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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 253 records · Page 14Linked to original sources

Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region.

Recent studies with avian embryos and murine embryonic stem cells have suggested that hematopoietic cells are derived from hemangioblasts, the common precursors of hematopoietic and endothelial cells. We molecularly cloned podocalyxin-like protein 1 (PCLP1) as a novel surface marker for endothelial-like cells in the aorta-gonad-mesonephros (AGM) region of mouse embryos, where long-term repopulating hematopoietic stem cells (LTR-HSCs) are known to arise. PCLP1+ CD45 cells in the AGM region incorporated acetylated low-density lipoprotein and produced both hematopoietic and endothelial cells when cocultured with OP9 stromal cells. Moreover, multiple lineages of hematopoietic cells were generated in vivo when PCLP1 +CD45-cells were injected into neonatal liver of busulfan-treated mice. Thus, PCLP1 can be used to separate hemangioblasts that give rise to LTR-HSCs.

Amino Acid Sequence↗

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias and reperfusion-induced arrhythmias in anesthetized rats.

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats. In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 micromol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 micromol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained. In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 micromol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 micromol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure. We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.

Anesthesia↗

Frequencies in the Japanese population of HFE gene mutations.

We studied the frequencies of C282Y and H63D mutations in the HFE gene, thought to be responsible for hereditary hemochromatosis (HH), in 504 chromosomes obtained from 252 unrelated Japanese. Allele-specific PCR and PCR-restriction fragment length polymorphism methods revealed that the C282Y mutation was not found and the H63D mutation was low in frequency (at only 0.99%) compared with data from European people. Since most HH is thought to be associated with the HFE gene mutation, the low incidence of these mutations is a likely reason for the rarity of this disease in the Japanese population.

Base Sequence↗

Effect of alpha 1-acidic glycoprotein in the ascitic fluid of cancer patients on human NK cells: selective suppression of interferon-induced NK activation.

The in vitro effect of C-AGP (pure alpha1-acid glycoprotein from the ascitic fluid of cancer patients) on NK cell cytotoxicity was tested using normal healthy human PBMC. C-AGP had no inhibitory effect on basal NK cell activity. C-AGP selectively suppressed the augmentation of NK cell activity by rIFNalphaA and rIFNgamma, but C-AGP did not prevent the NK activation by rIL-2. NK cells in PBMC treated with C-AGP for 12 h and then washed just once, to remove the C-AGP, fully recovered the ability to respond to rIFNalphaA. However, after the treatment of PBMC with C-AGP for 5 or 6 days, NK cells failed to respond to rIFNalphaA, in spite of washing to remove C-AGP from the cultures. Monocytes were necessary for the suppressive effect of C-AGP on rIFNalphaA activation of NK cells. Indomethacin restored the ability of NK cells to respond to rIFNalphaA in C-AGP-treated PBMC. These results suggest that monocytes are able to selectively suppress the response of NK cells to IFNs in the presence of, or following treatment with C-AGP.

Anti-Inflammatory Agents, Non-Steroidal↗

Monoclonal antibody ONS-M21 recognizes integrin alpha3 in gliomas and medulloblastomas.

The monoclonal antibody ONS-M21 recognizes an antigen found on the surface of glioma and medulloblastoma cells but does not react with the antigens of normal brain tissue. We purified and identified the 140-kDa protein by means of an antibody-binding affinity column. This 140-kDa antigen has sequences homologous to the amino-terminal region and five parts of the internal domain of integrin alpha3. When the integrin alpha3-related sequences was amplified and used to analyse the mRNA of glioma and medulloblastoma surgical specimens, the transcription level of integrin alpha3 mRNA appeared to be quantitatively correlated with the grade of malignancy. These findings suggest that the ONS-M21 antibody, which reacts with integrin alpha3, might be useful in the diagnosis of gliomas and medulloblastomas.

Amino Acid Sequence↗

Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion.

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.

Adjuvants, Immunologic↗

In vitro DNA synthesis in freshly separated human breast cancer cells assessed by tritiated thymidine incorporation assay: relationship to the long-term outcome of patients.

