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Biomedical subjects

M Nishio

Publications and source records attributed to M Nishio.

At least 91 records · Page 5Linked to original sources
PubMed1999

CH/pi interaction in the conformation of peptides. A database study.

A study was carried out, with use of the Cambridge Structural Database, to examine the role of the CH/pi interaction in the conformation of peptides. A number of short intramolecular CH/pi distances have been shown in the crystal structure of peptides bearing at least an aromatic residue in the sequence. The molecular structure in the crystal was inspected individually to know whether the conformation is merely a consequence of the so-called packing forces, or the CH/pi interaction plays a role. It has been demonstrated that the CH/pi interaction constitutes one of the key factors in controlling the conformation of peptides.

Amino Acid Sequence↗
PubMed1999

Gene expression during osteoclast-like cell formation induced by antifusion regulatory protein-1/CD98/4F2 monoclonal antibodies (MAbs): c-src is selectively induced by anti-FRP-1 MAb.

Human blood monocytes can differentiate into osteoclast-like cells when they are cultured in the presence of anti-FRP-1. Messenger (mRNA) expression of markers related to osteoclasts was analyzed during differentiation of osteoclasts from monocytes. As markers related to osteoclasts, we selected cathepsin-K, carbonic anhydrase (CA) II, vacuolar H(+)-ATPase (v-ATPase), vitronectin receptor (VNR), tartrate-resistant acid phosphatase (TRAP), osteopontin (OPN), galectin-3, c-src, c-fos, and c-fms. The mRNAs other than c-src mRNA were expressed in freshly isolated monocytes or monocytes incubated with control antibody or anti-FRP-1 monoclonal antibody (MAb) for 14 days. Of these mRNAs, cathepsin-K, CA II, v-ATPase, VNR, TRAP, OPN, and c-fms mRNAs were expressed at higher levels in the osteoclast-like cells than those in monocytes cultured with control antibody. On the other hand, galectin-3 mRNA was expressed at lower levels in the osteoclast-like cells, and there was no significant difference in c-fos mRNA expression between the monocytes cultured with control antibody and anti-FRP-1 MAb. c-src mRNA could not be detected in monocytes freshly isolated or incubated with control antibody. Surprisingly, expression of c-src mRNA was induced in monocytes by anti-FRP-1 MAb and was detectable as early as 3 h after anti-FRP-1 MAb treatment, indicating that c-src is selectively induced by anti-FRP-1 MAb treatment. Furthermore, the osteoclast-like cells expressed calcitonin receptor. Receptor activator of NF-kappaB (RANK) mRNA was detectable in freshly isolated monocytes or monocytes cultured with control antibody or anti-FRP-1 MAbs. Maximal expression of RANK was observed in osteoclast-like cells. On the other hand, no receptor activator of NF-KB ligand (RANKL) mRNA was detectable in any of the samples, suggesting that anti-FRP-1 mAb can induce osteoclast-like cells from blood monocytes without RANKL.

Antibodies, Monoclonal↗
PubMed1999

Relationship of portal pressure and colorectal vasculopathy in patients with cirrhosis.

We studied the relationship between portal pressure and colorectal mucosal vascular lesions in cirrhotics and the effectiveness of drug therapy in treating these lesions. Colonoscopy and hepatic venous pressure gradient (HVPG) studies were performed in 21 cirrhotics. Oral spironolactone plus transdermal nitroglycerin were given to patients who had diffuse mucosal cherry-red spots and/or rectal varices. The colonoscopy and HVPG determinations were repeated after four weeks. Colonoscopic findings included vascular ectasias in 13 patients (62%), diffuse cherry-red spots in the rectum in five patients (24%), and rectal varices in eight patients (38%). Overall, colorectal mucosal vascular lesions were found in 16 cirrhotics (76%). These findings were not found in 21 age- and sex-matched noncirrhotic controls. Vascular ectasias appeared without relationship to the HVPG. Patients with diffuse cherry-red spots (N = 5, 22.4+/-3.4 mm Hg) had a significantly higher HVPG than those without (N = 16, 16.6+/-3.3 mm Hg, P < 0.01). However, no significant difference was found in HVPG between patients with rectal varices (N = 8, 19.4+/-4.6 mm Hg) and patients without rectal varices (N = 13, 17.2+/-3.8 mm Hg). After four weeks of drug therapy, diffuse cherry-red spots became less obvious when the HVPG decreased more than 20%. Rectal varices did not change their appearance with HVPG reduction. We found that colorectal vascular lesions are common in cirrhotics. Diffuse cherry-red spots are probably dependent on elevated portal pressure, but vascular ectasias and rectal varices are not related to the degree of portal pressure. Chronic drug therapy with reduction of portal pressure improves colonoscopic findings such as diffuse cherry-red spots.

