Biomedical subjects

T Hayashi

Publications and source records attributed to T Hayashi.

At least 199 records · Page 11Linked to original sources

PubMed2001

NF-kappaB activation in peripheral blood monocytes/macrophages and T cells during acute Kawasaki disease.

Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis, and the levels of many proinflammatory cytokines are elevated in the serum at the acute stage. We investigated the activation of transcription factor NF-kappaB for genes that encode the proinflammatory cytokines in CD14+ monocytes/macrophages and CD3+ T cells in peripheral blood by means of Western blot and flow cytometric analyses. Western blot analysis demonstrated that NF-kappaB activation was more increased in CD14+ monocytes/macrophages than in CD3+ T cells in all children during the acute stage. Flow cytometric analysis revealed that NF-kappaB activation in CD14+ monocytes/macrophages was significantly higher than in CD3+ T cells at the acute stage (30.0 +/- 16.0% vs 11.4 +/- 5.0%, P < 0.01, Wilcoxon test). NF-kappaB activation in CD14+ monocytes/macrophages was significantly decreased after high-dose intravenous immunoglobulin therapy (P < 0.05). The present findings suggest that CD14+ monocytes/macrophages play an important role in cytokine production during acute KD.

Acute Disease↗

PubMed2001

Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats.

Exogenous application of transforming growth factors-beta (TGF beta) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGF beta trophic factors, we transplanted these tissues directly into the substantia nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K(+)-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K(+)-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors.

Age Factors↗

PubMed2001

Specific protein-DNA and protein-protein interaction in the hig gene system, a plasmid-borne proteic killer gene system of plasmid Rts1.

The hig (host inhibition of growth) gene system of plasmid Rts1 belongs to the plasmid-encoded proteic killer gene family. Among the proteic killer genes described so far, hig is unique in that the toxin gene (higB) exists upstream of the antidote gene (higA). There are two promoters in the hig locus, Phig and PhigA, and only the former, which expresses both higB and higA genes, is negatively controlled by HigA and HigB proteins. In this study, we purified HigA protein by means of GST fusion. The electrophoretic mobility shift assay using the purified protein revealed that HigA specifically bound to the Phig region, but not to PhigA. The HigA-binding sequence was determined by DNase I footprinting assay to be a 56-bp sequence that completely covered the -35 and -10 boxes of Phig. The presence of two inverted repeats in the binding sequence and the identification of a dimer form of HigA by cross-linking experiment suggested that the protein bound to the Phig region as a dimer. HigB was purified as a GST fusion protein as well, though it was achieved only in the presence of HigA. HigA and GST-HigB formed a highly stable complex where the two proteins were present in an equimolar ratio.

Amino Acid Sequence↗

PubMed2001

A case of basal cell carcinoma of the nipple and areola with intraductal spread.

We report an 82-year-old Japanese woman with basal cell carcinoma of the left nipple and areola extending into the lactiferous duct. The patient developed a small papular lesion of the left areola about 1 year before admission. The lesion, which had slowly progressed to involve the nipple, had become symptomatic showing weeping and bleeding. Mammography revealed microcalcification in the nipple. Although Paget's disease was suspected from these clinical features, histologically basal cell carcinoma was diagnosed. There was no axillary lymphadenopathy, and no evidence of distant metastasis. The lesion of the nipple and areola was resected with a 2 cm free margin along with the underlying mammary tissue. The patient has remained well without signs of recurrence for 2 years after surgery. We reviewed cases of basal cell carcinoma of the nipple or areola and discuss considerations and problems of this rare tumor.

Aged↗

PubMed2001

Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470.

BACKGROUND: To prevent tumor metastasis, we administered the cell-binding domain of fibronectin, in combination with the angiogenesis inhibitor TNP-470, to mice with hepatic metastasis. We then assessed the prevention of tumor metastasis resulting from the inhibition of adhesive interactions and the inhibition of angiogenesis. METHODS: A hepatic metastasis model was created by injecting 1 x 10(3) colon 26/TC-1 cells into the anterior mesenteric vein of CDF1 mice. The cell-binding domain obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. A fibronectin-binding domain (FND)-treated group, an FND plus TNP-470 group, and a control group were established. The animals were killed 4 weeks after the injections of the treatment agents had been completed and the number of metastatic liver nodules was counted. In a simultaneous experiment with the same design, the mice were not killed at 4 weeks, and their survival was observed. RESULTS: The mean number of nodules in the FND plus TNP-470 group was significantly lower than that in the control group (P = 0.019337). The inhibition rate was 51% in the FND group, 60% in the FND 10 micrograms plus TNP-470 10 mg/kg group, and 64% in the FND 10 micrograms plus TNP-470 100 mg/kg group compared with the control group. Mice from the FND group that were not killed died after 6-8 weeks, but mice from the FND plus TNP-470 group died after 8-12 weeks. CONCLUSION: The cell-binding domain of fibronectin may, potentially, be an effective form of antiadhesive therapy that competes with native adhesion molecules and blocks adhesion during the metastatic process. When the cell-binding domain of fibronectin is combined with TNP-470 to inhibit angiogenesis, more effective inhibition of metastatic tumor growth and prolongation of survival can be achieved than after treatment with the cell-binding domain alone.

