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Biomedical subjects

H Koga

Publications and source records attributed to H Koga.

At least 109 records · Page 6Linked to original sources
PubMed1998

Infections caused by multiple strains of methicillin-resistant Staphylococcus aureus--a pressing epidemiological issue.

The genotype of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from several foci in the same patient was studied to identify the rate of infections caused by multiple MRSA strains during hospitalization. Twenty-one patients with MRSA bacteraemia and other specimens diagnosed between 1990-1994 were studied. Clinical data were retrospectively collected from the medical records. Genotyping of 113 MRSA isolates was performed by pulsed-field gel electrophoresis (PFGE), using the Gene Navigator System. More than one type of MRSA was detected from different foci in eight of 21 (38%) patients, and three types were identified in a single patient. Our results indicate that epidemiological investigations must be conducted carefully, especially in immunocompromised hosts with MRSA bacteraemia, as the probability of infection with multiple strains among these patients is relatively high.

Adult↗
PubMed1998

Fibroblast-migration in a wound model of ascorbic acid-supplemented three-dimensional culture system: the effects of cytokines and malotilate, a new wound healing stimulant, on cell-migration.

To assess the migratory response of fibroblasts in vitro, normal human dermal fibroblasts (NHDF) were cultured in the presence of L-ascorbic acid 2-phosphate to induce a multilayered structure. Round wounds were made by punching, and the migratory response was evaluated by counting the number of migrating cells in the wounded areas. Collagenase activity in the culture-medium was then measured. When the wound model was treated with bFGF, IL-1 alpha or PDGF, the migratory response was facilitated with increased collagenase secretion. In contrast, treatment with TGF-beta reduced the migratory response and collagenase secretion. Since the multilayered structure is rich in collagenous matrix, degradation of the matrix by secreted collagenase is probably necessary for the cells to migrate into the wounded areas. Furthermore, malotilate, which is now under development as an agent for wound therapy, facilitated the migratory response of NHDF with increased collagenase secretion in this wound model, suggesting that the wound healing effect of malotilate is in part attributable to stimulated migration of fibroblasts to wounded areas subsequent to extracellular matrix-degradation.

Ascorbic Acid↗
PubMed1998

Glucose intolerance and adenomas of the sigmoid colon in Japanese men (Japan).

OBJECTIVES: The purpose was to investigate the relation between glucose tolerance and risk of sigmoid colon adenomas, a well-established precancerous lesion, in Japanese men. METHODS: In the consecutive series of 7,637 men aged 48 to 59 years who received a preretirement health examination at four hospitals of the Self Defense Forces (SDF) in Japan from 1986 to 1994, we identified 821 cases of sigmoid colon adenomas and 4,372 controls with normal sigmoidoscopy or colonoscopy at 60 cm or more from the anus. Glucose tolerance status was classified as normal, impaired glucose tolerance (IGT), newly diagnosed non-insulin dependent diabetes mellitus (NIDDM), or diabetes mellitus under treatment, based on a 75g oral glucose tolerance test and medical history. Statistical adjustment was made for body mass index (wt/ht2), cigarette smoking, alcohol use, rank of the SDF, and hospital. RESULTS: Modest increases in adenoma risk were observed for newly diagnosed NIDDM and diabetes mellitus under treatment while there was no association between IGT and adenoma risk. When small (< 5 mm in diameter) and large (5+ mm) adenomas were analyzed separately, increased risk associated with newly diagnosed NIDDM was more pronounced for small adenomas, and diabetes mellitus under treatment showed a slightly stronger association with large adenomas. CONCLUSIONS: The findings suggest that NIDDM is associated with modestly increased risk of sigmoid colon adenomas, and add to evidence that hyperinsulinemia increases colon cancer risk.

Adenoma↗
PubMed1998

The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas.

Neurofibromatosis type 2 (NF2) protein, also known as merlin or schwannomin, is a tumor suppressor, and NF2 is mutated in most schwannomas and meningiomas. Although these tumors are dependent on NF2, some lack detectable NF2 mutations, which indicates that alternative mechanisms exist for inactivating merlin. Here, we demonstrate cleavage of merlin by the ubiquitous protease calpain and considerable activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway.

Base Sequence↗
PubMed1998

Donor leukocyte infusion after allogeneic bone marrow transplantation was not effective for relapsed rhabdomyosarcoma.

A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling and received an allogeneic BMT. Recurrence was detected in the BM as the only site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10(7)/kg) were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died of disease progression 9 months after DLI.

Bone Marrow Transplantation↗
PubMed1998

Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes.

