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Biomedical subjects

T Tsukamoto

Publications and source records attributed to T Tsukamoto.

At least 181 records · Page 10Linked to original sources
PubMed1999

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.

Anti-Bacterial Agents↗
PubMed1999

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). II. Background of patients].

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 603 bacterial strains were isolated in 9 hospitals during the period from June, 1997 through May, 1998. 1. Distribution of age and sex of patients and type of infections Among males, those with ages less than 50 years were only 12.5%, and those in the 70's were most frequent (33.3%). Among females, those with ages less than 20 years were only 3.4%, and those in the 60's were the most frequent (22.9%). With regard to type of infections, more than a half of infections among males with ages 50 years or older were of complicated types, but most of infections among females were of uncomplicated types, especially those of ages less than 50 years. 2. Ages of patients and types of pathogens Escherichia coli was the most frequently isolated in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, Pseudomonas aeruginosa and Enterococcus faecalis had mainly detected, they had no relationship with ages. 3. Effect of antibiotic use on isolation frequencies of pathogens Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (183 isolates before antibiotics compared to 13 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (175 isolates before antibiotics compared to 53 after), but when indwelling catheters were in use, antibiotics slightly decreased (109 isolates before antibiotics compared to 70 after). 4. Surgical procedures and types of causative organisms for UTIs E. faecalis were more isolated when a surgical procedures were used, and E. coli were more isolated when, they were not used in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, E. coli and E. faecalis were more isolated when a surgical procedures were used, and P. aeruginosa and Staphylococcus aureus were more isolated when they were not used.

Adult↗
PubMed1999

[Early detection and prevention of cancers in various therapeutic areas. Discussion].

As illustrated by prostate cancer screening provides an opportunity for early intervention and treatment. However the screening test needs to detect patients with cancer with a low rate of false positives and at a stage which can be treated. Recently the concept of treating patients at high risk of developing breast cancer or suffering a recurrence has been highlighted by the western studies with Nolvadex (tamoxifen). Thus roundtable discussion (held in Tokyo) discussed the different strategies in Japan compared to US & Europe for screening & early intervention/prevention of cancer for breast, prostate, bladder, liver, lung, gynaecological & GI cancers. The range of strategies for cancer screening, how it is funded, whether it is appropriately targeted and whether there is any evidence for a beneficial effect on morbidity or mortality & future prospects for improved sensitivity through new methodology or markers were discussed. Although the relative rates of cancer vary between Japan & the West, the same factors seem to influence cancer development & the data on intervention were seen to be valid. The changing patterns of cancer in Japan suggest a clear opportunity for reducing, the incidence of cancer through lifestyle modification. For some cancers, e.g. cervical & bladder where there is a clear link between abnormal cytology & development cancer true prevention is already practiced. In other cases, preventive treatment is limited by the efficacy of available therapies. As far as drug treatment is concerned, funding of healthcare in Japan does not recognise the concept of prevention although there is, in practice, no barrier to the use of interventions where there is a clear link between biochemical/histological markers & development of cancer.

Breast Neoplasms↗
PubMed1999

Shiga-toxin producing Escherichia coli from healthy cattle in a semi-urban community in Calcutta, India.

From October to December 1998, single faecal samples from 67 healthy cattle in a semi-urban community near Calcutta were examined for Shiga toxin producing Esch. coli (STEC) using a multiplex PCR primary screen followed by plating on sorbitol MacConkey agar. STEC was isolated from the faeces of 7 (10.5%) animals. The eight strains isolated belonged to eight serotypes viz, O146:H1, O149:HNT, ONT:H34, ONT:H19, O88:HN, ONT:H2, O82:H8 and O28ac:H21. Bead enzyme linked immunosorbent assay showed that three strains produced Shiga toxin 1, one produced Shiga toxin 2 and four produced both.

Animals↗
PubMed1999

New animal model of glandular stomach carcinogenesis in Mongolian gerbils infected with Helicobacter pylori and treated with a chemical carcinogen.

