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Biomedical subjects

M Nishio

Publications and source records attributed to M Nishio.

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

Neuronal nitric oxide synthase-membrane phospholipid interactions.

Most of the neuronal nitric oxide synthase (nNOS) is present in the particulate fraction of tissue extracts. Here, we show that the calmodulin (CaM)-binding domain of nNOS interacts with anionic phospholipid vesicles but not with neutral ones. Identification of residues in the CaM-binding domain of nNOS as the key domain for the interaction is also documented. Recombinant wild-type nNOS was found to associate with phosphatidylserine (PS) or phosphatidic acid (PA) but not with phosphatidylethanolamine (PE) or phosphatidylcholine (PC), indicating that nNOS-phospholipid binding requires an electrostatic interaction. A synthetic peptide corresponding to residues 732-754 blocked the interaction of nNOS with PS. Furthermore, a purified fusion protein containing residues 724-755 interacted with PS in a competitive fashion with CaM. Inactive nNOS lacking CaM-binding ability, generated by mutation of (Lys732LysLeu) to (Asp732AspGlu) (Watanabe, Y., Hu, Y., and Hidaka, H., FEBS Lett. 403, 75-78, 1997) did not interact with PS. Preincubation of nNOS with PS protected subsequent limited proteolysis of the synthase by Staphylococcus aureus V8 protease, probably as a result of conformational changes in the protein. Wild-type nNOS was found almost entirely in the membrane fraction of Sf9 cells, whereas inactive nNOS was also found in cytosolic fraction in Sf9 cells expressing the mutant enzyme. These results demonstrate that the mutated hydrophobic/basic amino acid cluster in nNOS sequence, Lys732LysLeu, is essential for nNOS-PS and nNOS-CaM interactions.

Amino Acid Sequence↗
PubMed1998

Clinical studies on three cases of the interval form of carbon monoxide poisoning: serial proton magnetic resonance spectroscopy as a prognostic predictor.

Three patients with the interval form of carbon monoxide (CO) poisoning were studied for associations between their clinical courses and serial changes on: (1) MRI; (2) EEG; (3) single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP SPECT); and (4) proton magnetic resonance spectroscopy ([1HIMRS) to evaluate their usefulness as prognostic predictors. A hyperintense area on MRI T2-weighted images and a hypointense area on T1-weighted images, appearing in the deep white matter, persisted for a prolonged period even after improvement of the clinical symptoms, and did not become an accurate indicator of clinical evaluation or prognosis. [1H]MRS studies with the volume of interest set in the frontal lobe white matter revealed increases in choline-containing compounds, and reductions of N-acetylaspartate in all cases. These findings normalized in one subclinical case over time. Distinctive findings in the severe cases included increased lactate in two cases showing akinetic mutism, with a difference in prognosis noted according to the degree and period of persistence of this increase. EEG findings were relatively well correlated with clinical symptoms in the early period, with a good correlation no longer consistent after a certain period was exceeded. [123I]IMP SPECT findings did not always reflectclinical symptomatology either. These results indicate that [1H]MRS is the most useful indicator in the clinical evaluation of patients with the interval form of CO poisoning.

Adult↗
PubMed1998

Modulation by chloramine-T of 4-aminopyridine-sensitive transient outward current in rabbit atrial cells.

The effects of an oxidizing agent, chloramine-T, on the 4-aminopyridine-sensitive transient outward current (ITO) were investigated in rabbit atrial myocytes by using patch-clamp techniques. Extracellular application of chloramine-T at 20 microM irreversibly slowed the time course of inactivation of the whole-cell ITO, and increased the peak by 19.3% (n = 19) at +40 mV. At 100 microM, chloramine-T decreased the peak by 22.5% (n = 9) of the control, and subsequently induced a glibenclamide-sensitive time-independent outward K+ current. Under superfusion with dithiothreitol (3 mM), chloramine-T (100 microM) produced no change in ITO. The chloramine-T-induced slowing of ITO inactivation was partially reversed by subsequent application of 3 mM dithiothreitol. In single-channel recordings with the cell-attached patch configuration, chloramine-T (20 microM) increased the open probability of the ITO channel from 0.15 to 0.46 at a potential 100 mV positive to the resting potential, and the mean open lifetime from 5.1 ms to 7.0 ms (n = 5). The unitary current amplitude was not affected. As a result, chloramine-T increased the ensemble current in amplitude and slowed its decay. These results indicated that: (1) inactivation of the native A-type channels of rabbit heart is susceptible to oxidation; and (2) oxidation of ITO channels may contribute to the genesis of arrhythmias.

