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Biomedical subjects

S Tamura

Publications and source records attributed to S Tamura.

At least 253 records · Page 14Linked to original sources
PubMed1997

Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice.

Microcystin-LR (MCLR) is a hepatotoxic peptide produced by Microcystis aeruginosa, an alga found worldwide in reservoirs for drinking supply; however, acute oral toxicity of purified MCLR remains unknown. Therefore, a single dose of MCLR (more than 95% purity) ranging from 8.0 to 20.0 mg/kg body weight was orally given to female 6-week old BALB/c mice, and lethality and pathological changes were observed. Median lethal dose (LD50) of the orally given MCLR estimated by the up and down method was 10.9 mg/kg, which was 167 times higher than the i.p. LD50 value (65.4 microgram/kg by moving average method). Orally administrated toxin caused primarily hepatocellular injuries with characteristics of hemorrhage and necrosis. In situ end-labeling as well as electron microscopic observation revealed an induction of apoptotic cell death to hepatocytes. These results indicate the lethality of MCLR was much lower in oral dosage than by i.p. administration, but toxic effects are similar. In addition, apoptosis is considered one of major components in MCLR-induced hepatotoxicity.

Administration, Oral↗
PubMed1997

Efficacy of combination therapy of interferon-alpha with ursodeoxycholic acid in chronic hepatitis C: a randomized controlled clinical trial.

The efficacy of interferon-alpha therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon-alpha with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon-alpha (group A, n = 40) and the other with a combination of interferon-alpha and UDCA (group B, n = 40). In both groups, human interferon-alpha (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600 mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P = 0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significant (P = 0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P < 0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.

Administration, Oral↗
PubMed1997

A computerized analysis system in chest radiography: evaluation of interstitial lung abnormalities.

We evaluated the usefulness of a computerized analysis system in the detection of interstitial lung abnormalities in digitized chest radiography. This system uses the processes of four-directional Laplacian-Gaussian filtering, linear opacity judgment, and linear opacity subtraction. For qualitative analysis, we employed a combined radiographic index, which was calculated from two normalized radiographic indices obtained by linear opacity judgment and subtraction of linear opacities. We selected 50 regions of interest (ROIs) in patients with mild interstitial lung abnormalities, 50 ROIs in patients with severe interstitial lung abnormalities, and 50 ROIs in individuals with normal lung parenchyma. High-resolution computed radiography (HRCT) findings were used as the standard of reference for this study. These ROIs were processed by our computerized analysis system, and radiographic indices were obtained from each ROI. The area under the receiver operating characteristic curve (Az) was used as the measure of performance. The combined radiographic index provided better results in the mild interstitial lung abnormality group (Az = 0.94 +/- 0.02), but it also yielded good results in the severe interstitial lung abnormality group (Az = 0.98 +/- 0.01). These results indicate that this system of combining radiographic indices has improved the detection performance over that with our previous system.

Evaluation Studies as Topic↗
PubMed1997

Endoscopic diagnosis and treatment of early colorectal cancer.

Colorectal adenomas and early cancers are grossly classified into three groups: protruded, flush or slightly elevated (so-called flat adenomas), and depressed. Protruded lesions and flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when very small. It is not difficult to detect protruded and flat adenomas, but depressed carcinomas are often overlooked. Keys to the detection of depressed carcinomas are a slight color change, bleeding spots, interruptions of the capillary network pattern, slight deformation of the colonic wall, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves by the lesion. Spraying of indigo carmine dye helps to clarify the lesions. Pit pattern analysis with magnifying colonoscopy is useful for diagnosis of early colorectal cancer. Pit pattern analysis and histologic examination suggest that depressed carcinomas probably have arisen de novo, without going through an adenomatous step. Some adenomas appear at first to have a depression, but such cancer-mimicking adenomas with pseudodepression must be distinguished from depressed carcinomas because they are quite different in nature. Protruded and flat adenomas can usually be removed with polypectomy or hot biopsy techniques. Depressed carcinomas are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Some neoplastic lesions, which we call laterally spreading tumors, extensively and circumferentially spread along the colonic wall, although they are short in height. They tend to have a rather benign nature despite their large size; therefore EMR or a piecemeal EMR method is indicated.

Adenoma↗
PubMed1997

Cancellation of motion artifact in MRI due to 2D rigid translational motion.

