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Biomedical subjects

S Takano

Publications and source records attributed to S Takano.

At least 37 records · Page 2Linked to original sources

p53-independent upregulation of p21WAF1 in NIH 3T3 cells malignantly transformed by mot-2.

Mot-2 protein is shown to interact with p53 and inhibit its transcriptional activation function. Mot-2 overexpressing stable clones of NIH 3T3 cells were malignantly transformed, however, they had a high level of expression of a p53 downstream gene, p21WAF1. The present study was undertaken to elucidate possible molecular mechanism(s) of such upregulation. An increased level of p21WAF1 expression was detected in stable transfectants although an exogenous reporter gene driven by p21WAF1 promoter exhibited lower activity in these cells suggesting that some post-transcriptional mechanism contributes to upregulation. Western analyses of transient and stable clones revealed that upregulation of p21WAF1 in stable NIH 3T3/mot-2 cells may be mediated by cyclin D1 and cdk-2.

3T3 Cells↗

Phylogenetic investigation for the risk of hepatitis C virus transmission to surgical and dental patients.

Blood loss during treatment carries a potential risk for the transmission of blood-borne pathogens in hospital patients. To determine whether nosocomial transmission of hepatitis C virus (HCV) occurs in surgical wards and dental hospitals, we tested anti-HCV antibodies and HCV RNA in sera from these patients and analysed the hypervariable region 1 (HVR1) sequence of HCV phylogenetically in the HCV RNA-positive patients. Five of 83 patients from a surgical ward were positive for HCV RNA, and six patients from one dental hospital and nine patients from a second were found to be positive for HCV RNA during the examination period. The HVR1 sequences were amplified from these patients' serum, and after subcloning, multiple clones of the HVR1 sequence from each patient were determined. The phylogenetic analysis of these sequences showed that HVR1 species from each patient could be classified into one to three genetic clusters of HVR1 quasi-species and that these clusters were independent of each other among patients. Thus, there was no evidence of HCV transmission in our study, and unrecognized transmission of HCV may be a rare event in surgical and dental patients at university hospitals.

Adult↗

Antiinflammatory effect of heparin-coated circuits with leukocyte-depleting filters in coronary bypass surgery.

Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response. We examined combined use of heparin coating of the cardiopulmonary bypass circuit and a leukocyte-depleting arterial line filter to reduce this response. Thirty patients were allocated randomly to equal groups with a conventional circuit and arterial line filter (C group), a heparin-coated circuit with a conventional filter (H group), or a heparin-coated circuit with a leukocyte-depleting arterial line filter (HF group). Cytokines and respiratory function were repeatedly measured perioperatively. Plasma interleukin (IL)-6 concentrations in the HF group were lower than in the C group immediately following bypass and operation, at 4 h, and 12 h (p < 0.05). Plasma IL-8 was lower in the HF group than in the C group at 4 h (p < 0.05). The respiratory index was lower immediately after bypass in the HF group than the C group (0.61 +/- 0.2 versus 1.05 +/- 0.4, p < 0.05). Heparin-coated circuits with leukocyte-depleting filters decrease inflammatory responses and improve pulmonary function during operation.

Adult↗

[Two cases of typhoid fever with reduced susceptibility to fluoroquinolones].

Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.

Adult↗

[A case report of hemiparesis due to compression of the medulla oblongata by an elongated vertebral artery].