BACKGROUND: Tumour growth rate has a significant effect on the clinical course of various malignancies. The present study was designed to assess whether in vitro DNA synthesis in freshly separated breast cancer cells is a useful marker in evaluating growth rates and in predicting the clinical outcome of patients. METHODS: From 1982 to 1992, DNA synthesis was assessed by [3H]thymidine incorporation in 97 samples of primary lesions from 94 patients with breast cancer. The patients were followed for 5-15 years and their outcome was surveyed in January 1998. RESULTS: The level of DNA synthesis did not correlate with the patients' age, clinical stage or expression of oestrogen receptor. However, it correlated significantly with the histological grade. In 89 patients, whose outcome was reported, the survival rate in the group with a high rate of DNA synthesis (log10c.p.m. 3.0 or more) was significantly lower than that in the low-level group; the 5- and 10-year survival rates were 84 and 74 per cent for the low synthesis group (n = 46), and 60 and 46 per cent for the high synthesis group (n = 43) respectively. This was also noted in patients with stage 1 or 2 cancers, for whom the 5- and 10-year survival rates were 100 and 90 per cent for the low synthesis group (n = 25), and 75 and 70 per cent for the high synthesis group (n= 35). Multivariate analysis supported this significant correlation for DNA synthesis in the prognosis of patients after mastectomy. Furthermore, the level of DNA synthesis was significantly higher in 18 patients who died from a recurrence within 3 years after operation than in 56 survivors, and the level of DNA synthesis also correlated significantly with the survival period in the 33 patients who died. CONCLUSION: The level of DNA synthesis in breast cancer was variable, and was independent of the clinical stage or oestrogen receptor status. However, a high level of DNA synthesis was a positive indicator of a high risk of recurrence after operation, especially for stage 1 or 2 breast cancer. In vitro DNA synthesis may account for some of the clinical characteristics of breast cancers.

Analysis of Variance↗

Hepatic stellate cells (Ito cells) in veno-occlusive disease of the liver after allogeneic bone marrow transplantation.

AIMS: To evaluate the role of activated hepatic stellate cells (HSCs) in hepatic veno-occlusive disease (VOD) after bone marrow transcription (BMT), we studied the distribution and area of activated HSCs by immunohistochemistry for alpha-smooth muscle actin (SMA). METHODS AND RESULTS: We examined the liver of seven autopsy cases with hepatic VOD or without VOD after allogeneic BMT and five autopsy cases without liver disease as a control both microscopically and immunohistochemically. In normal liver tissues, SMA-positive cells were observed around the central veins, while they were more frequently noted along the sinusoidal walls as well as around the central veins in liver tissues with or without VOD after BMT. The area of activated HSCs increased significantly in zones 1 and 2, and more prominently in zone 3 of the liver tissues after BMT than normal liver tissues, and was much larger in zone 3 of liver tissues with VOD. The activated HSCs were immunohistochemically negative for the regulatory contractile proteins (heavy caldesmon and calponin). CONCLUSIONS: These results indicated that the activated HSCs may play an important role in sinusoidal fibrosis and luminal narrowing or occlusion of the central veins in VOD after BMT.

Actins↗

Protein interactions of Gts1p of Saccharomyces cerevisiae throughout a region similar to a cytoplasmic portion of some ATP-binding cassette transporters.

The GTS1 gene product, Gts1p, has pleiotropic effects on the timing of budding, cell size, heat tolerance, sporulation and the lifespan of the yeast Saccharomyces cerevisiae. In this study, we found (using the yeast two-hybrid system) that Gts1p forms homodimers throughout the 18-amino acid region 296-313 which has considerable similarity to a region downstream of the Walker nucleotide-binding motif A of some ATP-binding cassette (ABC) transporters. The region contains two aspartic acid residues at 301 and 310 preceded by hydrophobic amino acid residues, and Gts1p with an Asp310 to Ala substitution showed considerably reduced homodimerization, as shown by the two-hybrid assay. Overexpression of the point-mutated Gts1p did not efficiently induce the Gts1p-related phenotypes described above, suggesting that the homodimerization of Gts1p is required for it to function in vivo. The C-terminal cytoplasmic domain of the yeast ABC transporters Mdl1p (multidrug resistance-like transporter) and Ycf1p (yeast cadmium factor or glutathione S-conjugate pump) bound to Gts1p in the two-hybrid system, and the heterodimerization activity of the Gts1p with the Asp301 to Ala substitution was more affected than the Gts1p with the Asp310 to Ala substitution. Overexpression of GTS1 considerably reduced, and disruption of GTS1 slightly decreased, cellular resistance to cycloheximide, cadmium, cisplatin and 1-chloro-2,4-dinitrophenol, which (except for cycloheximide) are all substrates of Ycf1p. These results suggest that Gts1p interacts with some ABC transporters through the binding site overlapping that of homodimerization and modulates their activity.

ATP-Binding Cassette Transporters↗

Molecular basis of left-right asymmetry.

