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M Nishimura

Publications and source records attributed to M Nishimura.

At least 343 records · Page 19Linked to original sources
PubMed1999

Deletion in the beige gene of the beige rat owing to recombination between LINE1s.

We have determined the molecular genetic basis of the rat beige mutant, a model for human Chediak-Higashi syndrome. Deletion of a 578-bp sequence, which led to a frame shift and a presumably non-functional truncated BEIGE protein, was identified in beige cDNA. The beige rat had a deletion of about 20 kb of genomic DNA, including three exons, which constitute the deleted 578-bp cDNA fragment. LINE1s (Long Interspersed Nucleolar Element 1) were identified at the site of the deletion. Consensus recognition sequences for DNA topoisomerase I were clustered at the putative deletion junction sites in LINE1s. We conclude that the deletion in the beige gene mediated by recombination between LINE1s is the causative mutation in the beige rat. The recombination might have been induced by DNA topoisomerase I and the extensive sequence homology between LINE1s.

Amino Acid Sequence↗
PubMed1999

Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus.

The BAT2 gene lies within the class III region of the major histocompatibility complex. We investigated the frequency of the BAT2 microsatellite alleles (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) patients, 51 adult-onset IDDM patients, and 85 normal control subjects, and assessed the associations among these BAT2 alleles, TNFa microsatellite alleles (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was significantly increased in the young-onset IDDM patients (12.8 vs 4.1%, Pc=0.04896), whereas the frequency of BAT2.12 allele was significantly decreased in young-onset IDDM patients (0.0 vs 11.8%, Pc=0.00002) compared with control subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the BAT2.9 and HLA-DRB1 alleles. The BAT2.12 allele was strongly associated with TNFa13, and with DRB1*1502 in control subjects. These results suggest that the BAT2 microsatellite polymorphism is associated with the age-at-onset of IDDM and possibly with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. However, this association is not independent of TNFa polymorphisms.

Adolescent↗
PubMed1999

Murine cytomegalovirus immediate-early promoter directs astrocyte-specific expression in transgenic mice.

Murine cytomegalovirus (MCMV), which causes acute, latent, and persistent infection of the natural host, is used as an animal model of human cytomegalovirus (HCMV) infection. Transcription of MCMV immediate-early (IE) genes is required for expression of the early and late genes and is dependent on host cell transcription factors. Cell-type-specific expression activity of the MCMV IE promoter was analyzed in transgenic mice generated with the major IE (MIE) enhancer/promoter involving nucleotides -1343 to -6 (1338 bp) connected to the reporter gene lacZ. Distinct expression was observed in the brain, kidneys, stomach, and skeletal muscles. Weak expression was observed in a portion of the parenchymal cells of the salivary glands and pancreas, and expression was hardly detected in the lungs, intestine, or immune and hematopoietic organs such as the thymus, spleen, lymph nodes, and bone marrow. The spectrum of organs positive for expression was narrower than that of the HCMV MIE promoter-lacZ transgenic mice reported previously and showed a greater degree of cell-type specificity. Interestingly, astrocyte-specific expression of the transgene was observed in the brain and primary glial cultures from the transgenic mice by combination of beta-galactosidase (beta-Gal) expression and immunostaining for cell markers. However, the transgene was not expressed in neurons, oligodendroglia, microglia, or endothelial cells. Furthermore, the beta-Gal expression in glial cultures was stimulated significantly by MCMV infection or by addition of calcium ionophore. These observations indicated that expression activity of the MCMV IE promoter is strictly cell-type specific, especially astrocyte-specific in the brain. This specific pattern of activity is similar to that of natural HCMV infection in humans.

Animals↗
PubMed1999

Prognostic factors in clinical stage I non-small cell lung cancer.

