Search PubMed⌕ Search

Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 109 records · Page 6Linked to original sources

Characterization of the 25K FP gene of the baculovirus Bombyx mori nucleopolyhedrovirus: implications for post-mortem host degradation.

Mutagenesis experiments on the baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV) using 5-bromo-2'-deoxyuridine generated five mutants with a 'few polyhedra' (FP) phenotype. Sequence analysis of the 25K gene homologue of the BmNPV FP mutants revealed nucleotide substitutions in the coding region. Rescue experiments indicated that the FP phenotype of the BmNPV mutants resulted from mutations in the 25K coding region. Effects of infection by these FP mutants were analysed following injection of the viruses into silkworm (B. mori) larvae. Compared to infection with wild-type virus, infection with each FP mutant resulted in reduced host degradation (liquefaction). The degree to which liquefaction was blocked corresponded to the degree of functional disruption of the 25K gene product and to the extent to which polyhedron production was reduced. Electron microscopy revealed that (1) polyhedron production was reduced, (2) very few virions were occluded and those that were lacked envelopes, and (3) the basal lamina of fat-body tissue was not destroyed by infection and accumulations of virions occurred along the membrane. Typical NPV-induced liquefaction was observed following infection with a polyhedrin deletion mutant, indicating that host degradation was not related to polyhedron production. These results suggest that (1) the 25K gene product is involved in the host degradation process caused by virus infection and (2) the FP phenotype is an indirect result of disruption of the 25K gene; activation or suppression of a specific host or viral gene related to tissue degradation and polyhedron formation may be involved.

Amino Acid Sequence↗

Iron reductase for magnetite synthesis in the magnetotactic bacterium Magnetospirillum magnetotacticum.

Ferric iron reductase was purified from magnetotactic bacterium Magnetospirillum (formerly Aquaspirillum) magnetotacticum (ATCC 31632) to an electrophoretically homogeneous state. The enzyme was loosely bound on the cytoplasmic face of the cytoplasmic membrane and was found more frequently in magnetic cells than in nonmagnetic cells. The molecular mass of the purified enzyme was calculated upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be about 36 kDa, almost the same as that calibrated by gel filtration analysis. The enzyme required NADH and flavin mononucleotide (FMN) as optimal electron donor and cofactor, respectively, and the activity was strongly inhibited by Zn2+ acting as a partial mixed-type inhibitor. The Km values for NADH and FMN were 4.3 and 0. 035 microM, respectively, and the Ki values for Zn2+ were 19.2 and 23.9 microM for NADH and FMN, respectively. When the bacterium was grown in the presence of ZnSO4, the magnetosome number in the cells and the ferric iron reductase activity declined in parallel with an increase in the ZnSO4 concentration of the medium, suggesting that the ferric iron reductase purified in the present study may participate in magnetite synthesis.

FMN Reductase↗

Increased level of apolipoprotein B/apolipoprotein A1 ratio as a potential risk for osteonecrosis.

OBJECTIVE: This study was performed to investigate whether a high ratio of apolipoprotein B to apolipoprotein A1 (apo B/apo A1 ratio) is significantly associated with the risk of developing non-traumatic osteonecrosis of the femoral head (ON). METHODS: Fifty consecutive non-traumatic ON cases were compared with 50 age and sex matched controls, using both univariate and stepwise discriminant analyses, regarding the factors of corticosteroid, alcohol, cigarettes, cholesterol, triglyceride, and apo B/apo A1 ratio. To eliminate the possibility that ON or osteoarthritic change itself can increase the apo B/apo A1 ratio, a further 32 consecutive cases comprising nine traumatic ON and 23 osteoarthritis (OA) patients were analysed using Scheffe's test. RESULTS: There was a significant association between a high apo B/apo A1 ratio and the development of non-traumatic ON with both univariate (p=0.0001) and stepwise discriminant analyses (partial r(2)=0.1239, p=0.0004). The apo B/apo A1 ratio in the non-traumatic ON group was significantly higher than that in the traumatic ON (p<0.01), control (p<0.001), or the OA groups (p<0.001). CONCLUSION: A high apo B/apo A1 ratio is significantly associated with the risk of developing ON. This ratio may be useful for assessing the potential risk of developing osteonecrosis.

Adolescent↗

In vitro reconstitution of the tracheal epithelium.

