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Biomedical subjects

K Nagao

Publications and source records attributed to K Nagao.

At least 91 records · Page 5Linked to original sources

Effect of insulin resistance on the endothelial vasomotor function of the coronary artery of nondiabetic patients.

Attention has been paid to the relationship between insulin resistance and coronary artery disease. The present study investigated the relationship between insulin resistance and the endothelial vasomotor function of the coronary artery of nondiabetic patients with chest pain and a positive exercise tolerance test. Twenty-five nondiabetic patients with chest pain were included. Patients with a steady state plasma glucose (SSPG) level of greater than or equal to 135 mg/dl were placed in the insulin resistant (IR) group, and those with a SSPG level less than 135 mg/dl were placed in the noninsulin resistant (NIR) group. The effect of acetylcholine, papaverine, and isosorbide dinitrate on the vasomotor response of the coronary endothelium was studied. The percent change in diameter of the coronary artery after injection of acetylcholine (20 microg ml(-1) min(-1)) was 84+/-17% in the IR group, and 109+/-18% in the NIR group. The difference in the degree of the vasodilative response is statistically significant (p<0.01). The percent change in coronary flow velocity after injection of acetylcholine (20 microg ml(-1) min(-1)) in the IR group was 120+/-67%, whereas that in the NIR group was 256+/-58%; the increase in coronary artery flow velocity of the IR group was significantly smaller than that of the NIR group (p<0.01). Nondiabetic patients with insulin resistance have endothelial vasomotor dysfunction, which raises an important question as to whether nondiabetic patients with insulin resistance should be treated to prevent the development of coronary heart disease.

Acetylcholine↗

Effects of combined emergency percutaneous cardiopulmonary support and reperfusion treatment in patients with refractory ventricular fibrillation complicating acute myocardial infarction.

OBJECT: We conducted a prospective study to determine whether or not combined emergency percutaneous cardiopulmonary support (PCPS) and coronary reperfusion treatment are useful for acute myocardial infarction (MI) patients with unsynchronized electric shock-resistive ventricular fibrillation (VF). PATIENTS AND METHODS: Thirty-two acute MI patients who lapsed into the refractory VF were entered into the study. Group 1 consisted of 19 patients with VF outside the hospital, and Group 2 consisted of 13 patients with VF immediately after arrival at the hospital. The primary endpoint was successful reperfusion, return of spontaneous circulation and good recovery without neurologic disability. RESULTS: The infarct-related arteries showed a significant difference between Groups 1 and 2. However, the two groups had similar rates of successful reperfusion (84.6% vs 94.7%, respectively) and return of spontaneous circulation (89.5% vs 84.6%, respectively). The rates of good recovery were similarly low in both groups (5.3% vs 15.4%, respectively). CONCLUSION: Combined emergency PCPS and reperfusion treatment produced high return of spontaneous circulation, however the neurologic outcome was low.

Assisted Circulation↗

Improvement in detecting telomerase activity using silica-based resin treatment: An experience of urine in bladder carcinoma.

To improve the telomeric repeat amplification protocol (TRAP) assay to detect telomerase activity using a small amount of sample, we used a resin-column to purify and to concentrate the TS extension DNA sequence. We used 14 samples of naturally voided urine (10 ml) from patients with bladder carcinoma and 9 urine samples from patients with non-malignant urological neoplasias. We used ethylenediamine tetraacetic acid (EDTA) to stabilize telomerase activity and resin treatment to concentrate TS-extended DNA and to exclude PCR inhibitor(s), and then performed extract-based fluorescence TRAP to detect telomerase activity. None of the urinary samples without resin-column treatment had detectable telomerase activity, whereas, in resin-column treated samples, 4/9 (44%) urine samples without EDTA and 9/14 (64%) with EDTA treatment had detectable telomerase activity. A combination of EDTA treatment and resin-column thus may be available to detect telomerase activity using a relatively small amount of secretion fluids, including exfoliated urinary cells.

Adult↗

Levels of telomerase catalytic subunit mRNA as a predictor of potential malignancy.

