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Biomedical subjects

K Nagao

Publications and source records attributed to K Nagao.

At least 19 recordsLinked to original sources
PubMed1995

Modulation of erythrocyte membrane mechanical function by beta-spectrin phosphorylation and dephosphorylation.

The mechanical properties of human erythrocyte membrane are largely regulated by submembranous protein skeleton whose principal components are alpha- and beta-spectrin, actin, protein 4.1, adducin, and dematin. All of these proteins, except for actin, are phosphorylated by various kinases present in the erythrocyte. In vitro studies with purified skeletal proteins and various kinases has shown that while phosphorylation of these proteins can modify some of the binary and ternary protein interactions, it has no effect on certain other interactions between these proteins. Most importantly, at present there is no direct evidence that phosphorylation of skeletal protein(s) alters the function of the intact membrane. To explore this critical issue, we have developed experimental strategies to determine the functional consequences of phosphorylation of beta-spectrin on mechanical properties of intact erythrocyte membrane. We have been able to document that membrane mechanical stability is exquisitely regulated by phosphorylation of beta-spectrin by membrane-bound casein kinase I. Increased phosphorylation of beta-spectrin decreases membrane mechanical stability while decreased phosphorylation increases membrane mechanical stability. Our data for the first time demonstrate that phosphorylation of a skeletal protein in situ can modulate physiological function of native erythrocyte membrane.

Actins↗
PubMed1995

Cloning, sequence analysis, and chromosomal assignment of the mouse Apex gene.

APEX nuclease (Apex gene product) is a mammalian multifunctional DNA repair enzyme possibly involved in the repair of apurinic/apyrimidinic (AP) sites and single-strand DNA breaks with 3' termini blocked by nucleotide fragments and also in transcriptional regulation via redox activation of the AP-1 transcription factors. We cloned a 15-kb DNA fragment containing the Apex gene from a mouse leukocyte genomic library and determined a 4-kb stretch of its nucleotide sequence, including the complete sequence of the mouse Apex gene. The gene consists of 5 exons and 4 introns spanning 2.21 kb, and the boundaries between exons and introns follow the GT/AG rule. Two major and one minor transcription initiation sites were assigned to positions +1 and +24 and position +14, respectively, by a combination of ribonuclease protection, primer extension, and 5' RACE analyses. Position +1 is located 312 nucleotides upstream from the ATG initiation codon. The translation initiation and termination sites are located in exon II and exon V, respectively. The sequenced 5' flanking region (1.32 kb) lacks a typical TATA box, but contains a CAAT box and putative binding sites for several transcription factors, such as ATF, NF-IL6, Sp1, and AP2. The 0.8-kb region from position -410 (5' flanking region) to position +386 (intron II) contains a CpG island. The Apex gene locus was mapped to mouse chromosome 14C2-D1 using in situ hybridization.

Animals↗
PubMed1995

A case report of synovial sarcoma with translocation (X;18). Application of fluorescence in situ hybridization to paraffin-embedded tissue.

A 57-year-old female patient with synovial sarcoma in her right foot had a chromosome abnormality defined as translocation (X;18). The tumour was located in the subcutis, and histological investigation showed monophasic proliferation of oval to spindle-shaped cells with a fascicular arrangement lacking an epithelial component. Immunostaining disclosed no cytokeratin or epithelial membrane antigen in tumour cells. Karyotypic analysis revealed translocation (X;18) in addition to other nonspecific aberrations. Fluorescence in situ hybridization was carried out on paraffin-embedded tissue, using DNA probes for the centromeres of chromosomes X and 18 with whole chromosome painting probes for X and 18. The free nuclei showed two signals at a rate of 83-85% with the X and 18 centromeric probes, in contrast to three signals at a rate of 68-70% with the X and 18 painting probes.

Chromosomes, Human, Pair 18↗
PubMed1995

Neuronal cell loss in the dorsal raphe nucleus and the superior central nucleus in myotonic dystrophy: a clinicopathological correlation.

A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) was performed in seven patients with myotonic dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched controls. The densities of neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and control subjects. There was an appreciable positive correlation in the density of neurons between the DRN and the SCN in all MyD patients. These data suggest that the neuronal loss of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

Aged↗
PubMed1995

Usefulness of aspiration cytology in prostate cancer detection.

