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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 73 records · Page 4Linked to original sources
PubMed2001

Inverse correlation of thioredoxin expression with estrogen receptor- and p53-dependent tumor growth in breast cancer tissues.

Estrogen receptor (ER) and p53 are important transcription factors in the growth regulation of tumor cells in breast cancer. We reported previously that thioredoxin (TRX) regulates the DNA binding activities of ER and p53 in vitro. The expression of pS-2, a trefoil factor, is also correlated with that of ER. To clarify the regulation mechanism of tumor growth in breast cancer, here we investigated the expression of TRX, ER, pS-2, and p53 and the mitotic index (MI) in 147 breast cancer tissues using immunohistochemical analysis. Of 123 TRX+ cases, ER+ cases (n = 62) showed a higher pS-2 score and lower MI than did ER- cases (n = 61). Furthermore, p53- cases (no mutation in p53; n = 76) also showed a lower MI than did p53+ cases (n = 47). There was no significant correlation between pS-2 and ER, MI and ER, or p53 and MI in the TRX- group. Among the ER+ and p53- cases (ER+/p53- group; n = 61), MI was lower in the TRX+ group (n = 46) than in the TRX- group (n = 15). However, in all other groups (n = 86) with abnormalities in the immunohistochemical expression of either p53 or ER, there was no significant correlation between MI and TRX expression. In the TRX+ and ER +/p53- group (n = 46), histological grading was lower than that in all other groups (n = 101). These findings suggest that TRX expression is linked to the ER- and p53-dependent regulation of tumor growth in breast cancer. In addition, TRX expression in ER+ and p53 intact (wild-type p53+) groups may mean better prognosis than in other conditions.

Adult↗
PubMed2001

Outcome of acute otitis media and its relation to clinical features and nasopharyngeal colonization at the time of diagnosis.

Children (n = 115; age range 1-9 years) with a diagnosis of acute otitis media (AOM) were eligible for this study and were enrolled within 24 h of the onset of symptoms/signs. A nasopharyngeal culture was obtained at the initial visit. Children were treated with a single oral antibiotic for 7 days. Changes in symptoms/signs and tympanic membrane features assessed by a scoring system were monitored for 1 month and related to the nasopharyngeal pathogen recovered on Day 1. More than 80% of children had no symptoms/signs by Day 3, and 60% of cases had normal tympanic membranes by Day 29. Children without any symptoms/signs on Day 3 had significantly lower symptom/sign scores on Day 1 (p = 0.005). Seventy-nine percent of cases carried middle ear pathogens in the nasopharynx at diagnosis: Streptococcus pneumoniae (48%); Haemophilus influenzae (24%); and Moraxella catarrhalis (16%). Children with S. pneumoniae showed significantly higher tympanic membrane scores than children with no pathogen at Days 8, 15 and 29 (p < 0.01 for each comparison). Multivariate regression analysis revealed that lower tympanic membrane score on Day 1, the absence of S. pneumoniae in the nasopharynx and treatment with amoxillin were independent factors for rapid normalization of the tympanic membrane. These data suggest that the clinical course of AOM may be predicted, in part, at the time of diagnosis by means of careful evaluation of symptoms/signs and the tympanic membrane as well as knowledge of pathogens harbored in the nasopharynx.

Acoustic Impedance Tests↗
PubMed2000

Regulation of early chicken thymocyte proliferation by transforming growth factor-beta from thymic stromal cells and thymocytes.

We examined expression of TGF-betas in chicken thymic stromal cells and thymocytes and roles of TGF-betas in thymocyte development within the thymus. Thymic stromal cells expressed TGF-beta 2 and 3 genes but not TGF-beta 4 gene. Thymocytes showed expressions of TGF-beta 2, 3 and 4 genes and each TGF-beta gene was expressed more strongly in CD3- than CD3+ thymocytes. When anti-TGF-beta antibody was added with supernatants of stromal cells into thymocyte culture, only proliferative activity of CD3- thymocytes was enhanced and the cells in S and G2/M compartments of cell cycle increased. These results suggest that TGF-beta which is expressed in the thymus may regulate the ability of immature thymocytes to progress through the cell cycle and to differentiate to CD3+ thymocytes.

Animals↗
PubMed2000

Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas.