This study investigated the relationship between the levels of human telomerase reverse transcriptase (hTERT) mRNA and that of telomerase activity in hepatocellular carcinoma (HCC). A significant correlation between hTERT mRNA expression and telomerase activity by transfecting the gene encoding hTERT into telomerase-negative human fibroblast cells has clearly been demonstrated. However, the relationship between levels of telomerase activity and that of hTERT mRNA has yet to be elucidated. In this study, the levels of hTERT mRNA were analyzed in 24 HCC patients by real-time PCR. And the intensity of telomerase activity was analyzed by fluorescence-based TRAP method. The difference of hTERT mRNA level was highly significant between tumor tissues and non-cancerous liver tissues. And there were significant correlations between the levels of hTERT mRNA and that of telomerase activity (r=0.751) in tumor tissues. We observed a strong correlation between levels of hTERT mRNA and that of telomerase activity in HCC. Our results suggest that the levels of hTERT mRNA would be useful in genetic diagnostic tests, instead of telomerase activity, to screen at-risk patients of HCC in human liver tissues.

Adult↗

Detection of telomerase activity in exfoliated cancer cells obtained from bile.

Telomerase is detected by the telomeric repeat amplification protocol (TRAP) assay in more than 85% of primary cancers. In the present study, we determined telomerase activity using exfoliated bile cells obtained from biliary tract neoplasia specimens. The aim of this study was to provide additional information regarding minimally invasive approaches to the detection of biliary tract cancer in combination with routine cytologic examination. We analyzed for telomerase activity bile juice from patients with gallbladder carcinoma, cholangiocarcinoma, cholecystitis and cholangitis. Semiquantitative determination of telomerase activity was performed using both a fluorescence-based TRAP assay on cell extracts and at the cellular level by an in situ TRAP assay. The fluorescence-based TRAP assay detected bile telomerase activity in samples from 4 of 10 patients with biliary tract cancer. In contrast, the in situ TRAP assay detected telomerase positive cells in samples from 6 of 10 patients with biliary tract cancer. However, only one of these samples showed class V cytology. A combination of semiquantitative analysis and an in situ TRAP assay to detect telomerase positive cells may improve the diagnosis of biliary tract cancers with the combination of routine cytologic examination.

Adult↗

[Investigation of pulmonary hemodynamics and chest X-ray findings in patients with pulmonary tuberculosis sequelae and obstructive ventilatory impairment].

We investigated pulmonary hemodynamics and chest X-ray findings to explore significance of obstructive ventilatory impairment in patients with pulmonary tuberculosis sequelae. One hundred and two patients underwent examinations of blood gases, spirometry, and right cardiac catheterization. The patients were divided into two groups, according to forced expiratory volume in one second as the percentage of forced vital capacity (FVC), which was expressed as FEV1%. Group A (n = 38) had FEV1% of 55% or lower and Group B (n = 64), FEV1% above 55%. First, the values of blood gases and hemodynamics were compared between the two groups, regarding the percent predicted value of FVC as a covariate. Secondly, between 26 of Group A and 42 of Group B, the change of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes was compared. These comparisons were made by exploratory data analysis. Lastly, we described every case with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis and/or cavity; pulmonary resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored X-ray findings influenced on airway obstruction by ridit (abbreviation for "relative to an identified distribution") analysis, taking smoking status into consideration. The results were as follows. (1) The patients of Group A tended to show severer hypoxemia and tissue hypoxia than the patients of Group B. (2) The patients of Group A tended to show worse values of pulmonary hemodynamics than the patients of Group B. Under an even level of the arterial oxygen tension that was 60 Torr or lower, pulmonary artery mean pressure was higher in Group A than in Group B. (3) PAR after oxygen breathing was less likely to decrease in Group A than in Group B. (4) As any mean ridit was standardized and adjusted to 0.5 in Group B, every mean ridit of "emphysematous change" in Group A was the largest-0.63 in non-smokers, 0.74 in ex-smokers and 0.70 in current smokers. Therefore, "emphysematous change" was more influenced on airway obstruction than any other finding because of the largest mean ridit. We conclude as follows. Pulmonary hypertension is more serious in patients suffering from severe airway obstruction with pulmonary tuberculosis sequelae, and it may be attributable to reduction in capacity of anatomical pulmonary vascular bed rather than hypoxic pulmonary vasoconstriction. Pathological changes such as "emphysematous change" on the radiograph might be considered as an important cause of obstructive ventilatory impairment.