Administration, Cutaneous↗
PubMed1999

Isolation and characterization of monoclonal antibodies directed against murine FRP-1/CD98/4F2 heavy chain: murine FRP-1 is an alloantigen and amino acid change at 129 (P<-->R) is related to the alloantigenicity.

Nineteen mAb directed against murine fusion regulatory protein-1 (mFRP-1)/4F2/CD98 were isolated and their biological properties were analysed. Intriguingly, mFRP-1 was found to be an alloantigen, namely, FRP-1.1 (DBA/2 and CBA mice type) and FRP-1.2 (BALB/c, C57BL/6 and C3H/He mice type). The nucleotide sequences of FRP-1.1 and FRP-1.2 were determined, demonstrating that amino acid change at 129 (P<-->R) is related to the alloantigenicity. mFRP-1 is expressed on thymocytes, on spleen cells, on peripheral lymphocytes and on blood monocytes, suggesting that the physiological role in vivo of murine FRP-1 is different from that of human FRP-1. The biological activities of antimFRP-1 mAbs showed by the present study are: (i) enhancement of Newcastle disease virus-induced cell fusion; (ii) suppression of HIVgp160-mediated cell fusion; and (iii) induction of aggregation and multinucleated giant cells of monocytes/macrophages.

Amino Acid Sequence↗
PubMed1999

National average for the process of radiation therapy in Japan by Patterns of Care Study.

BACKGROUND: A nationwide effort is in progress to establish the actual state of radiotherapy and its quality assurance (QA) in Japan by using the Patterns of Care Study (PCS). In this study, national averages are calculated with a limited number of patients. A calculation program for national averages was prepared and applied to the radiotherapeutic processes used for esophageal cancer patients entered in the PCS. METHODS: The calculation program for national averages, which were revised on the basis of differences between individual facilities and institutional strata, was developed in accordance with Sedransk's equation for the original PCS in the USA. National averages for several aspects concerning the sampled patients who had esophageal cancer between 1992 and 1994 were calculated with these procedures. Data for facilities and stratification of institution were simulated from a national structure survey of radiation oncology in 1990. RESULTS: Values of the national average by Sedransk's equation were different from those of the simple sample average. There were significant differences in radiotherapeutic processes among stratification of institutions. For esophageal cancer, national averages were 0.129 for applications of endoscopic ultrasound, 0.599 for 'all fields treated each day' and 0.088 for application of brachytherapy. CONCLUSION: National averages for radiotherapy could be calculated. The values obtained in this PCS will be a useful measure for future QA in radiation oncology and in other specialties in Japan.

Esophageal Neoplasms↗
PubMed1999

Nucleolar protein B23.1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity.

Phosphorylated retinoblastoma protein and nucleolar protein B23 are putative stimulatory factors for DNA polymerase alpha. We showed that these two factors interacted with each other and stimulated the activity of DNA polymerase alpha synergistically. B23 exists in two isoforms designated as B23.1 and B23.2. While B23.1 bound to a retinoblastoma protein-conjugated column, B23.2 did not. These results indicate that B23.1 can directly bind to retinoblastoma protein. It was also shown that B23 was co-immunoprecipitated with both retinoblastoma protein and DNA polymerase alpha from a HeLa cell extract by monoclonal antibodies raised against these components. These results suggest that these three proteins exist as a complex in cells, at least in part. The simultaneous addition of both B23.1 and retinoblastoma protein caused stimulation of DNA polymerase alpha activity that is much higher than the sum of the stimulation by retinoblastoma protein and B23.1 alone. The maximal stimulation was attained at the molar ratio of DNA polymerase alpha/retinoblastoma protein/B23.1 = 1:1:12. Since B23 exists as a hexamer in solution, it may act as a stimulator of DNA polymerase alpha in a form of double-hexamer, in concert with the phosphorylated retinoblastoma protein.

Animals↗
PubMed1999

Evaluation of NOx in the cardiovascular system: relationship to NO-related compounds in vivo.

Diverse attention should be paid to evaluating NOx (NO2- and NO3-) in plasma as an index of endothelial nitric oxide (NO) formation in vivo. Nitric oxide, which subsequently appears as NOx, originates from different types of NO synthase and from nonenzymatic reactions. NOx also comes from exogenous sources such as food and gastrointestinal microorganisms. The fate of the NO incorporated into activation of guanylate cyclase, formation of nitrosyl hemoglobin (or nitrosohemoglobin), nitrosothiols, peroxynitrite and its derivatives and other possible compounds is not clear at present. However, some of these compounds would produce NOx as by-products or as final products through metabolism. Therefore, plasma NOx contains information about these pathways, although how extensively these factors contribute to plasma NOx has not been quantitatively defined. A theoretical simulation of NOx in the systemic circulation indicates that only small changes are expected by inhibition or stimulation of endothelial NO production. Measuring NOx production during coronary circulation has the advantage that some degree of NOx accumulation is expected from intact endothelial cells because an excretion system is absent in the heart.