4-Aminopyridine↗
PubMed1998

Scanning laser ophthalmoscopic findings in a patient with acute zonal occult outer retinopathy.

PURPOSE: To examine a 33-year-old woman who had an enlarged scotoma in her right eye and who was diagnosed with acute zonal occult outer retinopathy. METHODS: We performed a full ophthalmologic examination and scanning laser ophthalmoscopy. RESULT: With a 514-nm wavelength laser, scanning laser ophthalmoscopy demonstrated abnormal lesions bilaterally. No abnormalities were detected with a 630-nm wavelength laser. CONCLUSION: Scanning laser ophthalmoscopy can demonstrate retinal damage caused by acute zonal occult outer retinopathy, which is useful in differential diagnosis.

Acute Disease↗
PubMed1998

Characterization of a streptococcal antitumor glycoprotein (SAGP).

An acidic antitumor glycoprotein (SAGP) was purified from a crude extract of Streptococcus pyogenes, Su strain. Intraperitoneal injection with SAGP (20 mg protein/kg/day for 4 consecutive days) prolonged the life span of mice inoculated i.p. with Ehrlich ascite carcinoma cells and methylcholanthrene-induced fibrosarcoma cells (Meth A) up to 244% and 169% of that of the control mice, respectively. These in vivo antitumor effects were reduced in immunosuppressed mice. The effector spleen cells from the Meth A-inoculated and SAGP-injected mice showed a considerable cytostatic activity on Meth A cells in vitro, and immunosuppression studies suggested that carrageenan-sensitive and/or asialo-GM1 positive spleen cells are responsible for the in vivo antitumor effect of SAGP. SAGP inhibited the cell growth of cultured cell lines including transformed hamster embryonic lung cells, murine leukemia L 1210, Meth A and human promyelocytic leukemia HL60 cells. The IC50s for the cell growth of these cells were all below 0.1 microg protein/ml. SAGP inhibited the incorporation of nucleic acid precursors into Meth A cells. It seems that sulfhydryl groups of the SAGP molecule are essential for the expression of the antitumor action of SAGP. The cell growth-inhibitory activity of SAGP was diminished in Meth A cells preincubated with pertussis toxin (IAP), whereas it was augmented in the cells preincubated with cholera toxin (CTX), suggesting the involvement of toxin-sensitive GTP (G)-proteins in the SAGP-action. IAP and CTX-catalyzed ADP ribosylation assays confirmed that SAGP augmented the activity of IAP-sensitive G-protein. In addition, this augmentation was detected neither in Meth A cells incubated with heat-inactivated SAGP nor in SAGP-insensitive L929 cells. SAGP induced apoptosis in Meth A and HL60 cells as assessed by DNA fragmentation. A single dose injection of SAGP (100 mg protein/kg, i.v., s.c., or i.p.) into mice produced no toxic signs except occasional pain responses observed for one week after the injection. Thus, SAGP is a low toxic substance that shows in vivo antitumor activity by modulating immune responses of the host, and also exhibits in vitro cell-growth inhibition through IAP-sensitive G-protein.

Animals↗
PubMed1998

Pathologically-proven intracranial germinoma treated with radiation therapy.

BACKGROUND AND PURPOSE: A retrospective multi-institutional study was conducted to survey what percentage of intracranial germinomas were treated with pathological confirmation before radiotherapy and to investigate the influence of field selection on outcome. MATERIALS AND METHODS: Thirty-seven percent of patients (41 of 110 patients) were pathologically confirmed before radiotherapy during the past 16 years at eight institutions in Northern Japanese prefectures. Pathological confirmation was obtained in 26, 37 and 53% of cases during 1978-1983, 1984-1989 and 1990-1994, respectively. All 110 patients were examined using computed tomography (CT) scans. Among the 41 patients with pathologically confirmed germinoma, radiation fields were craniospinal in 23 patients, whole-brain in 10 patients and local without ventricle inclusion in eight patients. RESULTS: For the 41 patients with pathologically confirmed germinoma, the actuarial and cause-specific survival rates were 91/94% at 5 years and 87/90% at 10 years, respectively. The relapse-free survival rate at 10 years was 90. 76 and 22% for the craniospinal field, whole-brain field and local field without ventricle inclusion, respectively. CONCLUSION: Pathological confirmation was obtained in only 37% of CT-scan era cases, although the confirmations were more commonly carried out later in the study period. Limited local irradiation alone without ventricle inclusion cannot be recommended for localized tumors even with the help of CT scanning.

