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Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 451 records · Page 25Linked to original sources

[Antimicrobial susceptibility testing for Mycobacterium tuberculosis by measuring mycobacterial adenosine triphosphate].

The antimicrobial susceptibility test for Mycobacterium tuberculosis H37Rv and 43 clinical isolates was performed using a bioluminescence assay by measuring the content of adenosine triphosphate (ATP) derived from mycobacteria. The drugs tested were isoniazid (INH), rifampicin (RFP), ethambutol (EB), streptomycin (SM), and kanamycin (KM). The ATP contents of M. tuberculosis incubated in the Middle-brook 7H9 broth medium containing antituberculous agents were measured at days of 0, 1, 3, 5, 7 and 10. A reduction of ATP content, indicating growth inhibition, was observed in susceptible strains within 5 to 10 days of incubation. Optimal concentrations to distinguish between susceptible and resistant strains were determined as being INH 0.20, RFP 0.50, EB 5.0, SM 4.0, KM 6.0 g/ml. The agreements of ATP method (evaluated at 10 days) with Vite Spectrum and MIC determinations were 81.4% and 100%, respectively. Susceptibilities to most drugs, except for EB, could be determined within 7 days. This method is simple, rapid, nonradiometric, and can be used for drug susceptibility.

Adenosine Triphosphate↗

Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.

Albinism↗

Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.

UNLABELLED: The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. METHODS: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. CONCLUSION: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.

Animals↗

[Studies on recurrent breast cancer--clinicopathological factors and p53, p21Cip1/Waf1 and cyclin D1 protein expression].

Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.

Breast Neoplasms↗

Centrosome abnormalities in pancreatic ductal carcinoma.

The centrosome plays an important role in microtubule nucleation and organization, ensuring the establishment of cell polarity and balanced chromosome segregation. Recent studies have suggested that the loss of cell polarity and/or chromosome missegregation (aneuploidy) in human malignant tumors could result from defects in centrosome function. Using immunofluorescence analysis with an antibody to gamma-tubulin (a well-characterized centrosomal component), we examined surgically resected human pancreatic tissues for centrosome abnormalities. The tissues included ductal carcinomas (n = 13), adenomas (n = 3), endocrine tumors (n = 3), chronic pancreatitis (n = 5), and normal pancreatic tissues (n = 12). We found that most (85%) carcinomas and some adenomas displayed abnormal centrosome profiles, characterized by an increase in size and number of centrosomes, and by their irregular distribution. In contrast, none of normal ductal and stromal tissues showed these abnormalities. These findings suggest that centrosome abnormalities may develop at a relatively early stage of pancreatic ductal carcinogenesis.

Adenocarcinoma↗

[Ethanol-induced hepatic microcirculatory disturbance].

Alcoholic liver injury predominates in the pericentral region, in which oxygen tension is physiologically lowest. The enhanced injurious effect of ethanol at this site is postulated to be due to hypoxia, resulting from an enhanced oxygen demand of hepatocytes for the oxidative metabolism of ethanol. Moreover, we found that ethanol at higher concentrations induces hypoxia in the liver by causing microcirculatory disturbance. Upon initiation of ethanol infusion into the portal vein of isolated perfused rat liver at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phase). Sodium nitroprusside, a known vasodilator, diminished the ethanol-induced increase in portal pressure, increased oxygen consumption leading to inhibition of the reduction of the respiratory cytochromes of the liver, and diminished liver injury. The data indicate that the ethanol-induced hepatic vasoconstriction disturbs hepatic microcirculation, leading to hepatic hypoxia and hepatocellular injury. Endothelin-1 antiserum inhibited significantly hepatic vasoconstriction induced by ethanol. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, following the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phase the sustained the vasoconstriction. Based on the current results, we propose that the sinusoidal tone in the presence of ethanol is regulated predominantly by the actions of the two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide.

Animals↗

[Cell cycle-dependent change of the adhesive character of CD34+ progenitor cells and their VLA-4 expression].

We identified the cell cycle status of CD34+ cells of steady-state bone marrow (BM) and peripheral blood (PB) obtained from healthy volunteers, and those of BM and apheresis PB samples collected from donors who had been administered granulocyte colony-stimulating factor (G-CSF). Regardless of whether G-CSF treatment was undergone, more than 10% of CD34+ cells in the BM was in the S + G2/M phase. In contrast, less than 2% of CD34+ cells in the PB was cycling. After co-culturing BM CD34+ cells with a monolayer of the stromal cell line MS-5 for 1 hour, some cells adhered to the stroma. The percentage of cells in the S + G2/M phase among these adherent cells was higher than that among the non-adherent cells. Flow cytometric analysis revealed that CD34+ cells in mobilized PB expressed less VLA-4 than those in BM and that in in vitro-cultured non-adherent cells exhibited a lower level of VLA-4 expression than adherent cells. In addition, CD34+ cells in the G0/G1 phase expressed lower levels of VLA-4 than those in the S + G2/M phase. These findings suggested that the reduced expression of adhesion molecules such as VLA-4 by the progenitor cells in the G0/G1 phase of the cell cycle result in the release of progenitor cells from the hematopoietic microenvironment to peripheral blood.

