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Biomedical subjects

N Iwata

Publications and source records attributed to N Iwata.

At least 109 records · Page 6Linked to original sources
PubMed1996

Cholecystokinin-B/gastrin receptors mediate rapid formation of actin stress fibers.

Specific receptors for brain-gut peptide hormones, cholecystokinin (CCK) and gastrin, are expressed in a variety of human tumor cells. CCK and gastrin promote the growth of NIH3T3 cells into which the CCK-B/gastrin receptor had been introduced via a eukaryotic expression vector. In this study, we have examined the effect of CCK-8 on the actin cytoskeleton by using two mouse fibroblast cell lines expressing human CCK-B/gastrin receptors. Treatment with very low concentration of CCK-8 (10(-10) M) induced the formation of actin stress fibers within one minute. Stress fiber formation increased for 30 min. In contrast, a potent mitogen for fibroblasts, platelet-derived growth factor (PDGF), initially induced membrane ruffling and, later, a weak formation of stress fibers. Microinjection of rho GDP dissociation inhibitor or Clostridium botulinum ADP-ribosyltransferase C3 which is known to impair the function of a small GTP-binding protein, rho p21, inhibited the stress fiber formation by CCK-8 as well as by PDGF. These results indicate that CCK-B/gastrin receptor could regulate stress fiber formation in a rho p21-dependent manner. The signals from CCK-B/gastrin receptor might affect cell growth as well as cell motility or adhesion by regulating the actin cytoskeleton.

3T3 Cells↗
PubMed1996

Hormonal regulation of aldose reductase in rat ovary during the estrous cycle.

The physiological roles of aldose reductase [alditol:NAD(P)+1-oxidoreductase] have not been fully elucidated yet, although it has been implicated in the pathogenesis of diabetic complications. In the rat ovary we found remarkable changes in the enzyme level during the 4-day estrous cycle. After diestrus, the activity and protein content of aldose reductase increased to the maximum level on proestrous morning and rapidly fell off to the lowest level on the early morning of estrus. At this time its mRNA level in the ovary was significantly decreased compared with that on the morning of proestrus. Immunohistochemical staining of the diestrous ovary demonstrated localization of the enzyme protein in the granulosa cells and in the oocytes. At the end of proestrus when its level was low, immunoreactive aldose reductase in the granulosa cells was localized preferentially to the antrum side, with lesser staining in the cells lining the follicles. Administration of chlorpromazine to the rats on proestrus significantly restored the enzyme level on the following morning of the expected estrus. This effect of chlorpromazine was abolished when human chorionic gonadotropin was administered to the chlorpromazine-treated rats. When chlorpromazine was administered to the rats treated with bromocriptine, an inhibitor of pituitary prolactin secretion, aldose reductase activity in the ovary was significantly elevated compared with that in the rats treated with chlorpromazine alone. These findings suggest that in the rat ovary it is under hormonal regulation during the estrous cycle. The enzyme may possess a new functional role in the reproductive system of the female rat, which can be disordered under diabetic conditions.

Aldehyde Reductase↗
PubMed1996

Refractory thrombocytopenia with chromosome 11q23 abnormality.

Although cytopenia is a common manifestation of myelodysplastic syndrome (MDS), isolated thrombocytopenia is rare. The term "refractory thrombocytopenia" (RTC) has been proposed as a counterpart of refractory anemia. We describe here a case of RTC associated with chromosome abnormality on 11q23. A 59-year-old man was admitted because of severe thrombocytopenia. A bone marrow examination revealed an increased number of micromegakaryocytes and the absence of normal-sized megakaryocytes without obvious dysplasia in either the myeloid or the erythroid lineage. A remarkable increase of GPIIb/IIIa (CD41a)-positive precursor cells in the bone marrow was observed. Cytogenetic examination detected the chromosome abnormality, an addition on chromosome 11q23. Translocation of the HRX gene was not detectable by Southern blot analysis. The diagnostic problems of isolated thrombocytopenia and possible participation of gene(s) on chromosome 11q23 in megakaryocytopoiesis as well as early hematopoiesis are discussed.

Biopsy, Needle↗
PubMed1996

Distinct effects of N omega-nitro-L-arginine on seizures induced by several drugs in mice.