In 1994 WHO/IARC concluded that "Helicobacter pylori is a definite carcinogen" based on epidemiological studies, but there have been few reports demonstrating a relation between H. pylori and stomach cancer in animal models. We have succeeded in producing adenocarcinomas in the glandular stomachs of Mongolian gerbils with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methyl-N-nitrosourea as carcinogens and hope to establish an experimental stomach carcinogenesis model using H. pylori. Male Mongolian gerbils, 7 weeks old, were infected with H. pylori followed by MNNG administration at a concentration of 100ppm administration or treated with MNNG at a concentration of 300ppm in their drinking water followed by inoculation with H. pylori. They were then killed sequentially, and their excised stomachs underwent microbiological and histopathological examinations. H. pylori were detected in all infected gerbils. Hyperplastic change of pyloric mucosa was observed with high 5-bromo-2'-deoxyuridine incorporation in affected animals. H. pylori infection persists on administration of MMNG and enhances glandular stomach proliferation in Mongolian gerbils. Whether long-term colonization promotes carcinogenesis in the glandular stomach of Mongolian gerbils is a matter of great interest.

Adenocarcinoma↗
PubMed1999

[High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group].

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.

Adolescent↗
PubMed1998

Allelic loss on chromosome 9 in bladder cancer tissues and urine samples detected by blunt-end single-strand DNA conformation polymorphism.

Allelic loss on chromosome 9 is the most frequent and earliest genetic event in bladder carcinogenesis, and its detection in urine samples would be useful for detecting bladder cancer. A highly sensitive method to detect loss of heterozygosity (LOH) at 5 polymorphic loci on chromosome 9p and 9q was developed by the use of blunt-end single-strand DNA conformation polymorphism (blunt-end SSCP) analysis. Tumor tissues, urine samples and peripheral blood lymphocytes from 34 patients with transitional cell carcinoma of the bladder were analyzed. LOHs on 9p and/or 9q were found in 24 (71%) of 34 tumor samples and 23 (70%) of 33 urine samples, while no allelic loss was detected in 20 urine samples from benign urothelial diseases. The frequency of allelic loss in tumor tissues was 67%, 71% and 80% in the pTa, pT1 and > or = pT2 stages and 50%, 80% and 79% in G1, G2 and G3 tumors, respectively. In comparison with a urine cytological examination, LOH on chromosome 9 was detected in 70% of urine samples diagnosed as transitional cell carcinoma, 67% of those as atypia and 70% of those as no malignant cells. Thus, detection of LOH on chromosome 9 from urine samples by blunt-end SSCP is a more sensitive diagnostic modality than cytologic examination for detecting bladder cancer. It would be useful for postoperative management of bladder cancer, particularly when the allelic loss is revealed in the tumor tissues obtained at first surgery.

Carcinoma, Transitional Cell↗
PubMed1998

Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors.

To identify the proteins which may modulate the functions of peroxisome proliferator-activated receptor (PPAR), a rat liver cDNA library was screened by a yeast two-hybrid system, using the mouse PPARalpha as a bait. A protein named nuclear receptor binding factor-1 (NRBF-1) was identified, which interacts not only with PPARalpha, but also with various nuclear hormone receptors in the presence of the respective ligands. Both the hinge and ligand-binding domains of PPARalpha are required for the interaction. NRBF-1 seems to be translocated to the nucleus by a piggyback mechanism, together with PPARalpha. NRBF-1 has a significant homology to the yeast protein MRF1, a putative transcription factor regulating the expression of mitochondrial respiratory proteins. NRBF-1 might be another type of nuclear receptor co-operator.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of three human cDNAs encoding mRNA (guanine-7-)-methyltransferase, an mRNA cap methylase.

