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Biomedical subjects

S Niwa

Publications and source records attributed to S Niwa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of Am-80, a synthetic derivative of retinoid, on experimental arthritis in mice.

Am-80 is a newly snythesized retinoid with the structure of one aromatic amide among retinobenzoic acids. It exhibits specific biological activities of retinoic acid such as the activation of cellular differentiation and proliferation. We investigated the effect of Am-80 on collagen-induced arthritis (CIA) in mice and the immunopharmacological action on the production of several cytokines in the in vitro and in vivo models. Am-80, at doses of 0.3, 1 and 3 mg/kg, significantly inhibited the severity and development of the arthritis index, progression of foot pad swelling, bone damage and histopathological alterations. Am-80 also inhibited the production of anti-type II collagen (CII) IgG antibody, but did not affect the delayed-type hypersensitivity (DTH) response in arthritic mice. To determine the inhibitory mechanism of Am-80, we studied the effect of Am-80 on the production of cytokines. Am-80 did not affect the production of IFN-gamma by Th1 cells (1E10.H2 cells) and IL-4 by Th2 cells (D10.G4.1 cells), respectively. Am-80 selectively inhibited bacterial lipopolysaccharide (LPS)-induced IL-6, but not TNF-alpha and IL-1beta, production in mice. Moreover Am-80 inhibited IL-1beta induced IL-6 production and IL-6 mRNA expression in human osteoblast-like cells (MG-63). The inhibition of IL-6 production by Am-80 was due to downregulation of the pretranscription or the transcription of IL-6 in MG 63 cells. These findings suggest that the inhibitory effect of Am-80 on CIA is partially by modulating the production of the proinflammatory cytokine, IL-6.

Animals↗
PubMed1999

Increased expression of mitochondrial genes in human alcoholic brain revealed by differential display.

Polymerase chain reaction (PCR)-based differential display was used to screen for alterations in gene expression in the mesolimbic system of the human alcoholic brain. Total RNA was extracted from the nucleus accumbens of five alcoholic and five control brains. A selected subpopulation of mRNA was reverse-transcribed to cDNA and amplified by PCR. A differentially expressed cDNA fragment was recovered, cloned, and sequenced. Full sequence analysis of this 467 bp fragment revealed 98.2% homology with the human mitochondrial 12S rRNA gene. Dot-blot analysis showed increased expression of this gene in nucleus accumbens and hippocampus, but not in the superior frontal cortex, primary motor cortex, caudate, and pallidus/putamen in a total of eight human alcoholic brains, compared with seven control brains. A similar increased expression was observed by dot-blot analysis, using RNA from the cerebral cortex of rats chronically treated with alcohol vapor. Hybridization of a 16S rRNA oligonucleotide probe indicated that the expression of both rRNAs genes was significantly increased in nucleus accumbens. These results indicate that chronic alcohol consumption induces alteration in expression of mitochondrial genes in selected brain regions. The altered gene expression may reflect mitochondrial dysfunction in the alcohol-affected brain.

Adult↗
PubMed1998

Social cue perception in Japanese schizophrenic patients.

Although abnormal social cue perception in schizophrenia is thought to be a factor in impairing the acquisition of social skills, there have been no studies on social cue perception in Japanese schizophrenics. In order to clarify the characteristics of social cue perception in Japanese schizophrenic patients, 46 schizophrenics and 41 normal controls were presented 12 videotaped vignettes of interpersonal situations, and then they were asked true-false questions about the interaction viewed. Additionally, schizophrenics were administered the Bech version of the Brief Psychiatric Rating Scale. The results showed that the schizophrenic group showed a poorer performance on the cue recognition task than the normal group, and in particular, schizophrenics exhibiting false alarm errors were seen more often than schizophrenics exhibiting omission errors. This suggests that false recognition of information that does not actually exist in social situation is an important characteristic of social cue perception in schizophrenic patients. The false alarm rates on the cue recognition task in schizophrenics were related to the severity of positive-thought disorder, but not to that of negative symptoms. There was no significant relationship between the omission error rates and the two symptom scores in schizophrenics. Faulty cue recognition and positive-thought disorder may be due to a common factor.

Adult↗
PubMed1998

Contribution of proline residue for efficient production of MHC class I ligands by proteasomes.

Proteasomes are processing enzymes capable of generating major histocompatibility complex (MHC) class I ligands, but the mechanism of how they excise ligands without destroying them is largely unknown. Previously, we reported that most products of ornithine decarboxylase degraded in vitro by the 26 S ATP-dependent proteasome, which contained one or two Pro residues (Tokunaga, F., Goto, T., Koide, T., Murakami, Y., Hayashi, S., Tamura, T., Tanaka, K., and Ichihara, A. (1994) J. Biol. Chem. 269,17382-17385), which implied that the Pro residue has a role in the escape from random cleavage by proteasomes. Here, we examine the role of the Pro residue in producing MHC class I ligands in vitro. Proteasomes generated two cytotoxic T lymphocyte-epitopic precursor peptides, SIIPGLPLSL and DMYPHFMPTNL, from the 29-mer and 25-mer peptides harboring these sequences, which are derived from the c-akt proto-oncogene and the pp89 protein of mouse cytomagalovirus, respectively. Replacement of the first or second Pro residue within these epitopes by Ala resulted in a marked reduction of this epitope-derived production or their random cleavage by proteasomes, irrespective of the presence of PA28, which greatly accelerates the generation of unmodified ligands. Moreover, replacement of a single amino acid residue other than Pro in both epitopic and flanking regions by Ala or Leu had no or little appreciable effect on the SIIPGLPLSL or its derivative production. Thus, Pro residue(s) within these epitopic sequences presumably contributes to efficient production of MHC class I ligands through prevention of their random cleavage by proteasomes.