BACKGROUND: Management of patients with early-stage lung cancer but a poor prognosis is controversial. METHODS: Between January 1987 and December 1994, 365 patients with clinical stage I disease underwent surgical resection at our hospital. Eight preoperative clinical variables were entered into univariate and multivariate analyses to determine their impacts on 5-year survival. RESULTS: The 3-year and 5-year survival rates were 78.1% and 66.5%, respectively. In the multivariate analysis, clinical T2 status and preoperative high serum carcinoembryonic antigen levels were independent significant factors indicative of a poor prognosis (hazard ratio, 2.20 and 1.88, respectively). Patients with both of these factors had 3-year and 5-year survival rates of 65% and 38% (p<0.001), and the risk of death for this subgroup was 4.14 times greater than that of the overall clinical stage I population. CONCLUSIONS: A subgroup with clinical T2 disease and preoperative high serum carcinoembryonic antigen levels had a significantly poorer prognosis among patients with clinical stage I lung cancer. For this subgroup, a complete preoperative staging workup and multimodal therapy, especially induction chemotherapy, instead of surgical intervention alone could be beneficial.

Aged↗
PubMed1999

Postoperative mediastinal chyloma.

Anterior mediastinal mass developed in a 69-year-old woman who had undergone right upper lobectomy and systematic lymph node dissection. The mass was diagnosed to be a mediastinal chyloma and surgical intervention was necessary to resolve the compression to the superior vena cava. Although posttraumatic mediastinal chyloma is not rare, postoperative mediastinal chyloma has not been reported in the literature. However, it should be noted as a differential diagnosis for a postoperative mediastinal mass.

Adenocarcinoma↗
PubMed1999

Ureteral obstruction reverses glomerular proliferation in immune complex glomerulonephritis.

We investigated an effect of ureteral obstruction on a progressive immune complex glomerulonephritis in murine lupus erythematosus. Unilateral ureteral obstruction for 8 days significantly decreased the expanded glomerular mesangial area, as measured by computer-assisted morphometry (4.44 +/- 0.33 x 10(-4) mm2 to 3.60 +/- 0.34 x 10(-4) mm2, P < .05), and reduced the staining for IgG, C3, and extracellular matrix components, whereas the nephritis was exacerbated in the contralateral non-obstructed kidney. The renal concentration of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in the obstructed kidneys 8 days after obstruction significantly exceeded that of kidneys in sham-operated controls (344.2 +/- 83.9 pg/mg tissue protein vs 50.0 +/- 27.5 pg/mg tissue protein, P < .01; 71.9 +/- 11.4 pg/mg tissue protein vs 9.5 +/- 2.3 pg/mg tissue protein, P < .01), whereas thromboxane B2 (TxB2) levels were similar in the two groups (33.9 +/- 4.5 pg/mg tissue protein vs 31.3 +/- 2.6 pg/mg tissue protein). Next, an experiment was performed to evaluate the role of renal eicosanoids in the amelioration in the immune complex glomerulonephritis after ureteral obstruction. Treatment with the cyclooxygenase inhibitor indomethacin abolished the decrease in mesangial area induced by ureteral obstruction (7.7% +/- 6.9%). CV-4151, a thromboxane synthetase inhibitor, had no effect on the decrease in mesangial area (-25.8% +/- 6.8%, P < .05). We conclude that unilateral ureteral obstruction quickly decreased the mesangial expansion in immune complex glomerulonephritis, and vasodilatory eicosanoids such as PGE2 and PGI2 at least partly contribute to the amelioration of glomerular histology.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

The prognosis of surgically resected N2 non-small cell lung cancer: the importance of clinical N status.