A new algorithm for cancelling MRI artifact due to translational motion in the image plane is described. Unlike the conventional iterative phase retrieval algorithm, in which there is no guarantee for the convergence, a direct method for estimating the motion is proposed. In the previous approach, the motions in the readout(x-) direction and the phase encoding(y-) direction are estimated simultaneously. However, the feature of the each x- and y-directional motion is different. Based on the analysis of their features, each x- and y-directional motion is cancelled by different algorithms in two steps. First, we notice that the x-directional motion corresponds to a shift of the x-directional spectrum of the MRI signal, so the x-directional motion can be cancelled by shifting the spectrum in inverse direction. Next, the y-directional motion is cancelled using a new constraint, with which the motion component and the true image component can be separated. The algorithm is shown to be effective by simulations.

Algorithms↗
PubMed1997

Detection of Epstein-Barr virus transcripts in anaplastic large-cell lymphomas by mRNA in situ hybridization.

Anaplastic large-cell lymphoma (ALCL) is a recently proposed subset of non-Hodgkin's lymphoma. To determine whether Epstein-Barr virus (EBV) is associated with this lymphoma, we performed mRNA in situ hybridization on seven cases of ALCL using a probe consisting of an RNA sequence complementary to the transcripts of BamHIW fragment of the EBV genome. We detected BamHIW transcripts of EBV in the majority of atypical large cells of all cases of ALCL, but in none of three cases of lymphoblastic and small lymphocytic lymphomas. Furthermore, we detected latent membrane protein-1 (LMP1) in two cases of ALCL by means of immunofluorescence and immunoperoxidase stainings. These findings suggest that EBV is involved in the neoplastic transformation for ALCL as in the case of Hodgkin's disease, which shares several clinicopathologic features with ALCL.

Adolescent↗
PubMed1997

Association of cumulative allelic losses with tumor aggressiveness in hepatocellular carcinoma.

BACKGROUND/AIMS: Loss of heterozygosity on various chromosomal arms has been reported in hepatocellular carcinoma and a multistep accumulation of genetic alteration has become accepted as the mechanism underlying progression of the disease. Although cumulative genetic alterations may imply more malignant tumors with poorer prognosis, the assumption requires further investigation. METHODS: Presence of loss of heterozygosity was analyzed by microsatellite markers at 13 loci on six chromosomal arms in 56 hepatocellular carcinomas. Association with cumulative allelic losses and prognosis of the patient following curative resection was studied. RESULTS: Frequency of allelic losses at each chromosomal arm was 31% on 1p, 20.6% on 4q, 17.5% on 8p, 17.5% on 13q, 25.5% on 16q and 17.4% on 17p. Thirty-three tumors (59%) presented loss of heterozygosity. Tumors with more allelic losses were significantly more likely to be un-infected by hepatitis C virus, and to be histologically poorly differentiated, to have higher alpha-feto protein value, to be advanced in T classification and in tumor stage. Patients with more than one loss of heterozygosity revealed poorer 3-year disease-free survival than those with one or no (p=0.0004). A multivariate Cox model analysis revealed cumulative loss of heterozygosity as an independent and influential factor for disease recurrence (relative risk, 2.66; 95% confidence interval, 1.23-5.75; p=0.013), followed by tumor stage. CONCLUSIONS: Cumulative loss of heterozygosity reflects the multistep genetic mechanism of progression of hepatocellular carcinoma. The study confirms the potential significance of genetic analysis in the management of the disease.

Adult↗
PubMed1997

Suppression of delayed-type hypersensitivity and IgE antibody responses to ovalbumin by intranasal administration of Escherichia coli heat-labile enterotoxin B subunit-conjugated ovalbumin.

Oral administration of a small amount of antigen conjugated cholera toxin B subunit is known to induce tolerance to the antigen. In the present experiments, whether nasal administration of allergen conjugated to Escherichia coli heat-labile toxin B subunit (LTB) induced tolerance was examined in BALB/c mice. A single administration of a small amount of LTB-coupled ovalbumin (OVA) suppressed the induction of delayed-type hypersensitivity and IgE antibody responses to OVA which was administered parenterally after nasal administration of LTB-coupled OVA. The antigen-specific suppression was abrogated by the addition of the holotoxin to LTB-coupled OVA. The suppression, induced by nasal administration with a small amount of allergen conjugated to a mucosa-binding molecule, may be applicable for preventing the development of allergy.