We have developed a unique in vitro reconstitution system for tracheal epithelia of guinea pigs. In the system, a human amnion membrane was used as a basement membrane and the tracheal epithelial cells were cultured on the epithelial side of the membrane. Three weeks later, the tracheal fibroblasts were co-cultured on the serosal side of the amnion membrane and the culturing was continued for an additional 10 d. The morphology of the cultured epithelial cells consisted of a pseudostratified columnar ciliated epithelium from cuboidal ciliated epithelium during the last 10 d of the culture period. Epithelial cells included both goblet-like and basal cells. In addition, the frequency of each type of differentiated cells was almost identical to that of in vivo tracheas. Interestingly, the same results were obtained when the conditioned medium of the tracheal fibroblasts was used instead of the fibroblasts themselves. These results suggest that epithelial-mesenchymal interaction is likely involved in growth and differentiation of epithelial cells in vivo in a soluble factor(s)-mediated manner. As well as the epithelial cells, the fibroblasts also formed a multilayer during the last 10 d of co-culturing. This indicates that in vitro reconstitution of tracheal epithelia is achieved without addition of any exogenous growth or differentiation factors. The reconstitution system is shown to be useful for investigating the cellular and molecular interaction of epithelial and mesenchymal cells. Possible applications of the culture system and possible factors involved in growth and differentiation of epithelial cells are discussed.

Amnion↗

Progressive sensorineural hearing impairment in professional fishery divers.

There have been many reports of a high rate of hearing impairment in divers. A prospective study was performed to determine whether sensorineural hearing acuity in the same divers deteriorated faster than in a normal population as they continued diving. After an observation period of approximately 5 years, audiometric examination was performed on a group of professional fishery divers who had normal hearing or sensorineural hearing loss at the time of initial study. Thirty-three ears of 18 divers were included in statistical analyses. The average hearing deterioration in the divers in 5 years, after elimination of the aging effect, was 6.6 dB (SD 4.5) and was statistically significant. We concluded that the hearing acuity of our subjects deteriorated faster than that of normal Japanese.

Adult↗

Glucose transporter expression in developing fetal lungs and lung neoplasms.

Glucose uptake and metabolism are essential for proliferation and survival of cells, and are supposed to be enhanced in actively proliferating cell systems such as embryonic and cancer tissues. Glucose uptake is usually carried out through glucose transporters. In the developing fetal lung, metabolism of glucose is thought to be an important process in cell proliferation, differentiation and maturation. Active glucose uptake could result in accumulation of glycogen in epithelial cells, and utilization of glycogen could be a critical phenomenon for lung epithelial development. In hamsters, although facilitative glucose transporter isoform 1 (GLUT1) and isoform 4 (GLUT4) are not detected in adult lungs, expression of them is detected with immunohistochemical and Western blot analyses in the developing fetal lungs. In human lung carcinomas, GLUT1 expression is seen in most cases of lung carcinoma, and is seen especially frequently in squamous cell carcinoma. GLUT1 expression in adenocarcinoma of the lung is correlated with reduced cell differentiation, larger tumor size and positive lymph node metastasis. A few cases of lung carcinoma show positive staining for GLUT3 and GLUT4. Thus, expression of some facilitative glucose transporter isoforms is detected in developing fetal epithelium and in lung carcinomas. Overexpression of them could enhance uptake of glucose into these cells, and the increased influx of glucose could be involved in active cell proliferation, which is a common character of the developing lung epithelium and carcinoma.

Animals↗

Serum biochemical values in two inbred strains of mastomys (Praomys coucha).

Serum samples collected from 119 (72 male and 47 female) mastomys (Praomys coucha) of 2 specific-pathogen-free inbred strains (RI4 and RI7) were analyzed for 12 serum biochemical parameters. Sex-related differences (p < 0.01) were noted in alkaline phosphatase and glucose; the both higher in females than in males. Age-related changes (p < 0.01) were observed in total protein, albumin, total cholesterol, and alkaline phosphatase, with higher values for the first three parameters in the older group (200-250 days of age) than in the younger group (90-140 days of age). Four out of 12 parameters showed strain-related differences (p < 0.01), consistent with the large amount of genetic heterogeneity reported in this species. These serum biochemical reference values should provide information for the use of mastomys in laboratory research.

Animals↗

Gene expression of erythropoietin in renal cell carcinoma.

A 57-year-old man with renal cell carcinoma and erythrocytosis showed a high serum level of erythropoietin (EPO). High EPO signal was observed on Northern blot analysis and RT-PCR in the total RNA extracted from the renal tumor. Immunohistochemical staining also demonstrated tumor tissue with high immunostaining of EPO. Nucleotide sequences of EPO cDNA in the tumor were normal. To date, only one report has discussed the nucleotide sequences of a tumor's EPO gene; it showed mutant EPO cDNA in hepatocellular carcinoma tissue. This is the first demonstration of normal EPO cDNA in renal cell carcinoma.