A potent nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (L-NA), suppressed tonic seizure elicited by pentylenetetrazol (PTZ; 100 mg/kg, SC) in a dose-related manner (25 to 100 mg/kg, IP), but had no effect on clonic seizure. The effect was most potent at 1 h after the administration of L-NA. L-NA (100 mg/kg, IP) suppressed clonic seizure as well as tonic seizure in bicuculline-treated (3.0 or 4.5 mg/kg, SC) mice. However, it did not affect seizures elicited by picrotoxin (2.0 to 6.0 mg/kg, SC). On the other hand, N-methyl-DL-aspartate (NMDLA; 300 mg/kg or 350 mg/kg, IP) induced clonic seizure, but tonic seizure was not always noted. All mice with clonic and tonic seizures died, and some mice with clonic seizure died without accompanying tonic seizure. L-NA did not influence NMDLA-induced seizures, but it appeared to enhance NMDLA lethality, though without statistical significance. These findings suggest distinct roles of NO in seizures induced by different drugs in mice.

Animals↗
PubMed1996

Age differences among Japanese on the Center for Epidemiologic Studies Depression Scale: an ethnocultural perspective on somatization.

The Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D) was subjected to principal component (PC) analysis with oblique rotation, as well as an examination of internal consistency, using data obtained from 2,016 adult employees aged 19-63 years. Analyses focused on age differences in these psychometric properties of the CES-D. Coefficient-alpha was sufficiently high for all age groups but was lower than reported in U.S. studies. Positive affect items lowered internal consistency. The PC analyses extracted four factors for each age group. Depressive affect items did not group into one factor; some were combined with somatic or interpersonal items, and the remainder constituted the smallest factor. These three main factors, 'somatic+depressed', interpersonal + negative' and 'positive affect' were comparable across age groups except for those aged 50-63 years. For those aged 50-63 years, the first two factors were combined into a large 'general dysphoria' factor, suggesting a more unified conceptualization of depressive mood. Although 'positive affect' was stable cross-culturally, it was not related to depressive symptomatology as measured by the other items, for Japanese. The 'interpersonal + negative' appears unique for Japanese, indicating the association of interpersonal relations with depressive mood in Japanese. The effects of age-specific ethnocultural factors in Japan on depressive symptomatology are discussed.

Adult↗
PubMed1996

Prevalence of mood and anxiety disorders in a working population in Japan.

To learn the prevalence of mood and anxiety disorders (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised) in a working population in Japan, we analyzed data from a population-based survey. Among 140 respondents who had a job, 8% experienced any of seven mood and anxiety disorders in the past 6 months and 19% had in their lifetime. The 6-month and lifetime prevalence rates of major depressive episodes were 4% and 14%, respectively. The 6-month and lifetime prevalence rates of phobic disorders were both 4%. The lifetime prevalence rates for other anxiety disorders were 1% or less. The 6-month rate of any disorder, as well as 6-month and lifetime rates of phobic disorders, was higher in white-collar employees than in self-employed workers (P < 0.05). The multiple logistic regression confirmed the tendency after controlling for sex and age, although the result was not significant (P > 0.05).

Adolescent↗
PubMed1996

Antiproliferative effect of a novel cholecystokinin-B/gastrin receptor antagonist, YM022.

Cholecystokinin (CCK)-B and gastrin receptors are expressed on a variety of human tumor cells. Recently, we have demonstrated that the human brain CCK-B receptors are identical to the gastrin receptors derived from the stomach mucosa, and that the brain-gut peptides, CCK-8 and gastrin I are mitogenic for mouse NIH 3T3 fibroblasts expressing human CCK-B/gastrin receptors (N-hCCKBR). In this report, we evaluated the antiproliferative potency of CCK-B/gastrin receptor antagonists by using N-hCCKBR cells. Among several antagonists, a benzodiazepine derivative, YM022 had the most potent activities in competing with [125I]CCK-8 or [125I]gastrin I binding, inhibition of CCK-8- or gastrin I-induced phosphoinositide hydrolysis and increasing cytoplasmic free calcium. Interestingly, a potent antagonist for rat CCK-B/gastrin receptors did not have such activities in N-hCCKBR cells. YM022 inhibited the CCK-8- or gastrin I-induced [methyl-3H]thymidine incorporation of N-hCCKBR cells in a dose-dependent manner. In the absence of exogenous peptide ligands, YM022 also inhibited the proliferation of several human cancer cell lines expressing the genes for both gastrin and its receptor. These results suggest that YM022 could intervene in the autocrine stimulation of human tumor cell lines through CCK-B/gastrin receptors. N-hCCKBR cells are an excellent tool to screen for novel human CCK-B/gastrin receptor antagonists possessing antiproliferative activity for human cancer cells.

