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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 307 records · Page 17Linked to original sources

[Hypoxemia and tissue hypoxia in sleep apnea syndrome].

Hypoxemia is defined as abnormally reduced oxygenation of the blood, whereas tissue hypoxia indicates inadequate oxygen supply against oxygen demand in the integrity of cellular metabolic processes. Thus, the presence of tissue hypoxia may not be predicted by the level of hypoxemia alone. Obstructive sleep apnea syndrome is characterized by periodic apnea/hypopnea, which is often associated with severe hypoxemia. In this chapter, we discussed how tissue hypoxia should be assessed in this syndrome, and also what is the clinical usefulness and/or limitations of such assessment.

Adenosine Triphosphate↗

Clinical and analytical evaluation of an enzyme immunoassay for myelin basic protein in cerebrospinal fluid.

BACKGROUND: RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a biochemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. METHODS: The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody. The bound antibody complex was quantified with streptavidin-horseradish peroxidase. MBP was determined in CSF from 84 MS patients and 55 patients with other neurological diseases. RESULTS: The respective within- and between-assay CVs were 4.7% and 7.2% at 200 ng/L, and 6. 3% and 8.8% at 2000 ng/L. The detection limit was 30 ng/L. Most of the MS patients with acute exacerbations had markedly increased MBP in the CSF. Longitudinal studies of six MS patients with recurrent exacerbation confirmed this observation. MBP concentrations from 78 MS patients, as tested with our ELISA, correlated well with those obtained by RIA (r = 0.9; P: <0.01), but the detection limit of the ELISA was much lower than that of the RIA. CONCLUSIONS: This convenient ELISA with higher sensitivity than the existing assays is a suitable routine assay that provides a diagnostic indicator of myelin breakdown in the central nervous system; moreover, it is an excellent indicator of MS disease activity.

Adolescent↗

Evidence that the beta-catenin nuclear translocation assay allows for measuring presenilin 1 dysfunction.

BACKGROUND: Mutations in the presenilin (PSEN) genes are responsible for the majority of early-onset Alzheimer disease (AD) cases. PSEN1 is a component of a high molecular weight, endoplasmic reticulum, membrane-bound protein complex, including beta-catenin. Pathogenic PSEN1 mutations were demonstrated to have an effect on beta-catenin and glycogen synthase kinase-3beta(GSK-3beta), two members of the wingless Wnt pathway. The nuclear translocation and the stability of beta-catenin, and the interaction between GSK3beta and PSEN1 were influenced. MATERIALS AND METHODS: Stably transfected human embryonic kidney (HEK) 293 cells overexpressing wild-type (wt) and mutant (mt) PSEN1, treated with and without LiCl, were used to isolate cytoplasmic and nuclear fractions. By Western blot analysis, endogenous beta-catenin levels were examined. By analyzing cytosolic fractions of PSEN1, transfected and nontransfected HEK 293 cells, and total brain extracts of AD patients and controls, we evaluated the effect of PSEN1 overexpression on beta-catenin stability. Finally, we analyzed the effect of pathogenic PSEN1 mutations on the interaction between PSEN1 and GSK3beta by co-immunoprecipitation experiments. RESULTS: We report reduced nuclear translocation of beta-catenin in cells stably expressing I143T, G384A, and T113-114ins PSEN1. The G384A PSEN1 mutation showed a similar pronounced effect on nuclear translocation of beta-catenin, as reported for processing of amyloid precursor protein (APP) into amyloid beta(Abeta). Overexpression of PSEN1 and the presence of pathogenic mutations in PSEN1 had no significant effect on the stability of beta-catenin. Nonspecific binding of overexpressed PSEN1 to endogenous GSK3beta was observed when GSK3beta was immunoprecipitated. Immunoprecipitation of PSEN1 in cells overexpressing PSEN1 and in native cells, however, did not result in co-immunoprecipitation of endogenous GSK3beta. CONCLUSION: Our results further establish the nuclear translocation assay of beta-catenin as an adequate alternative for traditional Abeta measurement to evaluate the effect of PSEN1 mutations on biochemical processes. We detected no significant effect of overexpressed wt or mt PSEN1 on the stability of beta-catenin. Finally, co-immunoprecipitation between PSEN1 and GSK3beta was not observed in our experimental setup.

Active Transport, Cell Nucleus↗

[Successful weaning from mechanical ventilation in an infant with congenital tracheal stenosis and bronchial malacia using endobronchial stent, nasal CPAP and continuous sedation].