Adolescent↗

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 2. The problems of management of the patients diagnosed pulmonary tuberculosis after admission to the respiratory ward of university hospital having no an isolation ward for the tuberculous patients].

The management of 28 patients, diagnosed pulmonary tuberculosis by bacteriological or pathologic findings after the administration to the Koshigaya Hospital of Dokkyo university school of Medicine from January 1994 through September 1997, which had no an isolation ward for tuberculosis patients was analyzed. The mean age of the patients was 50.6 +/- 16.7 (18-85), and the number of male and female patients was 22 and 6 respectively. The underlying diseases found in 10 patients were gastric cancer, breast cancer, osteochondrosarcoma, collagen disease, diabetes mellitus, liver cirrhosis, pneumoconiosis, and bronchial asthma. Two patients were complicated by a lung cancer. Six of 28 patients showed smear-positive and culture-positive specimens and 22 of 28 patients showed smear-negative and culture-positive specimens. The detection of mycobacterial DNA in the samples after amplification by the polymerase chain reaction (PCR) used in 15 patients and was positive for 7 of 15 patients. The pathological study of the specimens obtained by Transbronchial lung biopsy was performed for 14 patients. The pathological findings were compatible with tuberculosis in 7 of 14 patients. The chief complaints of the 11 patients admitted to the hospital with in 3 days after first visit, were fever in all patients and in 5 patients with pleural effusion. A few patients showed smear-negative and PCR positive specimens and complicated by lung cancer or other malignancy, were treated in non isolation ward in the particular case of emergency evacuation before admission, careful examination such as a tuberculin test, bacterial examination, and PCR of sputum should be performed in the patients suspected of having pulmonary tuberculosis. The patients isolating tubercule bacilli after administration should be transferred to the hospital with isolated ward for tuberculosis or isolated room in general hospital in the particular case of emergency evacuation with the greatest care.

Adolescent↗

[Investigation of pulmonary hemodynamics and chest X-ray findings in hypercapnic patients with pulmonary tuberculosis sequelae].

We investigated pulmonary hemodynamics and chest X-ray findings to explore pathophysiological significance of chronic hypercapnia in patients with pulmonary tuberculosis sequelae. One hundred and seven patients underwent examinations of blood gases and right cardiac catheterization. The patients were divided into two groups, according to arterial carbon dioxide tension under room air breathing (PaCO2). Group I (n = 35) was defined as 45 Torr or lower of PaCO2, and Group II (n = 72) was the hypercapnic group whose PaCO2 was over 45 Torr. In addition, spirometry was done in 34 patients of Group I and 68 of Group II. First, the values of blood gases, spirometry and pulmonary hemodynamics were compared between the two groups. Secondly, between 22 of Group I and 50 of Group II, the values of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes were compared. These comparisons were made by exploratory data analysis. Lastly, we described in all cases with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis, and/or cavity (hereafter abbreviated as "fibrosis"); lung resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored the items of X-ray findings which may relate to hypercapnia by ridit (abbreviation for "relative to an identified distribution") analysis. The results were as follows. (1) Hypercapnic patients tended to have severer restrictive ventilatory impairment and hypoxemia. Under an even level of arterial oxygen tension (PaO2), tissue oxygenation was not poorer in Group II than in Group I. (2) Hypercapnic patients tended to have more unfavorable pulmonary hemodynamics. More than half of them had pulmonary hypertension defined as 20 mmHg or higher of pulmonary artery mean pressure (PAm). Under an even level of PaO2, PAm was higher in Group II. Although 34 patients of Group II showed PaO2 over 60 Torr, 23 of them had pulmonary hypertension. (3) PAR after oxygen breathing was more likely to decrease in Group II than in Group I. (4) As any mean ridit was standardized and adjusted to 0.5 in Group I, the maximum was the mean ridit of "pleural thickening" (= 0.67), next "fibrosis" (= 0.65) in Group II. The above two items of X-ray findings, in which each mean ridit was higher than in any other item, were more influential on hypercapnia. We conclude as follows. (1) Pulmonary hypertension is severer in hypercapnic patients with pulmonary tuberculosis sequelae; it may be mainly attributable to hypoxic pulmonary vasoconstriction. (2) An important cause of chronic hypercapnia may be pathological changes such as "pleural thickening" and "fibrosis" seen on the radiogram.