BACKGROUND: Clinical trials dealing with multimodal strategy for N2 non-small cell lung cancer are now being watched with keen interest, and the feasibility of this strategy is to be confirmed. N2 lung cancer, however, is composed of several subgroups with different prognoses. The prognostic factors still remain controversial. METHODS: Between January 1986 and July 1997, 222 patients with lung cancer underwent surgical intervention at our institute; these patients were eventually given a diagnosis of metastasis to ipsilateral mediastinal lymph nodes. All patients underwent mediastinal lymph node dissection or sampling. Sixteen clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Clinical N status was evaluated by computed tomographic scan. RESULTS: The overall 5-year survival was 27%. Multivariable analyses among overall patients revealed 4 significant prognostic factors (P <.05): clinical N2 status, incomplete resection, larger tumor size, and multiple diseased N2 nodes. Based on the result, 32 patients with both clinical N2 status and pathologic multiple N2 nodes showed a 5-year survival of 5%, whereas 76 patients with neither of the factors showed a 5-year survival of 57% (P <.001). CONCLUSION: The prognosis of surgically resected N2 disease varies tremendously according to the 4 significant prognostic factors. These factors should be clearly described in reporting clinical trials on N2 lung cancer. Clinical N status evaluated by computed tomographic scan should be 1 criterion to perform a clinical trial for N2 disease among a homogeneous population with respect to prognosis.

Adult↗
PubMed1999

Gene transfection of beta 2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist.

BACKGROUND: Beta-adrenergic receptor system has a major role in cardiac contraction. If the receptor can be increased by gene transfection by means of intracoronary infusion of beta 2-adrenergic receptor to the hearts in which the receptor is down-regulated, this maneuver may improve the cardiac function and may be applied as one therapeutic approach during cardiopulmonary bypass or percutaneous cardiopulmonary support. METHODS AND RESULTS: The beta 2-adrenergic receptor complementary DNA was transfected in vivo to the normal rat heart by intracoronary infusion by means of a hemagglutinating virus of Japan liposome method, and the transfected heart was transplanted into the abdomen of another rat. Four days after transfection, the sarcolemma of the cardiomyocytes was well labeled by immunohistochemical labeling. Expression of beta-adrenergic receptor in the heart was approximately 4 times greater than that in control hearts (134 +/- 42 vs 33 +/- 4 fmol/mg protein) according to a ligand binding assay. The cardiac response of the transfected heart to isoproterenol was shown to be enhanced in a Langendorff perfusion system: after isoproterenol, developed pressure and maximal derivative of the left ventricle were greater than in the control heart (200 +/- 12 vs 174 +/- 6 mm Hg and 4110 +/- 130 vs 3491 +/- 255 mm Hg/sec), and the minimal derivative of the left ventricle was markedly smaller (-3040 +/- 267 vs -2528 +/- 131 mm Hg/sec). CONCLUSIONS: These results indicate that expression of beta 2-adrenergic receptor was approximately 4 times greater than in normal rat hearts by gene transfection using a hemagglutinating virus of Japan liposome method, and the transfected hearts demonstrated marked enhancements in cardiac response to beta-agonist, suggesting that transfer of this gene by intracoronary infusion has potential as a novel approach to enhance cardiac function.

Adrenergic beta-Agonists↗
PubMed1999

Clinical predictors of N2 disease in the setting of a negative computed tomographic scan in patients with lung cancer.

OBJECTIVES: Although preoperative cervical mediastinoscopy is absolutely indicated for patients with lung cancer in whom computed tomography demonstrates mediastinal nodal enlargement, the indications when the computed tomographic scan is negative are controversial. To determine the indications in patients with negative computed tomographic scans, we retrospectively studied patients with surgically resected lung cancer. METHODS: Between 1992 and 1997, 379 patients with lung cancer who had clinical N0-1 disease underwent surgical resection of lung cancer. Mediastinal lymph nodes were pathologically examined for metastasis in all the patients. A clinical diagnosis of nodal involvement was determined on the basis of preoperative computed tomographic findings: that is, mediastinal or hilar lymph nodes 1.0 cm or larger in the shortest axis were diagnosed as metastatic. Univariate and multivariate analyses were performed to determine the relationships between 9 clinical factors and pathologically proven N2 disease. RESULTS: Among the patients with clinical N0-1 disease, 68 (17.9%) had pathologic N2 disease. Adenocarcinoma histology, large tumor dimension, and high serum carcinoembryonic antigen levels were significant predictors of pathologic N2 disease on the basis of multivariate analyses (P <.05). When these factors were combined, 43% of adenocarcinomas larger than 2.0 cm with high serum carcinoembryonic antigen levels (P <.001), 34.7% of adenocarcinomas with high serum carcinoembryonic antigen levels (P <.001), 25.6% of adenocarcinomas larger than 2.0 cm (P =.009), and 31.1% of patients with high serum carcinoembryonic antigen levels and large tumor dimension (P <.001) had pathologic N2 disease. CONCLUSION: Preoperative cervical mediastinoscopy should be considered in patients in whom computed tomography is negative for lung cancer and who have some pathologic N2 predictive factors.

