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Biomedical subjects

S Umemura

Publications and source records attributed to S Umemura.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between base blood pressure during sleep and health-related quality of life in healthy adults.

There are many reports indicating that night time blood pressure (BP) is closely associated with target organ damage. However, BP in the waking period is influenced by physical activity and also by the psychological status. Recently, base BP (BP0: minimum and stable BP during sleep) has been reported to correlate with organ damage in hypertensives. However, little is known about the implications of BP0. We examined how BP0 is associated with BP, heart rate variability and health-related quality of life (HRQOL) in healthy subjects. One hundred and thirty-five participants, composed of 88 male and 47 female (age: 21-33 years) underwent a 24-h ambulatory BP monitoring (ABPM). Sympathetic nervous activity (ratio of low-frequency to high-frequency component: LF/HF) and parasympathetic nervous activity (high-frequency component: HF) were calculated by electrocardiogram monitoring. BP0 was calculated as previously reported. HRQOL was assessed by Medical Outcome Study Short-Forum 36-Item Health Survey. Base systolic BP (SBP0) positively correlated with 24-h systolic BP (SBP) (r=0.662, P<0.0001) and night time SBP (r=0.810, P<0.0001). SBP0 positively correlated with 24-h LF/HF (r=0.214, P<0.02) and night time LF/HF (r=0.326, P<0.001). Moreover, SBP0 negatively correlated with the scores of body pain (r=-0.223, P<0.02). Multiple linear regression analysis showed that SBP0 correlated with gender (P<0.01), night time LF/HF (P<0.04) and the scores of body pain (P<0.04). In conclusion, SBP0 correlated with BP, LF/HF and the scores of body pain (HRQOL). SBP0 may be a useful indicator for assessing 24-h BP, sympathetic nervous functions and HRQOL in healthy subjects.

Adult↗
PubMed2006

Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules.

The renin-angiotensin system in the kidney plays a critical role in the regulation of renal hemodynamics and sodium handling through the activation of vascular, glomerular and tubular angiotensin II type 1 (AT1) receptor-mediated signaling. We previously cloned a molecule that specifically bound to the AT1 receptor and modulated AT1 receptor signaling in vitro, which we named ATRAP (for AT1 receptor-associated protein). The purpose of this study is to analyze the renal distribution of ATRAP and to examine whether ATRAP is co-expressed with the AT1 receptor in the mouse kidney. We performed in situ hybridization, Western blot analysis, and immunohistochemistry to investigate the expression of ATRAP mRNA and protein in the mouse kidney. The results of Western blot analysis revealed the ATRAP protein to be abundantly expressed in the kidney. Employing in situ hybridization and immunohistochemistry, we found that both ATRAP mRNA and the protein were widely distributed along the renal tubules from Bowman's capsules to the inner medullary collecting ducts. ATRAP mRNA was also detected in the glomeruli, vasculature, and interstitial cells. In all tubular cells, the ATRAP protein colocalized with the AT1 receptor. Finally, we found that the dietary salt depletion significantly decreased the renal expression of ATRAP as well as AT1 receptor. These findings show ATRAP to be abundantly and broadly distributed in nephron segments where the AT1 receptor is expressed. Furthermore, this is the first report demonstrating a substantial colocalization of ATRAP and AT1 receptor in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Effects of doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive Type 2 diabetic patients with overt nephropathy.

AIMS: Few studies have reported the effect of alpha(1)-adrenergic antagonists on 24-h blood pressure (BP) and sympathetic nervous activity in hypertensive patients with diabetic nephropathy. We assessed the effects of doxazosin on 24-h BP and spectral analysis of heart rate variability in hypertensive Type 2 diabetic patients with macroalbuminuria and compared the results with those in hypertensive Type 2 diabetic patients with normoalbuminuria and non-diabetic patients with essential hypertension. METHODS: Thirty-three patients in the macroalbuminuric group, 24 patients in the normoalbuminuric group, and 34 patients with essential hypertension underwent ambulatory BP monitoring before and after doxazosin treatment. Spectral analysis was performed to calculate the high-frequency (HF) components, a marker of parasympathetic nervous activity, and the low-frequency (LF) components, a marker of sympathetic nervous activity. RESULTS: Doxazosin decreased waking (from 158 +/- 17/88 +/- 10 to 148 +/- 15/80 +/- 7 mmHg, P = 0.001 for systolic and P < 0.001 for diastolic BP) and sleeping BP (146 +/- 20/79 +/- 10 to 137 +/- 17/72 +/- 9 mmHg, P < 0.001 and P < 0.001) in the macroalbuminuric group, but only decreased waking BP in the essential hypertension group (157 +/- 16/91 +/- 9 to 145 +/- 15/84 +/- 11 mmHg, P < 0.001 and P < 0.001) and normoalbuminuric group (159 +/- 15/89 +/- 9 to 150 +/- 16/82 +/- 10 mmHg, P = 0.014 and P < 0.001). Doxazosin decreased waking (from 1.48 +/- 0.11 to 1.42 +/- 0.12, P = 0.001) and sleeping (1.46 +/- 0.11 to 1.40 +/- 0.13, P = 0.001) LF components [unit: log(ms(2)/Hz)] only in the macroalbuminuric group without changing HF components. The normoalbuminuric and essential hypertension groups showed no differences (P = 0.637 and 0.492) in LF components during sleep. CONCLUSIONS: Doxazosin may be an antihypertensive agent that decreases both waking and sleeping BP through inhibiting sympathetic nervous activity in macroalbuminuric diabetes patients.

