Biomedical subjects

T Kawamura

Publications and source records attributed to T Kawamura.

At least 55 records · Page 3Linked to original sources

PubMed2001

Menstrual and reproductive factors for subarachnoid hemorrhage risk in women: a case-control study in nagoya, Japan.

BACKGROUND AND PURPOSE: We sought to examine the relationship between menstrual and reproductive factors and the risk of subarachnoid hemorrhage (SAH), using a case-control study. METHODS: Cases consisted of a consecutive series of 124 women patients with first spontaneous SAH aged 30 to 79 years and confirmed aneurysm(s) by angiography and/or CT scan. Hospital and community controls subjects were identified, matched to each case by age (+/-2 years). RESULTS: Increased SAH risk was associated with (1) earlier age at menarche (adjusted odds ratio [OR]=3.24 for age <13 years compared with age >/=13 years; 95% CI, 1.25 to 4.03) and (2) nulligravidity (adjusted OR=4.23; 95% CI, 1.05 to 7.56). No significant association of SAH risk was found with regularity of menstrual cycle, age at pregnancy, age at first birth, and number of births. The greatest risk was for the combined effect of nulligravidity and earlier menarche (<13 years) (adjusted OR=6.37; 95% CI, 1.12 to 36.2). CONCLUSIONS: The combined effect of several variables related to menstrual and reproductive history may exert a greater influence on risk of SAH compared with a single menstrual or reproductive variable.

Adult↗

PubMed2001

Palladium complex catalyzed acylation of allylic esters with acylsilanes.

Acylation of allylic esters (2) with acylsilanes (1) in the presence of a catalytic amount (5 mol %) of a palladium complex is reported. The reaction proceeds selectively to afford beta,gamma-unsaturated ketones (3) in high yields. [Pd(eta3-C6H5CH=CHCH2)(CF3COO)]2 (4a) showed the best catalytic activity. After the reaction, formation of CF3COOSiMe3 (5a) was confirmed by 29Si NMR measurement of the resulting reaction mixture, indicating the trimethylsilyl moiety effectively traps the CF3COO leaving group from 2. The leaving group of the allylic esters affects the reaction considerably: allylic trifluoroacetate gave the best result, while the corresponding acetates and trichloroacetates did not afford any acylation products at all. Stoichiometric reaction of 4a with 1 gave acylation product 3 with a formation of 5a and Pd(0), whereas no acylation reaction took place with the corresponding acetate complex [Pd(eta3-C6H5CH=CHCH2)(CH3COO)]2 (4b). A DFT calculation suggests that interaction of high-lying HOMO of 1 and low-lying LUMO of eta3-allylpalladium trifluoroacetate intermediate 4 would be indispensable in the catalytic cycle.

Journal Article↗

PubMed2001

Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival.

BACKGROUND: Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma. METHODS: Immunohistochemistry with anti-Glut1 antibody was performed on 617 gastric carcinomas and 50 tubular adenomas of the stomach. Glut1-positive and Glut1-negative carcinomas were analyzed for their clinicopathologic characteristics including histologic subtype, depth of invasion, vascular permeation, lymph node and hepatic metastasis, peritoneal dissemination, and prognosis. RESULTS: None of the adenomas expressed Glut1, whereas 182 of 617 carcinomas (29.5%) were positive for the protein. Signet ring cell carcinoma and mucinous adenocarcinoma rarely were positive (2.0% and 6.3%, respectively) and papillary adenocarcinoma (44%) showed slightly higher positivity for Glut1 than tubular (32%) or poorly differentiated adenocarcinoma (28%). Glut1-positive tumor cells were localized mainly in the central part of tumor nests with or without peripheral distribution (92%) but peripheral distribution alone was very limited (8%) (P = 0.0001). Glut1 positivity was associated with depth of invasion (P = 0.0001), lymphatic permeation (P = 0.0001), venous invasion (P = 0.0001), lymph node metastasis (P = 0.0001), hepatic metastasis (P = 0.0001), and carcinoma stage (P = 0.0001). However, peritoneal dissemination was not found to be associated with Glut1 positivity (P = 0.0833). The survival of patients who had tumors that expressed Glut1 was significantly shorter than that of patients with Glut1-negative tumors (P = 0.0001). CONCLUSIONS: In human gastric carcinoma, Glut1 is expressed late in carcinogesis and increases with disease progression. Glut1 expression is associated with tumor aggressiveness and patient survival.