Adolescent↗
PubMed1998

Retrospective multi-institutional study of radiotherapy for intracranial non-germinomatous germ cell tumors.

The treatment outcome of 24 patients with pathologically-proven non-germinomatous germ cell tumor was retrospectively investigated to determine the effectiveness of radiotherapy. The patients were divided into three groups as follows: group 1, five patients with mature teratoma with or without germinoma; group 2, six patients with immature teratoma with or without germinoma; group 3, 13 patients with other highly malignant tumors. The overall actuarial survival and relapse-free rates at 5 years were 82% and 59%, respectively, with a median follow-up period of 62 months. The actuarial relapse-free rate at 5 years was 100% for group 1, 63% for group 2 and 44% for group 3. There was no difference in the relapse-free rates between total resection and partial resection. Usage of chemotherapy was adversely related to survival probably due to selection bias. No local failure was observed with 10 Gy or more for group 1,40 Gy or more for group 2 and 54 Gy or more for group 3. In groups 1 and 2, there was no spinal relapses without craniospinal irradiation. In group 3, three of eight patients who did not receive craniospinal irradiation and none of five patients who received craniospinal irradiation experienced spinal relapse. In conclusion, highly malignant GCTs show a high incidence of spinal metastasis and craniospinal irradiation may reduce the risk of spinal metastasis. Radiation dose and volume are to be determined according to the histopathological aggressiveness.

Adolescent↗
PubMed1998

Radiotherapy for locoregional recurrent tumors after resection of non-small cell lung cancer.

Thirty-two patients with locoregional recurrence without documented distant metastasis after resection of non-small cell lung cancer were treated with radiotherapy. There were 29 male patients and three female patients. The age range was 49-79 years (median 66 years). Twenty patients had squamous cell carcinoma, 11 patients adenocarcinoma and one patient large cell carcinoma. Ten patients had bronchial stump recurrence alone, 14 patients bronchial stump recurrence with mediastinal and/or supraclavicular fossa lymph nodes recurrence, and eight patients mediastinal and/or supraclavicular fossa lymph nodes recurrence without bronchial stump recurrence. The total dose delivered ranged from 47.5 to 65 Gy. We achieved good results on improving on subjective complaints. Eighty-nine percent (17/19) of patients indicated subjective improvement. Eight of 32 (25%) patients showed a complete response, and 13 of 32 (40.6%) patients showed a partial response. Only one of seven patients (14.3%) with less than 60 Gy showed a complete response, but seven of 25 patients (28%) with 60 Gy and more showed a complete response. The survival rate was 56.2% at 1 year and 12.5% at 5 years. Four patients have survived more than 5 years. The survival rate of the patients with complete response was 50% at 3 and 5 years, that of the patients with non-complete was 12.5% at 3 years and 0% at 5 years (Cox-Mantel test, P < 0.05). In conclusion, high-dose radiotherapy for locoregional recurrent tumors after resection was effective for palliation and improved survival.

Aged↗
PubMed1998

CH/pi interactions as demonstrated in the crystal structure of guanine-nucleotide binding proteins, Src homology-2 domains and human growth hormone in complex with their specific ligands.

The CH/pi interaction is a weak attractive molecular force occurring between CH groups and pi-systems. Possibility has been examined for the role of CH/pi interaction, by use of a computer program, in the crystallographic data of several guanine-nucleotide binding proteins, src homology-2 domains and human growth hormone complexed with their specific ligands. Short CH/pi contacts have been found in every case where cohesive forces are expected. Comparison of the structures of functionary related proteins has shown that mutation may occur but necessary CH/pi interactions are conserved. A considerable part of the non-polar interactions, broadly ascribed in the past to the van der Waals interaction or the so-called hydrophobic effect, has been suggested to be attributed to a more specific attractive force, the CH/pi interaction.

Animals↗
PubMed1998

CH/pi interactions in the crystal structure of class I MHC antigens and their complexes with peptides.