Breast cancer is one of the most common malignancies among women. The molecular mechanisms involved in breast carcinogenesis, however, remain to be elucidated. Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res., 5:1249-1261, 1999), indicating its possible involvement even in sporadic breast carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain 1) and p53, all of which are involved in DNA repair. We have analyzed the expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e., BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two (35%) exhibited p53 overexpression. On the other hand, reduced expression level of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair pathway and are involved in colorectal carcinogenesis, was observed respectively in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic breast carcinomas with abnormal expression of either BRCA1 or the BRCA1-interactive proteins was 67% (76/113). These results indicate that there may be an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1-associated breast carcinomas, but also in sporadic breast carcinomas.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes.

This study was designed to investigate whether angiotensin II induces the interleukin (IL)-6 family of cytokines in cardiac fibroblasts and, if so, whether these cytokines can augment cardiac hypertrophy. Angiotensin II increased IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 mRNA by 6.5-, 10.2-, and 2.0-fold, respectively, but did not affect IL-11, ciliary neurotrophic factor, or oncostatin M in cardiac fibroblasts. Enzyme-linked immunosorbent assay revealed that angiotensin II-stimulated conditioned medium from cardiac fibroblasts contained 9.3 ng/ml IL-6 at 24 h, which was 24-fold higher than the control. It phosphorylated gp130 and STAT3 in cardiomyocytes, which was reduced with RX435 (anti-gp130 blocking antibody). It increased [(3)H]phenylalanine uptake and cell area by 44% and 86% in cardiomyocytes compared with mock medium. RX435 suppressed these increases by 26% and 38%, while TAK044 (endothelin-A/B-R blocker) suppressed them by 52% and 52%, respectively. Antisense oligonucleotides against LIF and cardiotrophin-1 blocked their up-regulation, and attenuated the conditioned medium-induced increase in [(3)H]phenylalanine uptake by 21% and 13%, respectively. The combination of antisense oligonucleotides to LIF and cardiotrophin-1 decreased their uptake by 33%. These results indicated that angiotensin II induced IL-6, LIF, and cardiotrophin-1 in cardiac fibroblasts, and that these cytokines, particularly LIF and cardiotrophin-1, activated gp130-linked signaling and contributed to angiotensin II-induced cardiomyocyte hypertrophy.

Angiotensin II↗
PubMed2000

Functional Fv fragment of an antibody specific for CD28: Fv-mediated co-stimulation of T cells.

The most predominant co-stimulation pathway, which is critical for T cell activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal antibody (mAb) also provides a co-stimulatory signal to T cells. In order to construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28 antibody using a bacterial expression system, cDNA encoding the variable regions of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in Escherichia coli. The Fv fragment was obtained as a soluble protein from the periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv fragment induced proliferation of peripheral blood mononuclear cells in the presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti-MUC1x(anti)-CD3 bispecific antibody when tested with lymphokine-activated killer cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising not only for the study of co-stimulation, but also for cancer immunotherapy.

Amino Acid Sequence↗
PubMed2000

Possible involvement of protein phosphorylation in the wound-responsive expression of Arabidopsis plastid omega-3 fatty acid desaturase gene.

The plastid omega-3 fatty acid desaturase (FAD7) catalyzes the conversion of linoleic acid to linolenic acid. Wounding enhances the expression of the FAD7 gene in leaves and induces its expression in stems and roots. The wound-induced expression of the FAD7 promoter was investigated in transgenic tobacco plants carrying the -825 Arabidopsis FAD7 promoter::beta-glucuronidase (GUS) fusion gene. The protein kinase inhibitor, staurosporine, and the protein phosphatase inhibitor, calyculin A, suppressed the wound induction of the FAD7 gene in stems. A tobacco mitogen-activated protein kinase (WIPK) was rapidly activated upon wounding not only in leaves but also in stems and roots, indicating that WIPK probably mediates the wound signals in most vegetative organs. The FAD7 promoter::GUS fusion gene was introduced into the transgenic tobacco plants in which the wipk gene was expressed constitutively at a high level or into the transgenic plants in which the wipk gene was suppressed possibly due to the transgene-induced gene silencing. The wound-induced expression of the FAD7 gene in stems was enhanced in the former transgenic tobacco plants and suppressed in the latter plants. These results suggest that the wound activation of the FAD7 promoter depends on both protein phosphorylation and dephosphorylation events especially in stems, and also that WIPK is involved in such signaling cascades.