Aspiration cytology and core needle biopsy were performed in 79 patients who were suspected of having prostate cancer. Aspiration cytology and TURP were done in 77 cases not suspected of the disease. In the former group, they were both positive in 13 cases, aspiration cytology was negative and core needle biopsy positive in 4, and the reverse in 3 cases in whom cancer was confirmed by repeat core biopsy. All of the latter group were judged by aspiration cytology as being benign. Three cancers were detected by TURP. Aspiration cytology is a recommendable method in subjects with suspected prostate cancer.

Adenocarcinoma↗
PubMed1995

Myotonic dystrophy with alveolar hypoventilation and hypersomnia: a clinicopathological study.

We present a case of myotonic dystrophy accompanied by alveolar hypoventilation and hypersomnia. Case history, pulmonary function tests, polygraphic recording, and multiple sleep latency test, concomitant with a restrictive ventilatory abnormality, suggested a central origin of alveolar hypoventilation and hypersomnia in our case. The most significant neuropathological findings were in the tegmentum of the brain stem. Severe neuronal loss and gliosis were observed in the midbrain and pontine raphe, particularly in dorsal raphe nucleus and superior central nucleus. Pontine and medullary reticular formation also showed a marked cell loss and fibrillary gliosis. The alveolar hypoventilation and the hypersomnia in our case may be attributed to these morphological abnormalities, and would appear to be central in nature.

Disorders of Excessive Somnolence↗
PubMed1995

Moyamoya disease in three siblings--follow-up study with magnetic resonance angiography (MRA).

Three siblings with moyamoya disease including identical twins are reported. Although the younger of identical twins had no neurological problems, CT and MRI detected cerebral infarctions and cerebral angiography showed the typical features of moyamoya disease. All three cases underwent encephalo-duro-arterio-synangiosis (EDAS), and serial magnetic resonance angiography (MRA) showed that the distal portions of the middle cerebral artery (MCA) were well perfused through surgically created anastomoses. There were no findings of disease progression. MRA might play an important role in follow-up studies of moyamoya disease.

Brain↗
PubMed1995

Interphase cytogenetics of gastric carcinoma: fluorescence in situ hybridization (FISH) applied to cells obtained from formalin-fixed paraffin-embedded tissues.

The interphase cytogenetics in formalin-fixed and paraffin-embedded gastric cancer tissues were examined by fluorescence in situ hybridization (FISH) with alpha-satellite DNA probes. Two gastric carcinoma cell lines, TMK-1 and MKN-28, were first analyzed cytogenetically. Of 25 TMK-1 cell karyotypes, chromosome 7 showed trisomy and chromosome 17 showed disomy in 18 cells. Most MKN-28 cells showed disomy of both chromosomes 7 and 17. Suspensions of singly isolated TMK-1 and MKN-7 cells were obtained from the cultured cells, and from paraffin-embedded tissue specimens fixed with formalin for 0, 1, 3 and 5 days obtained from xenotransplanted tumors in nude mice. The numbers of chromosomes 7 and 17 analyzed with the karyotypic preparations coincided well with those determined by FISH, even in the paraffin-embedded specimens. The number of tumor cells showing no signals, however, increased in the specimens after 5 days formalin fixation. In 10 surgically removed gastric carcinomas, the predominant signal number for chromosomes 7 and 17 in the cells of paraffin-embedded tissues was two (disomy), except in one papillary carcinoma, which was trisomic for chromosome 7. Large subpopulations (more than 20%) showing trisomy were found in four cases for chromosome 7 and in five cases for chromosome 17. A higher frequency of trisomy was found in well differentiated than in poorly differentiated carcinomas. These findings suggest that the FISH technique is a useful tool for detecting chromosomal aberrations in gastric adenocarcinoma cells, even in paraffin-embedded specimens, as long as the tissues are fixed with formalin for an appropriate time.

Adenocarcinoma↗
PubMed1995

bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily.

We have isolated a Schizosaccharomyces pombe gene, bfr1+, which on a multicopy plasmid vector, pDB248', confers resistance to brefeldin A (BFA), an inhibitor of intracellular protein transport. This gene encodes a novel protein of 1,531 amino acids with an intramolecular duplicated structure, each half containing a single ATP-binding consensus sequence and a set of six transmembrane sequences. This structural characteristic of bfr1+ protein resembles that of mammalian P-glycoprotein, which, by exporting a variety of anticancer drugs, has been shown to be responsible for multidrug resistance in tumor cells. Consistent with this is that S. pombe cells harboring bfr1+ on pDB248' are resistant to actinomycin D, cerulenin, and cytochalasin B, as well as to BFA. The relative positions of the ATP-binding sequences and the clusters of transmembrane sequences within the bfr1+ protein are, however, transposed in comparison with those in P-glycoprotein; the bfr1+ protein has N-terminal ATP-binding sequence followed by transmembrane segments in each half of the molecule. The bfr1+ protein exhibited significant homology in primary and secondary structures with two recently identified multidrug resistance gene products of Saccharomyces cerevisiae, Snq2 and Sts1/Pdr5/Ydr1. The bfr1+ gene is not essential for cell growth or mating, but a delta bfr1 mutant exhibited hypersensitivity to BFA. We propose that the bfr1+ protein is another member of the ATP-binding cassette superfamily and serves as an efflux pump of various antibiotics.

