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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 73 records · Page 4Linked to original sources
PubMed2001

Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily, which regulate the differentiation of osteoprogenitor cells. Here we show that among members of the BMP family, BMP-4 and growth/differentiation factor 5 (GDF-5) induce osteoblast differentiation through the activation of three receptor-regulated Smads (i.e. Smad1, Smad5 and Smad8). By contrast, BMP-6 and BMP-7 induce alkaline phosphatase activity through Smad1 and Smad5, but not through Smad8. Consistent with these findings, BMP-4 induced phosphorylation and nuclear translocation of Smad1, Smad5 and Smad8, but BMP-6 activated only Smad1 and Smad5. BMP-4 and GDF-5 are known to bind to activin receptor-like kinase 3 (ALK-3) and/or ALK-6 (also termed BMP type IA and type IB receptors, respectively), whereas BMP-6 and BMP-7 preferentially bind to ALK-2. Compared with the effects induced by only one of the type I receptors, the combination of constitutively active forms of ALK-2 and ALK-3 (or ALK-6) more strongly induced alkaline phosphatase activity in C2C12 cells. Moreover, addition of BMP-4 and BMP-6 to C2C12 cells resulted in higher alkaline phosphatase activity than that of only one of these BMPs. The combination of ALK-2 and ALK-3 also induced higher transcriptional activity than either receptor alone. Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways.

Activin Receptors↗
PubMed2001

Microvascular angina in a patient with aortic stenosis.

A 39-year-old woman had exercise-induced ST segment depression associated with chest pain. Cardiac evaluation revealed moderate aortic stenosis (AS), related to the bicuspid valves, with an aortic mean pressure gradient of 22 mmHg, a calculated aortic valve area of 1.3 cm2 and normal left ventricular (LV) peak systolic and end-diastolic pressures, but no LV hypertrophy, resulting in normal LV wall stress. Although the coronary arteries were angiographically normal, rapid atrial pacing and an intracoronary papaverine injection revealed a significantly decreased coronary flow reserve (CFR), which may have played an important role in the pathogenesis of angina pectoris in this patient. Though the CFR is usually decreased in patients with AS, as well as in microvascular angina, in this particular case, it appeared to have decreased as a consequence of microvascular dysfunction rather than of AS-related mechanisms.

Adult↗
PubMed2001

Acute pericarditis associated with 5-aminosalicylic acid (5-ASA) treatment for severe active ulcerative colitis.

A 17-year-old male who had been diagnosed with ulcerative colitis was prescribed 80 mg prednisolone and 1,500 mg 5-aminosalicylic acid (5-ASA) per day. Two weeks after initiating therapy, he was referred to our hospital for evaluation of chest pain and high fever. Electrocardiography (ECG) showed ST elevation in limb and precordial leads. Chest pain with high fever and ECG changes were resolved after 5-ASA was discontinued. Three weeks later, the administration of a low dose of 5-ASA was associated with the immediate recurrence of pericarditis associated with chest pain, suggesting a hypersensitive reaction to 5-ASA in this patient.

Adolescent↗
PubMed2001

[Present status and problems in medical care for demented patients using public counselling facilities].

To clarify the present status and problems in medical care for the elderly with dementia, 103 cases were studied according to the descriptive records obtained at a public counselling facility for dementia, based on interviews with patients' families. Their records were analysed based on their background, severity of dementia (clinical dementia rating: CDR), and counselling content. There were 75 demented patients with a CDR score of 1 or more, and 50 of them were women aged 54 to 90, while the remaining 25 men were aged 55 to 88. The consultation content was clustered into 5 codes: code 1, evaluation of dementia and/or dementia-related symptoms including psychiatric symptoms and behavioral disturbance; code 2, methods to manage patients; code 3, methods to take a patient to a medical institution; code 4, questions regarding medical treatment and drugs prescribed at present; code 5, information on the welfare resources provided. In most of the 75 patients, the degree of dementia deteriorated insidiously without any physical symptoms. The key person and/or caregiver was usually an elderly spouse, and the family noticed dementia only after cognitive impairment progressed with or without troublesome symptoms. Hallucination was a common troublesome symptom. Concerning consultation content, codes 1, 2, and 3 were common, while 13 cases had dissatisfaction with their medical treatment. Therefore, it was necessary to explain the significance of early diagnosis of dementia to families and their caregivers. There were also many families who felt strain and wondered about what hospital or department to take the patient to. In addition, it seemed that explanation on the clinical course and adverse drug reactions, advice for the correspondence with psychiatric symptoms and abnormal behaviour, and information services concerning utilization of social resources was not yet sufficient.