Administration, Intranasal↗
PubMed1997

Effects of frequent intranasal administration of adjuvant-combined influenza vaccine on the protection against virus infection.

In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB*) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans. The present study was designed to determine whether the effectiveness of a combined LTB*-HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB*-combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB* alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB*-combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB*-combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.

Adjuvants, Immunologic↗
PubMed1997

Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells.

Recently, many inhibitors of farnesyl protein transferase (FPTase) have been identified. Some of them interrupt cell growth in addition to Ras and nuclear lamin processing of Ras-transformed cells. We have tested the effect of the FPTase inhibitors manumycin, an analogue of farnesyl diphosphate, and KT7595, a gliotoxin derivative, on Ras farnesylation, DNA synthesis and the anchorage-dependent and -independent growth of human colon carcinoma (LoVo), hepatoma (Mahlavu and PLC/PRF/5) and gastric carcinoma (KATO III). Both drugs severely inhibited DNA synthesis, cellular proliferation and Ras farnesylation in LoVo and moderately reduced them in Mahlavu and PLC/PRF/5 but not in KATO III. Complete sequencing of ras genes, however, revealed that LoVo and KATO III have activated Ki-ras and activated N-ras, respectively, whereas Mahlavu and PLC/PRF/5 have no activated ras. We next checked whether the inhibition of the cellular proliferation is due to the blocking of nuclear lamin function. Neither drug disturbed lamin farnesylation and localization, as demonstrated using metabolic labelling, immunoblotting and indirect immunofluorescence. These results indicate that manumycin and KT7595 can inhibit Ras farnesylation and cell growth without disturbing the farnesylation and localization of the lamins on human tumour cell lines.

Alkyl and Aryl Transferases↗
PubMed1997

Planarian mitochondria sequence heterogeneity: relationships between the type of cytochrome c oxidase subunit I gene sequence, karyotype and genital organ.

Freshwater planarians Dugesia japonica from three localities were examined for cytochrome c oxidase subunit I (COI) gene sequence, karyotype and the presence of genital organ. The planarians from Mt Fujiwara in Japan were composed of two different groups; one revealed inter- and intraindividual COI gene heterogeneity, while another revealed no sequence heterogeneity. The sequence in planarians from Mt Alishan in Taiwan was homogeneous, while that from the Kenting National Park in Taiwan revealed a considerable heterogeneity. All the planarians having the homogeneous gene sequences carry the 2X karyotype and many of them had genital organs. These are assumed to belong to the sexual lineage. In contrast, almost all planarians having heterogeneous sequences carry the karyotype of either 3X plus 2X (mixoploid) or 3X, and all of them lack genital organs. These lineages are assumed to be asexual. The heterogeneity of COI gene sequences in the presumed asexual lineages would have resulted from an accumulation of mutations by repeated asexual reproduction.

Animals↗
PubMed1997

Increased circulating transforming growth factor beta1 in a patient with giant hepatic hemangioma: possible contribution to an impaired immune function.

A patient, having a huge hepatic hemangioma, presented with decreases in the number of peripheral lymphocytes and in serum concentrations of gamma-globulin and immunoglobulin (Ig) G, and a negative purified protein derivatives skin test, indicating that the patient's immunity was impaired. The plasma concentration of transforming growth factor beta1 (TGF-beta1), a potent immunosuppressor, in the patient was markedly elevated (113 ng/mL, normal < 5). After the surgical removal of the tumor, the plasma TGF-beta1 concentration decreased, and the patient's immunity was restored to normal. Northern blot analysis showed an overexpression of the TGF-beta1 gene in the hemangioma tissue, while normal control liver tissue expressed undetectable levels of TGF-beta1 messenger RNA. These results suggest that the elevated levels of TGF-beta1 in the plasma were derived from the giant hemangioma tissue and may have contributed to the impaired immune function in the patient.

Cytokines↗
PubMed1997

Longitudinal evaluation of time related bone remodeling after cementless total hip arthroplasty.