The crystal structure of class I major histocompatibility complex antigens (MHC) bound to their specific ligand peptides were analyzed, in the context of the CH/pi interaction, with use of a computer program CHPI. A number of short CH/Csp2 distances have been shown at the boundary of the heavy chain and beta2 microglobulin. These interactions are conserved between species, human versus murine. A number of contacts shorter than the conventional van der Waals distance have been disclosed between CH hydrogens and aromatic side-chain groups in the MHC/peptide complexes. The CH/pi interaction has been suggested to contribute to the specificity in the complex formation of class I MHC.

Amino Acid Sequence↗
PubMed1998

Recurrence with histological transformation 40 days after autologous peripheral blood stem cell transplantation (APBSCT) for cutaneous CD30-negative large T cell lymphoma.

Localized cutaneous nontender nodules appeared on the back of a 52-year-old Japanese woman. Skin biopsy revealed atypical large T-lymphocytes infiltrating the dermis. CD30 staining was negative in tumor cells. The diagnosis was CD30-negative cutaneous large T cell lymphoma. There was no evidence of peripheral lymphadenopathy or bone marrow involvement. Six cycles of induction chemotherapy were administered and a complete clinical remission (CCR) was attained. Local irradiation was not given. As the clinical course of CD30-negative cutaneous large T cell lymphoma is recurrent and often incurable with conventional chemoradiotherapy, she received high-dose chemotherapy without total body irradiation (TBI) followed by unpurged autologous peripheral blood stem cell transplantation (APBSCT). A relapse in the skin followed 40 days after APBSCT, but tumor cells transformed into a CD30-positive anaplastic large cell lymphoma (ALCL). We question the need for TBI in conditioning and for purged stem cells for APBSCT in patients with high risk cutaneous lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Patterns of care study of radiation therapy for esophageal cancer in Japan: influence of the stratification of institution on the process.

BACKGROUND: To improve the quality of radiation therapy in Japan, Patterns of Care Study (PCS), a widely known QA program in the USA, was introduced in Japan. The feasibility was tested by collecting nationwide data by extramural audit for esophageal cancer. METHODS: From July 1996 through February 1997, PCS audits were performed for 29 institutions. Based on the facility survey by Tsunemoto, 13 institutes were classified as A1 (university hospital/cancer center treating > 300 patients/year), 10 as B1 (other institutes > 120 patients/year) and six as B2 (other institutes < 120 patients/year). Medical charts for 455 patients with thoracic esophageal cancer between 1992 and 1994 were reviewed based on the data format of PCS in the USA. RESULTS: Concerning external beam equipment, linear accelerators of > or = 10 MV were used for 73% of patients in A1, whereas in B1-2, 60Co machines were still used for 13% of patients (P < 0.0001). The median number of full-time equivalent (FTE) radiation oncologists was 2.7 in A1, 0.65 in B1 and 0.2 in B2. Forty-five percent of patients had received surgery in A1 and 34% in B1-2 (P = 0.0068). In the non-surgery group, a higher radiation dose of > 60 Gy was delivered in A1 than in B1-2 (P = 0.0008). Chemotherapy was administered to 51% of the patients in A1 and to 30% in B1-2 (P < 0.0001). Brachytherapy was utilized for 17% in A1 and only for 5% in B1-2 (P = 0.0001). CONCLUSION: Institutional stratification, including equipment and personnel, significantly affected the patterns of care for esophageal cancer. Therefore, to improve the quality of radiation therapy nationwide, improvement of equipment and supply of FTE personnel is extremely important. PCS was found to have great potential for the practical evaluation of how much will be required in Japan.

Adult↗
PubMed1998

Endothelin-1 inhibits pacemaker currents in rabbit SA node cells.

Our recent study demonstrated that endothelin-1 (ET-1) inhibits the pacemaker activity of sinoatrial (SA) node cells via changes in the L-type Ca2+, delayed K+, and background K+ currents. Using the whole-cell patch-clamp technique in the same preparation, we found that ET-1 reduces other pacemaker currents, the T-type Ca2+ current (ICa,T) and the hyperpolarization-activated inward current (I(f)). The inhibitory actions of ET-1 on these currents were concentration-dependent, i.e., EC50 of 0.9 nM for ICa,T and 2.3 nM for I(f), with little reversal after washout of the peptide. In the presence of BQ485, both currents were not affected by ET-1. These results indicate additional mechanisms underlying negative chronotropic actions of ET-1 on the rabbit SA node.