Angiogenesis Inhibitors↗

PubMed2001

Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells.

Previous studies demonstrated that theophylline modulates NF-kappaB activation in mast cells and pulmonary epithelial cells. We examined whether or not this modulation of NF-kappaB activation by theophylline is due to inhibition of the degradation of the IKBalpha protein, which suppresses NF-kappaB activation. TNF-alpha-induced NF-kappaB activation in a human pulmonary epithelial cell line (A549) was evaluated by Western blotting and a chloramphenicol acetyltransferase (CAT) assay. Expression of the IkappaBalpha protein was evaluated by Western blotting. Western blotting of nuclear extracts of A549 cells demonstrated that theophylline suppresses NF-kappaB-p65 nuclear translocation. The CAT assay indicated that NF-kappaB-dependent reporter gene expression is inhibited in A549 cells pretreated with theophylline. Western blotting of cytoplasmic extracts of A549 cells revealed that this inhibition was linked to theophylline-induced protection of expression of the IkappaBalpha protein. Moreover, theophylline inhibited interleukin-6 production induced by TNF-alpha in A549 cells. These findings are consistent with the idea that theophylline suppresses the production of proinflammatory cytokines via inhibition of NF-kappaB activation through protection of the IkappaBalpha protein.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Characterization of the amyR gene encoding a transcriptional activator for the amylase genes in Aspergillus nidulans.

The Aspergillus nidulans amyR gene and its cDNA were cloned and sequenced. The genomic gene comprised 2,092 bp, interrupted by two short introns, and encoded a cys-6 zinc transcriptional activator (AMYR) of 662 amino acid residues with a calculated molecular mass of 72,862 Da. Disruption of the amyR gene caused defects in the utilization of maltose and starch and abolished expression of the taaG2 gene encoding A. oryzae Taka-amylase A, which is inducibly and abundantly expressed in the wild-type A. nidulans. Expression of the amyR gene was under the control of the carbon catabolite repressor, CREA. The growth defect of the malA1 mutant on maltose was complemented by the amyR gene; and the amyR gene derived from the mutant possessed a single mutation, from A to T, at position 1,483, resulting in a substitution of His478 to Leu. These results indicate that the amyR gene is identical to the genetically defined malA gene. AMYR possessed five domains (Zn and MH1-MH4) homologous to Mal63p, a transcriptional activator for the genes involved in maltose utilization in Saccharomyces cerevisiae. The His478 to Leu substitution lay within the MH3 domain, corresponding to the negative regulatory domain of Mal63p which relieves the inhibitory effect on the activation function in response to maltose.

Amino Acid Sequence↗

PubMed2001

Characterization of a SINE species from vicuna and its distribution in animal species including the family Camelidae.

Twenty-six sequences of a short interspersed repetitive element (SINE) with a size of approximately 150 base pairs (bp) were isolated from the genomic DNA of Vicugna vicugna (vicuna). RNA polymerase III split promoter sequence was observed in most of them, and many had direct repeats flanking to SINEs as well as a poly(A)-like structure. The SINE sequences were designated as "vic-1" sequences. Comparison of the vic-1 consensus sequence with sequences registered in the DNA database (DDBJ/ EMBL/GENBANK) revealed that the vic-1 sequence had a 79% homology with mouse ala-tRNA gene. In addition, the tRNA-related region of the consensus sequence was folded into a cloverleaf structure as with mouse ala-tRNA. These findings strongly indicated that vic-1 was a retroposon derived from ala-tRNA gene. The vic-1 sequences were used as a probe for dot-blot hybridization to examine the distribution of their homologous sequences in the genomes of various animal species spanning 14 orders, of which, homologous sequences were found only in the Camelidae family. In order to examine the phylogenetical relationship among vicuna, llama, and camel, vic-1 insertion analysis and homology analysis of vic-1 sequences were performed at each locus. The analyses indicated that vic-1 sequences were generated in a common ancestor of the animal species, and that camels first branched off from the clade Camelidae, followed by vicunas and llamas.