Journal Article↗
PubMed2000

Activation of NADPH oxidase in Alzheimer's disease brains.

The present study is the first to show that superoxide (O(-)(2)) forming NADPH oxidase is activated in Alzheimer's disease (AD) brains by demonstrating the marked translocation of the cytosolic factors p47-phox and p67-phox to the membrane. In conjunction with a recent in vitro study showing that amyloid beta activates O(-)(2) forming NADPH oxidase in microglia, where these phox proteins are localized in this study, the present results suggest that, in AD, NADPH oxidase is activated in microglia, resulting in the formation of reactive oxygen species which can be toxic to neighboring neurons in AD.

Aged↗
PubMed2000

Girl with accelerated growth, hearing loss, inner ear anomalies, delayed myelination of the brain, and del(22)(q13.1q13.2).

We report on an 18-month-old Japanese girl with 46,XX,del(22)(q13.1q13.2). To our knowledge, this is the first report of a case of interstitial deletion of a 22q13.1-q13.2 segment. Clinical features included hearing loss accompanied by inner ear anomalies, hypotonia and minor anomalies, such as a long philtrum, full eyelids, epicanthus, left transverse palmar crease and psychomotor developmental delay. Despite the chromosomal deletion, her physical growth was accelerated: her height was between the 75th and 90th percentiles for her age. Her brain MRI showed signs of delayed myelination. The three-dimensional MRI of the inner ear showed abnormalities of the cochlea and vestibule in both ears. Clinical features of the patient are similar to those of a patient with a del(22)(q13.1q13.33) karyotype previously reported by Romain et al.

Abnormalities, Multiple↗
PubMed2000

Autocrine/Paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation.

We recently reported that angiotensin II (AngII) biphasically activates the JAK/STAT pathway and induces delayed phosphorylation of STAT3 in the late stage (120 min) in cardiomyocytes. This study was designed to determine the mechanism of delayed phosphorylation of STAT3. Conditioned medium prepared from AngII-stimulated cardiomyocytes could reproduce the tyrosine phosphorylation of STAT3 at 5 min. This delayed phosphorylation was almost completely inhibited by anti-gp130 blocking antibody RX435, but not by TAK044 (ET-A/B-R antagonist), prazosin, or propranolol. AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3. AngII augmented IL-6, CT-1, and LIF mRNA expression at 30-60 min, but not CNTF expression. AngII increased IL-6 protein levels by 3-fold in the conditioned media at 2 h compared with the control. These findings indicated that AngII-induced delayed activation of STAT3 is caused by autocrine/paracrine secreted IL-6 family cytokines.

Angiotensin II↗
PubMed2000

Novel priming compounds of cystathionine metabolites on superoxide generation in human neutrophils.

Human peripheral blood polymorphonuclear leukocytes were preincubated with cystathionine and cystathionine metabolites found in the urine of patients with cystathioninuria. Among the cystathionine metabolites, cystathionine ketimine and N-acetyl-S-(3-oxo-3-carboxy-n-propyl) cysteine (NAc-OCPC) significantly enhanced the N-formylmethionylleucylphenylalanine (fMLP)-induced superoxide generation, but cystathionine, NAc-cystathionine, and cyclothionine did not enhance the superoxide generation. Cystathionine ketimine and NAc-OCPC also enhanced superoxide generation induced by opsonized zymosan (OZ) but not that induced by arachidonic acid (AA) and phorbol 12-myristate 13-acetate (PMA). Superoxide generation induced by cystathionine ketimine and NAc-OCPC was inhibited by genistein, an inhibitor of tyrosine kinase, and was enhanced by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. Cystathionine ketimine and NAc-OCPC markedly also increased phosphorylation of 45-kDa protein in human neutrophils and the phosphorylation depended on the concentrations of cystathionine ketimine and NAc-OCPC. The phosphorylation of 45-kDa protein induced by cystathionine ketimine and NAc-OCPC was inhibited by genistein and herbimycin A, inhibitors of tyrosine kinase, but was not inhibited by H-7 and staurosporine, inhibitors of protein kinase C. Cystathionine metabolites and l-cystathionine sulfoxides were separated into two diastereoisomers, CS-I and CS-II. CS-I enhanced the superoxide generation induced by AA and PMA but not that induced by fMLP and OZ. In contrast, CS-II enhanced the superoxide generation induced by fMLP and OZ, but not that induced by AA and PMA.