Adult↗

PubMed2001

Genetically modified bone marrow continuously supplies anti-inflammatory cells and suppresses renal injury in mouse Goodpasture syndrome.

In chronic inflammation, macrophages and neutrophils, which are derived from bone marrow, play a pivotal role. Therefore, reconstitution of bone marrow with anti-inflammatory stem cells may modify inflammation. In this study, transplantation-based gene therapy was applied to glomerular inflammation for a long-lasting suppression of the glomerular damage seen in chronic nephritis. Bone marrow cells were harvested from male donor mice, which had received 5-fluorouracil 3 days previously, and transduced with an interleukin 1 (IL-1) receptor antagonist (IL-1Ra) or a mock gene using a retrovirus vector. After confirmation that transduced cells possessed the transgene at approximately 0.7 copies per cell and secreted recombinant IL-1Ra, these cells were infused into sublethally irradiated (6 Gy) female recipients once daily for 4 consecutive days. These female recipient mice had the male Y antigen in bone marrow, liver, and spleen, and 10% to 20% of their spleen cells possessed the transgene even 8 weeks after transplantation. Glomerulonephritis was then induced in these mice. Renal function and histology were retarded in the mice whose bone marrow was reconstituted with IL-1Ra-producing cells compared with mock transduced cells. In situ hybridization using a Y painting probe revealed that transplanted donor cells were recruited into the glomerulus upon induction of nephritis, suggesting therapeutic effects were channeled through the secretion of IL-1Ra from these cells. Furthermore, the survival rate after a second challenge with nephrotoxic antibody was significantly improved in the IL-1Ra chimera. These results suggest that reconstitution of bone marrow for continuous supply of anti-inflammatory cells may be a useful strategy for the treatment of chronic inflammation.

Animals↗

PubMed2001

Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes.

Endothelin-1 (ET-1) acts not only as a growth-promoting peptide but also as a potent survival factor against myocardial cell apoptosis. However, the signaling pathways leading to myocardial cell protection by ET-1 are poorly understood. Using a culture system of primary cardiac myocytes derived from neonatal rats, we show in the present study that ET-1 almost completely blocked the hydrogen peroxide-induced increase in the percentage of TdT-mediated dUTP-biotin nick-end labeling-positive myocytes. Apoptosis inhibition by ET-1 was confirmed by cytofluorometric analysis as well as by examination of the ladder formation, morphological features, and caspase-3 cleavage. We have found that ET-1 converts the nuclear factor of activated T lymphocytes (NFATc) in cardiac myocytes into high-mobility forms and translocates cytoplasmic NFATc to the nuclei. In addition, ET-1 stimulates the interaction between NFATc and the cardiac-restricted zinc-finger protein GATA4 in these cells. The immunosuppressants cyclosporin A and FK506, which antagonize calcineurin, negated the inhibitory effect of ET-1 on apoptosis. Calcineurin activation de novo was sufficient to inhibit hydrogen peroxide-induced apoptosis. ET-1 induced the expression of an antiapoptotic protein bcl-2 in cardiac myocytes in a cyclosporin A-dependent manner, but it did not alter the expression of bax. Cyclosporin A also attenuated the ET-1-stimulated transcription of the bcl-2 gene in these cells. These findings demonstrate that the calcineurin pathway is required for the inhibitory effect of ET-1 on oxidant stress-induced apoptosis in cardiac myocytes.

Active Transport, Cell Nucleus↗

PubMed2001

Histamine production by cultured microglial cells of the mouse.

We previously reported that cells other than mast cells or neurons could synthesize histamine in response to lipopolysaccharide (LPS) or interleukin 1beta in the rat brain. To identify the responsible cells, we examined histidine decarboxylase (HDC) activity and the expression of HDC mRNA in GMI 6-3 mouse microglial cells. Both the activity and mRNA for HDC in GMI 6-3 cells were induced by LPS treatment, and the induction was sensitive to calmodulin-dependent kinase II inhibitor, KN62. These findings indicate that microglia is a third cell type producing histamine in the brain.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Association of intermediate T cell receptor cells, mainly their NK1.1(-) subset, with protection from malaria.

