic distortion, the measured Da was converted to an estimate of Pa, named P beta, using the stiffness parameter beta, which revealed the viscoelastic relationship between the vessel diameter and its internal pressure. P beta was then compared with the Pa pattern that was measured directly. Eight patients with ischemic heart disease who had undergone cardiac catheterization were examined by this method. Results showed that (1) the Da and Pa waveforms were similar; (2) the P beta waveform resembled the Pa waveform more closely than did the Da waveforms for a single cardiac cycle (r = 0.970); and (3) in particular, P beta resembled Pa most closely during the upslope phase of the ejection period (r = 0.996). Our results suggest that the Pa waveform can be accurately estimated from noninvasive measurements by this method.

Adult↗