The mRNA cap structure is synthesized by a series of reactions catalyzed by capping enzyme and mRNA (guanine-7-)-methyltransferase. mRNA (guanine-7-)-methyltransferase catalyzes the methylation of GpppN- at the guanine N7 position, which is an essential step for gene expression in eukaryotic cells. Here we isolated three human cDNAs encoding mRNA (guanine-7-)-methyltransferase termed hCMT1a, hCMT1b and hCMT1c. hCMT1a and hCMT1b encode 476 and 504 amino acids, respectively, and differ only at the region coding for the C-terminal portion of the enzyme after amino acid residue 465. The third cDNA hCMT1c seems to encode the same polypeptide as hCMT1a, however, the 3'-noncoding region of hCMT1c contains sequences corresponding to part of the C-terminal coding and noncoding regions of hCMT1b thus consisting of a mosaic of hCMT1a and hCMT1b. RT-PCR showed that all 3 types of mRNAs were expressed in every tissue examined. Comparison of the deduced amino acid sequences with those of other viral and cellular enzymes showed the regions which are highly conserved among mRNA (guanine-7-)-methyltransferases. The recombinant hCMT1a expressed in E. coli exhibited mRNA (guanine-7-)-methyltransferase activity. On the other hand, neither mRNA (guanine-7-)-methyltransferase nor mRNA (nucleoside-2'-O-)-methyltransferase activity was detected with the recombinant hCMT1b protein. Although the biological significance of the expression of these three mRNA (guanine-7-)-methyltransferase mRNA species remains unknown at present, the nucleotide sequences suggest that they are produced by alternative RNA splicing.

Amino Acid Sequence↗
PubMed1998

Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders.

BACKGROUND: Heils et al found a functional polymorphism in the transcriptional control region upstream of the serotonin transporter gene at the SLC6A4 locus. The transcriptional promoter activity of the short (s) form was less than twice that of the long (l) form of the serotonin transporter promoter gene. In addition, they found individuals with the s form with associated neurotic characteristics (e.g., anxiety, anger, hostility, and depression). The purpose of this study was to determine whether or not there is an association between this functional polymorphism and mood disorders. METHODS: The l/s polymorphism was studied in 80 patients with mood disorders and 92 control subjects. RESULTS: There was statistically no difference between mood disorders and healthy controls in either the genotype or the allele frequency. There was statistically no difference between the genotype and subdiagnosis, family history, single/recurrent episodes of depressive disorders, suicide attempts, or the mean age of onset. CONCLUSIONS: Our results suggest there is no association between the l/s polymorphism of the serotonin transporter gene and mood disorders.

Adult↗
PubMed1998

Cancer-associated expression of glycolipid sulfotransferase gene in human renal cell carcinoma cells.

Human renal cell carcinoma (RCC) tissue and a cell line derived therefrom, SMKT-R3, showed markedly increased glycolipid sulfotransferase [cerebroside sulfotransferase (CST); EC 2.8.2.11] activity and accumulated sulfoglycolipids. Recently, we cloned a human CST cDNA from a SMKT-R3 cDNA library (K. Honke et al., J. Biol. Chem., 272: 4864-4868, 1997). In this study, we investigated the expression of the CST gene in seven human RCC lines (SMKT-R1, SMKT-R2, SMKT-R3, SMKT-R4, TOS-1, TOS-2, and ACHN) and their normal counterpart, human renal proximal tubular cells. On Northern blot analysis, a marked increase of CST mRNA was observed in every RCC line, except for ACHN, as compared with normal cells. ACHN cells showed a slightly increased level of CST mRNA. CST activity was correlated with the amount of mRNA. Sulfoglycolipid analysis revealed that expression of lactosylceramide sulfate was correlated with the CST level. Furthermore, we examined the effects of epidermal growth factor (EGF), tetradecanoylphorbol-13-acetate, and genistein, which are known to regulate CST activity in SMKT-R3 cells, on CST-gene expression in various RCC cells. On treatment with EGF, CST mRNA time-dependently increased in accord with its activity in SMKT-R3 cells. Yet, augmentation by EGF was only observed in SMKT-R3. In contrast, a reduction of CST mRNA and activity by tetradecanoylphorbol-13-acetate and genistein was observed in all of the lines examined. Taken together, these findings indicate that in human RCC cells, the CST gene is generally overexpressed via a signaling pathway involving protein kinase-C and tyrosine kinases.

Carcinoma, Renal Cell↗
PubMed1998

Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma.

Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection.

