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Biomedical subjects

K Yamagata

Publications and source records attributed to K Yamagata.

At least 73 records · Page 4Linked to original sources
PubMed2000

c-Abl expression in oral squamous cell carcinomas.

c-Abl is proto-oncogene product. c-Abl has roles in signal transduction, cell cycle regulation, and inhibition of apoptosis. There are many reports about c-Abl function in hematopoietic cells, but few are concerned with solid tumors. In the present study, biopsy specimens from 44 patients with oral squamous cell carcinomas were subjected to immunohistochemistry, and the expression levels of c-Abl were correlated with clinicopathological features. Statistical analyses revealed that c-Abl expression was significantly associated with T-category (p = 0.011), sex (p = 0.014), and differentiation (p = 0.007), but no significant difference was observed with N-category, age, primary tumor region, or the other histological gradings. The low c-Abl expression group included more T4, male, and poorly differentiated cases. There was a trend towards longer tendency survival in the high expression group, but the difference was not significant. We conclude that c-Abl is a good candidate for a tumor-expansion marker.

Adult↗
PubMed2000

Genomic structure and mutations in adipose-specific gene, adiponectin.

BACKGROUND: Adiponectin is a collagen-like plasma protein specifically synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-specific. OBJECTIVE: To clarify the significance of the genetic variations in adiponectin gene on its plasma concentrations and obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20-83 y, BMI: 16-43 kg/m2) including 77 obese subjects (BMI>26.4 kg/m2). MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5'-flanking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (G/G: 4.5 microg/ml; G/T: 5.9 microg/ml; and T/T: 6.3 microg/ml), but were not statistically significant. The allelic frequency between the obese and the non-obese showed no significant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin. CONCLUSION: Two nucleotide changes have been identified in the adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.

Adipocytes↗
PubMed2000

Morphological and positional assessments of TMJ components and lateral pterygoid muscle in relation to symptoms and occlusion of patients with temporomandibular disorders.

Disc displacement is accepted as one of major findings in temporomandibular disorders (TMD). However, the associations of disc positions with morphological and positional changes of temporomandibular joint (TMJ) components and lateral pterygoid (LP), TMD clinical symptoms, and occlusion have rarely been discussed quantitatively. In this study, the morphological and positional changes of TMJ components and LP were assessed by means of magnetic resonance imaging (MRI) and tomography of the TMJ in 41 TMD and nine control (CN) subjects. Disc positions in TMD subjects were divided into normal position (NP) and anterior displacement with and without reduction (ADR+ and ADR-, respectively). From MRI scans and tomograms, the morphological and positional changes of TMJ components and LP were measured and compared among CN, NP, ADR+ and ADR- groups. Correlations between these measurements and the scored clinical symptoms and occlusal factors were analysed in TMD subjects. The results indicated that: (1) TMJ osseous structures and LP showed no significant difference among CN and the three TMD groups, except for a posterior seat of condyle and shorter/steeper condylar movement during jaw opening; (2) disc length and inclination were significantly shorter and steeper, respectively, in ADR+ and ADR-; (3) disc positions were not specified by clinical symptoms and occlusal factors, except for the dominant TMJ sounds in ADR+; (4) an uncoordinated movement of the condyle/disc complex was found in ADR+ and/or ADR-; (5) TMJ osseous structures and the disc were weakly associated with clinical symptoms and occlusal factors. However, the LP showed negative associations with palpable pain for both the TMJ and jaw muscles and the static occlusal factors. These findings suggest that TMJ internal derangements are more related to the positional changes or spatial relationships of TMJ components but less to the individual morphologies of TMJ osseous structures, disc and LP, as well as specific clinical symptoms and occlusal factors, which might be in disagreement with a large body of previous statements.

Adult↗
PubMed2000

Creatol, an oxidative product of creatinine in hemodialysis patients.