Mice were infected with Plasmodium (P.) yoelii blood-stage parasites. Both the liver and spleen were the sites of inflammation during malarial infection at the beginning of day 7. The major expanding cells were found to be NK1.1(-) intermediate alphabetaTCR (alphabetaTCR(int)) in the liver and spleen, although the population of NK1.1(+) alphabetaTCR(int) cells remained constant or slightly increased. These TCR(int) cells are of extrathymic origin or are generated by an alternative intrathymic pathway and are distinguished from conventional T cells of thymic origin. During malarial infection, the population of conventional T cells did not increase at all. TCR(int) cells purified from the liver of mice which had recovered from P. yoelii infection protected mice from malaria when they were transferred into 6.5-Gy-irradiated mice. Interestingly, the immunity against malaria seemed to disappear as a function of time after recovery, namely, mice which had recovered from malaria 1 year previously again became susceptible to malarial infection. The present results suggest that TCR(int) cells are intimately associated with protection against malarial infection and, therefore, that mice which had recovered from malaria 1 year previously lost such immunity.

Animals↗

PubMed2001

The KMDB/MutationView: a mutation database for human disease genes.

The KMDB/MutationView is a graphical database of mutations in human disease-causing genes and its current version consists of nine category-based sub-databases including diseases of eye, heart, ear, brain, cancer, syndrome, autoimmunity, muscle and blood. The KMDB/MutationView stores mutation data of 97 genes involved in 87 different disease and is accessible through http://mutview.dmb.med. keio.ac.jp.

Databases, Factual↗

PubMed2001

Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy.

In this study, we used genetically modified bone marrow-derived CD11b(+)CD18(+) vehicle cells to deliver IL-1 receptor antagonist (IL-1ra) for treatment of inflamed renal interstitium in an animal model of unilateral ureteral obstruction (UUO). Vehicle cells that expressed the ICAM-1 ligands, CD11b and CD18, were obtained from bone marrow cells of DBA/2j mice and adenovirally transduced with the IL-1ra gene or glucocerebrosidase (GC) gene ex vivo. In kidneys treated to develop UUO, levels of ICAM-1, IL-1 beta, and IL-1R expression increased within 3 days compared with contralateral untreated kidneys in the same mice. Similarly, the macrophage infiltration in the cortical interstitium increased after 3 days in UUO kidneys, but not untreated kidneys. After UUO developed, DBA/2j mice were injected i.v. with either IL-1ra(+) vehicle cells (IL-1ra-treated mice) or GC(+) vehicle cells (GC-treated mice) at 24 h after UUO. Six days after the injection of these vehicle cells, marked increase of CD11b(+) IL-1ra(+) vehicle cells was observed in the ICAM-1-positive interstitium of UUO kidneys from IL-1ra-treated mice. In contrast, no CD11b(+) IL-1ra(+) cells appeared in ICAM-1-negative contralateral kidneys from these mice. Furthermore, the infiltration of macrophages (p < 0.001), expression of ICAM-1 (p < 0.005), and presence of alpha-smooth muscle actin (p = 0.005) in the interstitium of UUO kidneys were significantly decreased in IL-1ra-treated mice compared with GC-treated mice. These findings suggest that IL-1 may contribute to the development of renal interstitial injury and that our method can deliver a functioning gene encoding an antiinflammatory cytokine gene specifically at that site by interacting with local adhesion molecules.

Animals↗

PubMed2001

Satisfactory remission in a case of IgD myeloma: effectiveness of glucocorticoid treatment.

IgD myeloma is an infrequent type of multiple myeloma and is characterized by an aggressive clinical behavior and a short survival time. No satisfactory treatments have thus far been established. Recently we treated a patient with IgD(lambda)-type myeloma with glucocorticoids, and succeeded in achieving a complete remission. This case seems to indicate a usefulness of glucocorticoid monotherapy for treating IgD myeloma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Serum cystatin C may predict the prognostic stages of patients with IgA nephropathy prior to renal biopsy.

The relationship between the levels of serum cystatin C and the prognostic stages of IgA nephropathy was determined in a multicenter trial in Japan. The levels of serum cystatin C in patients with IgA nephropathy were measured using the Dade Behring N Latex Cystain C assay. In 1995, the Joint Committee of the Special Study Group on Progressive Glomerular Diseases, Ministry of Health and Welfare of Japan, and the Japanese Society of Nephropathy reported four prognostic stages. These are: good prognosis group (Group I), relatively good prognosis group (Group II), relatively poor prognosis group (Group III), and poor prognosis group (Group IV), for this disease. Three-hundred and six patients with IgA nephropathy and other glomerular diseases were examined. There were no significant changes in the levels of serum creatinine (Cr) or creatinine clearance (CCr) between Group I and Group II. The mean levels of serum cystatin C in Group II were significantly higher than those in Group I (P < 0.05). The mean levels of serum cystatin C in Group III or IV were significantly higher than those in Group I (P < 0.001, P < 0.005, respectively). These suggest that the measurement of serum cystatin C may predict the prognostic stages of patients with IgA nephropathy prior to renal biopsy.