The authors report a case of a 53-year-old woman who developed symptoms and signs of compression of the left medulla oblongata by the elongated and curved left vertebral artery with normal diameter. Twelve days before admission to the hospital, the patient suddenly noticed severe occipital-nuchal headache and nausea with vomiting, while she was unloading a burden. Neurological examination revealed left facial hyperalgesia, right hemihypesthesia and mild right hemiparesis. Hoarseness was observed, but the movement of the uvula and tongue was normal. Hypertension was noticed (180/100). Cerebral and vertebral angiography revealed no aneurysm, but demonstrated an elongated and curved V4 portion of the left vertebral artery with normal diameter. Coronal plain of T2 weighted image of MRI and CT scan with metrizamide administered into the CSF, clearly demonstrated an elongated and curved left vertebral artery compressing the ventro-lateral portion of the left medulla oblongata, neurovascular decompression of the V4 from the medulla oblongata was performed. Through the operating microscope, it was observed that the elongated and curved V4 portion of the left vertebral artery with normal configuration was compressing the left medulla oblongata ventro-laterally, making a compression notch at the outlets of the cranial nerves IX and X. Transposition of the V4 portion was impossible. Some pieces of Taflon felt, thick enough to prevent the pulsatile movement of the V4 from compressing the medulla oblongata, were inserted between the V4 and the medulla oblongata. Two months after the operation, the patient's right hemiparesis and sensory disturbances were gradually improving and her blood pressure had become normal. The authors emphasize that, among patients with symptoms and signs of compression of the medulla oblongata, there is at least one patient for whom neurovascular decompression was an effective treatment.

Female↗

[Blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation?].

To investigate that blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation, a retrospective study was made with 20 adult patients who underwent coronary artery bypass grafting. The subjects were divided into two groups; transfusion group (group T) including 9 patients who received blood transfusion during cardiopulmonary bypass and the control group (group C) including 11 patients who did not undergo perioperative transfusion. Respiratory index as an indicator of respiratory functions was determined before and immediately after cardiopulmonary bypass, at the end of surgery and 4 hours thereafter. Cardiac index and arterial pressure were determined as the indicator of cardiac function. Moreover, interleukin 6 and 8 (IL-6 and IL-8), inflammatory cytokines were measured and compared between the two groups. The mean amount of blood transfusion was 2.1 units per individual of group T. The minimum value of hematocrit during cardiopulmonary bypass was significantly lower in group T (15.8 +/- 1.8%) than group C (19.1 +/- 1.4%), but the difference became not significant after cardiopulmonary bypass. There were no significant differences either in aortic pressure or cardiac index between two groups. The respiratory index at the end of surgery was higher in group T but the difference was not significant. Meanwhile IL-8 level at the end of cardiopulmonary bypass was significantly higher in group T (67.9 +/- 36 pg/ml) than group C (35.1 +/- 21 pg/ml). However, there was no difference in IL-6 level between the two. These results suggested that inflammation might be aggravated by an increase of IL-8 induced by blood transfusion.

Aged↗

Transcriptional inactivation of p53 by deletions and single amino acid changes in mouse mot-1 protein.

Mouse mortalin proteins, mot-1 and mot-2, differ by only two amino acid residues in their C-terminus. In previous studies we showed that they differ in their subcellular distributions and interactions with the tumor suppressor protein, p53. By using mot-1 deletion mutants and amino acid substitution constructs, we report here that inability of mot-1 to affect p53 activity in vivo is dependent on the presence of both of the unique mot-1 amino acids and all three of the predicted hsp70, EF hand, and leucine zipper motif regions. The two proteins and their single amino acid mutants showed different mobilities on SDS-polyacrylamide gel presenting an evidence for their different secondary structures. Taken together, the data suggest that each of the two differing amino acids between mot-1 and mot-2 is an important determinant of their secondary structures and in vivo activities.

Amino Acid Substitution↗

Cutting edge: differential production of prostaglandin D2 by human helper T cell subsets.

Several effector molecules, including cytokines, are differentially produced by Th1 and Th2 cells. We used a gene expression screen method to identify a gene encoding hematopoietic PG D synthase (hPGDS) which was preferentially expressed in human Th2 but not Th1 clones. Studies with anti-hPGDS mAbs confirmed the Th2-dominated expression of hPGDS protein. Upon stimulation with anti-CD3 plus anti-CD28 mAbs, coordinated cyclooxygenase-2 expression and PGD2 production were induced in Th2 lines. hPGDS expression was also observed in a small population (<1.0%) of peripheral blood CD4+ lymphocytes from healthy adults. Most hPGDS-expressing CD4+ lymphocytes showed a typical Th2-type cytokine pattern. Our results suggest that, at the sites of Ag presentation, at least part of the Th2 cell population produces PGD2, which may be involved in various aspects of Th2-related immune responses similar to mast cells.