3T3 Cells↗
PubMed1998

Mechanism-based inhibition of human folylpolyglutamate synthetase: design, synthesis, and biochemical characterization of a phosphapeptide mimic of the tetrahedral intermediate.

Folylpolyglutamate synthetase (FPGS) catalyzes anATP-dependent ligation reaction that results in the synthesis of poly(gamma-glutamate) metabolites of folates and some antifolates. We have synthesized and characterized the prototype of a new class of mechanism-based FPGS inhibitor in which a phosphonate moiety mimics the tetrahedral intermediate formed during the ligation reaction. This phosphonate, 4-amino-4-deoxy-10-methyl-pteroyl-L-glutamyl-gamma-[Psi¿P(O)(OH)-O¿] glutarate (4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi¿P(O)(OH)-O¿]glutarate), is not a substrate for human FPGS, but is a linear, competitive inhibitor (Kis = 46 nM) with respect to methotrexate as the variable substrate. Inhibition is not time-dependent and preincubation of FPGS with this phosphonate does not increase the degree of inhibition, suggesting that it is not a slow, tight-binding inhibitor involving a time-dependent isomerization, EI --> EI*. Substructures containing the phosphonate moiety but lacking the pterin are much less inhibitory to FPGS, indicating that a significant portion of the inhibitor binding energy is derived from the pterin moiety, a feature also observed in substrate binding. 4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi¿P(O)(OH)-O¿]glutarate is also an analog of a proposed tetrahedral intermediate in the reaction catalyzed by gamma-glutamyl hydrolase (gamma-GH), another enzyme of importance in controlling folate homeostasis in cells. This intermediate would arise from direct attack of H2O on the dipeptide, 4-NH2-10-CH3-Pte-L-Glu-gamma-L-Glu. The fact that 4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi¿P(O)(OH)-O¿]glutarate is not an inhibitor of gamma-GH strongly suggests that hydrolysis of poly-gamma-glutamates catalyzed by gamma-GH does not involve the direct attack of water at the scissile amide bond. Methotrexate, its gamma-glutamyl dipeptide metabolite, and 4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi¿P(O)(OH)-O¿]glutarate are equipotent as inhibitors of human dihydrofolate reductase (the primary target of methotrexate), but the phosphonate does not significantly inhibit another important folate-dependent enzyme, thymidylate synthase. Thus, the phosphonate moiety in this analog represents an important new lead in the development of FPGS inhibitors.

Animals↗
PubMed1998

Polymorphism in the promoter region of the alpha 2A adrenergic receptor gene and mood disorders.

Alpha 2 adrenergic receptors are thought to play a crucial role in the etiology or treatment of mood disorders. Polymorphism(s) in the promoter region of the alpha 2 receptor may affect the gene expression and be associated with mood disorders. We studied the previously reported polymorphisms of the alpha 2A receptor gene at position-1291 in 114 healthy controls and 103 mood disorder patients. There was statistically no difference between controls and patients in either the genotype or the allele frequency. There was statistically no difference between the genotype and the clinical characteristics. Our results suggest there is no association between this polymorphism in the promoter region of the alpha 2A receptor gene and mood disorders.

Alleles↗
PubMed1998

A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p.

Human PEX1 (HsPEX1) is the causative gene for peroxisome-deficiency disorders such as Zellweger syndrome of complementation group I, encoding the peroxin, Pex1p, a member of AAA family. Pex1p tagged with an epitope flag was expressed in wild-type Chinese hamster ovary (CHO) cell, CHO-K1. Pex1p was localized in the cytoplasm, as assessed by immunofluorescent microscopy. Cell-lysate of HsPEX1-transfected CHO-K1 was incubated with in vitro synthesized 35S-labelled Pex6p, an AAA family peroxin. Immunoprecipitation of Pex1p using anti-Pex1p antibody resulted in concomitant recovery of 35S-Pex6p. Conversely, 35S-Pex1p was obtained in immunoprecipitate from CHO-K1 expressing human Pex6p, using anti-Pex6p antibody. These results strongly suggest that Pex1p and Pex6p interact with each other.

ATPases Associated with Diverse Cellular Activitie↗