Bone remodeling after cementless total hip arthroplasty was evaluated by dual energy x-ray absorptiometry in a longitudinal study of 32 hips. After insertion of a fully porous surface anatomic stem made of cobalt chromium, bone mineral density was analyzed until at least 2 years postoperatively. Bone remodeling was evaluated in terms of regional bone density changes in the seven adjacent periprosthetic zones as well as the global change in bone density distribution over the entire periprosthetic area. At 12 months after the operation, the averaged regional bone mineral density in all seven zones showed a rapid decrease, ranging from 9% to 24% of the bone mineral density present at 2 weeks postoperatively. Thereafter, the bone density change appeared to be stabilized. The global change in the bone density distribution was expressed as two summarizing statistical indexes derived from principal component analysis: the first index represents the change of average bone mineral density over the entire periprosthetic area, and the second represents the severity of bone mineral density decrease in the proximal area versus the distal area. The second index proved that more bone density reduction occurred in the proximal area, but this was variable among patients and correlated significantly with the stem size and the initial bone mineral density in the distal part of the periprosthetic area. This longitudinal dual energy x-ray absorptiometry study suggests that a large part of the bone remodeling after cementless hip arthroplasty ceases within 1 year postoperatively, and stem size and the initial bone density around the distal portion are important considerations for predicting the proximal bone density decrease during the early rapid remodeling period.

Absorptiometry, Photon↗
PubMed1997

Use of a split bone graft to correct the cosmetic deformity associated with the transpetrosal-transtentorial surgical approach: technical report.

OBJECTIVE: Split bone graft reconstruction was performed after a standard transpetrosal-transtentorial approach to correct the cosmetic deformity in 18 patients. TECHNIQUE: The split bone graft was made by dividing the inner table of the temporosuboccipital bone graft and covered the bone effect created by petrosectomy and mastoidectomy. The split bone graft was created and shaped during closure of the dura, so that the operation was not prolonged. RESULTS: This technique produced excellent cosmetic results immediately after surgery; the results were maintained during the follow-up period of between 20 and 46 months. No complication associated with this technique was recognized. CONCLUSION: Split bone graft reconstruction is a simple and safe technique for preventing the cosmetic deformity associated with a transpetrosal-transtentorial approach.

Bone Transplantation↗
PubMed1997

Automatic extraction and measurement of leukocyte motion in microvessels using spatiotemporal image analysis.

This paper describes a computer vision system for the automatic extraction and velocity measurement of moving leukocytes that adhere to microvessel walls from a sequence of images. The motion of these leukocytes can be visualized as motion along the wall contours. We use the constraint that the leukocytes move along the vessel wall contours to generate a spatiotemporal image, and the leukocyte motion is then extracted using the methods of spatiotemporal image analysis. The generated spatiotemporal image is processed by a special-purpose orientation-selective filter and a subsequent grouping process newly developed for this application. The orientation-selective filter is designed by considering the particular properties of the spatiotemporal image in this application in order to enhance only the traces of leukocytes. In the subsequent grouping process, leukocyte trace segments are selected and grouped among all the segments obtained by simple thresholding and skeletonizing operations. We show experimentally that the proposed method can stably extract leukocyte motion.

Algorithms↗
PubMed1997

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

Antiviral Agents↗
PubMed1997

[Efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin in healthy volunteers].

We conducted a field trial to evaluate the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in preventing or attenuating influenza among volunteers during the winter season of 1994-1995. A trivalent inactivated influenza vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H2N2) and B/Mie/1/93 influenza virus strains, was administered intranasally together with recombinant LTB containing 1% recombinant LT (LTB*). Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum HI antibodies were measured before and 8 weeks after the primary vaccination. Thirty-two volunteers were enrolled in this study; 18 volunteers (mean age 37.7 +/- 11.3) were given LTB*-combined vaccine and 14 volunteers (mean age 44.1 +/- 11.3) given placebo. Outbreaks of H3N2 subtype and B type virus were observed during this study period. Six (42.9%) of the 14 volunteers in the placebo group and 3 (16.7%) of the 18 receiving the LTB*-combined vaccine contracted influenza. There was no statistically significant difference between the two groups, because the number of subjects was small. Higher percentage of positive IgA and HI antibody responses among vaccines given vaccine with LTB* were observed as compared with those in the placebo group. Positive IgA antibody response to all vaccine strains were observed in 46.7% (7/15) of the vaccine group. On the other hand, none of the placebo group showed positive IgA antibody response to all vaccine strains. These results suggest that nasal influenza vaccine with LTB* appears to be effective in preventing influenza.

Administration, Intranasal↗