Adult↗

Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass.

Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 +/- 44 and 60.6 +/- 8.0 ml/kg for the control and PDE III inhibitor groups. respectively). Four hours after surgery and beyond no significant changes in BV were observed in either group. The body fluid balance was negative in both groups. In conclusion, a single administration of PDE III inhibitor during CPB was found to sustain BV soon after operation and, therefore, is useful for postoperative management of open-heart surgery.

Aged↗

Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors.

Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.

Antigens, Nuclear↗

Divergence of glyceraldehyde-3-phosphate dehydrogenase isozymes in Saccharomyces cerevisiae complex.

Although sake yeasts are placed in Saccharomyces cerevisiae, we have been interested in their difference from the other subgroups of the species, and examined their proteins. When SDS-PAGE patterns of their soluble proteins were compared, specific differences between subgroups were found in their 36,000 Da regions. Proteins isolated therefrom were found to be subunits of three isomers of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from their N-terminal amino acid sequences and identified with anti-GAPDH serum. Therefore, comparison of zymogram was carried out by a modified method: denatured monomers were observed and the enzyme activity of their oligomers was not considered. SDS-PAGE patterns of all the sake yeasts differed from those of the other strains of S. cerevisiae. Strains of Saccharomyces bayanus showed uniform patterns which are different from the above two groups. Saccharomyces pastorianus strains resembled S. bayanus and were partly similar to S. cerevisiae in their patterns, in agreement with the hypothesis that S. pastorianus is a hybrid between these two species. Patterns of S. paradoxus appeared to be rather similar to those of sake yeasts. Results on the other species of the genus and on the preliminary experiments on PAGE of native isozymes are also described.

Alcoholic Beverages↗

Induction of apoptosis in WEHI 231 cells by cationic liposomes.

PURPOSE: Liposomes are of considerable interest as drug carriers and immunoadjuvants. However, few investigators have studied the changes exerted by liposomes in the cells with which they interact. The purpose of this study was to investigate whether liposomes induce apoptosis in B cells. METHODS: The mouse immature B cell line WEHI 231 cells and mouse splenic B cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring changes in DNA content, DNA fragmentation and chromatin condensation by flow cytometry, agarose gel electrophoresis and by morphological investigation. RESULTS: Cationic liposomes induced apoptosis in WEHI 231 cells, but neutral and anionic liposomes did not. A contact time of 30 min between WEHI 231 cells and cationic liposomes was sufficient to induce apoptosis, and 80% of the cells showed hypodiploid DNA content. Apoptosis induced by cationic liposomes composed of stearylamine was inhibited by addition of the oxidant scavenger, N-acetyl-cysteine. CONCLUSIONS: Cationic liposomes induced apoptosis in WEHI 231 cells, and the production of reactive oxygen species is important in the regulation of apoptosis induced by cationic liposomes. It is well known that cationic liposomes show cytotoxicity, and apoptosis may be one of the causes of this toxicity.

Animals↗

Retrospective analysis of type of hepatic resection for hepatocellular carcinoma.