3T3 Cells↗
PubMed1996

Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlic.

Ajoene, a garlic-derived sulfur-containing compound that prevents platelet aggregation, exhibited broad-spectrum antimicrobial activity. Growth of gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis, Mycobacterium smegmatis, and Streptomyces griseus, was inhibited at 5 micrograms of ajoene per ml. Staphylococcus aureus and Lactobacillus plantarum also were inhibited below 20 micrograms of ajoene per ml. For gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, and Xanthomonas maltophilia, MICs were between 100 and 160 micrograms/ml. Ajoene also inhibited yeast growth at concentrations below 20 micrograms/ml. The microbicidal effect of ajoene on growing cells was observed at slightly higher concentrations than the corresponding MICs. B. cereus and Saccharomyces cerevisiae were killed at 30 micrograms of ajoene per ml after 24 h of cultivation when cultivation was started at 10(5) cells per ml. However, the minimal microbicidal concentrations for resting cells were at 10 to 100 times higher concentrations than the corresponding MICs. The disulfide bond in ajoene appears to be necessary for the antimicrobial activity of ajoene, since reduction by cysteine, which reacts with disulfide bonds, abolished its antimicrobial activity.

Anti-Bacterial Agents↗
PubMed1996

Antimutagenic effects of ajoene, an organosulfur compound derived from garlic.

The antimutagenic effects of ajoene, which is an organosulfur compound derived from garlic, were investigated by the Ames test. Ajoene inhibited mutagenesis induced by both benzo[a]pyrene (B[a]P) and 4-nitro-1,2-phenylenediamine (NPD) in a dose-dependent manner. In particular, NPD-induced mutagenesis was more effectively suppressed by ajoene than the B[a]P-induced type. Furthermore, the inhibition of mutagenesis by ajoene was more effective for transition-type mutations than for the frame shift type. HPLC analysis of B[a]P metabolism in the presence of the rat liver microsomal fraction (S-9) showed that ajoene dose-dependently inhibited the metabolic activation of B[a]P. This suggests that ajoene affected the metabolic enzymes in the S-9 fraction.

Animals↗
PubMed1996

Rapid and large-scale isolation of microsomal fraction of mouse liver by lyophilization and low speed centrifugation.

We could prepare the microsomal fraction of mouse liver, without using an ultracentrifuge but with a low speed centrifuge. The procedure includes 1) lyophilization of post-mitochondrial fraction (9,000 x g supernatant) of mouse liver, 2) powdering of the lyophilized sample, 3) the addition of 1.15 per cent potassium chloride solution or distilled water, which afforded microsomal aggregates, 4) sedimentation of microsomal fraction by low-speed centrifugation (20,000 x g, 20 min). The sedimented microsomal fraction showed normal contents of cytochrome P-450 and cytochrome b5, and gave a normal pattern on SDS polyacrylamide gel electrophoresis and normal electron microscopic feature. This method should be convenient for rapid and large-scale preparation of microsomes, especially for the preparation of cytochrome b5 and cytochrome P-450.

Animals↗
PubMed1996

Measuring activities of daily living among haemophiliacs.

To explore the activities of daily living (ADL) status and/or changes in functional limitations among haemophiliacs, 97 patients were studied longitudinally using a 41-item checklist. The total number of data items was 239 with repeated inquiries. Hierarchical factor analyses yielded a clear separation of items into five factors by the analogous trunk and limb motion, and the existence of one higher-order factor which indicated that the items measured the same underlying concept. Analyses of ratings showed that in haemophiliacs full flexion of the lower limbs was easily limited, and this deterioration was difficult to prevent. The functional limitation level differed significantly by age group, but some patients showed a slight improvement in a follow-up observation. The ADL of haemophiliacs should be explored separately for trunk and limb motion, not for the traditional categories.

Activities of Daily Living↗
PubMed1996

[Cholecystokinin-B/gastrin receptor is a novel molecular probe for human small cell lung cancer].