In vertebrates visceral asymmetry is conserved along the left-right axis within the body. Only a small percentage of randomization (situs ambiguus), or complete reversal (situs inversus) of normal internal organ position and structural asymmetry is found in humans. A breakdown in left-right asymmetry is occasionally associated with severe malformations of the organs, clearly indicating that the regulated asymmetric patterning could have an evolutionary advantage over allowing random placement of visceral organs. Genetic, molecular and cell transplantation experiments in humans, mice, zebrafish, chick and Xenopus have advanced our understanding of how initiation and establishment of left-right asymmetry occurs in the vertebrate embryo. In particular, the chick embryo has served as an extraordinary animal model to manipulate genes, cells and tissues. This chick model system has enabled us to reveal the genetic pathways that occur during left-right development. Indeed, genes with asymmetric expression domains have been identified and well characterized using the chick as a model system. The present review summarizes the molecular and experimental studies employed to gain a better understanding of left-right asymmetry pattern formation from the first split of symmetry in embryos, to the exhibition of asymmetric morphologies in organs.

Animals↗

An analysis of T cell antigen receptor variable beta genes during the clinical course of patients with chronic hepatitis B.

BACKGROUND: The degree of hepatocyte injury in patients with chronic hepatitis B appears consistent with the number of T cells that respond to hepatitis B virus-related antigens. METHODS: By using a polymerase chain reaction (PCR)-based approach, we monitored a ratio of the T cell antigen receptor (TcR) variable (V) beta gene families against a total TcR V beta gene expression in the peripheral T cells obtained from five patients and four healthy controls. RESULTS: In the healthy controls, there was no significant change in the ratios at an interval of four or eight weeks. In contrast, several TcR V beta families showed the significant changes in the ratios of their gene expression during the follow-up period in all patients. No common highly fluctuated TcR V beta, however, was found among the patients. Furthermore, there was no correlation between their changes and serum levels of alanine aminotransferase. CONCLUSIONS: These findings suggest that the skewing of the TcR family with multiclone is the result of T-cell responses to viral antigens in peripheral blood.

Adult↗

Magnitude of activity in chronic hepatitis C is influenced by apoptosis of T cells responsible for hepatitis C virus.

BACKGROUND: The mechanisms of hepatitis C virus (HCV) persistence are unknown, but down-regulation of immune response in a host is likely to play a major role in it. METHODS: To investigate whether T cell apoptosis contributes to such down-regulation, we compared peripheral T cell apoptosis in patients with chronic hepatitis C (CHC) with the serum titre of HCV-RNA, serum alanine aminotransferase (sALT) levels and its change, or peripheral T cell proliferation to the recombinant core antigen of HCV, JCC-1. RESULTS: The percentage of apoptosis in T cells was 0.30 +/- 0.31% (mean +/- SD) in 44 patients with CHC and 0.10 +/- 0.05% in 10 normal volunteers (P < 0.05). In patients with CHC there was no statistical correlation between apoptosis in T cells and sALT levels, titre of HCV-RNA or T cell proliferation to JCC-1 antigen. But, in patients showing relatively more apoptosis in T cells (more than mean + 2SD of apoptosis in T cells from normal volunteers), sALT levels decreased. CONCLUSIONS: Thus, T cell apoptosis in patients with CHC is considered to cause a reduction in sALT, contributing to HCV persistence in patients with CHC.

Alanine Transaminase↗

Prostatic signet-ring cell carcinoma: case report and literature review.

Signet-ring cell carcinoma (SRCC) of the prostate is a very rare neoplasm and there have been only 38 cases reported to date. Here the 39th case of prostatic SRCC containing a small amount of neutral mucin, prostatic specific antigen (PSA) and prostatic specific acid phosphatase (PSAP) in the signet-ring cells is reported. It was also found that some intracytoplasmic lumina were derived from the shallow or deep invagination of luminal membranes of cancer cells that formed the neoplastic glands. Using immunohistochemistry, a combination of monoclonal antibodies against cytokeratins 7 and 20 as well as PSA and PSAP may be useful in differentiating prostatic primary SRCC from metastatic SRCC originating in the gastrointestinal tract.

Aged↗

Molecular analysis of enterohemorrhagic Escherichia coli isolates in Japan and its application to epidemiological investigation.

Many outbreaks of enterohemorrhagic Escherichia coli (EHEC) O157 infections occurred in Japan in 1996. Molecular epidemiological analyses of the isolates by methods such as XbaI-digested, pulsed-field gel electrophoresis (PFGE), revealed that a variety of PFGE type strains have spread all over Japan. They also showed that such molecular methods are very useful for confirming the epidemiologically related isolates and in assisting the epidemiological investigation. Recent characteristic features of the infection are that the incidence of patients experiencing symptoms such as abdominal cramps, diarrhea and hemorrhagic colitis is higher in children younger than 9 years old; however, that of asymptomatic carriers seems to be higher in adults; and that EHEC O157:H7-serotyped strains are still the main isolates, while the isolation frequency of other serotype strains, such as O26 and O111, is increasing.