Aged↗
PubMed2001

[Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome].

To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n = 33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n = 69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function.

Adult↗
PubMed2001

[Extraction of RNA from paraffin embedded tissues and analysis of p53 gene expression in colonic cancer].

We examined, immunohistochemically and molecular biologically, p53 gene expression in 10 patients with colonic cancer. RNA was extracted from paraffin embedded normal and colonic cancer tissues by using RNA isolator kit and proteinase K. The most effective time and concentration of proteinase K for RNA extraction was 24 hours and 100 micrograms/ml, respectively. P53 gene expression was analyzed by ABI PRISM 7700 Sequence Detection System(ABI 7700 System, Perkinelmer). Gene expression level in each sample was estimated on the basis of the standard curve of ABI 7700 System. Human G3PDH gene was used as the internal control. Immunohistochemically, the tumor cells in all examined cases showed a strong positivity for anti-p53 gene antibody. In ABI 7700 System, expression of p53 gene in the malignant tissues revealed a high level in only 2 cases that had a clinical stage IV, however, in remaining 8 cases a clinical stage was I to III and expression level of p53 was relatively lower. These results suggest that colonic cancer cells show mutant-p53 gene expression, and a ratio of mutant- to wild-p53 gene may have something to do with a relationship between gene expression and clinical stage.

Adenocarcinoma↗
PubMed2001

[A new protocol of dual energy acquisition on stress 201Tl and rest 99mTc-tetrofosmin myocardial scintigraphy].

We carried out stress 201Tl (Tl) and rest 99mTc-tetrofosmin (TF) myocardial scintigraphy with dual energy acquisition in 24 patients with suspected ischemic heart disease performed coronary arteriography and elucidated the sensitivity of this method. One hour after light meal eating, TF (555 MBq) was injected intravenously at rest and after 3 minutes from injection of TF exercise or pharmacologic stress was performed. During stress Tl (111 MBq) was injected intravenously before end-point or at adequate point of pharmacologic stress. Dual energy acquisition using triple energy windows (TEW) was started after 5 minutes (early) and 4 hours (delayed) from stress. The sensitivity (Sn), specificity (Sp) and accuracy (Ac) in diagnosis of non-infarcted branches by using Tl (early)-TF (rest) and Tl (early)-Tl (delayed) were 79% vs. 53% (Sn), 78% vs. 96% (Sp) and 79% vs. 71% (Ac) respectively. Accordance of uptake score of infarcted region between TF (rest) and Tl (delayed) was 70%. In conclusion, this protocol is seemed to be useful as usual protocol for detection of myocardial ischemia and viability during about only 1 hour.

Aged↗
PubMed2001

[A clear cell type meningioma in the upper eyelid ascertained by immunohistochemical examination].

BACKGROUND: We encountered a rare case of clear cell meningioma in the upper eyelid. CASE: A 66-year-old man presented with a slow by progressive, well-defined, soft globelar tumor in the left upper eyelid. The tumor showed homogeneous isodensity and was contrasty in a computed tomograph. Histologically, oval-shaped cells with clear cytoplasm had both streamed and whorl configurations, but showed neither psammomas nor calcification. Immunohistochemically, vimentin, epithelial membrane antigen, and protein S-100 were expressed by the tumor cells. CONCLUSIONS: Eyelid meningioma may originate from embryonal remains of the arachnoid in the sheath around the trigeminal nerve, and may vary histologically. Immunohistochemical examination helps to define cases of uncommon subtypes of meningioma.

Aged↗
PubMed2001

Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998-1999.