Animals↗

PubMed2001

Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia.

We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects.

Anemia, Aplastic↗

PubMed2001

Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case.

We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP.

Adenocarcinoma↗

PubMed2001

Ruptured aneurysm of the visceral artery: report of two cases.

We present herein two cases of a ruptured aneurysm of the visceral artery. The first case involved a 74-year-old man with abdominal pain who was admitted to our hospital with a tentative diagnosis of intra-abdominal bleeding of unknown origin. Computed tomography revealed a hematoma in the greater curvature of the stomach. At surgery, a hematoma along the right gastroepiploic artery was found and totally removed. Histological examination showed a pseudo-aneurysm of unknown etiology. The second case involved a 68-year-old man with progressive anemia who presented with spontaneous intra-abdominal bleeding. A ruptured aneurysm of the accessory middle colic artery was diagnosed by superior mesenteric angiography. The ruptured aneurysm was ligated and totally resected without a colectomy. Histological examination showed a pseudoaneurysm of unknown etiology. The postoperative courses were uneventful, and both patients were doing well at the time of writing.

Abdomen, Acute↗

PubMed2001

Magnetic resonance imaging findings in schizophrenia and atypical psychoses.

The differences among MRI findings were studied in schizophrenic psychoses. The schizophrenics and atypical psychotics had significant reductions in bilateral hippocampal volumes compared to controls, but the two patient groups did not differ from each other. As for ventricle volume, the schizophrenics showed significantly larger temporal horns and third ventricle than normal controls, whereas atypical psychotics did not. Moreover, the left temporal horn in the schizophrenics was significantly larger than that seen in the atypical psychotics. By cluster analysis, schizophrenics and atypical psychotics were found to have a tendency to be distributed in different groups. These results might be considered to support the classification of schizophrenic psychoses into schizophrenia and atypical psychoses.

Adult↗

PubMed2001

A HMG-CoA reductase inhibitor possesses a potent anti-atherosclerotic effect other than serum lipid lowering effects--the relevance of endothelial nitric oxide synthase and superoxide anion scavenging action.

We have determined whether the anti-atherosclerotic effect of a 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor (fluvastatin) is mediated through nitric oxide (NO) as well as affecting plasma lipids. NO related vascular responses, endothelial nitric oxide synthase (eNOS) mRNA and superoxide anion (O(2)(-)) release were examined in vascular walls of oophorectomized female rabbits fed 0.5% cholesterol chow for 12 weeks with or without fluvastatin (2 mg/kg per day). Serum lipid profile was not different between two groups. NO dependent responses stimulated by acetylcholine and calcium ionophore A23187 and tone related basal NO response induced by N(G)-monomethyl-L-arginine acetate (L-NMA); nitric oxide synthase inhibitor were all improved by fluvastatin treatment. Endothelium independent vasorelaxation induced by nitroglycerin was not different between the two groups of rabbits' arteries. Fluvastatin treatment increased cyclic GMP concentration in aorta of rabbits. eNOS mRNA expression and O(2)(-) release were measured in aorta using competitive reverse transcription-polymerase chain reaction (RT-PCR) and with lucigenin analogue, 2-methyl-3,7-dihydroimidazol [1,2-a]pyrazine-3-one (MCLA) chemiluminescence methods. eNOS mRNA in the endothelial cells of aorta was significantly up-regulated and O(2)(-) production was significantly reduced in fluvastatin treated rabbit aorta. Anti-macrophage staining area, but not anti-smooth muscle cell derived actin stained area in the aorta was also reduced by fluvastatin treatment. Conclusion, fluvastatin, a HMG-CoA reductase inhibitor, retards the initiation of atherosclerosis formation through the improvement of NO bioavailability by both up-regulation of eNOS mRNA and decrease of O(2)(-) production in vascular endothelial cells, and this means that part of the anti-atherosclerotic effect of fluvastatin may be due to nonlipid factors.

Acetylcholine↗

PubMed2001

Suppression of spermatogenesis in ipsilateral and contralateral testicular tissues in patients with seminoma by human chorionic gonadotropin beta subunit.