Amino Acid Sequence↗
PubMed1998

Expression pattern of a novel death-promoting gene, DP5, in the developing murine nervous system.

We examined the expression patterns of the DP5 gene, which encodes a protein with apoptosis-inducing activity, in the developing nervous system of mice. This gene was primarily expressed in the spinal motor neurons and peripheral sensory ganglia of mouse embryos and transiently in the postnatal brain, particularly in the entorhinal cortex and hippocampus. These expression patterns suggest that the DP5 gene may be involved in the apoptosis, if not all, of the developing nervous system.

Amino Acid Sequence↗
PubMed1998

Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. METHODS: Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. RESULTS: The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. CONCLUSIONS: Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.

Adenocarcinoma↗
PubMed1998

Epimorphin functions as a key morphoregulator for mammary epithelial cells.

Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

Animals↗
PubMed1998

Mechanical strength of calcium phosphate cement in vivo and in vitro.

Two different kinds of calcium phosphate cement were developed for implant fixation: cement A comprised of alpha-tricalcium phosphate (alpha-TCP) 95% and dicalcium phosphate dihydrate (DCPD) 5%, and cement B comprised of alpha-tricalcium phosphate 90% and dicalcium phosphate dihydrate 10%. The compression strength and pullout force of the new materials were tested both in vitro and in vivo. Microscopic observations were performed on the interface between bone and cement. Cement A showed a greater mechanical strength than cement B. The results suggest the clinical possibility of this calcium phosphate cement, which could be used as a material for enhancing implant fixation.

Animals↗
PubMed1998

Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors.

Borna disease virus (BDV) p24 RNA was detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients and blood donors by nested reverse transcriptase PCR (RT-PCR). The prevalences of BDV p24 RNA in patients with mood disorders (4%) and schizophrenia (4%) were not significantly different from that in blood donors (2%). This finding was inconsistent with previous reports that showed either a high prevalence or absence of BDV p24 RNA in patients with psychiatric disorders. The differences in BDV p24 RNA prevalence in these studies may be due to differences in the criteria for positivity, the number of PBMCs used for RNA extraction, or the amount of RNA tested for nested RT-PCR or to laboratory contamination. Sequence analysis of BDV p24 RNA from the PBMCs of patients and blood donors showed a high nucleotide sequence conservation but definite nucleotide mutations compared with horse BDV p24 RNA sequences. In comparison with human BDV p24 RNA sequences previously reported from Japan and Germany, there were several positions with silent nucleotide mutations among these clones.

Adult↗
PubMed1998

Correlation of lining thickness and expression of alpha 2 and alpha 3 integrins within the epithelial lining of odontogenic cysts.

Using monoclonal antibodies, we performed immunohistochemical investigations of the expression of alpha 2, alpha 3 and beta 4 integrin subunits within the squamous epithelial linings of odontogenic cysts. Tissue samples consisted of both follicular cysts and odontogenic keratocysts from 15 patients. It was found that beta 4 integrin was expressed on the basement membrane regardless of the histological type of the cyst. The degree of immunostaining for alpha 2 and alpha 3 integrin expression corresponded to the thickness of the epithelial cyst wall. We found that the thickness of the epithelial lining of odontogenic cysts had a direct correlation with the expression of integrin molecules.

Antigens, CD↗
PubMed1998

Enhanced expression of a new class of liver-enriched b-Zip transcription factors, hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas of rats and humans.

Rat hepatocarcinogenesis-related transcription factor (HTF) was earlier identified as a b-Zip transcription factor in chemically induced rat hepatocellular carcinoma (HCC) by cDNA subtraction, and its structure was found to be different from that of the conventional b-Zip proteins. We investigated htf gene expression in rat tissues by Northern analysis and found that HTF expression was ubiquitous but was enriched in the liver. HTF expression increased concomitantly with HCC development in rat liver, and the HTF-containing DNA-binding factor also increased. Stimulated HTF gene expression also was observed in rat regenerating livers. From the results of various assays, X-box-binding protein 1/Tax-response element binding factor 5 was suggested to be a human homologue of rat HTF. In humans, HTF gene expression was also abundant in the liver and was revealed to be specifically stimulated in HCCs, but not in other types of cancers. To our knowledge, HTF is the first example of a liver-enriched transcription factor that exhibits HCC-associated gene expression. Injection of anti-HTF antibody decreased the growth rate of cultured HCC cells. Consequently, HTF is thought to participate in hepatocyte growth as well as in hepatocarcinogenesis.