Adult↗

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis.

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.

Adult↗

Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases.

BACKGROUND: Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully. METHODS: Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison. RESULTS: The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics. CONCLUSIONS: MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.

Actins↗

Intracellular aggregate formation of dentatorubral-pallidoluysian atrophy (DRPLA) protein with the extended polyglutamine.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by the abnormal CAG triplet-repeat expansion resulting in an elongated polyglutamine (polyQ) stretch. We have recently showed that the DRPLA protein is cleaved during apoptosis by caspase-3, one of the cysteine protease family members known to be activated during apoptosis. We report here the subcellular localization of the DRPLA protein by fusing the green fluorescent protein as a tag. The full length DRPLA protein is localized predominantly but not exclusively in the nucleus regardless of the length of the polyQ stretch. In contrast, an N-terminal-deleted fragment containing polyQ produced by the proteolytic cleavage with caspase-3 is found both in the nucleus and the cytoplasm. Moreover, the same fragment with the elongated polyQ showed aggregation when overexpressed. Some cells with aggregate formation showed apoptotic phenotype. These findings raise the possibility that the DRPLA protein processed by caspase-3 may lead to aggregation of the protein resulting in the development of neurodegeneration.

Apoptosis↗

Cut1 is loaded onto the spindle by binding to Cut2 and promotes anaphase spindle movement upon Cut2 proteolysis.

BACKGROUND: The Cut1 and Cut2 proteins of the fission yeast Schizosaccharomyces pombe form a complex and are required for the separation of sister chromatids during anaphase. Polyubiquitinated Cut2 degrades at the onset of anaphase and this degradation, like that of mitotic cyclin, is dependent on the anaphase-promoting complex/cyclosome. Expression of Cut2 that cannot be degraded blocks sister chromatid separation and anaphase spindle elongation. Here, we have investigated the role of the Cut1-Cut2 interaction in sister chromatid separation. RESULTS: The carboxyl terminus of Cut2 interacts with the amino terminus of Cut1, and temperature-sensitive Cut2 mutants expressed Cut2 proteins that contain substitutions in the carboxyl terminus and fail to interact with Cut1, resulting in aberrant anaphase. Localization of Cut1 alters dramatically during the cell cycle. Cut1 is retained in the cytoplasm during interphase and moves to the mitotic spindle pole bodies and the spindle upon entry into prophase, when spindles are formed. The association between Cut2 and Cut1 is needed for the localization of Cut1 to the spindles, as Cut1 remains unbound to the spindle if complex formation is impaired. Cut2 degrades during anaphase, but Cut1 remains bound to the anaphase spindle. This association with the anaphase spindle requires the conserved carboxyl terminus of Cut1. CONCLUSIONS: Complex formation between Cut1 and Cut2 is needed for the onset of normal anaphase. Cut2 is required for loading Cut1 onto the spindle at prophase and Cut2 proteolysis is needed for the active participation of Cut1 in sister chromatid separation.

Anaphase↗

Establishment of two human small cell lung cancer cell lines: the evidence of accelerated production of parathyroid hormone-related protein with tumor progression.