Adult↗

PubMed2001

Low levels of productive HIV infection in Langerhans cell-like dendritic cells differentiated in the presence of TGF-beta1 and increased viral replication with CD40 ligand-induced maturation.

Langerhans cells (LC) represent dendritic cells (DC) within mucosal epithelium that are purported initial targets for HIV following sexual exposure to virus. Here, morphologic, phenotypic, functional and HIV infection experiments were performed using monocyte-derived DC cultured in the presence of GM-CSF, IL-4 and TGF-beta1 (G4T-DC), GM-CSF and IL-4 (G4-DC), and G4T-DC incubated for an additional 3 days with CD40 ligand (CD40L-DC). G4T-DC, which demonstrated characteristics of immature LC, could be productively infected by either R5- or X4-HIV strains. Infection levels, however, were markedly lower than those observed in immature G4-DC. Surprisingly, CD40L-DC, which demonstrated features of mature LC, could be productively infected with HIV at higher levels than immature G4T-DC. Productive HIV infection in these three DC populations correlated positively with cell surface expression of CD4, CCR5 and CXCR4. We suggest that low levels of HIV infection in LC-like G4T-DC indicate an inefficient mechanism by which HIV can initially infect individuals, perhaps explaining the relative difficulty in becoming infected during sexual exposure to virus. In addition, enhanced HIV infection in LC-like G4T-DC following CD40L treatment suggests a mechanism by which inflammatory CD40L(+) T cells, if present in mucosal tissue, could lead to increased HIV transmission rates.

Adult↗

PubMed2001

Abundance of unconventional CD8(+) natural killer T cells in the large intestine.

Natural killer T (NKT) cells are mainly present in the liver and thymus, and the majority of these T cells express either a CD4(+) or a double-negative (DN) CD4(-)8(-) phenotype. In the present study, we examined whether such NKT cells were present in the intestine. NKT cells were rare in all sites of the small intestine, including an intraepithelial site. However, a considerable number of NKT cells were found at an intraepithelial site in the large intestine. This result was confirmed by both immunofluorescence and immunohistochemistry. In contrast to conventional NKT cells, NKT cells in the large intestine were CD8(+) or DN CD4(-)8(-). In the case of conventional NKT cells, their existence is known to depend on non-classical MHC class I-like antigens (i. e. CD1d) but not on classical MHC class I antigens. However, the NKT cells in the large intestine were independent of the presence of both CD1d and classical MHC class I antigens. These results were obtained using knockout mice lacking the corresponding genes and molecules. NKT cells in the large intestine were mainly alpha betaTCR(+) (> 75 %) but did not use an invariant chain of Valpha14Jalpha281, which is preferentially used by conventional NKT cells. These NKT cells did not bias the TCR-Vbeta usage toward Vbeta8. These findings suggest that the large intestine is a site in which unconventional NKT cells carrying the CD8(+) phenotype (or DN CD4(-)8(-)) are abundant and that these cells are independent of MHC and MHC-like antigens.

Animals↗

PubMed2001

Mitotic index and ki-67 nuclear antigen labeling index as predictors of chemotherapy response in uterine cervical carcinoma.

OBJECTIVE: The aim of this study was to determine if the mitotic index (MI) and the Ki-67 nuclear antigen labeling index (Ki67LI) obtained from biopsy specimens could be used as predictors of chemotherapy response in uterine cervical carcinomas. METHODS: Six patients with squamous cell carcinoma who received neoadjuvant chemotherapy before radical surgery were entered into the study. The MI and the Ki67LI were evaluated using hematoxylin and eosin (H&E)-stained and immunostained slides before and after chemotherapy. Tumor size was measured three-dimensionally by magnetic resonance imaging. We compared the values of MI and Ki67LI with changes in tumor size. RESULTS: The cases were classified according to the percentage reduction in tumor mass: one case showed a marked response (98%), four showed a moderate response (53-78%), and one showed a slight response (approximately 0%). In the case with a marked response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 15, 2, and 0, respectively. The corresponding Ki67LI values were 51, 16, and 0, respectively. In the moderate response cases, the corresponding MI values before and 3 and 7 days after chemotherapy were 3.9-13.6, 0.8-1.6, and 1.6-4.0, respectively. The Ki67LI was 21.8-44.2 before chemotherapy, with two cases increasing and two decreasing at 7 days after chemotherapy. In the case showing a slight response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 0.5, 0.8, and 1.0, respectively. The Ki67LI was 4.0 before chemotherapy and increased slightly to 6.0 at 7 days after chemotherapy. CONCLUSIONS: In six cases examined, high MI and Ki67LI values before chemotherapy and a marked decrease in MI shortly after chemotherapy appeared to be predictors of good neoadjuvant chemotherapy response in uterine cervical carcinomas.