BACKGROUND: Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid-binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin-conjugating enzymes. Nedd4 has been reported to be involved in the selective ubiquitination of some regulatory proteins in transcription and membrane transport. RESULTS: Three mRNA species for human Nedd4 were found to be 6.4-, 7.8- and 9.5-kb in size, and their expression patterns varied among normal tissues and cancer cell lines, indicating the tissue- and cell-specificities of Nedd4 expression. The Nedd4 protein, approximately 120 kDa in weight, was found in the cytoplasm, mainly in the perinuclear region and cytoplasmic periphery, of human cultured cells. Neural differentiation induced not only the down-regulation of Nedd4 but also the localization of the protein to both the cytoplasm and neurites. To identify the ubiquitination pathway that is linked to Nedd4, we demonstrated that specific E2 enzymes, including human Ubc4, UbcH5B, UbcH5C, UbcH6 and UbcH7, could transfer ubiquitin molecules to Nedd4 at the active cysteine residue, whereas E6AP accepted ubiquitins from Ubc4, UbcH5B, UbcH5C and UbcH7. Furthermore, nuclear localization of N-terminal deletion mutant Nedd4 enabled us to investigate the interaction between Nedd4 and E2 enzyme (Ubc4 or UbcH7) in the cell. The simultaneous expression of the full-length Nedd4 and E2 enzyme revealed the both proteins mostly colocalized in the cytoplasmic periphery, while the N-terminal deleted Nedd4 induced the nuclear and perinuclear colocalization with E2 enzyme. CONCLUSION: Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways.

Cell Differentiation↗
PubMed1998

Aortitis syndrome (Takayasu's arteritis) with cataract and elevated serum level of vascular endothelial growth factor.

The aortitis syndrome is a chronic inflammatory process that affects the aorta and its primary branches. Patients with aortitis syndrome exhibit various ocular changes. We present a patient in whom cataract was the initial objective finding. The serum concentration of vascular endothelial growth factor, a cytokine that affects neovascularization, and vasopermeability, was elevated before the initiation of prednisolone treatment. Cataract should be considered as a possible characteristic initial finding in patients with aortitis syndrome. Vascular endothelial growth factor may be involved in the progression of aortitis syndrome.

Adult↗
PubMed1998

Genetic mapping of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.

Chromosome Mapping↗
PubMed1998

Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.

We compared the in-vitro antimycobacterial activities of rifabutin and KRM-1648, two rifamycin derivatives, with that of rifampicin against 163 strains of Mycobacterium tuberculosis. We also evaluated the correlation between the level of resistance to rifampicin, rifabutin and KRM-1648 and genetic alterations in the rpoB gene. All 82 strains susceptible to rifampicin or resistant to rifampicin with MICs < or = 16 mg/L were susceptible to rifabutin and KRM-1648 with MICs < or = 1 mg/L. Seventy-six of 81 strains resistant to rifampicin with MICs > or = 32 mg/L were resistant to both rifabutin and KRM-1648, but with lower MICs than those of rifampicin. KRM-1648 showed more potent antimycobacterial activity than rifabutin against organisms with low MICs (< or = 1 mg/L), while rifabutin was more active than KRM-1648 against organisms with high MICs (> or = 2 mg/L). A total of 96 genetic alterations around the 69 bp core region of the rpoB gene were detected in 92 strains. Alterations at codons 515, 521 and 533 in the rpoB gene did not influence the susceptibility to rifampicin, rifabutin and KRM-1648. Point mutations at codons 516 and 529, deletion at codon 518 and insertion at codon 514 influenced the susceptibility to rifampicin but not that to rifabutin or KRM-1648. With the exception of one strain, all alterations at codon 513 and 531 correlated with resistance to the three test drugs. The resistant phenotype of strains with an alteration at codon 526 depended on the type of amino acid substitution. Our results suggest that analysis of genetic alterations in the rpoB gene might be useful not only for predicting rifampicin susceptibility, but also for deciding when to use rifabutin for treating tuberculosis. Further studies may be required to determine the usefulness of KRM-1648.

Amino Acid Sequence↗
PubMed1998

Detection of Mycobacterium tuberculosis in preserved tuberculous lymph nodes by polymerase chain reaction.

We evaluated the usefulness of three types of polymerase chain reaction (PCR) targeting 16S rRNA, protein antigen b and IS6110 in detecting Mycobacterium tuberculosis in preserved tuberculous lymph nodes. The detection limit of all PCR methods was 100 colony forming unit (CFU) of M. tuberculosis in tissue. The test samples included eight paraffin-embedded tuberculous lymph nodes containing microscopical epithelioid cell granuloma with caseous necrosis and Langhans giant cells. Although acid-fast stained organisms in lymph node tissue were not detected in any sample, all three types of PCR tests were positive in four of eight lymph nodes. Our results suggest that PCR is not only a rapid and sensitive diagnostic method for tuberculous lymphadenitis, but also clinically significant in retrospective study for detecting M. tuberculosis even in some preserved lymph node tissues without evidence of acid-fast stained organisms.