ATP-Binding Cassette Transporters↗
PubMed1995

[Studies on atrial arrhythmias in atrial septal defect. The influences of aging on atrial fibrillation].

Clinical characteristics of aging in congenital atrial septal defect (ASD) without significant right-to-left shunt (> 10%), were examined especially focusing on atrial arrhythmias such as atrial fibrillation (Af) and atrial premature contraction (PAC) in serial 48 patients, aged 42.6 +/- 2.3, ranging 16-67 years, Af was found in 12 (25%) out of 48 patients. Comparing patients with Af and those without Af, the average age (52.8 +/- 2.6 vs 38.6 +/- 2.8 years, p < 0.05), functional class of New York Heart Association (2.0 +/- 0.2 vs 1.6 +/- 0.1, p < 0.05) and left atrial dimension (41.4 +/- 1.1 vs 34.7 +/- 1.2 mm, p < 0.01) were significantly higher in the patients with Af than those without Af. Hemodynamic variables, i.e., mean right or left atrial pressure, Pp/Ps, Qp/Qs, left-to-right shunt, electrocardiographic R/S ratio in the lead V1 and tricuspid regurgitation had no relation either with aging or Af. Furthermore, daily PAC counts on Holter electrocardiograms significantly correlated with the age of the patients (r = 0.642, p < 0.05). These results suggest that the incidence of Af in congenital ASD is significantly related with aging/duration of ASD, but not with hemodynamic variables.

Adolescent↗
PubMed1995

Repression of fat-dependent intestinal apo A-IV mRNA abundance by medium chain triacylglycerols and proteins, and elevation by carbohydrates of fat-dependent apo A-IV transport in suckling rat pups.

Nutrients regulating intestinal apo A-IV synthesis and secretion in developing rats have not been clearly defined. We examined the effect of ingestion of fats, carbohydrates and proteins on the abundance of intestinal apo A-IV mRNA and the serum concentration of apo A-IV in 14-day-old suckling rat pups fasted overnight. In pups ingesting long-chain fatty acid-fat (soybean oil, triolein: LCT), there was a prompt elevation of the mRNA at 1.5 h after ingestion, although a graded dose of soybean oil did not result in a comparable elevation of the apo A-IV mRNA. In pups on MCT, but not trilaurin, there was a repression of the LCT-dependent elevation of the message. In pups on Intralipid (composed of soybean oil, lecithin and glycerol), mRNA was elevated at 6 h after ingestion. Administration of Intralipid with lactose, glucose, fructose and sucrose induced a rapid elevation of mRNA together with elevation of serum apo A-IV, although administration of casein, whey proteins and soybean proteins resulted in repression of the Intralipid-dependent mRNA elevation. The message correlated weakly to the serum apo A-IV and triacylglycerols and with no correlation to intestinal fat accumulation. These results suggest that metabolic events following the ingestion of milk components modulate intestinal apo A-IV expression in developing rats, possibly through mucosal fatty acid utilization.

Animals↗
PubMed1995

[Puerperal secondary pulmonary hypertension in a patient with mixed connective tissue disease].

A woman with mixed connective tissue disease (MCTD) developed pulmonary hypertension after delivery of a child, but had little evidence of parenchymal lung disease. This 29-year-old woman had been given a diagnosis of MCTD when she was 19 years old. She was admitted to our department two days after delivery of a child, because of dyspnea on exertion. Acute thromboembolism was suspected because of: (1) chest roentgenogram showing cardiomegaly and enlargement of the left main pulmonary artery, (2) a lung perfusion scan showing a segmental defect in the left S6 and S8 areas, (3) laboratory studies showing abnormally high WBC, LDH, FDP, and D-D dimer, and (4) arterial blood gas analyses showing mild hypoxemia and hypocapnia. Thrombolytic therapy with heparin and urokinase was begun, and was followed by a loop diurtic and anticoagulation with warfarin. One month after admission, cardiac enlargement and the A-aDO2 were found to have decreased. At that time, cardiac catheterization was done and revealed pulmonary hypertension (mean PA pressure: 45 mmHg) and low cardiac output with no detectable thrombosis in the left pulmonary artery. The patient was subsequently treated with a calcium antagonist and a prostacyclin derivative, and her condition was stable for 5 months. Then her exercise tolerance gradually decreased due to shortness of breath, and cardiomegaly gradually increased over the next 3 months. Eight months after delivery of the child, the patient died of right heart failure. In clinically stable patients with MCTD, delivery of a child may lead to pulmonary thromboembolism and pulmonary hypertension.