Adenocarcinoma↗
PubMed1999

Handwashing before entering the intensive care unit: what we learned from continuous video-camera surveillance.

Handwashing is one of the most important factors in controlling the spread of bacteria and in preventing the development of infections. This simple procedure does not have a high compliance rate. The Association for Professionals in Infection Control and Epidemiology, Inc, guideline recommends that hands must be washed before and after patient contact. In our intensive care unit (ICU), we have made it a rule that everyone should wash their hands before entering the ICU. The purpose of this study was to ascertain the handwashing compliance of all personnel and visitors to the ICU. A ceiling-mounted video camera connected to a time-lapse video cassette recorder recorded each person's actions when they entered the ICU during a 7-day period. Handwashing compliance was assessed for 3 different categories: ICU personnel, non-ICU personnel, and visitors to patients. There were 1030 entries to the ICU during the observation period. ICU personnel complied with handwashing in 71% of entries, non-ICU personnel in 74% of entries, and visitors to patients in 94% of entries. Handwashing compliance by visitors to patients was significantly higher than among personnel (P <.001). Handwashing compliance among personnel before entering the ICU was low. Continuous effort is needed to raise awareness of the handwashing issue, not only to ensure compliance with APIC recommendations but also in our facility, to ensure that health care personnel wash their hands on entry to the ICU.

Guideline Adherence↗
PubMed1999

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗
PubMed1999

Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension.

We examined the circadian rhythm of urinary sodium excretion and the effects of sodium restriction on rhythm in both dipper and nondipper types of essential hypertension. Patients (n = 26) with essential hypertension were maintained on relatively high- (10 to 12 g/d of sodium chloride) and low-sodium (1 to 3 g/d) diets for 1 week each. On the last day of each diet, 24-hour blood pressures (BPs) were measured every 30 minutes noninvasively with an automatic device, and on the last 3 days, urinary samples were collected for both daytime (7:00 AM to 9:30 PM) and nighttime (9:30 PM to 7:00 AM). Eight patients were classified as dippers based on a more than 10% reduction in mean arterial pressure (MAP) from daytime to nighttime on a high-sodium diet, and 18 patients were classified as nondippers. A nocturnal decrease in urinary sodium excretion rate (U(Na)V) on the high-sodium diet was observed in dippers (from 7.5 +/- 2.1 during the day to 5.3 +/- 2.5 mmol/h at night; P < 0.0001), but not in nondippers (6.7 +/- 2.1 v 7.6 +/- 2.3 mmol/h; not significant). In nondippers, the night-day ratio of sodium excretion was significantly reduced from 1.2 +/- 0.4 to 0.8 +/- 0.3 (P < 0.003) by sodium restriction; at the same time, the night-day ratio of MAP was reduced from 0.98 +/- 0.04 to 0.93 +/- 0.05 (P < 0.05). In dippers, the night-day ratios of MAP and U(Na)V were not affected by sodium restriction, and both ratios remained constant at less than 1. Before sodium restriction, the night-day ratio of sodium excretion correlated with that of MAP (r = 0.78; P < 0.0001), whereas there was no significant correlation (r = -0.05) after sodium restriction. These findings showed that the circadian rhythm of renal sodium excretion differed between the two types of essential hypertension. The enhanced nocturnal natriuresis and diminished nocturnal BP fall on a high-sodium diet, recognized in nondippers, were both normalized by sodium restriction, resulting in circadian rhythms with nocturnal dips in U(Na)V and BP.

