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Biomedical subjects

N Kinoshita

Publications and source records attributed to N Kinoshita.

At least 19 recordsLinked to original sources
PubMed1995

The identification of two novel ligands of the FGF receptor by a yeast screening method and their activity in Xenopus development.

We have developed a functional screen in yeast to identify ligands for receptor tyrosine kinases. Using this method, we cloned two Xenopus genes that activate the fibroblast growth factor (FGF) receptor. These encode novel secreted proteins, designated FRL1 and FRL2, distantly related to the epidermal growth factor and angiogenin/ribonuclease families, respectively. Both genes activate the FGF receptor in Xenopus oocytes as well as in yeast. Overexpression induces mesoderm and neural-specific genes in Xenopus explants; induction is blocked by a dominant negative inhibitor of the FGF receptor. FRL1 is broadly expressed during gastrulation and neurulation, while FRL2 is expressed principally in the axial mesoderm and brain at later stages. Our results indicate that despite their lack of similarity with FGF, FRL1 and FRL2 are ligands for the FGF receptor that play distinct roles in development.

Amino Acid Sequence↗
PubMed1995

Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement.

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome (n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome (n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations, may partially account for the pathogenesis of deficit syndrome.

Adult↗
PubMed1995

Vasospastic angina pectoris associated with apical hypertrophic cardiomyopathy.

As the chest symptoms and electrocardiographic changes of hypertrophic cardiomyopathy are occasionally very similar to those of angina pectoris, there are some difficulties in the diagnosis and treatment of cases of ischemic heart disease associated with hypertrophic cardiomyopathy. Here we report a case of vasospastic angina pectoris associated with hypertrophic cardiomyopathy diagnosed by coronary spasm provocation test performed by intracoronary administration of acetylcholine. In the treatment of such cases, beta blockers, which have the effect of decreasing the oxygen demand of the heart and the potential to induce coronary spasm, must be administered carefully.

Acetylcholine↗
PubMed1995

Belactins A and B, new serine carboxypeptidase inhibitors produced by Actinomycete. I. Taxonomy, production, isolation and biological activities.

Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp. MK19-42F6. They were purified by ethyl acetate extraction, silica gel chromatography, Sephadex LH20 chromatography, Capcellpak C18 SG120 reversed phase HPLC and centrifugal partition chromatography (CPC) following their inhibitory activity against carboxypeptidase Y (CP-Y). The inhibition constants (Ki) of belactins A and B against CP-Y are 0.14 and 0.27 microM respectively. Belactins A and B have highly specific inhibitory activities for CP-Y among various peptidases, have no antimicrobial activities at 100 micrograms/ml and have low toxicities.

Benzamides↗
PubMed1995

Tetrodecamycin and dihydrotetrodecamycin, new antimicrobial antibiotics against Pasteurella piscicida produced by Streptomyces nashvillensis MJ885-mF8. I. Taxonomy, fermentation, isolation, characterization and biological activities.

The novel antimicrobial antibiotic against Pasteurella piscicida, tetrodecamycin (1) and weakly active dihydrotetrodecamycin (2) were isolated from the fermentation broth of Streptomyces nashvillensis MJ885-mF8. They were purified by adsorption on Diaion HP-20, silica gel column chromatography and crystallization. The MICs of 1 were 6.25 approximately 12.5 micrograms/liter and 1.56 approximately 6.25 micrograms/ml against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and 12 strains of P. piscicida, respectively.

Animals↗
PubMed1995

Azicemicins A and B, a new antimicrobial agent produced by Amycolatopsis. I. Taxonomy, fermentation, isolation, characterization and biological activities.

A new structural class of the antibiotic, azicemicins A (1) and B (2) were isolated from the culture broth of the strain MJ126-NF4, which was closely related to Amycolatopsis sulphurea. They were purified by adsorption on Diaion HP-20, silica gel column chromatography and preparative TLC. The molecular formulas of 1 and 2 were determined to be C23H25O9N and C22H23O9N by HRFAB-MS, respectively. Azicemicins A and B have moderate growth inhibiting activity against Gram-positive bacteria and mycobacteria.

Actinobacteria↗
PubMed1995

Isolation from Streptomyces of a novel naphthoquinone compound, naphthablin, that inhibits Abl oncogene functions.

In the course of our screening for inhibitors of abl oncogene function, a culture filtrate of Streptomyces aculeolatus, induced normal flat morphology in v-abl-expressing NIH3T3 cells. The active substance was isolated through ethyl acetate extraction, silica gel column chromatography, and reverse-phase HPLC. Mass and NMR spectroscopy including HMBC revealed that it had a novel naphthoquinone structure with a monoterpene, and we named it "naphthablin". Naphthablin inhibited Abl-induced morphological transformation in v-ablts-NIH3T3 cells at around 30 micrograms/ml, and specifically inhibited RNA synthesis.

Cells, Cultured↗
PubMed1994

Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients.

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

Adult↗
PubMed1994

Sudden hearing loss associated with interferon.

With the increasing long-term use of interferon, several new adverse effects have been recognised. We have prospectively assessed auditory function in 49 patients receiving interferon, after we saw a case of sudden sensorineural hearing loss during interferon therapy. Auditory disability (tinnitus, hearing loss, or both) occurred in 22 patients (45%) during treatment with audiometry-documented sensorineural hearing loss in 18 (37%). The auditory disability often developed in the late stage of treatment and resolved in all patients within 7-14 days after discontinuation of interferon.

Adult↗
PubMed1994

The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania.

