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Biomedical subjects

N Kanemoto

Publications and source records attributed to N Kanemoto.

At least 19 recordsLinked to original sources

Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus.

To elucidate the genetic factors underlying non-insulin-dependent diabetes mellitus (NIDDM), we performed genome-wide quantitative trait locus (QTL) analysis, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is an excellent animal model of NIDDM because the features of the disease closely resemble human NIDDM. Genetic dissection with two kinds of F2 intercross progeny, from matings between the OLETF rat and non-diabetic control rats F344 or BN, allowed us to identify on Chromosome (Chr) 1 a major QTL associated with features of NIDDM that was common to both crosses. We also mapped two additional significant loci, on Chrs 7 and 14, in the (OLETF x F344)F2 cross alone, and designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3 respectively. With regard to suggestive QTLs, we found loci on Chrs 10, 11, and 16 that were common to both crosses, as well as loci on Chrs 5 and 12 in the (OLETF x F344)F2 cross and on Chrs 4 and 13 in the (OLETF x BN)F2 cross. Our results showed that NIDDM in the OLETF rat is polygenic and demonstrated that different genetic backgrounds could affect "fitness" for QTLs and produce different phenotypic effects from the same locus.

Animals

Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia.

We isolated a novel human ATP-binding cassette (ABC) transporter cDNA, determined its nucleotide sequence, and designated it human ABC7 (hABC7). The nucleotide sequence was highly homologous to the ATM1 gene in yeast, which encodes an ABC transporter (yAtm1p) located in the mitochondrial inner membrane. The deduced human product, a putative half-type transporter, consists of 752 amino acids that are 48.9% identical to those of yAtm1p. A computer-assisted protein structural and localization analysis revealed that the mitochondrial targeting signal of yAtm1p is conserved in the N-terminal region of the primary sequence of the hABC7 protein, and therefore this product is also likely to be located in the mitochondrial inner membrane. The evidence strongly suggests that the hABC7 gene is a counterpart of ATM1 and that its product is probably involved in heme transport. We mapped the hABC7 gene to chromosome Xq13.1-q13.3 by fluorescence in-situ hybridization. As band Xq13 has been implicated in X-linked sideroblastic anemia with spinocerebellar ataxia, hABC7 becomes a candidate gene for this heritable disorder.

5-Aminolevulinate Synthetase

Identification and characterization of a novel human phosphatidylinositol 4-kinase.

The extensive sequence homology that exists among the catalytic domains of phosphatidylinositol 3- and 4-kinases allowed us to clone a novel human gene encoding a putative phosphatidylinositol kinase, NPIK. Among other known phosphatidylinositol 3- and 4-kinases, NPIK was most closely related to yeast PIK1 phosphatidylinositol 4-kinase. Several forms of NPIK cDNAs were isolated, and expression of NPIK message was detected in a wide variety of tissues. Fluorescence in situ hybridization and radiation hybrid analyses assigned the NPIK gene to human chromosome 1. Recombinant NPIK protein catalyzed a conversion from phosphatidylinositol to phosphatidylinositol 4-phosphate. The catalytic activity of NPIK was augmented by Triton X-100, and was reduced in the presence of adenosine. Using green fluorescent protein system we determined that NPIK is localized in the cytoplasm. Taken together, the data suggest that NPIK may play a pivotal role in regulating the synthesis of phosphatidylinositol 4-phosphate at the site(s) accessible from cytoplasm.

1-Phosphatidylinositol 4-Kinase

Cloning and characterization of a novel member of the human Mad gene family (MADH6).

MAD (mothers against decapentaplegic)-related proteins (MADRs) are intracellular components that play critical roles in signal-transduction pathways involving the transforming growth factor beta (TGFbeta) superfamily. Some Mad genes are candidates for tumor-suppressor functions. From a human fetal brain cDNA library we have isolated a novel Mad-related gene. Two alternatively transcribed mRNAs encode deduced 430- and 467-amino-acid peptides that showed high levels of similarity to MADR1/Smad1/hMAD1 (about 80% identity at the amino acid level). This gene, which we designated MADH6, resides on 13q12-q14 between BRCA2 and RB, a region that frequently displays loss of heterozygosity in breast, liver, and prostate cancers.

Amino Acid Sequence

Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats.

From a human fetal-brain cDNA library we isolated two novel genes encoding peptides containing six EGF-like repeats. Both showed significant homologies with nel, a gene strongly expressed in neural tissues of chicken. The cDNAs, designated NELL1 (nel-like, type 1) and NELL2 (nel-like, type 2), contained open reading frames encoding 810 and 816 amino acids, respectively. NELL2 is strongly expressed in brain of adult and fetus but only weakly in fetal kidney. NELL1 and NELL2 were mapped by FISH to chromosomal bands 11p15.1-p15.2 and 12q13.11-q13.12, respectively.

Adult

New markers of remote ischemia in patients with evolving inferior myocardial infarction.