A 1.9 kg male infant who showed respiratory distress at his birth, was diagnosed by bronchoscopy as having congenital segmental stenosis of trachea with complete ring. Tracheoplasty was performed and the infant was admitted to ICU. After admission to ICU, we suspected the residual tracheal stenosis and the left main bronchial malacia by bronchoscopy. Although we tried to wean him from mechanical ventilation, but failed and re-intubated him four times because of marked respiratory acidosis after extubation. Bronchoscopy was performed repeatedly, and the residual tracheal stenosis and the left main bronchial malacia were apparent. After patch tracheoplasty of the costal cartilage to the residual tracheal stenosis and implantation of angioplastic expandable metallic stent to the left main bronchus, he was successfully extubated under continuous sedation. In addition, nasal CPAP was effective to reduce retraction and wheezing after extubation. He was discharged from ICU on the 183rd ICU day.

Bronchi↗

Analysis of 70Kd heat shock protein expression in patients with internal derangement of the temporomandibular joint.

Recent studies have demonstrated that the expression of heat shock protein (HSP) was enhanced under stress in joint diseases, such as rheumatoid arthritis and osteoarthritis. The purpose of this study was to analyze the expression of 70Kd HSP in patients with internal derangement of the temporomandibular joint (TMJ) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods. For immunohistochemistry, 5 extirpated discs and 16 synovial biopsy specimens from patients with TMJ internal derangement and 2 extirpated discs from normal subjects were examined. For ELISA, synovial fluid from 11 patients with TMJ internal derangement and from 6 normal volunteers were investigated. The results showed that the 70Kd HSP staining intensity in chondrocytes around the damaged area of the articular discs from patients with TMJ internal derangement was higher than that in chondrocytes in control specimens. In addition, 70Kd HSP expression in synovial fluid from patients with TMJ internal derangement was slightly higher than that in normal subjects. These findings suggest that elevated 70Kd HSP expression is related to the progression of TMJ internal derangement.

Case-Control Studies↗

Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia. Kouseisho Leukemia Study Group.

We compared interferon-alpha (IFN-alpha therapy with bone marrow transplantation (BMT) after initial conventional chemotherapy in patients with chronic myelogenous leukemia (CML) in a multicenter prospective study. Ninety patients with Philadelphia chromosome-positive CML in chronic phase were enrolled between 1991 and 1994. Sixty-six of 89 evaluable patients received IFN-alpha after conventional chemotherapy with hydroxyurea or busulfan (IFN-alpha group). Twenty-three patients received allogeneic BMT (BMT group). Fifteen of them received transplants from HLA-identical family donors and 8 from HLA-matched unrelated donors. Forty-seven of 66 patients (71%) in the IFN-alpha group and 17 of 23 patients (74%) in the BMT group achieved complete hematologic response, and 12% in the IFN-alpha group and 13% in the BMT group achieved partial hematologic response. Complete cytogenetic response was induced in 5 (8%), partial cytogenetic response in 8 (12%), and minor cytogenetic response in 12 (18%) in the IFN-alpha group. At a median follow-up of 54 months (range, 30-76 months), in the IFN-alpha group, the predicted 6-year survival rate was 54.5% and the predicted 6-year rate of those remaining in chronic phase was 45.7%. Compared with patients with no cytogenetic response, the patients with some cytogenetic response after IFN-alpha treatment had significantly superior survival and duration of the chronic phase even after correction for the time to response using landmark analysis (P < .05). In the BMT group, the predicted 5-year survival rate was 93.3% for family-donor BMT and 21.9% for unrelated-donor BMT Acute graft-versus-host disease of grade III or IV was observed in 1 of 15 patients who received family-donor BMT and 3 of 8 patients who received unrelated donor BMT. Prior treatment with conventional cytotoxic drugs induced early hematologic response and did not reduce the effect of IFN-alpha on CML. Unrelated-donor transplantation should be offered to some patients according to patient age, HLA-matching status, time from diagnosis to BMT, and risk factors.

Adolescent↗

[Acute transient swelling of the submandibular glands after laryngeal mask airway insertion].

A 40-year-old woman was scheduled for abdominal hysterectomy. Moderate difficulty in tracheal intubation was expected on preoperative evaluation. A size 3 laryngeal mask airway (LMA) was inserted after the induction of general anesthesia. The LMA insertion was accomplished smoothly at the first attempt and there was no air leakage during manual ventilation. Soon after the insertion, acute swellings were noted in the bilateral submandibular triangle regions. Enlargement and deformity of the submandibular glands were diagnosed by ultrasonography. The enlargements increased with elevated pressure of the LMA cuff, but disappeared completely in five minutes after removal of the LMA. Such enlargement did not occur with subsequent tracheal intubation. The patient had an uneventful postoperative course without any residual sequelae. We should pay attention to possible submandibular gland swelling by LMA insertion.