OBJECTIVES: The clinical features of myocarditis that developed during the influenza epidemic of winter 1998-1999 were investigated to emphasize the need for medical attention to this disease. METHODS: Nine patients were treated under diagnoses of acute myocarditis during the winter of 1998-1999. Five (two males and three females, mean age 52 +/- 18 years) were examined with myocarditis associated with influenza A. The diagnosis of influenza A myocarditis was based on electrocardiographic and echocardiographic abnormalities, increased creatine kinase levels and at least a four-fold increase in influenza A virus titers using paired sera. RESULTS: All patients had preceding flu-like symptoms and fever. Cardiac involvement developed between 4 and 7 days after the onset of influenza symptoms. Dyspnea progressively worsened in three patients, one went into shock and one had persistent fever, cough and mild dyspnea without apparent cardiac symptoms. Three patients had ST elevation associated with Q waves and one had complete left bundle branch block. The creatine kinase levels were abnormally increased and global wall motion of the left ventricle on echocardiography was decreased in all patients. Two patients had diagnoses of fulminant myocarditis. One patient died of pneumonia following cerebral infarction, but the left ventricular dysfunction normalized in the remaining four patients. CONCLUSIONS: Cardiac involvement occurred between 4 and 7 days after the onset of influenza symptoms, and worsening dyspnea was the most common symptom. Electrocardiography, echocardiography and creatine kinase levels should be checked to determine the potential for cardiac involvement when patients present with suspected influenza associated with worsening dyspnea or prolonged weakness. Increasing the awareness of influenza myocarditis may help in the earlier identification and treatment of this disease during influenza epidemics.

Adult↗
PubMed2001

[A case of acute disseminated encephalomyelitis after renal transplantation].

We report a patient of acute disseminated encephalomyelitis (ADEM) in a recipient of renal transplantation. A 43-year-old man suffered from generalized convulsion and consciousness disturbance followed by coma on day 53 of after the transplantation. He was receiving several immunosuppressants, and an increase of serum antigen for cytomegalovirus was observed one day before the ictus. T2 and diffusion-weighted image of MRI showed high intensity lesions in the bilateral cerebral white matter, basal ganglia, thalamus, midbrain, pons and cerebellum. Examination of cerebrospinal fluid revealed elevated myelin basic protein level. The patient was diagnosed as having ADEM and was treated with methylpredonisolone pulse therapy in combination with intravenous immune globulin. He gradually recovered and became capable to eat and sit on a wheel chair. White matter lesions on MRI were also diminished. ADEM may occur in recipients of organ transplantation even if they have immunosuppressive treatment.

Acute Disease↗
PubMed2000

Negative regulation of BMP/Smad signaling by Tob in osteoblasts.

Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.

Alleles↗
PubMed2000

Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression.

The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay. Using immunochemical co-precipitation methods, we also found that the two proteins are bound in vivo. Deletion analysis showed that three independent domains of YB-1, one at the N-terminal and two at the C-terminal, interact with p53. Conversely, a 14 amino acid sequence at the C-terminal of p53 was required for its interaction with YB-1. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. Using a p53-responsive p21 promoter linked to a reporter gene, it can be shown that antisense expression of YB-1 inhibits the induction of this promoter by p53 in transient transfection assays. These findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction.

CCAAT-Enhancer-Binding Proteins↗
PubMed2000

Interaction with p53 enhances binding of cisplatin-modified DNA by high mobility group 1 protein.

A nonhistone chromosomal protein, high mobility group (HMG) 1, is ubiquitous in higher eukaryotic cells and binds preferentially to cisplatin-modified DNA. HMG1 also functions as a coactivator of p53, a tumor suppressor protein. We investigated physical interactions between HMG1 and p53 and the influence of p53 on the ability of HMG1 to recognize damaged DNA. Using immunochemical coprecipitation, we observed binding of HMG1 and p53. Interaction between HMG1 and p53 required the HMG A box of HMG1 and amino acids 363-376 of p53. Cisplatin-modified DNA binding by HMG1 was significantly enhanced by p53. An HMG1-specific antibody that recognized the A box of this protein also stimulated cisplatin-modified DNA binding. These data suggest that an interaction with either p53 or antibody may induce conformational change in the HMG1 A box that optimizes DNA binding by HMG1. Interaction of p53 with HMG1 after DNA damage may promote activation of specific HMG1 binding to damaged DNA in vivo and provide a molecular link between DNA damage and p53-mediated DNA repair.

Cell Nucleus↗
PubMed2000

The osmotic shock-induced glucose transport pathway in 3T3-L1 adipocytes is mediated by gab-1 and requires Gab-1-associated phosphatidylinositol 3-kinase activity for full activation.