Animals↗
PubMed1998

Identification of regions on the fusion protein of human parainfluenza virus type 2 which are required for haemagglutinin-neuraminidase proteins to promote cell fusion.

Using a plasmid expression system in HeLa cells, we have previously shown that the fusion (F) protein of simian virus 41 (SV-41) induces cell fusion when coexpressed with the haemagglutinin-neuraminidase (HN) protein of human parainfluenza virus type 2 (PIV-2), while the PIV-2 F protein does not induce cell fusion with the SV-41 HN protein. In the present study, we found that the PIV-2 F protein induced extensive cell fusion with the HN protein of mumps virus (MuV), whereas the SV-41 F protein did not. Chimaeric analyses of the F proteins of PIV-2 and SV-41 identified two regions (designated M1 and M2) on the PIV-2 F protein, either of which was necessary for chimaeric F proteins to show fusogenic activity with the MuV HN protein. Subsequently, two additional regions (P1 and P2) were identified on the PIV-2 F protein, both of which were necessary for chimaeric F proteins to prevent induction of cell fusion with the SV-41 HN protein. Consequently, it was proved that a given chimaeric F protein, harbouring regions P1 and P2 together with either of region M1 or M2, induced cell fusion specifically with HN proteins of PIV-2 and MuV, the same as the PIV-2 F protein. Region M2 was located at the membrane proximal end of the PIV-2 F1 ectodomain, while regions P1, M1 and P2 clustered together in the middle of the ectodomain. These regions on the PIV-2 F protein may be involved in a putative functional interaction with HN proteins, which is considered to be a prerequisite for cell fusion.

Amino Acid Sequence↗
PubMed1998

Mammary fibroblast-derived hepatocyte growth factor stimulates growth and morphogenesis of mouse mammary tumor cells in primary culture.

We have recently isolated a mammary growth factor from the conditioned medium of mouse mammary stromal fibroblasts and identified it as a mouse homologue of human HGF (hepatocyte growth factor). To elucidate the role of HGF in mouse mammary tumorigenesis, we produced recombinant mouse HGF and examined its effects on primary cultures of mouse mammary tumor cells in this study. HGF at concentrations above 20 ng/ml maximally stimulated the growth of mammary tumor cells in primary monolayer culture. HGF also stimulated the three-dimensional growth and branching morphogenesis of mammary tumor cells cultured inside collagen gels. A comparison of the growth-stimulating activity of HGF with that of EGF (epidermal growth factor) and KGF (keratinocyte growth factor) revealed that HGF is the most potent growth factor among the three. Immunological studies using an antibody against mouse HGF demonstrated that 74% of the growth-stimulating activity present in the mammary fibroblast-conditioned medium was abolished by the antibody, indicating that HGF is the major growth factor produced by the fibroblasts. These observations thus suggest a role for HGF as a mammary stromal fibroblast-derived factor which stimulates growth and morphogenesis of adjacent mammary tumor cells in vivo.

Animals↗
PubMed1998

Echocardiographic evaluation of cardiac valvular abnormalities in adults with Down's syndrome.

It is well known that congenital heart abnormalities are common in children with Down's syndrome. However there are few studies on cardiac abnormalities in adults with Down's syndrome. Therefore, we estimated cardiac abnormalities by means of echocardiography in 30 institutionalized Japanese adults with Down's syndrome, but without cardiac symptoms. Two-dimensional echocardiography showed an incidence of 26.7% in mitral valve prolapse and 20% increase of echo brightness in the mitral valve. Doppler echocardiography revealed an incidence of 16.7% in mitral valve regurgitation, and 13.3% in aortic valve regurgitation. Thus, even adults with Down's syndrome who are apparently free of cardiac symptoms may be at risk for valvular disease.

Adult↗
PubMed1998

TMC-49A, a novel transcriptional up-regulator of low density lipoprotein receptor, produced by Streptomyces sp. AS1345.

Microbial metabolites were screened for a transcriptional up-regulator of low density lipoprotein (LDL) receptor by a reporter assay. TMC-49A was discovered as an up-regulator obtained from the fermentation broth of Streptomyces sp. AS1345. The structure of TMC-49A was elucidated to be butyl N-phenethylcarbamate by spectroscopic analyses. This compound enhanced the synthesis of LDL receptor in human hepatoma HepG2 cells as assessed by a receptor binding assay. Taxonomy of the producing strain is also described.

Carbamates↗