Adult↗

[Clinical evaluation of urinary basic fetoprotein and the BTA test for detection of bladder cancer].

We compared the results of urinary basic fetoprotein (BFP) and the BTA test with those of urinary cytology in patients with bladder cancer. We also analyzed the urinary BFP and the BTA test results in patients with benign diseases and postoperative bladder cancer with no evidence of recurrence. The cutoff value for urinary BFP was set at 10 ng/ml. Classes 4 and 5 according to urinary cytology were defined as positive. The sensitivity of urinary BFP for Ta, 1 bladder cancer was significantly higher than that of urinary cytology (p < 0.05). The urinary cytology positive rate for Ta, 1 bladder cancer improved when combined with urinary BFP and the BTA test. The urinary BFP positive rate for benign diseases was significantly higher in patients with pyuria than in patients without pyuria (p < 0.05). The BTA test positive rate for benign diseases was higher in patients with pyuria than in patients without pyuria. The urinary BFP and the BTA test positive rates for postoperative bladder cancer with no evidence of recurrence was significantly higher in patients with urinary diversion than in patients without urinary diversion (BFP: p < 0.01, BTA: p < 0.05).

Adult↗

Effects of supine floating on heart rate, blood pressure and cardiac autonomic nervous system activity.

It is known that heart rate, oxygen uptake and body temperature during exercise in water are affected by water temperature, buoyancy and so on. Relaxation in water (supine floating) has been performed in hydrotherapy and aqua exercise. But there were few reports about supine floating (Schulz and Kaspar 1994). The purpose of this study was to make clear the effects of supine floating on heart rate, blood pressure and cardiac autonomic nervous system activity in males.

Adult↗

[Relaxative effects of supine floating on heart rate, blood pressure and cardiac autonomic nervous [correction of nerveous] system activity].

The purpose of this study was to make clear the relaxative effects of supine floating (SF) on heart rate, blood pressure and cardiac autonomic nervous activity in males. Ten males served as subjects (n=10, mean age: 22.4 yrs). All subjects gave informed consent before participating. Water and room temperature were 30 degrees C. Heart rate and blood pressure were measured during SF or control (C) conditions. Cardiac autonomic nerve activity was estimated with the power spectrum analysis of heart rate variability (HRV) by using the Fast Fourier Transformation (FFT). High frequency (HF; 0.15-0.40 Hz) and the ratio of low frequency (LF; 0.04-0.15 Hz) to HF (LF/HF) were used as an indicator of cardiac vagal activity and sympatho-vagal balance, respectively. Those values were showed logarithmically (LogHF and LogLF/LogHF). LogHF during SF condition was significantly increased, LogLF/LogHF, heart rate and blood pressure were significantly decreased. These data indicate that cardiac vagal activity is enhanced and sympathetic nervous activity is suppressed by reciprocal response.

Adult↗

Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses.

BACKGROUND: A number of prognostic factors have been reported for resected nonsmall cell lung carcinoma. None of them, however, has been reported to have greater prognostic impact than the pathologic TNM staging system. The authors evaluated 18 conventional clinicopathologic prognostic factors in each pathologic stage. METHODS: A retrospective study was conducted on surgically resected 836 lung carcinoma patients, and the following conventional prognostic factors were evaluated in multivariate analyses: age, gender, pack-year smoking, serum carcinoembryonic antigen and squamous cell carcinoma antigen levels, laterality of tumor, clinical N status, histologic type of tumor, greatest tumor dimension, grade of differentiation, pleural involvement, lymphatic invasion, vascular invasion, degree of fibrosing scarring, nuclear atypia, mitotic activity, and curativity of resection. RESULTS: The overall 5-year survival rate was 63.8%. In 430 cases of pathologic Stage I disease, multivariate analyses revealed 3 significant prognostic factors: clinical N status (P < 0.001), vascular invasion (P = 0.001), and curativity of resection (P < 0.001). In 406 cases of more advanced disease, i.e., pathologic Stage II, IIIA, IIIB, or IV, multivariate analyses revealed 4 factors as significant: histology (P = 0.001), pathologic N status (P < 0.001), tumor size (P < 0.001), and curativity of resection (P = 0.002). CONCLUSIONS: Conventional clinicopathologic prognostic factors had a different impact on prognosis in each pathologic TNM stage among patients who underwent surgical resection of nonsmall cell lung carcinoma. These factors should be analyzed separately in each pathologic TNM stage.

Adult↗

High dose chemotherapy for refractory urothelial carcinoma supported by peripheral blood stem cell transplantation.