Adolescent↗

Nasal lymphomas in Japan: a high prevalence of Epstein-Barr virus type A and deletion within the latent membrane protein gene.

The majority of nasal lymphomas are of the natural killer (NK)/T cell lineage. We analyzed 33 specimens of nasal lymphoma from Japanese patients for Epstein-Barr virus (EBV). Phenotypic and genetic analyses showed 28 cases with NK/T cell type and 5 cases with B cell type. All NK/T lymphomas were of pleomorphic cell type except 2 large cell (centroblastoid) and one lymphoblastic lymphoma. All cases with nasal B cell lymphoma were of large (centroblastoid) cell type. EBV was detected in all cases of NK/T cell type with the exception of one lymphoblastic case, and was monoclonally integrated in all cases examined (14/14 cases). All but one case had subtype A of EBV infection with 30-base paired deleted LMP-1 gene. One case of B cell lymphoma showed the presence of EBV infection with subtype A and deletion of LMP-1. Our results indicate that the majority of nasal lymphomas in Japanese patients are of the nasal NK/T cell type, have pleomorphic morphology, a high prevalence of EBV with a monoclonal integration, subtype A and deleted LMP-1 gene. In contrast, nasal B cell lymphoma showed monomorphic appearance and rare EBV infection.

Adolescent↗

Alteration of perceived fragrance of essential oils in relation to type of work: a simple screening test for efficacy of aroma.

The perceptional change of fragrance of essential oils is described in relation to type of work, i.e. mental work, physical work and hearing environmental (natural) sounds. The essential oils examined in this study were ylang ylang, orange, geranium, cypress, bergamot, spearmint and juniper. In evaluating change in perception of a given aroma, a sensory test was employed in which the perception of fragrance was assessed by 13 contrasting pairs of adjectives. Scores were recorded after inhaling a fragrance before and after each type of work, and the statistical significance of the change of score for 13 impression descriptors was examined by Student's t-test for each type of work. It was confirmed that inhalation of essential oil caused a different subjective perception of fragrance depending on the type of work. For example, inhalation of cypress after physical work produced a much more favorable impression than before work, in contrast to orange, which produced an unfavorable impression after physical work when compared with that before work. For mental work, inhalation of juniper seemed to create a favorable impression after work, whereas geranium and orange both produced an unfavorable impression then. From these studies, together with those conducted previously with lavender, rosemary, linalool, peppermint, marjoram, cardamom, sandalwood, basil and lime, we thus concluded that the sensory test described here might serve not only as a screening test for efficacy of aroma but also as a categorized table for aroma samples which can act as a reference to each other.

Adult↗

Relationship of the CCA sequence of tRNA with the early evolutional aspect of aminoacyl-tRNA synthetases.

The CCA sequence is common to the 3'-ends of all tRNAs. We investigated the requirement of the CCA sequence in aminoacylation with the cognate aminoacyl-tRNA synthetases (aaRSs) and several interesting conclusions could be drawn. In tRNAs belonging to the class I aaRSs, decreased aminoacylation activities resulted from the substitution of A76 with a pyrimidine, whereas in tRNAs belonging to the class II aaRSs, decreased aminoacylation activities resulted from the substitution with guanine. The results suggest that aminoacylation of proto-tRNA might have started through the direct hydrophobic (or stacking) interaction between the large, hydrophobic amino acid residue (now utilizing a class I aaRS) of aminoacyl-AMP and the 3'-terminal adenine. The shorter distance between the adenine and the 2'-OH position than the 3'-OH position, and the bulkiness and hydrophobicity of amino acids may be important reasons why class I aaRSs select the 2'-OH position in aminoacylation. Molecular mechanics-based conformation modeling also indicated that the resulting positioning of the adenine and the amino acid residue of 2'-aminoacyl-adenosine for large amino acid is in the vicinity. In contrast, in the case of small amino acids (with class II aaRSs) which would not be able to use the hydrophobic interaction, a protein enzyme might have participated in the aminoacylation reaction from an early stage. The active-site folds of aaRSs belonging to each class reflect the history of evolution: typical nucleotide-binding fold (Rossman fold) in the case of class I aaRSs, and primitive fold which is found also among the family of nonribosomal peptide synthetases in the case of class II aaRSs.

Amino Acyl-tRNA Synthetases↗