Animals↗
PubMed1999

A pilot study of a response oriented chemotherapeutic regimen combined with autologous peripheral blood progenitor cell transplantation in aggressive non-Hodgkin's lymphoma.

Fourteen consecutive patients with poor-risk aggressive NHL who at presentation had any one of four risk factors underwent response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation. After treatment with three cycles of conventional CHOP with G-CSF support (CHOP-G), the response was evaluated. For patients who achieved a complete remission (CR), an additional three cycles of CHOP-G were administered, while for partial response patients, another induction regimen including some non-cross-resistant agents was given; three cycles of VIPDexa-G (etoposide, ifosfamide, cisplatinum and dexamethasone) +/- two cycles of ENAP-G (mitoxantrone, etoposide, cytosine arabinoside and prednisone), were given. The scheduled induction chemotherapy, was followed by treatment with a high-dose cytoreductive regimen followed by autologous PBPC transplantation. After three cycles of CHOP-G, four patients (29%) achieved a CR, and 10 (71%) achieved a partial response (PR). When all scheduled induction therapy was completed, 10 patients (71%) had a CR. All 14 patients received high-dose therapy and obtained a complete hematologic recovery, except for one with a bone marrow relapse two months after transplantation. Evaluation of response after high-dose therapy showed 12 CRs (86%) which included three additional CRs, one PR, and one toxicity-related death. With a median follow-up of 12 months (range, 4 to 40), 12 are alive, with 11 in continuous first CR, and one relapse. The 2-year overall survival (OS) rate and event-free survival (EFS) rate are 77% and 79%, respectively, while the disease-free survival (DFS) rate is 92%. In conclusion, this pilot study suggests that response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation is commendable and can be associated with a high rate of remission and DFS for poor risk subjects with aggressive NHL.

Adolescent↗
PubMed1999

TMC-86A, B and TMC-96, new proteasome inhibitors from Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094. I. Taxonomy, fermentation, isolation, and biological activities.

TMC-86A, B and TMC-96, new 20S proteasome inhibitors with an epoxy-beta-aminoketone moiety, were isolated from the fermentation broth of Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094, respectively. TMC-86A, B and TMC-96 inhibited the chymotrypsin-like and peptidylglutamyl-peptide hydrolyzing activities of 20S proteasome with the following IC50 values: TMC-86A, 5.1 microM and 3.7microM; TMC-86B, 1.1 microM and 31 microM; TMC-96, 2.9 microM and 3.5 microM, respectively. TMC-86A, B and TMC-96 exhibited the weak inhibitory activity against the trypsin-like activity of 20S proteasome with IC50 values of 51 microM, 250 microM, and 36 microM, respectively. They did not inhibit m-calpain, cathepsin L, and trypsin at 100 microM, suggesting their high specificity for proteasome. Taxonomy of the producing strains is also described.

Actinomycetales↗
PubMed1999

TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282.

Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.

Anti-Bacterial Agents↗
PubMed1999

TMC-66, a new endothelin converting enzyme inhibitor produced by Streptomyces sp. A5008.

A new endothelin converting enzyme (ECE) inhibitor, TMC-66 was isolated from the fermentation broth of Streptomyces sp. A5008. The structure of TMC-66 was elucidated by spectroscopic analyses to be a new member of benzo[a]naphthacenequinone class of antibiotics. TMC-66 had a highly selective inhibitory activity for ECE with an IC50 value of 2.9 microM. Taxonomy of the producing strain is also described.

Animals↗
PubMed1999

[Nontuberculous mycobacterial disease in a general hospital].

Annual incidence of nontuberculous mycobacterial (NTM) disease has been gradually increasing in the last 10 years in Japan. It is likely to encounter this disease not only in hospitals specialized in mycobacterial diseases but also in general hospitals. NTM were isolated from 97 cases between January 1990 and June 1996 at our hospital. Out of them, 41 patients were diagnosed as NTM disease. Mycobacterium avium complex (MAC) was the most frequent pathogens (68.3%) and M. kansasii (22%) was the next. Other pathogens were M. chelonae (4.9%), M. fortuitum (2.4%) and M. szulgai (2.4%). Results obtained in our hospital were very similar to the rates which have been reported previously. Patients with MAC infection showed relatively poor prognosis (eight patients were died out of 28 patients with MAC) in this study compared with the cases reported in previous papers, and this result could be explained by the severity of illness when they were admitted to our hospital, the insufficiency of the initial treatment which should be started with the combined use of three to four antibacterial drugs including clarithromycin, and to a low dosage of clarithromycin compared with conventionally adopted dosage. Unlike tuberculosis, human to human transmission is considered to be negligible in the case of NTM disease, and general hospitals are able to provide medical care to the patients with NTM disease. Rather, if general hospitals which are located in the region near to the patients residence can play more active role in the treatment of NTM disease, it would be more beneficial to patients requiring long-term follow-up observation. Based on the result that similar therapeutic results were obtained for infections with other NTM as reported in previous papers, it is indicated that general hospitals are able to provide medical care to patients with NTM disease if therapeutic regimens recommended by specialist are sufficiently understood and applied.