BACKGROUND: Hepatic resection for hepatocellular carcinoma is now considered a relatively safe procedure, owing to refined surgical techniques and management. METHODS: Three hundred different types of hepatic resection performed in one hospital were reviewed retrospectively. The operative morbidity and mortality rates and long-term survival were assessed. RESULTS: Tumours were extirpated by lobectomy or extended lobectomy in 48 patients, by segmentectomy in 53, by subsegmentectomy in 94 and by partial resection in 105. The overall hospital mortality rate was 4 per cent (13 of 300). No operative death occurred after lobectomy or extended lobectomy. Segmentectomy and subsegmentectomy were associated with high postoperative complication and hospital mortality rates. There was a significant difference in survival rate between patients with and without a cancer-free surgical margin of more than 1.0 cm. The overall 5- and 9-year survival rates were 51 and 9 per cent respectively. Rates were 56 and 24 per cent for lobectomy or extended lobectomy. CONCLUSION: For tumours of 2.1 cm or more in size lobectomy appears to carry the least risk of postoperative complications and death in hospital and best achieves a cancer-free surgical margin.

Carcinoma, Hepatocellular↗

Pancreaticojejunostomy versus pancreaticogastrostomy in reconstruction following pancreaticoduodenectomy.

BACKGROUND: Pancreaticogastrostomy (PG) after pancreaticoduodenectomy has been reported to have a lower incidence of pancreatic fistula than pancreaticojejunostomy (PJ) but this was not confirmed in a recent prospective randomized study. METHODS: Different methods of reconstruction after pancreaticoduodenectomy were used between January 1994 and January 1999 in two university-affiliated hospitals, PJ (n = 69) in one hospital and PG (n = 73) in the other. Operations at both hospitals were performed by the same surgical team. All pancreatic anastomoses were carried out in two layers with pancreatic duct stents. Pancreatic fistula was identified by the presence of more than 1000 units/l of amylase-rich fluid in the drains 7 days or more after operation, by radiography from the pancreatic duct stent and by water-soluble contrast upper gastrointestinal studies. RESULTS: The two groups of patients were similar in terms of age, sex, findings at preoperative assessment, disease status, operative time, intraoperative blood loss and nature of non-tumorous pancreatic tissue. The amylase level in ascites at 7 days after operation was significantly lower after PG than PJ (P = 0.032). The incidence of pancreatic fistula in the PG group (zero) was significantly less than that after PJ (13 per cent) (P = 0.014). Intra-abdominal haemorrhage and intra-abdominal abscess occurred in three (4 per cent) and four patients (6 per cent) respectively, with two hospital deaths (3 per cent) in the PJ group, but these complications did not occur after PG. CONCLUSION: This controlled clinical study supports the hypothesis that PG is safer than PJ, particularly with regard to the incidence of pancreatic fistula.

Aged↗

Discrimination of histamine H1 and muscarinic receptor-mediated signalling pathways by phorbol ester in human astrocytoma cells.

1. Histamine H1 receptor-mediated signalling was compared with muscarinic receptor-mediated signalling in 1321N1 human astrocytoma cells. 2. Short-term (2 min) treatment of cells with phorbol 12-myristate 13-acetate (PMA) resulted in a reduction of increases in intracellular Ca2+ ([Ca2+]i) induced by carbachol or histamine. 3. Carbachol-induced increases in [Ca2+]i were 10-fold more sensitive to PMA than the histamine-induced increases. 4. When cells were treated with PMA for 48 or 72 h (long-term treatment), protein kinase C (PKC) was down-regulated and PMA did not inhibit carbachol-induced increases in [Ca2+]i. 5. Histamine-induced increases in [Ca2+]i were significantly reduced by long-term treatment with PMA. 6. These findings suggest that the signalling pathways mediated by histamine H1 and muscarinic receptors can be distinguished by using PKC in 1321N1 human astrocytoma cells.

Astrocytoma↗

Multimodality treatment for patients with hepatocellular carcinoma: a single institution retrospective series.