Adult↗
PubMed1999

Cardiovascular complications in patients with primary aldosteronism.

Primary aldosteronism (PA) is widely believed to be a relatively benign form of hypertension associated with a low incidence of vascular complications. However, several recent studies showed that cardiovascular complications were not rare in PA. PA is known as one of the most typical forms of sodium-sensitive hypertension. Recently, we found that the sodium sensitivity of blood pressure was a marker for greater risk for cardiovascular complications, especially stroke, in patients with essential hypertension. Therefore, we investigated cardiovascular complications in 58 patients with PA confirmed to be Conn's adenoma. Cardiovascular complications were found in 34% of 58 patients. Coronary artery disease was found in only one patient (1.7%), as angina pectoris. Stroke was found in nine patients (15.5%), four patients (6.9%) with cerebral infarctions and five patients (8.6%) with cerebral hemorrhages. Proteinuria and renal insufficiency were found in 14 (24.1%) and 4 (6.9%) patients, respectively. The incidence of cerebral infarction and renal insufficiency was greater in men than women. The prevalence of proteinuria was greater in patients with than without stroke (P = 0.03) among those aged older than 40 years. These results indicated that cardiovascular complications, especially stroke and proteinuria, were common in patients with PA, and proteinuria might be an indicator for stroke as target-organ damage.

Cardiovascular Diseases↗
PubMed1999

Developmental changes in the regional Na+/glucose transporter mRNA along the small intestine of suckling rats.

We investigated the postnatal development of Na(+)-dependent glucose transporter (SGLT1) as a change in the level of the gene expression of the transporter during the suckling period in rats. We measured the changes in the expression of SGLT1 mRNA in various regions of the intestine during the development of rat pups, using a Northern blot analysis. We found a pronounced gradient in SGLT1 mRNA, with a high level in the duodenum declining gradually, but significantly, to a relatively low level near the ileocecal junction. The level of SGLT1 mRNA in the jejunum region increased in proportion to postnatal age. SGLT1 mRNA was not found at the colon. These data indicate that the glucose uptake in the small intestine of rat pups changes according to regional and age-related transporter activity.

Actins↗
PubMed1999

Determinants of circadian blood pressure rhythm in essential hypertension.

It has been postulated that the lack of nocturnal blood pressure fall in patients called nondippers is associated with more serious end organ damages by hypertension than in dippers whose blood pressure falls during the night. Recently, we found that sodium restriction shifted circadian rhythm of blood pressure from that of a nondipper to a dipper in patients with essential hypertension. In the present study, we aimed to clarify these important findings from the different approaches, and examined which factors affected the diurnal rhythm of blood pressure. A total of 70 patients with essential hypertension were maintained on high and low sodium diets for 1 week each. Nocturnal fall in mean arterial pressure was calculated in each patient, and, based on multiple regression analysis, independent factors affecting this nocturnal fall were examined. Thirty-eight patients were classified as non-sodium-sensitive, whereas 32 were considered sodium sensitive, based on a >10% change in 24-h mean arterial pressure by sodium restriction. In all 70 patients, sodium sensitivity of blood pressure, as well as an interaction between sodium sensitivity and sodium restriction, were identified as independent factors affecting the nocturnal fall. In sodium-sensitive types, in addition to sodium restriction, glomerular filtration rate was identified, whereas, in non-sodium sensitive types, there was no significant factor. Based on multiple regression analysis, the present study reached the same important conclusion as our previous findings: namely, that the enhanced sodium sensitivity was an independent determinant for the diminished nocturnal fall in essential hypertension and that sodium restriction could restore the nocturnal decline, especially in patients with enhanced sodium sensitivity whose nocturnal decline was diminished. Reduced renal sodium excretory capability may be one of the mechanisms involved in nondipping.

Adult↗