Antigens, Bacterial↗
PubMed1998

[High-resolution CT findings in cytomegalovirus pneumonitis after bone marrow transplantation].

In order to explore the high-resolution CT (HRCT) findings of cytomegalovirus (CMV) pneumonitis after bone marrow transplantation, we retrospectively reviewed the HRCT findings in nine patients with CMV pneumonitis cytologically proven by bronchoalveolar lavege. In 67% of cases, HRCT showed ground-glass attenuation. Consolidation and bronchial wall thickening were demonstrated in 33%, pleural effusion in 22%, and micro centrilobular nodules, bronchiectasis, and reticulation in 11%, respectively. Lymphadenopathy and masses were not seen. The areas of ground-glass attenuation were distributed bilaterally in all cases, diffusely in 67%, centrilobularly in 50%, and panlobularly in 50%. Subpleural lung regions were spared in 83%. The areas of consolidation were bilateral in 67%, nonsegmental in 67%, and involved the lower lobe in all cases. A total of 25 follow-up HRCT were performed in six patients. Small centrilobular ground-glass opacities disappeared after treatment in one patient. Micro centrilobular nodules vanished after treatment in one patient. Small centrilobular ground-glass opacities developed into consolidation and resolved after treatment in one patient. In one patient, diffuse ground-glass opacities progressed to consolidation, and the patient died due to respiratory failure. No abnormal findings were observed in two patients. It may be considered that in the early phase of CMV pneumonitis HRCT shows small or micro centrilobular ground-glass opacities and nodules and that in the advanced phase these lesions progress to dense alveolar opacities as CMV infection advances, although a variety of HRCT appearances is observed in the course of CMV pneumonitis.

Adult↗
PubMed1998

[Establishment of new diagnostic technique and its clinical application for nontuberculous mycobacterial infections].

The clinical futures of 52 patients with pulmonary Mycobacterium avium complex infection (MAC group), 7 M. kansasii infection (MK group), and 5 M. chelonae infection (MC group) were studied. Aged female was dominant in MAC and MC group, while middleaged man was dominant in MK group. Although body mass index (BMI) was the lowest in MAC group, there was no difference between the groups in clinical sign, symptom, and laboratory data. Type III radiological finding was dominant in MAC group, while type II in MK and MC groups. Bacteriological eradication rate of causative organisms was 86% in MK group, 54% in MAC group, and 40% in MC group. However, the relation between clinical efficacy of chemotherapy, BMI, serum protein level, and cavity formation in chest radiogram was not observed. MAC was detected in clinical samples such as sputum, bronchial washing fluid, and gastric juice with 5 to 10% in frequency by Amplicor, one of commercially available PCR detection kits for mycobacteria. Furthermore 60% to 80% of the MAC positive cases were diagnosed and treated as nontuberculous mycobacteriosis. Although MAC is occasionally exist in oral cavity or clinical environment, the positive result of genetic diagnostic method such as Amplicor should be carefully considered.

Aged↗
PubMed1998

Development of novel reversal agents, imidazothiazole derivatives, targeting MDR1- and MRP-mediated multidrug resistance.

Three newly synthesized imidazothiazole derivatives (N276-12, N276-14, N276-17) were examined regarding their ability and mechanism as a chemosensitizing agent against multidrug resistance 1 (MDR1)-mediated and multidrug resistance-associated protein (MRP)-mediated MDR. All three N276 compounds almost completely reversed the acquired resistance to vincristine (VCR), vinblastine (VBL), and doxorubicin (DXR) in MDR1-overexpressing human cancer cell lines (KB/VJ300 and T24/VCR). Their reversal effect against acquired resistance to VCR, DXR, and etoposide (VP16) was partial but clearly observed in the cell line expressing MRP (KB/VP4). All three N276 compounds enhanced the intracellular accumulation of [3H]VCR in MDR1-overexpressing KB/VJ300 cells through the inhibition of the increased efflux of the drug. They (100 microM) almost completely inhibited the photoaffinity labeling of P-glycoprotein encoded by the MDR1 gene. All the N276 compounds also remarkably enhanced the sensitivity to VBL and DXR in both MDR1- and MRP-overexpressing renal cell carcinoma (RCC) cell line (NKK1), whereas they showed no potentiation of these anticancer agents in an RCC cell line (KPK1) expressing neither MDR1 nor MRP. The combination chemotherapy of VCR or VP16 with N276-12 significantly increased the life span of mice inoculated i.p. or i.v. with drug-resistant P388/VCR cells without any significant side effects, whereas chemotherapy with the anticancer agent alone did not increase the life span at all. These results suggest that these newly synthesized imidazothiazole derivatives can be a useful chemosensitizing agent against not only MDR1- but also MRP-mediated MDR.

ATP-Binding Cassette Transporters↗