Animals↗
PubMed1997

Acute methamphetamine administration increases tyrosine hydroxylase mRNA levels in the rat locus coeruleus.

Tyrosine hydroxylase (TH) mRNA levels in the rat substantia nigra (SN), ventral tegmental area (VTA) and locus coeruleus (LC) were measured by in situ hybridization histochemistry 1, 4, 6 and 24 h after a single injection of methamphetamine (MAP, 4 mg/kg, i.p.) or an equivalent volume of saline. TH mRNA levels in LC were transiently increased (130% of control saline group, P < 0.05) at 1 h after MAP injection, and returned to basal levels within 4 h. In contrast, acute MAP administration did not significantly affect TH mRNA levels in SN and VTA. These findings are the first to demonstrate TH mRNA expression in the different responses of catecholaminergic neurons to acute MAP administration.

Animals↗
PubMed1997

Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. METHODS: The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. RESULTS: Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8). Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas. For all four tumor types, risks were higher among those with low income or education. CONCLUSIONS: Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases. IMPLICATIONS: Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

Adenocarcinoma↗
PubMed1997

Residential exposure to magnetic fields and acute lymphoblastic leukemia in children.

BACKGROUND: Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification since known as "wire coding"), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields. METHODS: We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors measured magnetic fields for 24 hours in the child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories; based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls). RESULTS: The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects. CONCLUSIONS: Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children.

Case-Control Studies↗
PubMed1997

Behavioral and P3 amplitude enhancement in schizophrenia following feedback training.

In order to clarify the remediability of behavioral and electrophysiological abnormalities in schizophrenia, hit rate, reaction time, and P3 amplitude from auditory event-related potentials were evaluated before and after feedback training of a task in 14 schizophrenics and 12 age-matched normal controls. Although mean changes in the three indices due to the training were nonsignificant in both schizophrenic and normal control groups as a whole, the changes in hit rate and reaction time correlated significantly with the P3 amplitude change in the schizophrenic (r = 0.60 and -0.58, respectively) but not in the normal control group. The P3 amplitude change also correlated with the P3 amplitude before the training only in the schizophrenic group (r = -0.68), suggesting that the training was more effective for the schizophrenic patients with marked P3 amplitude reduction. The observed P3 amplitude increase due to training may represent an electrophysiological correlate of a remediable aspect of behavioral deficits in schizophrenics, which may underlie the effectiveness of nonpharmacological treatments.

Adult↗
PubMed1997

Attention deficits assessed by Continuous Performance Test and Span of Apprehension Test in Japanese schizophrenic patients.

To examine whether attention deficits in the Continuous Performance Test (CPT) and in the Span of Apprehension Test (SPAN) are observed in Japanese schizophrenics, 49 chronic medicated schizophrenics and 43 normal controls were administered the UCLA version of CPT and SPAN. To investigate whether each measure of the CPT and the SPAN is independently correlated to symptoms, a hierarchical multiple regression was conducted with the attentional measures and age as independent variables and with the conceptual disorganization scores on the Brief Psychiatric Rating Scale (BPRS) as a dependent variable in schizophrenic subjects. Decreased performance on the CPT and SPAN measures was observed in the Japanese patients. This indicates that the CPT and the SPAN can detect the attention deficits of schizophrenics in Japan as well as Europe and the US. The SPAN scores in the present study were lower than in previous studies. This may be due to a lower level of familiarity of Japanese subjects with the Roman alphabet. Each measure of the CPT and the SPAN was significantly correlated with the conceptual disorganization scores after controlling for the other measure and age. We concluded that each deficit in sustained attention and processing capacity was independently related to formal thought disorder in schizophrenia.

Analysis of Variance↗
PubMed1997

Effects of repeated methamphetamine administration on dopamine D1 receptor, D2 receptor and adenylate cyclase type V mRNA levels in the rat striatum.

Dopamine D1 receptor (D1R), D2 receptor (D2R) and adenylate cyclase type V (AC5) mRNAs in the rat dorsal striatum (CPu) and ventral striatum (Acb) were measured by in situ hybridization histochemistry (ISHH) after repeated methamphetamine (MAP) administration. MAP (4 mg/kg) or an equivalent volume of saline was administered intraperitoneally once daily for 10 days to male Wistar rats. After 7 days of abstinence, behavioral experiment with MAP-challenge revealed that a significant behavioral sensitization was achieved in MAP-treated animals. The animals were sacrificed 7 days after the last injection and brain sections were analyzed by ISHH using 35S-labeled antisense oligonucleotide probes. We found that D1R mRNA levels in the CPu were significantly increased (124% of control, P < 0.01). In contrast, repeated MAP-treatment did not significantly affect the expression of D1R mRNA in Acb or mRNA for D2R or AC5. It was concluded that MAP-induced behavioral sensitization is accompanied by increased D1R mRNA levels in CPu.

Adenylyl Cyclases↗