Adult↗

PubMed2001

Risk factors for sudden unexpected death among workers: a nested case-control study in central Japan.

UNLABELLED: BACKGROUND; Few studies have focused on sudden death among apparently healthy workers, and the risk factors have not been fully discussed. METHODS: A nested case-control study was conducted among 164,017 male employees receiving annual medical checkups in Japan. Most recent medical checkup data of 242 sudden death victims (mean age, 48.0 years) were compared with corresponding data of 505 age-, workplace-, and job-type-matched male controls. Odds ratios (ORs) and their 95% confidence intervals (CIs) for each variable were calculated by logistic regression. RESULTS: OR (95% CI) significantly increased with advancing blood pressure, reaching 6.6 (3.4-13.1) for systolic blood pressure > or =160 mm Hg relative to that <120 mm Hg. Hypo-HDL-cholesterolemia, hyperuricemia, increased aminotransferases, and abnormal urinary findings were associated with the risk in a dose-dependent manner. The presence of arrhythmias and ST-T abnormalities as well as abnormal Q waves on electrocardiograms yielded a 3.5 to 4.8 times greater risk of sudden death. As for lifestyles, heavy smoking was a positive, and light drinking was a negative risk factor. Multivariate analysis revealed that hypertension, proteinuria, glucosuria, arrhythmias, ST-T abnormalities, and light drinking were independent predictors for sudden death. CONCLUSION: These findings suggest that periodic medical checkups can help to predict and prevent employee sudden death.

Blood Pressure↗

PubMed2001

Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome.

The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.

Aged↗

PubMed2001

Cerebral abnormalities in lumbosacral neural tube closure defect: MR imaging evaluation.

OBJECTS: It was decided that patients with caudal neural tube closure defect should be evaluated by means of cranial MR scans, with special attention devoted to cerebral malformations other than craniospinal abnormalities. METHODS: Twenty-four patients with lumbosacral neural tube closure defects, classified into myeloschisis (MS, 9 cases), meningo(myelo)cele (MMC, 10 cases) and spina bifida occulta with lumbosacral lipoma (LL, 5 cases), were evaluated in this way, and cerebral anomalies were found to be present in all MS patients, 8 with MMC and 2 with LL. The cerebral hemispheres were mildly to moderately hypoplastic in 6 patients, and hydrocephalus was present in 6 patients with MS and in 5 with MMC; LL was not associated with ventriculomegaly in any patient. Polymicrogyria was present in 6 patients with MS, in 3 with MMC, and in none of those with LL. Heterotopic gray matter was observed in only 2 patients with MS. Partial agenesis of the corpus callosum was found in 6 MS patients and in 6 patients with MMC, but was not seen in patients with LL. Cervicomedullary anomalies, such as herniation of the cerebellar tonsils through the foramen magnum, were found in 7 patients with MS, in 4 with MMC and in 2 with LL. While patients with LL were accompanied by only mild forebrain anomalies, cerebral abnormalities in MS and MMC were generally more severe in degree than those in LL. Among 21 patients in whom intellectual and performance status was evaluated, 9 of the 17 patients with cerebral anomalies had some degree of retardation, and the 4 without cerebral anomalies were normal. CONCLUSIONS: Caudal neural tube closure defect is not a single developmental abnormality, and can be regarded as one part of the spectrum of malformations causing primary insults that are as yet unidentified to the developing central nervous system.

Adolescent↗

PubMed2001

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy.

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32 +/- 1.42 versus 0.75 +/- 0.78 g/day; P = 0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45 +/- 1.50 versus 0.63 +/- 0.56 g/day; P = 0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children.

Adolescent↗