Amino Acids↗
PubMed2000

Trienoic fatty acids and plant tolerance of high temperature.

The chloroplast membrane of higher plants contains an unusually high concentration of trienoic fatty acids. Plants grown in colder temperatures have a higher content of trienoic fatty acids. Transgenic tobacco plants in which the gene encoding chloroplast omega-3 fatty acid desaturase, which synthesizes trienoic fatty acids, was silenced contained a lower level of trienoic fatty acids than wild-type plants and were better able to acclimate to higher temperatures.

Adaptation, Physiological↗
PubMed2000

New approach to cell lineage analysis in mammals using the Cre-loxP system.

The Cre-loxP site-specific recombination system was used for cell lineage analysis in mammals. We constructed an expression plasmid, pCETZ-17, which consists of cytomegalovirus enhancer/chicken beta-actin promoter (CAG), a portion of the rabbit beta-globin gene, loxP-flanked DNA sequence (containing enhanced green fluorescent protein (EGFP) cDNA), and lacZ gene encoding E. coli beta-galactosidase (beta-gal). When circular pCETZ-17 plasmid DNA was microinjected into the pronuclei of fertilized eggs and these eggs were allowed to develop to two-cell stage, 62.8% (59/94) of the two-cell embryos exhibited distinct fluorescence in one or both blastomeres, but never expressed lacZ protein, as evaluated by histochemical staining with X-Gal, a substrate for beta-gal. When both circular plasmids, pCETZ-17 and pCAG/NCre (containing CAG and DNA sequences encoding nuclear location signal and Cre), were co-injected into fertilized eggs, almost all (87.0%, 47/54) embryos exhibited low or no fluorescence, but 51.9% (27/52) exhibited positive staining for beta-gal activity. This indicates that transient expression of the Cre recombinase gene removed the loxP-flanked DNA sequence in pCETZ-17 and then caused expression of the downstream lacZ sequence. We next microinjected pCETZ-17 into the pronuclei of fertilized eggs, cultured these injected eggs for 1 day, and collected only two-cell embryos expressing EGFP in both blastomeres. One blastomere of the EGFP-expressing two-cell embryos was microinjected with pCAG/NCre, and these treated embryos were cultured for 1 day up to four-cell stage. When the developing four-cell embryos were subjected to staining with X-Gal, cell lineage-related staining pattern for beta-gal activity was observed in most (77.8%, 7/9) embryos. These findings were further confirmed using two-cell embryos derived from a transgenic mouse line carrying CETZ-17 transgene. Thus, our system, which is based on transient expression of the Cre recombinase gene directly introduced into nuclei of embryonic cells by microinjection, is a powerful means for cell lineage analysis in mammals.

Animals↗
PubMed2000

Cosmetic results and complications after breast conserving therapy for early breast cancer.

BACKGROUND: The cosmetic and functional results of breast conserving therapy for early breast cancer were evaluated. These are important endpoints in the assessment of breast conserving therapy in addition to tumor control and survival. The factors suspected to influence cosmesis were also analyzed. METHODS: In 206 patients with stage I and II breast cancer treated by wide excision and axillary dissection followed by radiation therapy, the cosmetic results and complications were analyzed. The cosmetic outcome was assessed by a scoring method and breast retraction assessment (BRA). As complications, arm edema and restriction of shoulder movement and late skin reactions were analyzed. RESULTS: Of the 206 patients 92% showed an excellent to good cosmetic score before radiation therapy. The score deteriorated, but gradually improved and stabilized after 1 year. Eighty-one percent of the patients had an excellent to good cosmetic score at 3 years. The BRA of the 206 patients was 1.8 cm on average before radiation therapy. It increased to 2.3 cm after termination of radiation therapy, and did not change thereafter. Tumor size over 2 cm (p = 0.005) and tumors in the inner quadrant (p = 0.003) were factors which negatively affected the cosmetic score at 3 years. Tumor size over 2 cm (p = 0.003), tumors in the upper quadrant (p = 0.005), or a nipple-tumor distance of more than 2 cm (p = 0.01) were also negative factors for the BRA at 3 years. Arm edema, restriction of shoulder movement, and late skin reaction were generally mild, and were observed in 12%, 0% and 34% of patients at 3 years, respectively. CONCLUSIONS: The overall cosmetic results of breast conserving therapy are acceptable and the complication rate is low. Tumor characteristics, tumor size, location and nipple-tumor distance are factors that affect cosmesis.