Carcinoma, Renal Cell↗

[A case report of successful mitral valve replacement for congenital mitral stenosis associated with coarctation of the aorta and ventricular septal defect].

A 5-month-old infant with coarctation of the aorta, ventricular septal defect and mitral stenosis known as "Shone's anomaly" is presented. He underwent the repair of coarctation of the aorta by means of the extended aortic arch anastomosis and banding of the pulmonary trunk at 1 month of age and the patch closure of ventricular septal defect and debanding of the pulmonary trunk at 3 months of age in our institution. About 2 months after second surgery, he had been admitted to our institution due to developing tachypnea and he needed the support of mechanical ventilation. The chest X-ray showed pulmonary congestion and the echocardiography revealed only one papillary muscle of mitral valve and pressure gradient about 30 mmHg through mitral valve. Mitral stenosis due to parachute mitral valve was suspected and he was subjected to an emergent surgery. Initially we performed mitral valve repair for parachute mitral valve but echocardiography during the surgery revealed moderate grade of mitral regurgitation and a hemodynamics was not satisfactory. Eventually mitral valve replacement was successfully done with Carbo-Medics mechanical valve (19 mm in diameter) in the position of left atrial wall because his mitral annulus was so small as 10 mm in diameter. The postoperative course was uneventful and the patient has been doing well.

Aortic Coarctation↗

[Methicillin-resistant Staphylococcus aureus subdural abscess in an elderly patient with dementia].

A 74-year-old man was admitted to our hospital because of a fever of 38.2 degrees C and drowsiness. Two months before admission, he was admitted to another hospital with the diagnosis of Alzheimer's disease. One week before admission, he had a fever which was judged to be due to pyelonephritis. Because imipenem cilastatin and minocycline were not effective in relieving symptoms, he was transferred to our hospital. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured from the blood, and vancomycin was started on the 5th hospital day. Because of the persistent fever and signs of inflammation, Gallium-scintigraphy was performed, showing abnormal accumulation in the left fronto-parietal region of the brain and the sacral region. Enhanced brain CT revealed a crescentic low density area and a fine, intense line of enhancement in the left fronto-parietal region. An emergency drainage of abscess was performed via single left fronto-parietal burr hole. A slightly yellowish, bloody, purulent fluid was obtained. The subdural space was irrigated with saline containing antibiotics and a drain was inserted. MRSA was cultured from the obtained fluid. The fever gradually subsided and drowsiness disappeared. He had had decubitus ulcer, stage I on the surface, in the sacral region, which later turned out to have unexpectedly deep undermining lesion reaching to periosteum. MRSA was cultured from this decubitus lesion. MRSA which entered into blood stream from the decubitus site might have been implanted in the subdural hematoma. Thus, subdural abscess should be kept in mind as an active differential diagnosis in elderly patients with fever and drowsiness.

Aged↗

Hip arthroscopy.

Explore the source record for details and available documents.

Arthroscopes↗

Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers.

Irinotecan (CPT-11) and carboplatin have broad anti-tumor activities. We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer. The aim of the study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this regimen. In addition, we prospectively evaluated the Chatelut formula for predicting carboplatin clearance. Patients with advanced cancer were treated with CPT-11 (days 1, 8, and 15) and carboplatin (day 1) of a fixed-target area under the concentration-time curve (AUC) of 5 mg x min/ml. Carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The CPT-11 dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2. A total of 27 patients, 26 lung cancer patients and 1 colon cancer patient, were enrolled in this study. Dose-limiting leukoneutropenia, thrombocytopenia, and diarrhea, including one treatment-related death, were observed at 60 mg/m2 CPT-11, indicating that this level was the MTD. In 11 patients, the actual AUCs of carboplatin almost achieved the target AUC of 5. Fifteen (60%) of 25 evaluable patients showed an objective response, with an 85% response rate [11 of 13 patients (complete response, 31%; partial response, 54%)] in small cell lung cancers and a 36% response rate (4 of 11 patients) in non-small cell lung cancers. Neutropenia, thrombocytopenia, and diarrhea were the dose-limiting toxicities in this regimen. CPT-11 (50 mg/m2) under the carboplatin target AUC of 5 using the Chatelut formula was the recommended dose for further Phase II study, and this regimen seems to be active for small cell lung cancer.