Creatol (CTL) is a product resulting from the reaction of creatinine (Cr) with the hydroxyl radical and is identified as a precursor of methylguanidine (MG), a uremic toxin. In this study, we investigated serum CTL levels together with those of Cr and MG in 66 patients who were on maintenance hemodialysis (HD). Prior to dialysis, the mean serum levels of Cr, CTL and MG were 967 (= 11.1 mg/dl)+/-267 microM, 11.1+/-4.8 microM and 5.8+/-2.9 microM, respectively. The mean CTL level was about 1.1% that of Cr, and the CTL plus MG level was about 1.4% that of the Cr level. The reduction rates of Cr, CTL and MG by a single HD were 62.6 6.1%, 71.0+/-10.3% and 51.9+/-11.6%, respectively. The CTL level at 0.5, 1 and 6 h after HD increased rapidly by 20.7+/-8.7%, 31.7+/-14.7% and 80.1+/-27.3%, respectively. There was a significant correlation between CTL or CTL/Cr and parathyroid hormone in patients who had just undergone parathyroidectomy. No significant correlation was found between CTL or CTL/Cr and those factors which seems to be related to the predialysis levels of reactive oxygen. Therefore, because of the good clearance of CTL and its rapid conversion to MG, its usefulness for the estimation of hydroxyl radical generation in HD patients is limited.

Adult↗
PubMed2000

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

Adult↗
PubMed2000

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Adult↗
PubMed2000

Activation of an effector immediate-early gene arc by methamphetamine.

As immediate-early genes (IEGs) are thought to play a critical role in mediating stimulus-induced neural plasticity, IEG response induced by methamphetamine (METH) has been characterized to define the changes in gene expression that may underlie its long-lasting behavioral effects. Although activation of several transcription factor IEGs has been described, little is known about effector IEGs. Here, we have examined whether METH administration affects expression of an effector IEG arc (activity-regulated, cytoskeleton-associated) that encodes a protein with homology to spectrin. Using in situ hybridization, we observed that METH caused a rapid and transient dose-dependent increase in arc mRNA level in the striatum and cortex that was abolished by pretreatment with the specific dopamine D1 receptor antagonist SCH-23390 but not by an atypical neuroleptic clozapine. METH induced arc mRNA in layers IV and VI of the cortex which dopamine receptor are localized to. These results suggest that D1 receptors are coupled to activation of arc gene, which may be involved in functional or structural alterations underlying neural plasticity triggered by METH.

AIDS-Related Complex↗
PubMed2000

Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion.

Betacellulin (BTC), a member of the epidermal growth factor family, is expressed predominantly in the human pancreas and induces the differentiation of a pancreatic acinar cell line (AR42J) into insulin-secreting cells, suggesting that BTC has a physiologically important role in the endocrine pancreas. In this study, we examined the in vivo effect of recombinant human BTC (rhBTC) on glucose intolerance and pancreatic morphology using a new mouse model with glucose intolerance induced by selective alloxan perfusion. RhBTC (1 microg/g body wt) or saline was injected subcutaneously every day from the day after alloxan treatment. The intraperitoneal glucose tolerance test revealed no difference between rhBTC-treated and rhBTC-untreated glucose-intolerant mice at 2-4 weeks. However, glucose tolerance was significantly improved and body weight was significantly increased in rhBTC-treated mice compared with untreated mice at 8 weeks. Islet-like cell clusters, consisting mainly of beta-cells, were increased in the pancreas and were localized in contact with the ductal lining cells and sometimes with acinar cells. In conclusion, administration of rhBTC improved glucose tolerance in this mouse model by increasing beta-cell volume, primarily through accelerated neogenesis from ductal lining cells.

Animals↗
PubMed2000

Experimental study of lymphogenous peritoneal cancer dissemination: migration of fluorescent-labelled tumor cells in a rat model of mesenteric lymph vessel obstruction.

Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and other parts of the peritoneum, and these deposits are generally considered to be induced by intraperitoneal seeding from the primary lesion. However, a few peritoneal metastatic cases or cases with positive intraperitoneal lavage cytology, without serosal infiltration, have been reported. Most of peritoneal dissemination is certainly attended with serosal involvement of gastrointestinal malignancy. Nevertheless, we observe an unusual case of peritoneal dissemination without definite serosal invasion of the malignancy. And peritoneal dissemination is likely to be concomitant with lymph node metastasis in both cases with and without definite serosal invasion. In this study, we examined peritoneal cancer dissemination from the viewpoint of lymphogenous metastasis. For the model of lymphatic invasion, we established an animal experimental model of mesenteric lymph vessel obstruction. With these models, lymphangiographical studies were made on the fourth postoperative day (ten animals each) and we obtained mesenteric lymphangiograms of extensive mesenteric lymph vessels and reflux of lymph distal to the obstruction point from all ten animals. Next, in these experimental models, fluorescent-labelled tumor cells (rat hepatoma cell line, N1-S1) were infused from the mesenteric lymph node distal to the obstruction point on the fourth postoperative day (five animals each), and the migration of these tumor cells was investigated via fluorescent micrography. Subsequently, the fluorescent-labelled tumor cells were revealed in the mesenteric lymph nodes, mesenteric lymph vessels, interstitial tissues of the mesentery, submucosal lymph nodules and mucosal layer of the small intestine. Hence, lymphatic invasion and obstruction may cause extensive peritoneal dissemination via the lymphatic route.