Adult↗
PubMed2000

Rapid-growing carcinosarcoma of the esophagus arising from intraepithelial squamous cell carcinoma: report of a case.

A case of carcinosarcoma arising from the intraepithelial spreading area of esophageal squamous cell carcinoma (SCC) is reported herein. A 64-year-old man was referred to our hospital for investigation of a sore throat and dysphagia. An endoscopic examination revealed a 2. 5-cm polypoid mass in the mid-esophagus. Esophagograms taken 1 month prior to consultation by our hospital and just before surgery revealed marked change within a period of less than 2 months from a 2-cm sessile elevated mass to a 4-cm polypoid mass with a lobular appearance. The resected specimen contained two lesions in the esophagus. The larger one measured 4.0 x 2.0 x 2.0 cm and had a pedunculated polypoid shape, while the smaller one, measuring 1 cm in diameter, was a plateau-type elevated lesion located 3 cm distal from the larger mass. Histologically, the distal smaller lesion was diagnosed as primary SCC associated with a high frequency of intraepithelial spread, while the larger polypoid mass was composed of spindle-shaped sarcomatous cells, arising from the intraepithelial spread of SCC. To our knowledge, this is the only reported case of esophageal carcinosarcoma arising from an area of intraepithelial spread of SCC that showed such surprisingly rapid growth.

Carcinoma in Situ↗
PubMed2000

Involvement of superoxide generated by polymorphonuclear leukocytes in endotoxin-induced uveitis.

BACKGROUND: Although superoxide is thought to be involved in the development of endotoxin-induced uveitis (EIU), the role of superoxide generation by polymorphonuclear leukocytes (PMNs) has not been fully elucidated. The purpose of this study was to investigate the role of peripheral blood PMNs in the development of EIU. METHODS: EIU was induced in Lewis rats by injection of lipopolysaccharide (LPS) in one hind footpad. Superoxide generation was assayed by measuring the reduction of ferricytochrome c (cyt c). EIU severity was assessed by histological examination, and the relationship between the injected dose of LPS in vivo and the intensity of superoxide generation by peripheral PMNs or intraocular PMNs was studied. Twenty-four hours after the injection of LPS (2, 20, or 200 microg/rat), peripheral blood PMNs were collected and stimulated with phorbol 12-myristate 13-acetate (PMA). The time course of superoxide generation by PMNs after LPS injection (3, 6, 12, 24, 48, and 72 h) was also investigated. To test the possible inhibition of superoxide generation by protein kinase C (PKC) inhibitors, H-7 and staurosporine were added for the incubation. In addition to the measurement of cyt c reduction, western blotting was used to detect PKC activity. The direct effect of LPS on PMNs was tested by priming naive PMNs with LPS in vitro. RESULTS: The intensity of superoxide generation by PMNs and the severity of EIU were dependent on the dose of injected LPS. No apparent superoxide generation was detected from intraocular PMNs. The time course of superoxide generation was similar to that of EIU severity. H-7 or staurosporine inhibited superoxide generation dose dependently and suppressed phosphorylation of PKC. Priming with LPS in vitro prompted minimal superoxide generation by naive PMNs. CONCLUSION: Superoxide generation by peripheral blood PMNs but not by intraocular PMNs from rats with EIU was demonstrated, and it is suggested that superoxide generation by PKC cascade might be involved in the pathogenesis of EIU.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association.

Wilson disease (WND) is caused by a deficiency of the copper-transporting enzyme, P-type ATPase (ATP7B). Twelve different mutations have previously been identified in Taiwan Chinese with Wilson disease. We, herein, report another 4 missense mutations, 1 of which is novel. We did haplotype analysis of Taiwanese WND chromosomes, using three well characterized short tandem repeat markers (haplotype was assigned in the order of D13S314-D13S301-D13S316). Association correlation was found between the mutations and their respective haplotypes. Haplotype-deduced pedigree analysis was shown to be helpful in the mutation analysis of WND chromosomes and in the molecular assessment of both pre-symptomatic WND patients and carriers. Given the complexity and heterogeneity of the mutation spectrum of ATP7B, we suggest that haplotype analysis should be performed before full-scale mutation analysis.

Adenosine Triphosphatases↗