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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 199 records · Page 11Linked to original sources
PubMed1998

Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line.

BACKGROUND: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos. RESULTS: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs. CONCLUSIONS: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.

Activin Receptors↗
PubMed1998

Phenotypic diversity of neurofibromatosis 2: association with plexiform schwannoma.

AIMS: Plexiform schwannoma (PS) is a rare variant of benign schwannoma characterized by a multinodular and plexiform growth pattern. In contrast to plexiform neurofibroma. PS is not associated with neurofibromatosis 1 (NF-1; von Recklinghausen's disease) and has no propensity for malignant transformation. The purpose of this study was to clarify the relationship between PS and the entities of neurofibromatosis 2 (NF-2; bilateral acoustic neurofibromatosis) and schwannomatosis. METHODS AND RESULTS: Six cases of PS associated with NF-2 or meningioma were retrospectively studied clinicopathologically and immunohistochemically. Four cases of PS were found among the patients with NF-2, and all of these had multiple PSs; three cases also had multiple schwannomas of the spinal nerve roots and two of these had meningioma. Two other patients had meningioma, but not NF-2. Four patients were male and two were female. The ages ranged from 18 to 52 years (mean 29.6 years). Histologically, PS showed the histological features that have been previously described, i.e. schwannoma composed of a predominant Antoni A-type component with a plexiform growth pattern. Immunohistochemically, the tumour cells were positive for S100 protein. Each nodule was surrounded by perineural cells which were positive for epithelial membrane antigen. CONCLUSIONS: It is important to recognize that PS could be associated with NF-2 or meningioma. The combination of PS and meningioma may be a 'formes frustes' of NF-2, and is clinically overlapped with schwannomatosis.

Adolescent↗
PubMed1998

Localization of rat FGF-5 protein in skin macrophage-like cells and FGF-5S protein in hair follicle: possible involvement of two Fgf-5 gene products in hair growth cycle regulation.

It has been reported that the gene for murine fibroblast growth factor-5 (Fgf-5) is expressed in the rat hair follicle and that this expression may be associated with catagen induction (Hebert et al, 1994). In this study, we analyzed the Fgf-5 gene product in skin because the gene generates two mRNA that translate into the FGF-5 protein and a short form of the FGF-5 protein (FGF-5S) as a result of an alternative splicing (Hattori et al, 1996; Ozawa et al, 1996). Indeed, we detected both types of FGF-5 mRNA in rat skin samples. Two monoclonal anti-FGF-5 antibodies, one (E723) being specific for FGF-5 long-form protein and the other (B2B6) being reactive with both FGF-5 and FGF-5S proteins, were used to locate these proteins by immunohistochemistry. Staining of the rat skin revealed that only the B2B6 antibody reacted with hair follicles and that both antibodies reacted with macrophage-like round cells, suggesting that the product of the Fgf-5 gene in the hair follicle is FGF-5S. The immunoreactivity of the FGF-5S protein increased during early anagen VI and decreased rapidly during catagen. The density of FGF-5-positive macrophage-like cells in the dermis increased during anagen and decreased during catagen and telogen, whereas the density of these cells in the panniculus adiposus did not change during anagen and increased during catagen and telogen. There was no apparent association between the density of FGF-5-positive macrophage-like cells and that of FGF-5-negative, dendritic macrophage-like cells. Thus, the results suggest the possible involvement of FGF-5S in the hair follicle in anagen VI and catagen development and that the density of FGF-5-positive macrophage-like cells may also be associated with the hair growth cycle.

Animals↗
PubMed1998

An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic carcinomas.

BACKGROUND: Only a few articles have examined the relationship between bcl-2 expression and clinical findings or bcl-2 expression and p53 expression in pancreatic carcinomas. METHODS: We investigated bcl-2 protein and p53 protein expression by means of immunohistochemical methods. RESULTS: The immunostaining for bcl-2 was positive in 16 (20%) of 81 cases of pancreatic carcinoma. There were no significant correlations between bcl-2 expression and the age, gender, region of sampling, or clinical stage of the patients. Bcl-2 protein was detected more frequently in histologically high-grade pancreatic carcinomas (grade III, 31%; grade II, 14%; grade I, 0%); however, there was no significant difference in prognosis between patients with and without bcl-2 protein expression. Immunostaining for the p53 protein was positive in 45 (56%) of 81 cases of pancreatic carcinoma. There was no significant correlation between bcl-2 protein expression and p53 protein expression. CONCLUSION: Bcl-2 was often detected in histologically high-grade pancreatic carcinomas, although there was no significant correlation between bcl-2 expression and the prognosis.

Adenocarcinoma↗
PubMed1998

Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.

Decapentaplegic (Dpp) plays an essential role in Drosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracellular signaling of the TGF-beta superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified in Drosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

Amino Acid Sequence↗
PubMed1998

Generation and characterization of a monoclonal antibody recognizing a fetal brain enriched O-linked sialoglycoprotein, FOG100.