Adrenergic alpha-Antagonists↗
PubMed2005

Amelioration of 2,4,6-trinitrobenzene sulphonic acid induced colitis in angiotensinogen gene knockout mice.

BACKGROUND: A number of recent studies have demonstrated a protective effect of renin-angiotensin system (RAS) antagonism against immune mediated diseases such as myocarditis, chronic allograft rejection, and antiglomerular basement membrane nephritis. To our knowledge, there has been no report on the immunological contribution of the RAS in colonic tissue. AIMS: We evaluated the direct effect of angiotensin II (AII) on the pathogenesis of immune mediated colitis using angiotensinogen deficient homozygous (Atg-/-) mice. SUBJECTS: 2,4,6-Trinitrobenzene sulphonic acid (TNBS) colitis was induced in Atg-/- and wild-type (Atg+/+) mice. METHODS: Levels of proinflammatory cytokines in the colon were determined by enzyme linked immunosorbent assay. Histological analysis was performed simultaneously. RESULTS: Although Atg-/- mice developed colitis, the degree was much milder than that in Atg+/+ mice (p<0.05). Colonic cytokine analysis showed that the production of proinflammatory cytokines (interleukin (IL)-1beta, interferon gamma (IFN-gamma)) was impaired in Atg-/- mice. Furthermore, expression of cytokines such as IL-4 and IL-10 in the colon was predominant in Atg-/- compared with Atg+/+ mice after TNBS instillation (p<0.005, p<0.01, respectively). Similarly, subcutaneous infusion of losartan suppressed colitis (p<0.05) and the production of proinflammatory cytokines (IL-1beta, IFN-gamma). These results indicate that the RAS is directly involved in the pathogenesis of TNBS colitis through regulation of proinflammatory and anti-inflammatory cytokines in the colon. CONCLUSIONS: This study revealed that the RAS is involved in the immune system in the colon. Antagonism of the RAS is a potential prophylactic strategy for the treatment of human inflammatory bowel disease.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Gallbladder wall thickening associated with infectious mononucleosis.

Acute infectious mononucleosis is a typical self-limited lymphoproliferative illness characterized by fever, tonsillar pharyngitis, and lymphadenopathy in adolescents and young adults. Thickening of the gallbladder wall is rarely observed. We report a case of infectious mononucleosis in which marked thickening of the gallbladder wall was detected by ultrasonography and computed tomography.

Adolescent↗
PubMed2003

Quantitative assessment of the total myocardial uptake ratio of 123I-BMIPP by using the Ishii-MacIntyre method is useful for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

We evaluated the usefulness of the total myocardial uptake ratio (TMUR) of 15-(p-[123I]iodophenyl)-3(R,S)-methyl-pentadecanoic acid (123I-BMIPP) for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy. Six patients with mitochondrial encephalomyopathy, four with myotonic dystrophy, and 10 control subjects were studied. Quantitative assessment of 123I-BMIPP dynamic myocardial imaging was performed, and the TMUR of 123I-BMIPP was calculated according to the Ishii-MacIntyre method. Then, the TMUR was compared in the 10 patients and 10 healthy controls, and all patients were followed for 56.1+/-22.1 months to evaluate cardiac complications. TMUR in patients (2.69+/-0.64) was significantly (P =0.01) lower than that in controls (3.28+/-0.25). Three patients in whom the TMUR value was above 3.00 had no cardiac complications. On the other hand, all patients in whom TMUR was below 3.00 had some kind of cardiac complication during the follow-up period. Two patients showed progressive conduction abnormality and underwent pacemaker implantation, one patient had sick sinus syndrome and underwent pacemaker implantation, another patient showed non-sustained ventricular tachycardia and paroxysmal atrial fibrillation, and four of seven patients, including one with a pacemaker, showed an increased cardiothoracic ratio value over 50%. In conclusion, measurement of the TMUR by the Ishii-MacIntyre method is useful for evaluating the development of cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

Adult↗
PubMed2002

Sonodynamic therapy with photofrin II on AH130 solid tumor. Pharmacokinetics, tissue distribution and sonodynamic antitumoral efficacy of photofrin II.