Animals↗
PubMed2000

[A case of tuberculous epididymitis which was difficult to distinguish from a testicular tumor].

A 70-year-old man complaining of painless right scrotal swelling was referred to our hospital. He had a past history of left nephrectomy for renal tuberculosis at the age of 28. Power Doppler ultrasonography revealed a hypoechoic and hypovascular tumor with septa in the scrotum. We suspected a right testicular tumor and therefore, performed a right high inguinal orchiectomy. On macroscopic findings, the fluid of the tumor was yellowish and mucinous and the ipsilateral testis was remarkably atrophic. The pathological diagnosis was tuberculous epididymitis with central necrosis. In recent years, tuberculous epididymitis is rare, and this case was considered to be the first report of power Doppler ultrasonographic findings in tuberculous epididymitis.

Aged↗
PubMed1999

Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor.

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. We have examined the effects of five diabetes-associated mutations (L12H, G191D, R263C, P379fsdelCT, and L584S585fsinsTC) on HNF-1alpha function including DNA binding ability, intracellular localization, and transactivation activity. L12H, P379fsdelCT, and L584S585fsinsTC mutations were found in patients with a clinical diagnosis of MODY, while G191D and R263C mutations were identified in patients diagnosed with type 2 diabetes. These mutations had diverse effects on the functional properties of HNF-1alpha. Comparison of the functional data with clinical information suggested that transactivation activity of mutant HNF-1alpha in beta cells like MIN6 may be the primary determinants of the phenotypic differences observed among diabetic patients with HNF-1alpha mutations.

Adolescent↗
PubMed1999

A homologue of pancreatic trypsin is localized in the acrosome of mammalian sperm and is released during acrosome reaction.

We have identified cDNA and genomic clones encoding a homologue of pancreatic trypsin, termed TESP4, as a candidate protein involved in the sperm penetration of the egg zona pellucida in mouse. The deduced amino acid sequence indicates that TESP4 is 90% identical to pancreatic trypsin. Analysis of Northern blotting and reverse transcriptase-polymerase chain reaction reveals that the mouse TESP4 gene is ubiquitously expressed in all tissues tested, including the pancreas and testis, and the transcript is present in the haploid stages of male germ cells. Moreover, immunochemical analysis of mouse cauda epididymal sperm using an affinity-purified antibody against bovine pancreatic trypsinogen shows that TESP4 is localized only in the sperm acrosome and is released during the acrosome reaction induced by calcium ionophore A23187. These findings may open a new point of view regarding the molecular mechanisms of the sperm/egg interactions, including the sperm penetration of the egg zona pellucida.

Acrosome↗
PubMed1999

Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta.

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, early-onset, and impaired insulin secretion. The type 3 and type 5 forms of MODY result from mutations in the genes encoding the transcription factor, hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta, respectively. The mechanism by which mutations in one allele of the HNF-1 gene impair pancreatic beta cell function is unclear. We studied the effects of wild-type and four mutant (L12H, R263C, P379fsdelCT, and L584S585fsinsTC) HNF-1alpha, which were identified in Japanese subjects with MODY3 on human insulin gene transcription. Both wild-type (WT) HNF-1alpha and HNF-1beta bound to the oligonucleotide containing the A3 element sequence in the human insulin promoter and transactivated the insulin-luciferase reporter gene by 30- and 31-fold, respectively. In contrast, binding of L12H, R263C and L584S585fsinsTC-HNF-1alpha to the probe was impaired. Transactivation activity by the four mutant HNF-1alpha was reduced (4.3 to 43.3% of WT). These data suggest that the insulin gene is a candidate target gene of HNF-1alpha/HNF-1beta and the impairment of insulin gene transcription by mutations in the HNF-1 gene might be involved in the pathogenesis of MODY.

Animals↗
PubMed1999

Arcadlin is a neural activity-regulated cadherin involved in long term potentiation.

Neural activity results in long term changes that underlie synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartate-dependent synaptic activity in long term potentiation. The extracellular domain of Arcadlin is most homologous to protocadherin-8; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses and shows a homophilic binding activity in a Ca2+-dependent manner. Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential amplitude and blocks long term potentiation in hippocampal slices. Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory.