With the aim of identifying molecules that are expressed specifically in the brain during neurogenesis, we tried to generate monoclonal antibodies which recognize molecules showing unique temporal expression patterns and molecular characteristics. We used a homogenate of the rat fetal forebrain (day 12 of fetal life, E12) as an immunogen, and antibodies which reacted with this preparation were screened by immunoblotting. One of the antibodies, Mab3C8, recognized a 100-kDa antigen that is enriched in fetal brain. This 100-kDa antigen was constantly expressed during fetal life (from E12 to E20) and became scarcely detectable two days after birth. The antigen was detected in the insoluble fraction of fetal brain and its isoelectric point ranged from 6 to 7, suggesting that it was a membrane-coupled glycoprotein. Analysis by glycosidase treatment and lectin blotting suggested that it was an O-linked glycoprotein with an alpha2,6 sialyl linkage. Thus, a molecule unique to the fetal brain, an O-linked sialoglycoprotein with a molecular mass of 100 kDa (FOG100), was found by generating an antibody.

Animals↗
PubMed1998

Members of the throat microflora among infants with different feeding methods.

Normal throat microflora have an important role of antagonistic activity against pathogenic bacteria. We studied members of throat microflora of 30 exclusively breastfed, 15 mixed-fed and 15 exclusively formula-fed infants at the age of 1 month. All infants harboured alpha haemolytic Streptococcus. The incidence of gamma Streptococcus and coagulase negative Staphylococcus's isolation from breastfed infants was higher. We also found that coagulase negative Staphylococcus is one of three predominant bacterial species in breastfed infants.

Analysis of Variance↗
PubMed1998

Bromocriptine treatment for perseveration in demented patients.

Some forms of behavioral perseveration may reflect the disruption of specific neurotransmitter systems including mesencephalic dopaminergic projection. We present an open-labeled trial of a dopamine agonist for treating perseveration in dementia. Eight patients with ischemic vascular or degenerative dementia completed a 25-day trial of bromocriptine with a maximum daily dose of 10 mg. Patients were assessed with neuropsychological scales and a test battery for detecting perseveration. Recurrent and stuck-in-set types of perseveration significantly improved during the treatment, whereas measures for general attention and overall cognitive function showed no significant changes. We assume that bromocriptine supplemented the mesolimbocortical or ventral mesostriatal dopamine system ameliorated a certain frontal lobe function such as focused attention or working memory and improved the patients' perseverations. Although this study is preliminary because of the small sample size and open-labeled design, the results underline the possibility of pharmacotherapy for perseveration and recommend a double-blind, placebo-controlled study.

Aged↗
PubMed1998

Age at onset and visuocognitive disturbances in Alzheimer disease.

We examined the relation of age at onset and visuocognitive disturbances in Alzheimer disease (AD) using a large sample of patients, quantitative neuropsychological measures, and multivariate statistics controlling for gender, education, stage of dementia, and disease duration. Significant positive coefficients were obtained with forward and backward digit and visual spans, visual counting, copying Rey complex figure, and block design task. The results indicated that patients with early-onset AD performed worse than late-onset AD patients on these tasks. There was no significant effect of age at onset on identification of overlapping figures, visual form discrimination, or Raven's colored progressive matrices. These findings confirm the greater attentional and visuospatial impairments in early onset patients when these confounding factors were controlled for, although no significant effect of age at onset in visuoperceptual function was observed.

Age Factors↗
PubMed1998

Lack of association of apolipoprotein E epsilon4 allele dose with cerebral glucose metabolism in Alzheimer disease.

Parietal cerebral glucose metabolism is reduced before substantial impairments appeared in subjects carrying the apolipoprotein E (APOE) epsilon4 allele, but the effect of the APOE epsilon4 allele on cerebral metabolism in Alzheimer disease (AD) is still undetermined. To investigate the effect of the APOE epsilon4 allele on cerebral metabolism in AD, we examined regional cerebral glucose metabolism in 83 patients with AD by using 18F-fluorodeoxyglucose and positron emission tomography. Cerebral glucose metabolism in the fronto-parieto-temporal association and limbic cortices was significantly decreased in the AD patients compared with 26 age- and sex-matched normal controls. Regional cerebral glucose metabolic rate was not correlated significantly with the number of APOE epsilon4 alleles in any region, which was consistent even after controlling the effects of age, sex, and severity of dementia, and in a subgroup analysis of those aged between 60 and 75. These results supported the view that the APOE epsilon4 allele is not associated with specific deficits in brain metabolism in AD despite evidence of preclinical alterations.

Aged↗
PubMed1998

Hypofunction in the posterior cingulate gyrus correlates with disorientation for time and place in Alzheimer's disease.

The relation between orientation for time and place and regional cerebral glucose metabolism was examined in 86 patients with probable Alzheimer's disease of minimal to moderate severity. Regional glucose metabolic rates in the posterior cingulate gyri and in the right middle temporal gyrus were significantly correlated with temporal orientation, and the glucose metabolic rate in the right posterior cingulate gyrus was significantly correlated with locational orientation irrespective of age, sex, education, and memory impairment. The results suggest that dysfunction of these structures plays an important part in producing disorientation in patients with Alzheimer's disease.