Cloning of CCK-B/gastrin receptor cDNAs showed that they possess the feature of serpentine G protein coupled receptors. In this study, the receptor mRNA was detected selectively in all SCLCs (10 cases) with a RT-PCR assay. By contrast, it was detectable in only one of thirteen squamous cell carcinomas or twenty-one adenocarcinomas of lung. Thus, CCK-B/gastrin receptor has been demonstrated to provide a novel molecular marker for the diagnosis of small cell lung cancer (SCLC) by using biopsy specimens.

Biomarkers, Tumor↗
PubMed1995

Japan-U.S. comparison of responses to depression scale items among adult workers.

The operating characteristics of the Center for Epidemiologic Studies Depression Scale were compared between Japanese and U.S. adult workers. Data were analyzed from age- and education-matched male white collar workers (n = 368 for each) selected from 2016 workers in Japan and 3059 in the United States. The U.S. data were obtained from the 1974-75 Augmentation Survey of the National Health and Examination Survey I. The Japanese responses to positively worded items markedly differed from those of U.S. workers, whereas responses to negatively worded items were generally comparable in the two groups. Thus, spuriously higher positive subscale and whole scale scores were found among the Japanese workers compared with U.S. workers (mean scores: 6.03 vs. 1.83 for the positive subscale and 9.94 vs. 5.35 for the whole scale, respectively; both differences were statistically significant). Negative subscale scores did not differ significantly in the two samples (3.91 vs. 3.52). The present study confirmed the hypothesis of Iwata et al. that Japanese respondents have a tendency to suppress the expression of positive affect.

Adult↗
PubMed1995

A Klebsiella aerogenes moaEF operon is controlled by the positive MoaR regulator of the monoamine regulon.

A 30-kDa protein accumulated upon induction by a high concentration of tyramine or dopamine in cells of Klebsiella aerogenes (Ka). These cells carried a plasmid (pAS123) that included the arylsulfatase operon (atsBA). Deletion analysis showed that the region essential for induction of the 30-kDa protein was located within a 2.0-kb cloned segment downstream of the atsBA operon. The nucleotide (nt) sequence of the 2.0-kb fragment revealed two open reading frames (ORFs), moaE and moaF. Transcription from a putative promoter of moaE was induced by the addition of tyramine, and the moaF gene was co-transcribed from this monoamine-inducible Ka promoter. The deduced Ka MoaE protein was homologous to insect-type alcohol dehydrogenase. The sequence of the 18 amino acids from the N-terminus of the purified 30-kDa protein agreed with that deduced from the nt sequence of moaF. Using a Ka strain with a mutant moaR gene, we found that MoaR, that acts as the positive regulator of the monoamine regulon, also acts as the positive regulator of the moaEF operon.

Alcohol Dehydrogenase↗
PubMed1995

Ischaemia-induced change in clathrin preceding delayed neuronal death.

The mechanism underlying the change in clathrin immunohistochemistry preceding delayed neuronal death (DND) was studied in gerbils. The ischaemic change observed with chc5.9 anti-clathrin antibody in hippocampal CA1 was initially ameliorated by pentobarbital, which blocks DND, but 1 day after ischaemia, no change in the immunoreactivity of the SDS-denatured clathrin molecule was detected by Western blotting and no change in the clathrin content in CA1 was detected by SDS-PAGE. No ischaemia-induced change in immunohistochemistry was observed with another monoclonal anti-clathrin antibody, X-22. The above results imply that some modifications that affect the structure of clathrin molecules around the chc5.9 specific epitope may be a crucial step in the course of DND.

Animals↗
PubMed1995

Cholecystokinin-B/gastrin receptor: a novel molecular probe for human small cell lung cancer.

The brain-gut hormones, gastrin and cholecystokinin, have a trophic effect on the gastrointestinal mucosa in vivo and promote the growth of several neoplastic cell lines. In this study, cholecystokinin-B/gastrin receptor has been demonstrated to provide a novel molecular marker for the diagnosis of small cell lung cancer by using biopsy specimens. Physiological expression of the receptor mRNA is detectable in particular areas of the human brain, stomach, and pancreas but not in the lung. The receptor mRNA was detected selectively in all small cell lung cancer (10 cases) with a RT-PCR assay. By contrast, it was detectable in only 1 of 13 squamous cell carcinomas or 21 adenocarcinomas of the lung. Thus, the cholecystokinin-B/gastrin receptor could be an attractive therapeutic target for small cell lung cancer.

Adenocarcinoma↗