Female↗
PubMed1999

[Prognosis and organ preservation in oropharyngeal cancer treated with radiotherapy].

The records of 102 patients with squamous cell carcinoma of the oropharynx treated at National Sapporo Hospital with external and/or interstitial radiotherapy between 1978 and 1996 were reviewed to evaluate the treatment results, focusing on primary control and functional preservation. Ninety-five patients had been primarily treated with curative intent initially. Of these 95 patients, 4% were in stage I, 19% in stage II, 42% in stage III and 34% in stage IV. Twenty-one patients (22%) had been treated with multidisciplinary chemotherapy, and 19 patients (20%) had been boosted with brachytherapy mainly using Au-198 grains. The cause-specific survival rates at 5 and 10 years were 63% and 52%, respectively. The local control rates at 5 and 10 years were 70% and 51%, respectively. The most important factors affecting local control were the subsite of the primary tumor and N stage. Based on these findings, it is considered that radiotherapy combined with/without chemotherapy except for N3 and the posterior wall type is an effective method of achieving tumor control and preserving organ function, compared with other methods including surgical procedures.

Adult↗
PubMed1998

Clinical implications of p53 autoantibodies in the sera of patients with non-small-cell lung cancer.

BACKGROUND: The presence of autoantibodies to p53 protein has been associated with the presence of p53 (also known as TP53) gene mutations in primary tumors and with poor prognosis. This study was undertaken to determine the clinical significance of p53 autoantibodies in patients with non-small-cell lung cancer (NSCLC). METHODS: We studied 188 consecutive patients with NSCLC who underwent pulmonary resection and for whom preoperative serum was available. The presence of p53 autoantibodies, detected by use of two amino-terminal and two carboxy-terminal peptides (20-30 mers) as antigens and an enzyme-linked immunosorbent assay, was related to various clinicopathologic parameters and to overexpression of p53 protein in the primary tumor. For 22 patients who had p53 autoantibodies before surgery, we also examined sera taken during postoperative follow-up. Reported P values are two-sided. RESULTS: Autoantibodies to p53 protein were detected in 38 patients. Patients with squamous cell carcinoma, those with more advanced disease (stage III-IV), and those with tumors that overexpressed p53 had a significantly higher incidence of p53 autoantibodies (P = .05,.0079, and .02, respectively). In all but one of the patients with postoperative serum samples, the antibody titer declined after surgery; however, there was no relationship between clinical course and this change in antibody titer. In addition, there was no relationship between the presence of p53 autoantibodies and overall survival in 171 patients who underwent potentially curative resection (P = .28); however, 13 patients with autoantibodies to amino-terminal peptides had a worse overall survival (P = .02). CONCLUSIONS: In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC.

Adult↗
PubMed1998

Inter-isoformal regulation of nitric oxide synthase through heteromeric dimerization.

Biochemical characterization of neuronal nitric oxide synthase (nNOS) has demonstrated a unique complexity with the native protein being a homodimer. To cast light on its enzyme structure-activity relationship, inactive nNOS, generated by mutation of (Lys732-Lys-Leu) to (Asp732-Asp-Glu) (Watanabe et al., FEBS Lett., 403 (1997) 75-78), and active nNOS were co-expressed using the Sf9 and COS-7 cell expression system. Co-transfectants of active and inactive nNOS resulted in attenuation of Ca2+/calmodulin (CaM) dependent NOS enzyme activity to a level 46.4+/-4.30% as much as active homomeric enzyme. Dimerization between active and inactive nNOS was observed by low temperature SDS-PAGE in the co-transfectants. The dimerization and attenuation of Ca2+/CaM dependent activity were not observed when active and inactive nNOS were combined in vitro, indicating that nNOS dimerization occurs intracellularly to form an active enzyme. Furthermore, we co-expressed inactive nNOS with active inducible NOS (iNOS) to analyze inter-isoformal regulation of NOSs. Interestingly, inactive nNOS also showed similar effects on enzyme activity and heteromeric dimerization against iNOS, thus indicating that inter-isoformal regulation of the two isoforms might also be involved in control of neuron function.

Animals↗