BACKGROUND: The main therapeutic options for hepatocellular carcinoma (HCC) are hepatic resection, transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT) and regional chemotherapy (RC). METHODS: This study retrospectively examined the results of primary treatment of 600 patients with hepatocellular carcinoma selected according to the treatment guidelines of our facility and the results of various combination therapies for recurrent cases. The selection criteria of therapeutic options included the number and size of tumours and hepatic function. RESULTS: The selected primary treatment was hepatic resection for 53.7% of the cases, TAE for 31.5%, PEIT for 8.2% and RC for 6.6%,. The treatment for post-resection recurrence was TAE alone for 62.4% of the cases, TAE + RC for 4.0%, PEIT for 15.2%, TAE + PEIT alone for 4.8%, RC for 8.0% and hepatic resection for 5.6%. The treatment for post-TAE recurrence was TAE alone for 83% of the cases, TAE + PEIT for 9%, TAE + RC for 3%, RC alone for 3% and PEIT alone for 2%. For post-PEIT, therapy was PEIT alone for 71.4% of the cases and PEIT + TAE for 28.6%. For post-RC, RC alone was used for 92.5% and RC + PEIT for 7.5%. The cumulative 3 and 5-year survival rates were 84.4% and 70.6%, respectively for stage I; 61.5% and 48.6% for stage II; 52.7% and 20.5% for stage III; and 22.8% and 17.1% for stage IVA. The cumulative 5 and 7-year survival rates after the primary treatments were 52.% and 40.1%, respectively, for hepatic resection; 46.5% and 38.7%, for TAE; 49.6% and 33.1% for PEIT; and 16.7% and 8.3% for RC. CONCLUSIONS: To improve the treatment results for HCC, early detection is essential and various modalities of treatments in combination should be used for recurrence after primary treatment.

Adult↗

Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in human gliomas. VEGF-induced proteins in endothelial cells, tissue factor (TF), osteopontin (OPN) and alphavbeta3 integrin have been implicated as important molecules by which VEGF promotes angiogenesis in vivo. Sixty-eight gliomas were immunohistochemically stained with TF, VEGF, OPN and alphavbeta3 integrin antibody. Twenty-three tumours, six normal brains and nine glioma cell lines were evaluated for their mRNA expression of VEGF and TF by reverse transcription polymerase chain reaction analysis. The data indicated that TF as well as VEGF was a strong regulator of human glioma angiogenesis. First, TF expression in endothelial cells which was observed in 74% of glioblastomas, 54% of anaplastic astrocytomas and none of low-grade astrocytomas, correlated with the microvascular density of the tumours. Double staining for VEGF and TF demonstrated co-localization of these two proteins in the glioblastoma tissues. Second, there was a correlation between TF and VEGF mRNA expression in the glioma tissues. Third, glioma cell conditioned medium containing a large amount of VEGF up-regulated the TF mRNA expression in human umbilical vein endothelial cells. OPN and alphavbeta3 integrin, were also predominantly observed in the microvasculature of glioblastomas associated with VEGF expression. Microvascular expression of these molecules could be an effective antiangiogenesis target for human gliomas.

Brain Neoplasms↗

Sprint performance is related to muscle fascicle length in male 100-m sprinters.

The purpose of this study was to investigate the relationship between muscle fascicle length and sprint running performance in 37 male 100-m sprinters. The sample was divided into two performance groups by the personal-best 100-m time: 10.00-10.90 s (S10; n = 22) and 11.00-11.70 s (S11; n = 15). Muscle thickness and fascicle pennation angle of the vastus lateralis and gastrocnemius medialis and lateralis muscles were measured by B-mode ultrasonography, and fascicle length was estimated. Standing height, body weight, and leg length were similar between groups. Muscle thickness was similar between groups for vastus lateralis and gastrocnemius medialis, but S10 had a significantly greater gastrocnemius lateralis muscle thickness. S10 also had a greater muscle thickness in the upper portion of the thigh, which, given similar limb lengths, demonstrates an altered "muscle shape." Pennation angle was always less in S10 than in S11. In all muscles, S10 had significantly greater fascicle length than did S11, which significantly correlated with 100-m best performance (r values from -0.40 to -0.57). It is concluded that longer fascicle length is associated with greater sprinting performance.

Adult↗