Adult↗
PubMed1995

[The potential of anastomosis of the gastroepiploic artery to the left anterior descending artery in coronary artery bypass grafting].

It would be a great contribution in coronary artery bypass grafting (CAGB) using arterial graft (AG) if right gastroepiploic artery (GEA) could be grafted onto left anterior descending artery (LAD) in situ. In this study, we discussed 22 cases where anastomosis of GEA to LAD was made in situ. The subjects were limited to high stenotic cases of > 90% stenosis or more > 75% stenoses recognized in the proximal segment of coronary artery from the anastomosed site. The sex ratio of 18 (male): 4 (female) and the age varied from 40 to 78 years (the mean age: 58 years). The details were 2 cases of single CABG, 6 cases of double CABG, 11 cases of triple CABG and 3 cases of quadruple CABG and 22 GEA's were anastomosed onto 32 vessels. There was no operative death. Postoperative angiography performed on the 21 cases showed the patency of 95.2% (20/21). These finding indicate that the use of GEA is effective for multivessel CABGs in LAD.

Aged↗
PubMed1995

[A case of idiopathic pulmonary arteritis with positive anti-myeloperoxidase antibodies].

A 38-year-old woman was referred to our hospital for severe pulmonary hypertension (pulmonary arterial pressure 63/36 mmHg). Digital subtraction angiography showed complete obstruction of the right main pulmonary artery and severe stenosis of the left main pulmonary artery. Although there were no symptoms or signs of systemic arterial lesions, the initial diagnosis was aortitis syndrome with pulmonary arterial involvement, and prednisolone therapy was started (60 mg/day). Pulmonary arterial pressure decreased to 53/12 mmHg. At a dosage of 20 mg/day, however, multiple nodular shadows were present on the X-ray film of the chest, but they disappeared after the dosage was increased. The level of anti-myeloperoxidase antibodies in her serum changed at almost the same time as multiple nodular shadows appeared on the chest X-ray film. Because anti-MPO antibodies have been never detected in patients with aortitis syndrome, polyangitis overlap syndrome was suspected. However, we found no evidence of systemic vasculitis; that is, vasculitis in other organs, including the kidney and the skin. Therefore, we made a diagnosis of idiopathic pulmonary arteritis with positive anti-MPO antibodies.

Adult↗
PubMed1995

[Prediction of left ventricular functional recovery in patients with acute myocardial infarction using single photon emission computed tomography with thallium-201 and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid].

The relationships between myocardial perfusion, fatty acid metabolism, and cardiac function were investigated using dual single photon emission computed tomography (SPECT) with thallium and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) during the acute (10 +/- 1 days) and recovery (60 +/- 14 days) phases in 29 patients with acute myocardial infarction. There were 18 patients who underwent successful primary coronary angioplasty (PTCA group) and 11 patients who received conservative therapy (non PTCA group). Thallium and BMIPP uptakes were scored visually by a 4-point system and left ventricular ejection fraction (LVEF) was calculated by radionuclide ventriculography. Although significant positive correlations between thallium and 123I-BMIPP scores were observed during both phases, BMIPP scores were significantly lower than thallium scores in both acute and recovery phases in the PTCA group. No significant difference in thallium and 123I-BMIPP scores was observed at the recovery phase in the non PTCA group. LVEF significantly correlated with thallium and 123I-BMIPP scores in both phases in the PTCA group. Furthermore, the difference between thallium and 123I-BMIPP scores during the acute phase significantly correlated with the improvement of LVEF during the follow-up period in the PTCA group (y = 0.92x-0.77, r = 0.65, p < 0.005). These findings suggest that mismatch of perfusion and metabolism in infarcted myocardium assessed by thallium and 123I-BMIPP SPECT is increased by reperfusion therapy and persists at least until the recovery phase of myocardial infarction. The recovery of left ventricular function depends on the extent of the mismatched uptake, indicating a predictor for functional recovery following acute myocardial infarction.

Adult↗