Two small cell lung cancer (SCLC) cell lines have been established from malignant effusions obtained from an SCLC patient with hypercalcemia during a 3-month follow-up period. The two cell lines established were shown to transcribe the parathyroid hormone-related protein (PTHrP) gene and to constantly secrete fairly large amounts of PTHrP into the culture medium. The efficiency of PTHrP gene transcription and secretion was greater in the cell line established in the late stage (KOT-2) as compared with that obtained in the early stage (KOT-1). Immunohistochemical studies showed that these cells also coexpress neuroendocrine (NE) products such as chromogranin A and neuron-specific enolase (NSE).

Adult↗

Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2.

BACKGROUND: Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here and compared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics. METHODS: Formalin fixed, paraffin embedded sections of 11 cases of BCAC and 9 cases of BCA, selected from the authors' files of 1851 primary tumors of the major salivary gland, were examined using immunostaining for Ki-67 (MIB-1), p53, bcl-2, and EGFR. In addition, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling. RESULTS: The incidence of BCAC was 0.6% among patients with major salivary gland tumors in the current series. Nine cases of BCAC arose in the parotid gland and two were of submandibular gland origin. Approximately 50% of the patients had recurrences, but no patient developed metastases or died of disease. Vascular involvement (75%), perineural invasion (36%), and necrosis (45%) were common features. Cell proliferative activity, including mitotic count, Ki-67 labeling index (LI), and apoptotic index were significantly higher in BCAC than BCA. More than four mitotic figures per ten high-power fields or a Ki-67 LI > 5% appeared to be limited to cases of BCAC. Considering those cases expressing p53 or EGFR in > 10% of tumor cells as positive, 6 of the 11 BCAC cases were positive for p53 and 3 were positive for EGFR. In contrast, all BCA cases were negative for p53 and EGFR. Although all cases of BCA were strongly positive for bcl-2 (> 50% of tumor cells), 3 of 11 cases of BCAC were completely negative. CONCLUSIONS: BCAC is a rare salivary gland tumor with a relatively high recurrence rate. Examination of cell proliferation, apoptosis, and expression of p53, bcl-2, and EGFR were found to be useful in distinguishing malignant basal cell tumors from their benign counterparts arising in the salivary gland.

Adenocarcinoma↗

Primary transitional cell carcinoma of the fallopian tube: a case report and review of the literature.

Primary carcinoma of the fallopian tube is extremely rare and the preoperative diagnosis is often misdiagnosed as an ovarian carcinoma. We report a patient with primary carcinoma of the fallopian tube, strongly suspected preoperatively on the basis of characteristic clinical symptoms, elevated CA125 levels, and transvaginal sonography, computed tomography, and magnetic resonance imaging findings. The histology of fallopian tube carcinoma was demonstrated as transitional cell carcinoma. Extensive review of the literature showed that our case seemed to be the 14th case of primary transitional cell carcinoma of the fallopian tube.

Carcinoma, Transitional Cell↗

[Reoperative coronary artery bypass grafting without cardiopulmonary bypass].

Between October 1995 and February 1997, 2 men and 4 women aged 53 to 75 years (mean, 66.3) underwent reoperative coronary artery bypass grafting without cardiopulmonary bypass. Isolated reoperative circumflex or intermediate artery bypass was performed through a left thoracotomy (n = 2), reoperative bypass to the left anterior descending coronary artery was performed through a median sternotomy (n = 3), and bypass to the right coronary artery was performed through an upper median laparotomy (n = 1). Single coronary bypass grafting utilizing arterial grafts (left internal thoracic artery: 3, right gastroepiploic artery: 3) was performed in all cases. There were no operative deaths. All cases required neither cathecolamine nor intraaortic balloon pumping). Peri/post operative blood transfusion was necessary in only one case. Postoperative coronary angiography revealed that the 6 arterial grafts were patent. Reoperative coronary artery bypass grafting without cardiopulmonary bypass can be performed with low perioperative morbidity and mortality, easy postoperative management, satisfactory graft patency, and good symptomatic improvement.

Aged↗