Multivessel disease and decreased left ventricular ejection fraction (LVEF) are believed to be significant predictors of the outcome in patients with acute inferior myocardial infarction (AIMI). We attempted to determine new electrocardiographic (ECG) markers for detecting concomitant left anterior descending (LAD) disease and/or decreased left ventricular function in patients with AIMI. Eighty patients with AIMI were evaluated within 6 h of the onset of symptoms and grouped according to the presence (Group 1) or absence (Group 2) of concomitant LAD disease. All of the patients underwent coronary angiography and left ventriculography 4-6 weeks from the onset of their infarction. We studied the validity of two new ECG markers: S-T depression deeper in lead V5 than in V4 (S-T decreases V5 > V4) and negative U waves (NUs) > 0.5 mm (50 muV) in leads V4-6. The sensitivity and specificity of S-T decreases V5 > V4, NUs in V4-6, or both, in detecting concomitant LAD disease were 56% and 83%, 59% and 87%, and 35% and 98%, respectively. LAD lesions in patients who showed either of these new markers (74% of those with S-T decreases V5 > V4 and 80% of those with NUs in V4-6) were mostly in the proximal segments (AHA segments #6 or #7). Patients with either S-T decreases V5 > V4 or NUs in V4-6 tended to have asynergy in the anterolateral segment, while there was a strong correlation between the asynergy of the anterolateral and septal segments in patients who showed both ECG markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Electrocardiographic characteristics of patients with left circumflex-related myocardial infarction in the acute phase without tented T waves or definite ST elevation].

Acute myocardial infarction (AMI) causing ST depression and T wave inversion has been diagnosed as subendocardial or non-Q myocardial infarction. However, some patients eventually develop strictly posterior infarction with a lesion of the left circumflex coronary artery (LCX). This study attempted to determine the electrocardiographic (ECG) characteristics of such myocardial infarction in 32 patients with definite AMI in whom ECG showed no hyperacute T waves or ST elevation and the LCX was an infarct-related coronary artery. ECG on admission (< 6 hours from the onset), at 24 hours, and on the 14th day were analyzed to evaluate QRS, ST, T, and U waves using calipers and magnifying lens. Sixty-six patients with normal circulation served as controls. The characteristic ECG findings on admission were ST depression in chest leads, and prominent positive U waves in leads V2 or V3 with relatively small T waves. Based on these results we proposed new ECG criteria: 1) ST depression > or = 0.1 mV in 2 consecutive chest leads, 2) prominent positive U wave > or = 0.1 mV in leads V2 or V3, 3) T/U ratio in leads V2 or V3 < or = 4. Considering two of the above criteria as positive, the sensitivity was 71.9%, the specificity 97.0%, and the diagnostic accuracy 88.8%. In 85.2% of the patients, ST depression returned to the baseline by 24 hours. As the amplitude of the U waves decrease gradually, the T/U ratio increased. The R/S ratio in leads V1 or V2 became > or = 1 by 24 hours in 46.4% and the amplitude of R wave in lead V1 increased gradually. T waves in the right precordial leads increased with time. These findings were consistent with isolated strictly posterior myocardial infarction. From these results we identified new ECG criteria: 1) R/S ratio in leads V1 or V2 > or = 1, 2) R wave > or = 0.7 mV in lead V1, 3) T wave > or = 0.5 mV in lead V1. Considering any of the above criteria as positive, the sensitivity was 72.0%, the specificity 87.9%, and the diagnostic accuracy 86.7% on the 14th day. These new ECG criteria of strictly posterior myocardial infarction with the LCX as an infarct-related coronary artery apply at less than 6 hours or at 24 hours from the onset of the symptoms.

Aged

[Identical male twins showing progression from hypertrophic cardiomyopathy to dilated cardiomyopathy-like features].

Twenty-three-year-old identical male twins with hypertrophic cardiomyopathy which progressed into the dilated phase are reported. The younger brothers first presented at age 16 with an abnormal electrocardiogram. Hypertrophic nonobstructive cardiomyopathy with an asymmetric septal hypertrophy was diagnosed. He was treated with beta-blocker, but he stopped taking the drug as he had no symptoms at that time. He presented again at age 21 years with symptoms of apparent congestive heart failure. Echocardiography showed marked dilatation of the left ventricle with thin wall which was compatible with dilated cardiomyopathy. The elder brother presented with an initial echocardiogram showing systolic anterior movement of the mitral valve without asymmetric septal hypertrophy. He presented again with his brother aged 21 years when his echocardiogram showed slight dilatation of the left ventricle, although he did not complain of cardiac symptoms. These identical twins are the first reported cases of hypertrophic cardiomyopathy progressing to the deteriorated dilated phase.

Adult

Structure and action of MIP (Mytilus inhibitory peptide)-related tetrapeptides synthesized with a multipeptide synthesizer.

Using a multipeptide synthesizer we synthesized 19 peptide libraries, each of which consisted of 19 MIP-related tetrapeptides, and isolated a number of peptides, which have an inhibitory effect on phasic contraction of the ABRM of Mytilus, from the libraries. To the present, the structures of about 30 species of the peptides were determined, and the peptides with the determined structures were synthesized. The structure and action of each synthetic peptide was compared with those of others to explain structure-activity relationship of MIPs.