BACKGROUND: The pharmacokinetics and tissue distribution of photofrin II (PF) and its efficacy in sonodynamic therapy were studied in rats bearing AH130 solid tumors. MATERIALS AND METHODS: In order to find the optimum timing of the ultrasound exposure after administration of PF, the PF concentrations in plasma, skin, muscle and tumor were measured and pharmacokinetically analyzed. Antitumor effects were estimated by measuring tumor size. RESULTS: Since the highest concentration of PF in tumors occurred 24 h after administration, ultrasound administration 24 h after the intravenous administration of PF was chosen. Ultrasound alone showed a slight antitumor effect, which became increasingly significant as the dose of PF was increased, while PF alone showed no significant effect. CONCLUSIONS: PF significantly sensitized solid tumors to the antitumor effect of ultrasound in a synergistic manner.

Animals↗
PubMed2002

Clinical implications of cardiac (123)I-meta-iodobenzylguanidine scintigraphy and cardiac natriuretic peptides in patients with heart disease.

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

3-Iodobenzylguanidine↗
PubMed2001

In situ expression of corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin.

Systemic stresses induce corticotropin-releasing hormone (CRH) expression in hypothalamus. CRH is released to the pituitary gland, where it stimulates proopiomelanocortin (POMC) production acting via the CRH receptor (CRH-R). CRH and POMC peptides are also detected in sites outside of the central nervous system (CNS), such as the skin. However, it has not been elucidated whether these peptides detected in the skin are derived from CNS or are produced locally. Using immunohistochemical and in situ reverse-transcription (RT)-PCR techniques, we demonstrated coexpression of CRH and POMC mRNAs in the epidermis and pilosebaceous units of the human skin. This coexpression was confirmed by the combination of laser-capture microdissection (LCM) with RT-PCR, analyzing mRNA expressions in captured sebaceous cells. Immunoreactivities and expressions of CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus, seborrheic keratosis, and also in the periphery of the benign tumor. These findings suggest that CRH and POMC peptides are produced locally in the skin and are regulated by inflammatory cells as well as by autocrine mechanisms. The skin may have "a local stress response system," whose activity is mediated by CRH and POMC peptides, in an equivalent to hypothalamus-pituitary adrenal axis.

Corticotropin-Releasing Hormone↗
PubMed2001

Electrocardiographic criteria for predicting total occlusion of the proximal left anterior descending coronary artery in anterior wall acute myocardial infarction.

BACKGROUND: Patients with occlusion of the left anterior descending coronary artery (LAD) proximal to both the first septal branch and the first diagonal branch may benefit most from early reperfusion therapy due to extensive area at risk. HYPOTHESIS: The aim of the study was to examine whether 12-lead electrocardiograms (ECGs) in the acute phase of acute myocardial infarction (AMI) could identify total occlusion of the LAD proximal to both the first septal and the first diagonal branch. METHODS: A 12-lead electrocardiogram was recorded on admission in 128 patients with anterior AMI within 12 h from symptom onset. Patients were divided into three groups according to the culprit lesion: 33 patients had total occlusion of the LAD proximal to both the first septal perforator and the first diagonal branch (Group P), in 51 it was proximal to either the first septal perforator or the first diagonal branch (Group D-a), and in 44 it was distal to both the first septal perforator and the first diagonal branch (Group D-b). RESULTS: Sensitivity and specificity of a greater degree of ST-segment depression in lead III than that of ST-segment elevation in lead aVL were 85 and 95%, respectively, which was better than the results derived by all other ECG criteria (p< 0.001). CONCLUSIONS: We conclude that a greater degree of ST-segment depression in lead III than that of ST-segment elevation in lead aVL is a useful predictor of proximal LAD occlusion in patients with anterior AMI.

Adult↗
PubMed2001

Implications of the absence of ST-segment elevation in lead V4R in patients who have inferior wall acute myocardial infarction with right ventricular involvement.