Adult↗

Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor-alpha expression in skeletal muscle.

The roles of tumor necrosis factor (TNF)-alpha and the facilitative glucose transporter (GLUT) 4 on the induction of insulin resistance in peripheral tissues of cancer patients was examined by quantitative competitive PCR on biopsies of abdominal rectal muscle from patients with gastrointestinal cancer. The degree of insulin resistance in these patients was measured by the euglycemic hyperinsulinemic glucose clamp using a high physiologic insulin concentration (100 microU/ml). Quantitative competitive PCR was carried out using DNA competitors constructed by deleting 20-30 bp between the two primer annealing sites. Decreased glucose uptake (M value) in peripheral tissues was accompanied by a significantly increased TNF-alpha mRNA in skeletal muscle (r=0.867, p=0.0025). GLUT4 mRNA, however, was positively correlated with M values (r=0.739, p=0.015). The amounts of mRNAs for TNF-alpha and GLUT4 in skeletal muscle were not correlated. Serum TNF-alpha concentrations remained below the limit of detection. These findings suggest that the insulin resistance in peripheral tissues of cancer patients is in part due to the induction TNF-alpha mRNA and the down regulation of GLUT4 mRNA in peripheral tissues.

Female↗

A leukotriene receptor antagonist, ONO-1078, modulates drug sensitivity and leukotriene C4 efflux in lung cancer cells expressing multidrug resistance protein.

ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.

ATP-Binding Cassette Transporters↗

Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes. Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression.

The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27, cyclin D1, and the activities of Cdk4 and Cdk-activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG-CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.

ADP Ribose Transferases↗

Newly synthesized Rho A, not Ras, is isoprenylated and translocated to membranes coincident with progression of the G1 to S phase of growth-stimulated rat FRTL-5 cells.

Ras and Rho are involved in the regulation of signal transduction events governing cell growth and cell proliferation. Protein prenylation is essential for the activation and/or the translocation of these small GTPases; however, protein geranylgeranylation rather than farnesylation is required for G1/S transition. We studied prenylation and translocation of Ras and Rho A during G1/S progression in growth-stimulated rat thyroid FRTL-5 cells. Immunoblot analysis revealed that both Ras and Rho A were detected in membrane fractions at G0. Rho A was eliminated from the membrane fraction during G1 and was not detected on the membrane at mid-G1. Translocation of Rho A from the cytoplasm back to the membranes was observed during late G1 phase. In contrast, Ras remains in the membrane fraction through the cell cycle progression from G1 to S phase. The immunoprecipitation of Rho A from the membrane fraction demonstrated that newly synthesized Rho A, labeled by pulsing cells with [35S]methionine and [35S]cysteine, was geranylgeranylated and associated with the membrane in late G1. These results indicate that Rho A, not Ras, was eliminated from membrane fraction during G1 progression and that newly synthesized Rho A is geranylgeranylated and translocated to membranes during G1/S progression in growth-stimulated FRTL-5 cells.

Animals↗

Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes.

A growing number of human tumor antigens have been described that can be recognized by cytotoxic T lymphocytes (CTLs) in a major histocompatibility complex (MHC) class I-restricted fashion. Serological screening of cDNA expression libraries, SEREX, has recently been shown to provide another route for defining immunogenic human tumor antigens. The detection of antibody responses against known CTL-defined tumor antigens, e.g., MAGE-1 and tyrosinase, raised the question whether antibody and CTL responses against a defined tumor antigen can occur simultaneously in a single patient. In this paper, we report on a melanoma patient with a high-titer antibody response against the "cancer-testis" antigen NY-ESO-1. Concurrently, a strong MHC class I-restricted CTL reactivity against the autologous NY-ESO-1-positive tumor cell line was found. A stable CTL line (NW38-IVS-1) was established from this patient that reacted with autologous melanoma cells and with allogeneic human histocompatibility leukocyte antigen (HLA)-A2(-), NY-ESO-1-positive, but not NY-ESO-1-negative, melanoma cells. Screening of NY-ESO-1 transfectants with NW38-IVS-1 revealed NY-ESO-1 as the relevant CTL target presented by HLA-A2. Computer calculation identified 26 peptides with HLA-A2-binding motifs encoded by NY-ESO-1. Of these, three peptides were efficiently recognized by NW38-IVS-1. Thus, we show that antigen-specific humoral and cellular immune responses against human tumor antigens may occur simultaneously. In addition, our analysis provides a general strategy for identifying the CTL-recognizing peptides of tumor antigens initially defined by autologous antibody.

Aged↗