Amino Acid Sequence

Evaluation of a nine-lead Holter monitor for identifying and localizing ischemia and coronary artery disease detected by quantitative thallium-201 tomography.

We devised a nine-lead Holter monitor system with a lead-switching technique to record electrocardiograms from multiple sites in the anterior and the posterior or lateral chest. Leads CM1 to CM6, high lateral (HL), low lateral (LL), and low posterior chest (LB) were used. The sensitivity, specificity, and predictive accuracy of this system for identifying specific regions of myocardial ischemia and coronary artery disease were investigated in 130 patients with coronary artery disease. Anterolateral leads (CM4 to CM6, HL, and LL) showed high sensitivity for detecting anterior and lateral ischemia (69% to 100%) but low specificity (4% to 44%) compared with tomographic results. The specificity of these leads for identifying single-vessel disease was low (6% to 47%) although some leads showed high sensitivity (69% to 100%). In contrast, the LB lead exhibited high sensitivity and specificity for detecting inferior ischemia (70% and 95%, respectively) and right coronary artery (RCA) disease (74% and 93%, respectively). Consequently, ST depressions in the LB lead (anode) are specific for identifying inferior ischemia and RCA disease, whereas those in the anterior and lateral chest leads do not identify the ischemic region or the obstructed coronary artery.

Coronary Angiography

An adult case of cardiac fibroma.

The patient, a 48-year-old woman with cardiac fibroma, is the second oldest patient with this disease in Japan. Her electrocardiogram showed findings compatible with old high lateral, posterior and possibly lateral myocardial infarction, regions which corresponded to the tumor site. In patients whose electrocardiogram suggests a previous myocardial infarction (pseudo myocardial infarction), the possibility of intramyocardial tumor should be taken into consideration.

Diagnosis, Differential

[Successful excision of a left ventricular fibroma in an adult patient].

A 48-year-old woman with negative T waves in leads I, a VL and V4-6 in the ECG was examined. The cross-sectional echography and the MRI revealed that she had a tumor in the free wall of the left ventricle. Under the cardiopulmonary bypass, the intramural fibroma (6 by 6 by 4 cm) of the left ventricle was resected and the defect was repaired by sutures of the outer myocardial layers to keep the left ventricular volume. Forty eight days after the initial operation, a reoperation was performed by interrupted sutures of the whole myocardial layers. She is doing well without any troubles 14 months after the reoperation.

Electrocardiography

[Early diagnosis and management of acute pulmonary embolism: clinical evaluation those of 225 cases].

To contribute for making early diagnosis and treatment of acute pulmonary embolism (APE), we investigated on clinical pictures of 225 patients with APE. Common underlying factors were heart disease, prolonged bed rest, post-surgical state, thrombophlebitis, malignant tumor and post-catheterization state in this order. Dyspnea, chest pain, tachycardia and shock were frequently seen as initial symptoms and signs. Blood screening showed leukocytosis, hypoxemia, hypocapnia and elevated serum LDH. Electrocardiographic findings highly demonstrated were ST.T abnormalities, such as T inversion with ST elevation in V1-3, ST depression in V4-6 and sinus tachycardia. Chest X-rays showed diminished pulmonary vascular marking and pulmonary artery dilation. Right ventricular dilatation were frequently seen on 2-dimensional echocardiograms. Pulmonary artery pressure were elevated up to 49/20 (30) mmHg. Twenty-five percent of the patients died, and the recurrence was seen in 4%. Thus, as soon as APE is suspected by above clinical findings, definitive diagnosis should be obtained by the lung perfusion scan and pulmonary arteriography, then oxygen and thrombolytic agents should be given immediately to prevent the fatal outcome.

Acute Disease

A case of accessory mitral valve leaflet associated with solitary mitral cleft.

Accessory mitral valve leaflet is a rare congenital anomaly. More than half of the cases show other congenital cardiac defects and almost all of the cases show subaortic obstruction. We report a case of an accessory mitral valve tissue without outflow obstruction associated with mitral cleft of the posterior mitral leaflet. To our knowledge, this is the first reported case of the combination of these two congenital anomalies.

Adult

Giant negative U waves in a patient with uncontrolled hypertension and severe hypokalemia.

A 66-year-old woman with a long history of hypertension had an electrocardiogram with giant negative U waves in left precordial leads despite hypokalemia. This seems to be the first report of giant negative U waves induced by uncontrolled hypertension with hypokalemia. The occurrence of negative U waves in the presence of profound hypokalemia is an important observation because it masks the electrocardiographic manifestation of hypokalemia.

Aged

Intermittent anterior divisional block and far advanced right bundle branch block induced by vasospasm during exercise testing.

A patient is reported in whom exercise induced reversible ischemic left anterior fascicular block and far advanced right bundle branch block. Master's two step exercise test for pre-operative check-up revealed significant ST elevation in leads V1-5, negative U waves in leads V3-5 and fascicular blocks with retrosternal anginal chest pain. Long acting nitrate and nicorandil relieved the fascicular blocks.

Aged