1. Zonisamide, an anticonvulsant developed in Japan, is structurally similar to serotonin. Zonisamide has been proven to have a pharmacological profile that is very similar to that of carbamazepine. Thus, the effect of zonisamide was examined in 24 psychiatric patients: 15 with bipolar manic state, 6 with schizoaffective manic state, and 3 schizophrenic excitement. 2. Approximately 25% of all the patients and 33% of the bipolar manic patients showed remarkable global improvement with the addition of zonisamide. Approximately 71% of all the patients and 80% of the bipolar group had more than moderate global improvement. 3. No serious adverse reactions were found and no patients required zonisamide withdrawal. One patient developed both leukocytosis and mildly abnormal liver function test. One developed leukocytosis and another reported mild sleepiness. These reactions disappeared when zonisamide was discontinued.

Adult↗
PubMed1994

Effects of krestin (PSK) on tumorigenesis induced by two-stage and complete chemical carcinogenesis.

The effects of PSK on tumorigenesis in mouse skin were investigated either when mouse skins were initiated by benzo(a)pyrene and promoted by 12-O-tetradecanoyl-phorbol-13-acetate (Group I, two-stage carcinogenesis) or when both initiated and promoted by benzo(a)pyrene (Group II, complete carcinogenesis). Twelve mice in each group were fed chow with or without 0.4% PSK. This concentration of PSK was determined by calculation to give mice enough PSK to exert antitumorigenic activity without cytotoxicity. By the end of the experimental periods (26 weeks), two carcinoma-burdened mice in Group I without PSK were dead, but no carcinomas at all were identified in the mice fed with PSK, although considerable numbers of papillomas developed in both groups. In Group II, carcinomas started to evolve at the 15th week of the experiment regardless of PSK feeding. The number of carcinomas observed in the mice fed with PSK in Group II was statistically significantly lower than that in the mice fed without PSK. Histologically, mild inflammatory infiltrations were seen around the papillomas, and moderate to dense infiltrations, mainly composed of neutrophils, T lymphocytes, and macrophages, were observed in squamous cell carcinomas. There were apparently no significant differences in the number of the infiltrating cells around carcinomas in PSK (+) and PSK (-) groups in both early and fully developed lesions. However, considerable numbers of cells infiltrating into the nests were observed in the early lesions of elicited carcinomas in the mice fed with PSK, while such cells were rarely seen in carcinoma nests in the group without PSK at that stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Incidence of second primary cancers in Osaka residents, Japan, with special reference to cumulative and relative risks.

This study was conducted to examine the incidence rates and cumulative risks of second primary cancers in Osaka and to compare the observed number of second primary cancers with the expected number calculated using cancer incidence rates among Osaka residents. Study subjects were all reported cases aged 0-79 who were first diagnosed as having a first primary cancer between 1966-86. Incidence of second primary cancer among the study subjects was examined through to the end of 1989. The total number of study subjects was 217,307. During the follow-up period (mean duration: 3.7 years), second primary cancers developed in 5,071 patients (2.3%). Incidence of synchronous (interval < 3 months) and metachronous (interval > or = 3 months) second primary cancers increased in the later years. Incidence rates of second primary cancers were significantly associated with gender (male), age and calendar year at diagnosis of the first cancer. Based on the incidence rates, cumulative risk of developing metachronous second primary cancer was calculated. The ten-year cumulative risk was estimated as 10% for those who developed their first cancer during their sixties in 1978-83. The observed number of second primary cancers (including synchronous) was compared with the expected number. The ratios of observed-to-expected numbers were generally lower than 1.0 among those who developed their first cancer in 1966-77, while these ratios were higher than 1.0 among those who developed their first cancer in 1978-86. The ratios were much higher than 1.0 among those who developed their first cancer in their childhood and youth. Patients who had developed cancer of the colon, larynx, lung, bladder, or breast (female) showed significantly higher risk of developing second primary cancer during the period 1-4 years after diagnosis of the first cancer.

Adult↗
PubMed1994

[Effect of mesalazine, an agent for the treatment of idiopathic inflammatory bowel disease, on reactive oxygen metabolites and LTB4 formation].

Mesalazine microgranules (Pentasa) were developed as a drug for idiopathic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In this study, we examined the effect of mesalazine on radical scavenging, lipid peroxidation and the formation of LTB4. Mesalazine reduced the free radical 1,1-diphenyl-2-picrylhydrazyl with an IC50 value of 9.5 microM. It scavenged hydrogen peroxide and hypochlorite (IC50: 0.7 microM and 37.0 microM, respectively), but had no effect on superoxide. Lipid peroxidation in rat liver microsomes was inhibited by mesalazine (IC50: 12.6 microM). Mesalazine significantly inhibited (P < 0.01) gastric mucosal lipid peroxidation induced by ischemia and reperfusion in rats at a dose of 50 mg/kg, p.o. Mesalazine also inhibited the formation of LTB4 in rat peritoneal neutrophils (IC50: 44.9 microM). N-Acetyl-mesalazine, the metabolite of mesalazine, had no effect on radical scavenging and lipid peroxidation. Only a high concentration (1 mM) of the metabolite inhibited the formation of LTB4. These studies suggest that mesalazine inhibits cell injury in the inflamed mucosa by scavenging reactive oxygen metabolites and prevents the invasion of neutrophils by inhibition of LTB4 formation.

Aminosalicylic Acids↗
PubMed1994

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties.

A new antibiotic, aldecalmycin, has been discovered in the culture broth of Streptomyces sp. MJ147-72F6. Aldecalmycin was purified by solvent extraction, Diaion HP-20 chromatography, silica gel chromatography, Sephadex LH-20 chromatography, HPLC and centrifugal partition chromatography. The 1H and 13C NMR spectra of aldecalmycin showed the presence of keto-enol tautomers. Aldecalmycin is equipotent in inhibiting the growth of sensitive and methicillin-resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