Antigens, CD34↗

[Fenestrated basilar artery aneurysm: case report].

The authors reported an operated case with an aneurysm arising from the proximal end of basilar artery fenestration, and discussed its etiology and surgical strategy. A 47-year-old woman presented with slight memory disturbance. Neuroradiologic examination revealed an aneurysm located on the proximal end of the basilar artery 12 x 9 mm in size at the level of the outer auditory meatus. The union of vertebral arteries had deviated toward the right side, and the aneurysmal dome had projected into the fenestration. Through the right far lateral approach, we applied two straight fenestrated clips X configuration to the aneurysm. Several authors have reported a variety of approaches for vertebrobasilar aneurysms along the midline with consideration of the height of the aneurysmal. However, another point of view is that attention should be paid to the direction of the clip blade and applied at the final clipping, because, for vertebrobasilar aneurysms adjacent to the midline, the surgical view and working space are extremely restricted.

Basilar Artery↗

Adenovirus-mediated p53 gene transduction inhibits telomerase activity independent of its effects on cell cycle arrest and apoptosis in human pancreatic cancer cells.

Evidence for a relationship between overexpression of wild-type p53 and telomerase activity remains controversial. We investigated whether p53 gene transduction could cause telomerase inhibition in pancreatic cancer cell lines, focusing on the relation of transduction to growth arrest, cell cycle arrest, and apoptotic cell death. The cells were infected with recombinant adenovirus expressing wild-type p53 or p21WAF1 at a multiplicity of infection of 100 or were continuously exposed to 10 microM VP-16, which is well known to induce apoptosis. Adenovirus-mediated p53 gene transduction caused G1 cell cycle arrest, apoptosis, and resultant growth inhibition in MIA PaCa-2 cells; the cell number 2 days after infection was 50% of preinfection value, and 13% of the cells were dead. Moreover, the transduction resulted in complete depression of telomerase activity through down-regulation of hTERT mRNA expression. In contrast, p21WAF1 gene transduction only arrested cell growth and cell cycle at G1 phase, and VP-16 treatment inhibited cell growth with G2-M arrest and apoptosis; after treatment, the cell number was 73% of pretreatment, and 12% of the cells were dead. Neither p21WAF1 gene transduction nor VP-16 treatment caused telomerase inhibition. Similar results were obtained in two other pancreatic cancer cell lines, SUIT-2 and AsPC-1. Thus, our results demonstrate that the p53 gene transduction directly inhibits telomerase activity, independent of its effects on cell growth arrest, cell cycle arrest, and apoptosis.

Adenoviridae↗

[Automated anesthesia billing by electronic anesthesia record keeping system].

There has been loss of anesthesia fee by errors of filling out billing sheets manually. A large loss of anesthesia fee was pointed out by the audit during the past several years. In order to prevent these billing error, we have developed an automated anesthesia billing system combined with an electronic anesthesia record keeping (EARK) system. The system derives all the anesthesia cost-related parameters from the EARK database and calculates anesthesia fee according to the logic of the Japanese health care insurance system. After implementing the system, anesthesiologists and circulating nurses became free from filling out billing sheets. The accuracy of the automated billing was proved by the comparison with hand filled sheets. The survey showed that the system prevented 2.5 million yen of billing loss in a month. Such an economic impact of the system proves the rationale of an EARK as a cost containment tool.

Anesthesia↗

Asialoglycoprotein receptor scintigraphy in evaluation of auxiliary partial orthotopic liver transplantation.