Osmotic shock treatment of 3T3-L1 adipocytes causes an increase in glucose transport activity and translocation of GLUT4 protein similar to that elicited by insulin treatment. Insulin stimulation of GLUT4 translocation and glucose transport activity was completely inhibited by wortmannin, however, activation by osmotic shock was only partially blocked. Additionally, we have found that the newly identified insulin receptor substrate Gab-1 (Grb2-associated binder-1) is tyrosine-phosphorylated following sorbitol stimulation. Treatment of cells with the tyrosine kinase inhibitor genistein inhibited osmotic shock-stimulated Gab-1 phosphorylation as well as shock-induced glucose transport. Furthermore, pretreatment with the selective Src family kinase inhibitor PP2 completely inhibited the ability of sorbitol treatment to cause tyrosine phosphorylation of Gab-1. We have also shown that microinjection of anti-Gab-1 antibody inhibits osmotic shock-induced GLUT4 translocation. Furthermore, phosphorylated Gab-1 binds and activates phosphatidylinositol 3-kinase (PI3K) in response to osmotic shock. The PI3K activity associated with Gab-1 was 82% of that associated with anti-phosphotyrosine antibodies, indicating that Gab-1 is the major site for PI3K recruitment following osmotic shock stimulation. Although wortmannin only causes a partial block of osmotic shock-stimulated glucose uptake, wortmannin completely abolishes Gab-1 associated PI3K activity. This suggests that other tyrosine kinase-dependent pathways, in addition to the Gab-1-PI3K pathway, contribute to osmotic shock-mediated glucose transport. To date, Gab-1 is the first protein identified as a member of the osmotic shock signal transduction pathway.

3T3 Cells↗
PubMed2000

Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness.

Cysteine proteinases (gingipains) elaborated from Porphyromonas gingivalis exhibit enzymatic activities against a broad range of host proteins and are considered key virulence factors in the onset and development of adult periodontitis and host defense evasion. In this study, we examined the ability of arginine-specific gingipains (high molecular mass Arg-specific gingipain (HRGP) and Arg-specific gingipain 2) and lysine-specific gingipain (KGP) to cleave monocyte CD14, the main receptor for bacterial cell surface components such as LPS. Binding of anti-CD14 mAb MY4 to human monocytes was almost completely abolished by 0.3 microM HRGP and KGP treatments for 15 min, and 1 microM RGP2 for 30 min. In contrast, the expressions of Toll-like receptor 4, and CD18, CD54, CD59, and HLA-A, -B, -C on monocytes were slightly increased and decreased, respectively, by 0. 3 microM HRGP and KGP. This down-regulation resulted from direct proteolysis, because 1) gingipains eliminated MY4 binding even to fixed monocytes, and 2) CD14 fragments were detected in the extracellular medium by immunoblot analysis. Human rCD14 was degraded by all three gingipains, which confirmed that CD14 was a substrate for gingipains. TNF-alpha production by monocytes after HRGP and KGP treatments was decreased at 1 ng/ml, but not at 20 microg/ml LPS, indicating that gingipains inhibited a CD14-dependent cell activation. These results suggest that gingipains preferentially cleave monocyte CD14, resulting in attenuation of the cellular recognition of bacteria, and as a consequence sustain chronic inflammation.

Adhesins, Bacterial↗
PubMed2000

C(2)-Symmetric bis-sulfoxide: A novel chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols

A new heterocyclic compound, C(2)-symmetric bis-sulfoxide 1, has been found to be an efficient chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal fission. Both (R,R)- and (S,S)-1 are readily synthesized with high optical purity via asymmetric oxidation of 1, 5-benzodithiepan-3-one (2). After acetalization of meso-1,2-diols 6a-e and a mono-TMS ether 6f with this chiral auxiliary 1, the resulting acetals 7a-f were subjected to base-promoted acetal fission upon treatment with potassium hexamethyldisilazide (KHMDS) followed by acetylation or benzylation to give the desymmetrized diol derivatives 8a-f with high diastereoselectivity. The chiral auxiliary 1 is readily removed by acid-promoted hydrolysis and can be recovered without a loss in enantiomeric excess.

Journal Article↗