OBJECTIVES: The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. METHODS: Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen's score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. RESULTS: A significant linear relationship (r = -0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. CONCLUSIONS: A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.

Adult↗

PubMed2001

Predictive values of acute phase reactants, basic fetoprotein, and immunosuppressive acidic protein for staging and survival in renal cell carcinoma.

OBJECTIVES: To determine the clinical significance and predictive value of three acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, and ferritin), as well as basic fetoprotein (BFP) and immunosuppressive acidic protein, in patients with renal cell carcinoma. METHODS: Erythrocyte sedimentation rate, C-reactive protein, ferritin, BFP, and immunosuppressive acidic protein levels were measured in 92 patients with renal cell carcinoma diagnosed in 1989 to 1999. The levels were compared with the clinical stage and nuclear grade, and their predictive values of survival were evaluated statistically. RESULTS: All markers, with the exception of BFP, correlated with each other and with the clinical stage and nuclear grade. BFP did not correlate with the acute phase reactants. The log-rank test revealed that the levels of C-reactive protein, immunosuppressive acidic protein, and ferritin significantly influenced survival. Multivariate stepwise analysis identified ferritin as the only independent and significant prognostic marker (hazard ratio = 5.624, P = 0.001). However, when age, sex, clinical stage, and nuclear grade were entered into the same analysis, only clinical stage was an independent marker of prognosis. CONCLUSIONS: The results of our study demonstrated that serum ferritin is the most useful marker among five tested factors for staging and predicting survival, although the clinical stage is the best parameter that predicts the prognosis of patients with renal cell carcinoma accurately.

Adult↗

PubMed2001

Successful treatment of metastatic adenocarcinoma of the urachus: report of 2 cases with more than 10-year survival.

Metastatic urachal cancer is often considered lethal. We report 2 cases of metastatic urachal carcinoma successfully treated with surgical excision followed by combinations of surgery, radiation, and chemotherapy against local recurrence and/or distant metastases, with a recurrence-free survival period of more than 10 years. These cases provide support for multimodal treatments of metastatic urachal cancer.

Adenocarcinoma↗

PubMed2001

Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors.

Cytoskeletal proteins are important in protein trafficking, membrane protein clustering, dendrite growth and the morphological maintenance of neurons. Sigma(1) receptors are unique endoplasmic reticular (ER) proteins that bind (+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Cocaine, via sigma(1) receptors, can cause the dissociation of a cytoskeletal adaptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] receptors on the ER as a sigma(1)-receptor-ankyrin complex, which then translocates to the plasma membrane and nucleus. The dissociation of sigma(1)-receptor-ankyrin from Ins(1,4,5)P(3) receptors also increases the intracellular Ca(2+) concentration [[Ca(2+)](i)], which affects the activity of cytoskeletal proteins. Furthermore, cocaine might increase [Ca(2+)](i) via phospholipase C (PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause life-long changes in neurons via cytoskeletal proteins by interacting with both D1 receptors and sigma(1) receptors.

Animals↗

PubMed2001

Pulmonary artery reflection for differentially diagnosing primary pulmonary hypertension and chronic pulmonary thromboembolism.

OBJECTIVES: The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by means of the indexes of pulmonary arterial reflection. BACKGROUND: These differences in the primary lesions would make pulmonary artery reflection occur earlier in CPTE than in PPH. Although the analysis of pulsatility of pulmonary arterial pressure is useful in the differential diagnosis of PPH and CPTE, it is not known whether the analysis of pulmonary artery reflection can differentiate CPTE from PPH. METHODS: Since CPTE predominantly involves the proximal arteries, whereas PPH involve the peripheral arteries, we hypothesized that patients with CPTE have a large augmentation index and a short inflection time. For this study, we enrolled 62 patients who had CPTE (31 patients) and PPH (31 patients). We measured pulmonary arterial pressure using a fluid filled system that included a balloon-tipped flow directed catheter. To quantify the pulmonary artery reflection, we used the augmentation index and inflection time. RESULTS: The augmentation index was markedly higher in CPTE than it was in PPH (27.4% +/- 15.2% [SD] and -25.1% +/- 26.9%, respectively, p < 0.001) and was diagnostic in separating the two groups. Inflection time separated the two groups reasonably well (97 +/- 20 ms and 210 +/- 49 ms, respectively, p < 0.001). CONCLUSIONS: The analysis of pulmonary arterial reflection is useful in the differential diagnosis of CPTE and PPH.

Adult↗