Aged↗
PubMed1998

Factors associated with psychotic symptoms in Alzheimer's disease.

OBJECTIVES: Many clinical and biological factors have been reported to be associated with the presence of psychosis in patients with Alzheimer's disease, although the associations were variable. The aim of this study was to clarify factors associated with the presence of psychosis in patients with Alzheimer's disease. METHODS: Psychiatric functioning was studied in 228 patients with Alzheimer's disease based on the results of the behavioural pathology in Alzheimer's disease rating scale or the neuropsychiatric inventory. The effects of sex, education level, age, duration of illness, cognitive function, and apolipoprotein E genotype were investigated for dichotomous psychotic status with a multiple logistic regression analysis. RESULTS: Of the 228 patients with Alzheimer's disease, 118 (51.8%) showed evidence of delusions or hallucinations. Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and more severe cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was not significantly related to either educational level or apolipoprotein E genotype. CONCLUSIONS: Age, sex, and severity of illness were independent factors associated with the presence of psychosis in patients with Alzheimer's disease. The reason why some patients with Alzheimer's disease develop psychosis remains unclear. There may be distinctive subtypes of Alzheimer's disease or the presence of individual factors which affect the development of psychosis.

Aged↗
PubMed1998

Regional metabolism: associations with dyscalculia in Alzheimer's disease.

OBJECTIVES: The ability to calculate, which is an important aspect of social daily living, is commonly impaired in patients with Alzheimer's disease even early in the course of the disease. Dyscalculia is often accompanied by focal brain damage, and has been argued to be an independent sign localised around the left temporoparietal region. However, the region most responsible for dyscalculia in Alzheimer's disease has not been determined. The relation between calculation ability and regional cerebral glucose metabolism in Alzheimer's disease was therefore examined. METHODS: The calculation ability, In 91 patients with probable Alzheimer's disease of minimal to moderate severity, was assessed using the arithmetic subtest of the Wechsler adult intelligence scale-revised and the performance correlated with regional cerebral glucose metabolism determined by "F-fluorodeoxyglucose and PET. RESULTS: Regional glucose metabolism in the left inferior parietal lobule and in the left inferior temporal gyrus was significantly correlated with the calculation performance irrespective of age, sex, education, and severity of disease. CONCLUSIONS: The results suggest that dysfunction of the left inferior parietal lobule and the left inferior temporal gyrus plays an important part in producing dyscalculia in patients with Alzheimer's disease.

Aged↗
PubMed1998

Inhibition of guinea pig skin allergic reactions by nonpeptide bradykinin B2 receptor antagonist FR173657.

BACKGROUND: Kinins, which cause vascular permeability enhancement (VPE) through bradykinin (BK) B2 receptors, are released at allergic reaction sites; however, the role kinins play in the lesions is still unknown. To determine whether kinins contribute to allergic reactions, the effect of a potent, nonpeptide BK B2-receptor-specific antagonist, FR173657, on VPE induced in the reaction sites was investigated. METHODS: Type I allergic reaction was induced by intradermal injections of dinitrophenol (DNP)-bovine serum albumin (BSA) into guinea pigs having received an intravenous injection of anti-DNP antiserum a week before. Type III allergic reaction was induced by intradermal injections of BSA into animals sensitized with subcutaneous injections of complete Freund's adjuvant-emulsified BSA 2 weeks before. VPE and swelling were measured by the leakage of intravenously injected dye and double thickness, respectively, at allergic reaction sites. FR173657 (4 mg/kg body weight) was administered orally 30 min before antigen injection. RESULTS: In the type I allergy model, FR173657 inhibited 34% of the early-phase VPE, which occurs a few minutes after antigen injection, and 50% of the subsequent swelling at the allergic reaction sites. In the type III allergy model, FR173657 also inhibited 30% of the early VPE but neither the late VPE, which occurs from 1 h to at least 24 h after the antigen injection, nor the following swelling at the allergic reaction sites. FR173657 inhibited BK-induced VPE almost completely without affecting histamine-induced VPE. CONCLUSIONS: Kinins contribute significantly to the VPE induced in the animal allergy models. FR173657 may be useful for the therapy of human allergic diseases.

Animals↗
PubMed1998

Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes.

Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2+/-0.5 fmol/10(5) cells/48 hours (mean+/-SEM). Angiotensin II (1 micromol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micromol/L significantly reduced the 10(-6) mol/L angiotensin II- and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10(-6) mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10(-6) mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.

Adrenomedullin↗
PubMed1998

Alteration of regional cerebral glucose utilization with delusions in Alzheimer's disease.

The authors examined 65 patients with Alzheimer's disease for delusions and explored the relationship of delusions with regional cerebral glucose metabolism determined by [18F]fluorodeoxyglucose PET. In patients with delusions (n = 26), normalized glucose metabolism was significantly increased in the left inferior temporal gyrus and significantly decreased in the left medial occipital region as compared with those without delusions (n = 39). The two groups were similar in age, sex, and dementia severity. These results suggest that delusions in Alzheimer's disease are attributable to a dysfunction in specific brain areas rather than a simple reaction to intellectual deficits.

Aged↗