BACKGROUND: ST-segment elevation of > or = 1.0 mm in lead V4R has been shown to be a reliable marker of right ventricular involvement (RVI), a strong predictor of a poor outcome in patients with inferior acute myocardial infarction (IMI). However, patients with no ST-segment elevation in lead V4R despite the presence of RVI have received little attention. HYPOTHESIS: The study was undertaken to study the clinical features of patients with no ST-segment elevation in lead V4R despite the presence of RVI, which means false negative, as such patients have received little attention in the past. METHODS: We studied 62 patients with a first IMI, who had total occlusion of the right coronary artery (RCA) proximal to the first right ventricular branch and successful reperfusion within 6 h from symptom onset, to examine the implications of the absence of ST-segment elevation in lead V4R despite the presence of RVI. RESULTS: A standard 12-lead electrocardiogram (ECG) and right precordial ECG (lead V4R) were recorded on admission, and three posterior chest ECGs (leads V7 to V9) were additionally recorded in 34 patients. Patients were classified according to the absence (Group 1, n = 18) or presence (Group 2, n = 44) of ST-segment elevation of > or = 1.0 mm in lead V4R on admission. Patients in Group 1 had a greater ST-segment elevation in leads V7 to V9 (2.9+/-2.4 vs. 1.4+/-3.0 mm. p < 0.05), a higher frequency of a dominant RCA (defined as the distribution score > or = 0.7) (72 vs. 11%, p < 0.001), and a higher peak creatine kinase level (3760+/-1548 vs. 2809+/-1824 mU/ml, p < 0.05) than those in Group 2. CONCLUSIONS: In patients with IMI caused by the occlusion of the RCA proximal to the first right ventricular branch, no ST-segment elevation in lead V4R can occur because of concomitant posterior involvement. In such patients, the incidence of RVI may be underestimated on the basis of ST-segment elevation in lead V4R.

Aged↗
PubMed2001

Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.

Adult↗
PubMed2001

Evaluation of HER2 status: for the treatment of metastatic breast cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab) (Pathological committee for optimal use of trastuzumab).

For the treatment of patients with metastatic breast cancer by humanized anti- human epidermal growth factor receptor type 2 (HER2) antibody (trastuzumab), it is important to evaluate HER2 status adequately. "A guideline for HER2 testing" and "HER2 atlas" produced by the "Pathological committee for optimal use of trastuzumab" are introduced in this report. Appropriate evaluations of biological markers are essential for targeting therapy.

Antibodies, Monoclonal↗
PubMed2001

Linkage disequilibrium and haplotype analysis among eight novel single-nucleotide polymorphisms in the human tissue-type plasminogen activator (t-PA) gene.

Tissue-type plasminogen activator (t-PA), a serine protease, activates the conversion of plasminogen to the fibrinolytic protein, plasmin. The t-PA gene, mapped to chromosome 8p12-p11.2, contains 14 exons. An Alu insertion/deletion (I/D) polymorphism in this gene has been associated with an increased risk for myocardial infarction. In the work reported here we sequenced 11 kilobases (kb) of genomic DNA from 50 normal Japanese volunteers (100 alleles), to include all 14 exons of the t-PA gene, flanking intronic sequences, and 6kb of the 5' sequence. These experiments identified eight novel single-nucleotide polymorphisms (SNPs), in addition to the known Alu I/D polymorphism, from which genotypic data we constructed 12 haplotypes in the tested population. Two-way comparisons of SNPs and the Alu polymorphism revealed strong linkage disequilibrium between the Alu site and SNPs at positions 20,209 (chi2 = 92.263) and 27,555 (chi2 = 47.53), and between SNPs at positions 27,849 and 28,902 chi2 = 66.331). A phylogenic tree was constructed to infer a process of genome construction that would reflect the sequence variations we observed. Our results help to explain the lack of agreement among results of various disease-association studies in which a contribution of the human t-PA gene has been suspected but not always confirmed.

Alleles↗
PubMed2001

Human calcitonin receptor-like receptor for adrenomedullin: genomic structure, eight single-nucleotide polymorphisms, and haplotype analysis.

Adrenomedullin (ADM), a peptide characterized by persistent hypotensive activity, is thought to be involved when the control mechanism of blood pressure is deranged, because its plasma concentration is upregulated in hypertensive patients. The receptor for ADM, a molecular complex consisting of calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 2 (RAMP2), is activated through a unique intracellular transport mechanism. By analyzing the nucleotide sequences of bacterial artificial chromosome (BAC) clones, we have established that the gene encoding CRLR is spread over a genomic distance of 103,145 bases; it contains 15 exons interrupted by 14 introns, including 1 that spans more than 60 kilobases. Exons 1-3 constitute the 5' noncoding region; exons 4 through 15 are coding elements, of which exons 8 to 14 encode seven transmembrane domains. Eight novel single-nucleotide polymorphisms (SNPs) and their allelic frequencies in the Japanese population were found by direct sequencing of 32 alleles; two SNPs were in the 5' flanking region, one in exon 2, and the other five around intron-exon junctions. Eight haplotypes were constructed using these alleles in our Japanese population sample. The data establish a basis for investigations to detect molecular variants in the ADM receptor that might alter control of blood pressure and confer on individuals a predisposition to essential hypertension.

Alleles↗