UNLABELLED: The purpose of this study was to evaluate asialoglycoprotein receptor scintigraphy in the post-transplant monitoring of liver graft and native liver functions in recipients of auxiliary partial orthotopic liver transplantation (APOLT) from living donors. METHODS: We performed 36 asialoglycoprotein receptor scintigraphies on 13 patients who had undergone APOLT for noncirrhotic metabolic liver diseases or for small-for-size grafts. The portal vein of the native liver was separated in 12 patients. Anterior dynamic images including the heart and both livers were obtained for 16 min after intravenous injection of 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA), and thereafter static SPECT images of both livers were obtained. Uptake rates from the blood to the graft and to the native liver were determined separately by Patlak plot graphical analysis. Relative uptake of GSA by the graft was calculated from transverse SPECT images. The relative volume of the graft liver was determined by CT. RESULTS: The relative uptake of GSA by the graft was higher or increased more rapidly than the relative volume of the graft in 8 of 11 patients with no severe complications concerning the graft. The relative uptake by severely damaged graft liver in 2 patients was much lower than the relative volume. The uptake rate of GSA by the graft was low in these 2 patients. The uptake rate by the native liver decreased when the portal vein was separated. CONCLUSION: The relative uptake of GSA was a better indicator of graft liver function than was anatomic volume. The uptake rate provided additional independent information of each liver. Asialoglycoprotein receptor scintigraphy is useful for distinguishing and monitoring the graft and native liver functions in patients who had undergone APOLT.

Adolescent↗

Recent epidemiologic trends in alveolar echinococcosis prevalence in humans and animals in Hokkaido.

We investigated chronological and geographical changes of alveolar echinococcosis (AE) prevalence in 14 administrative districts of Hokkaido based on the data of our epizootiologic and seroepidemiologic surveys. The results suggest that the chronological transitions of the enzootic state of AE in Hokkaido markedly reflect those of human AE prevalence, and that new prevalence of human AE has been emerging from central and western Hokkaido.

Animals↗

[A case of primary brain-stem injury recovered from persistent vegetative state after L-dopa administration].

A 51-year-old male was transferred to our hospital just after traffic accident. On admission, the patient was comatose (Glasgow Coma Scale of 6) and showed a left hemiparesis with a left oculomotor nerve palsy. Computed tomography demonstrated a traumatic subarachnoid hemorrhage without mass lesion. Magnetic resonance imaging showed high intensity lesions on the left dorsolateral midbrain and the right cerebral peduncle. The distribution of lesions implied diffuse axonal injury involving dopaminergic systems such as the substantia nigra and the ventral tegmental area. After several months of conservative management, the patient showed no recovery and was diagnosed as persistent vegetable state. The administration of L-dopa was then started and the patient showed remarkable neurological improvement. Therefore the patient's neurological status was thought to be modified with primary brain stem injury and accompanying traumatic Parkinson's syndrome. It is important to understand "pseudo" persistent vegetative state in the management of patients showing prolonged consciousness disturbance. L-dopa should be considered as the drugs of pharmacological intervention for the patients of masked parkinsonism behind "pseudo" persistent vegetative state whose dopaminergic systems might have been damaged.

Accidents, Traffic↗

Inhibition of retinoic acid-inducible transcription by COUP-TFI in human salivary gland adenocarcinoma cell line HSG.

Human salivary gland adenocarcinoma cells (HSG) express nuclear receptors, all-trans-retinoic acid (at-RA) receptors (RARs), and retinoid X/9-cis-retinoic acid (9-c-RA) receptors (RXRs). In order to investigate whether the endogenous RARs or RXRs of HSG cells can induce transcription activation, the thymidine kinase promoter (TK)-driven luciferase reporter gene containing the retinoic acid response element (RARE), of RARbeta, betaRARE2-TK-Luc, was transfected into HSG cells and ligand-dependent transcription activation was examined. Luciferase activity of cell lysate increased by the treatment with either at-RA or 9-c-RA. Co-transfection of RARalpha and (or) RXRalpha-expression plasmids with the reporter gene enhanced the luciferase activity, suggesting that endogenous RARs and RXRs work as ligand-dependent transfactors in HSG cells. Reverse transcriptase - polymerase chain reaction analysis revealed that HSG cells express chicken ovalbumin upstream promoter - transcription factor I (COUP-TFI). Co-transfection of COUP-TFI-expression plasmid suppressed the at-RA-induced transcription activation of the reporter gene. Similar results were shown using a chromatin-integrated reporter gene system, using a stably transfected beta-RARE2-TK-beta-galactosidase (beta-Gal) reporter gene. The at-RA-dependent increase in the beta-Gal expression was completely inhibited by COUP-TFI. The transfection of antisense oligonucleotide of COUP-TFI squelched the RA-dependent growth inhibition induced by RAR-RXR heterodimers. Conclusively, RARs and RXRs of HSG cells are functional and play roles as transactivators in at-RA-sensitive processes such as the proliferation or differentiation of cells. COUP-TFI very likely regulates these processes by repressing the functions of these transactivators.

Adenocarcinoma↗

9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells.

There is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53.

Antimetabolites, Antineoplastic↗