Amino Acid Sequence↗
PubMed1999

Loss-of-function and dominant-negative mechanisms associated with hepatocyte nuclear factor-1beta mutations in familial type 2 diabetes mellitus.

Hepatocyte nuclear factor (HNF)-1beta, a homeodomain-containing transcription factor, regulates gene expression in a dimerized form in pancreas, liver, and some other tissues. Recent genetic studies have identified two HNF-1beta mutations, R177X and A263fsinsGG, in subjects with a monogenic form of type 2 diabetes. Despite the defects being in the same gene, diverse severities of disease are observed in the affected subjects. To investigate the molecular mechanism by which mutations might cause various phenotypic features, wild type and mutant proteins were transiently expressed in insulin-producing (MIN6) and hepatic (HepG2) cells. Luciferase reporter assay showed that both mutations resulted in a marked reduction of transactivation activity. Because their dimerization activity was found to be intact by the yeast two-hybrid system, it was possible that they were dominant-negative to wild type activity. When co-expressed with wild type, both of the mutants significantly decreased wild type activity in HepG2 cells. In contrast, although A263fsinsGG functioned similarly in MIN6 cells, R177X failed to affect wild type activity in this cell line. Immunohistochemical analysis of the mutants suggests that this functional divergence might be generated by the modification of nuclear localization. These results suggest that HNF-1beta mutations may impair pancreatic beta-cell function by loss-of-function and dominant-negative mechanisms.

Base Sequence↗
PubMed1999

RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.

The recently discovered family of RGS (regulators of G protein signaling) proteins acts as GTPase activating proteins which bind to alpha subunits of heterotrimeric G proteins. We previously showed that a brain-specific RGS, RGS8 speeds up the activation and deactivation kinetics of the G protein-coupled inward rectifier K+ channel (GIRK) upon receptor stimulation (Saitoh, O., Kubo, Y., Miyatani, Y., Asano, T., and Nakata, H. (1997) Nature 390, 525-529). Here we report the isolation of a full-length rat cDNA of another brain-specific RGS, RGS7. In situ hybridization study revealed that RGS7 mRNA is predominantly expressed in Golgi cells within granule cell layer of cerebellar cortex. We observed that RGS7 recombinant protein binds preferentially to Galphao, Galphai3, and Galphaz. When co-expressed with GIRK1/2 in Xenopus oocytes, RGS7 and RGS8 differentially accelerate G protein-mediated modulation of GIRK. RGS7 clearly accelerated activation of GIRK current similarly with RGS8 but the acceleration effect of deactivation was significantly weaker than that of RGS8. These acceleration properties of RGS proteins may play important roles in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.

Amino Acid Sequence↗
PubMed1999

Difference of acrosomal serine protease system between mouse and other rodent sperm.

A fraction of acrosomal proteins dispersed during calcium ionophore A23187-induced acrosome reaction was prepared from cauda epididymal sperm of wild-type and acrosin-deficient mice, rat, and hamster. The acrosome-reacted sperm were further extracted by Nonidet P-40 to obtain the detergent-soluble protein fraction. Activities of serine proteases in the two protein fractions were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of gelatin. A mixture of 42- and 41-kDa gelatin-hydrolyzing proteases was found in both fractions of the wild-type mouse sperm, whereas the acrosin-deficient mouse sperm contained the active 42-kDa protease and apparently lacked the activity of the 41-kDa protease. However, exogenous bovine pancreatic trypsin compensated for the absence of acrosin in the protein fractions of the mutant mouse sperm; the gelatin-hydrolyzing activity of the 41-kDa protease appeared when the sperm proteins of the mutant mice were treated with pancreatic trypsin. Two-dimensional polyacrylamide gel electrophoresis revealed that the 42- and 41-kDa proteases were distinguished from acrosin by the isoelectric point and immunoreactivity with affinity-purified antibody against an oligopeptide corresponding to the N-terminal amino acid sequence of mouse proacrosin. Moreover, the gelatin-hydrolyzing proteins corresponding to these two proteases were not detected in rat and hamster sperm, in spite of the treatment of the sperm extracts with pancreatic trypsin, and the total amount of gelatin-hydrolyzing activities in mouse was much smaller than those in rat and hamster. These results may reflect the difference of the serine protease system for the sperm penetration through the egg zona pellucida between mouse and other rodent animals, possibly explaining why the acrosin-deficient mouse sperm are capable of penetrating the zona pellucida.

Acrosin↗