BACKGROUND: Chemotherapy with methotrexate (MTX), vinblastine, doxorubicin, and cisplatin (M-VAC) is reported to be the most effective regimen for urothelial carcinoma. Complete response (CR) is observed in many cases. However, to the authors' knowledge there is no alternative therapy for nonresponders. Thus, the authors attempted high dose chemotherapy (HDC) supported with peripheral blood stem cells (PBSCs) collected after a modified method of mobilization to yield sufficient PBSCs for the HDC regimen employed. METHODS: PBSCs were collected from ten patients, all of whom had recurrent and/or refractory transitional cell carcinoma. They were treated by modified M-VAC (with pirarubicin in place of doxorubicin) for PBSC harvest. Seven micrograms per kilogram of body weight of granulocyte-colony stimulating factor was injected subcutaneously daily from Day 10 of treatment to the end of the harvest. Harvest was initiated from the day when peripheral leukocyte counts exceeded 10,000/microL and usually continued for 3 consecutive days. Each patient received two courses of HDC. Therefore, 20 courses of HDC comprised of 300 mg/body of MTX, 1500 mg/m(2) of etoposide, and high dose carboplatin (CBDCA) were given to these 10 patients. The dose of CBDCA was determined by the formula of Calvert et al., in which the target area under the concentration versus time curve of CBDCA was adjusted to 21 mg. minute/mL. RESULTS: Sufficient PBSCs were collected for myeloablative chemotherapy in all patients. No patient responded to the treatment with modified M-VAC. Response to HDC was observed in nine of ten patients. CR was achieved in seven patients and a partial response was noted in two patients. A patient with multiple bone metastases showed no response. All patients rapidly recovered after PBSC transplantation. No patient died of treatment-related toxicity. CONCLUSIONS: HDC supported by PBSC transplantation was found to have a remarkable response against refractory urothelial carcinoma, for which there was no alternative therapy.

Aged↗

Adenovirus-mediated transfer of p33ING1 with p53 drastically augments apoptosis in gliomas.

The p53 tumor suppressor gene is an important target for the gene therapy of cancers, and clinical trials targeting this gene have been conducted. Some cancers, however, are refractory to p53 gene therapy. Therefore, it has been combined with other therapies, including chemotherapy and radiotherapy, to enhance the cytopathic effect of p53 induction. The p33ING1 gene cooperates with p53 to block cell proliferation. In this study, we investigated whether adenovirus (Adv)-mediated coinduction of p33ING1 and p53 enhances apoptosis in glioma cells (U251 and U-373 MG), which showed no genetic alterations but low expression levels of p33ING1. Although the single infection of Adv for p33ING1 (Adv-p33) at a multiplicity of infection (MOI) of 100, or Adv for p53 controlled by myelin basic protein (MBP) promoter (Adv-MBP-p53), a glioma-specific promoter, at a MOI of 50, did not induce apoptosis in U251 and U-373 MG glioma cells; coinfection of Adv-p33 and Adv-MBP-p53 at the same MOIs induced drastically enhanced apoptosis in both cell lines. Apoptosis was not induced in NGF-treated PC-12 cells infected with a high MOI (300) of Adv-p33 nor in those coinfected with Adv-p33 (100) and Adv-MBP-p53 (50). Coinfection of Adv-p33 and Adv-MBP-p53 demonstrated morphological mitochondrial damage during the initial stage of apoptosis, which likely led to apoptotic cell death. Our results indicate that this coinfection approach can be used as a modality for the gene therapy of gliomas, sparing damage to normal tissues.

Adenoviridae↗

Ketamine stereoselectively inhibits rat dopamine transporter.

Ketamine is usually administered as a racemate, which is composed of the two isomers, S(+)-and R(-)-ketamine. Recently, we have shown that racemic ketamine at clinical relevant concentrations specifically inhibits the transporter proteins for norepinephrine, dopamine and serotonin heterologously expressed in HEK-293 cells (Nishimura, M., Sato, K., Okada, T., Yoshiya, I., Schloss, P., Shimada, S. and Tohyama, M., Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells. Anesthesiology, 88 (1998) 768-774). Since ketamine interacts stereoselectively with most of its targets, we now investigated whether ketamine also exhibits stereoselectivity on the monoamine transporters. Only the dopamine transporter was found to be stereoselectively inhibited with S(+)-ketamine being almost eight times more potent than R(-)-ketamine (Ki = 46.9 microM for S(+)-ketamine, 390 microM for R(-)-ketamine). In contrast, ketamine exhibited no stereoselectivity for norepinephrine and serotonin transporters.

Animals↗