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Biomedical subjects

N Narita

Publications and source records attributed to N Narita.

At least 19 recordsLinked to original sources
PubMed2002

A serotonin malfunction hypothesis by finding clear mutual relationships between several risk factors and symptoms associated with sudden infant death syndrome.

In our recent study allele variants in the promoter of serotonin transporter (5-HTT) gene have been shown as a novel risk factor for sudden infant death syndrome (SIDS). L and XL alleles were more frequent and S allele was less frequent in SIDS victims compared to age-matched controls. Serotonin (5-HT) is suggested as a major agent that is closely involved in the etiology of SIDS. Although many risk factors of SIDS looked mutually unrelated each other, we found in literature many of them other than prone position to change 5-HT levels in the brain. Along with the genetic factors, environmental and temporal factors appear additively to lower the excitatory function of 5-HT to the respiratory center, and finally SIDS might occur. Now the pathophysiological mechanisms and symptoms of SIDS are explained by decreased levels of 5-HT.

Alleles↗
PubMed2002

Transcription factors GATA-4 and GATA-6 during mouse and human adrenocortical development.

Our earlier work implicates transcription factors GATA-4 and GATA-6 in the murine adrenal. We have now studied their expression during mouse and human adrenal development in detail. GATA-4 and GATA-6 mRNAs are readily detectable from embryonic day 15 in mouse and gestational week 19 in human adrenal cortex. In postnatal adrenal, GATA-4 expression is down-regulated, whereas GATA-6 mRNA and protein continue to be abundantly present. In a human adrenocortical cell line NCI-H295R, GATA-6 mRNA is up-regulated by cAMP. This cell line does not express GATA-4. Our findings suggest that GATA-6 expression is hormonally controlled, and required throughout adrenal development from fetal to adult age. GATA-4, on the other hand, may serve a role in fetal adrenal gene regulation.

Adrenal Cortex↗
PubMed2001

Enhanced low shear stress induced platelet aggregation by Shiga-like toxin 1 purified from Escherichia coli O157.

The effect of Shiga-like toxin 1 (Stx1) produced by Escherichia coli O157 on platelets was studied with an argon laser light-assisted shear-induced platelet aggregometer and with binding assays. Stx1 markedly enhanced the platelet aggregation under low shear stress but did not affect it under high shear stress. Minimal concentration of Stx1 required for the enhancement was 0.25 ng/ml, and almost maximal enhancement was observed at a final concentration of > or =2.5 ng/ml. This enhanced platelet aggregation disappeared after leukocyte depletion from normal platelet-rich plasma with a specific filter. In contrast, a standard platelet aggregometer was unable to detect this enhanced platelet aggregation in either the presence or the absence of ADP. 125I-labeled purified Stx1 did not specifically bind to normal washed platelets depleted of leukocytes, and thin-layer chromatographic analysis of glycolipids extracted from normal platelet lysates also confirmed that leukocyte-depleted normal platelets lack Stx1-specific receptor globotriaosylceramide (Gb3). Supernatant from the monocyte suspension stimulated with Stx1 exhibited the enhanced low shear stress induced platelet aggregation, but that from the polymorphonuclear cell suspension did not. Several cytokines produced from monocytes reproduced this event in vitro. Further, plasmas from six out of seven patients with hemolytic uremic syndrome (HUS) had activity similar to the purified Stx1. This activity was almost totally impaired after treatment of HUS plasmas with Gb3 in accord with reduction of plasma Stx1 levels. Taken together, these results indicate that platelets lack Gb3, and Stx1 appears to modulate platelet aggregation in an indirect fashion, presumably by the release of cytokines or chemical compounds from the target tissues.

Bacterial Toxins↗
PubMed2001

A biogenic amine-synapse mechanism for mental retardation and developmental disabilities.

Recent studies have demonstrated that biogenic amines have a function of facilitating formation and maintenance of synapses in diverse regions of the central nervous system in developing and adult animals. The normal number of synapses maintained by biogenic amines are crucial to acquire learning and memory. The level of biogenic amines was reported to decrease in the brain by several neurodevelopmental disorders associated with mental retardation and developmental disabilities such as Rett syndrome, autism and Down syndrome. Taken into consideration this fact together with the function of biogenic amines for synapses, the density of synapses appears to decrease considerably in the brains of patients suffered from the neurodevelopmental disorders. The synaptic overproduction during the critical period of development especially 1 year after birth has been considered as a background mechanism to provide plasticity for the developing brain. Synaptic overproduction does not appear to occur in the brains of patients suffered from the neurodevelopmental disorders, which they are observed mental retardation occurring in the first 1 year after birth. Along with the neurodevelopmental disorders, environmental factors (stress, drugs and nutrition) during pre- and post-natal critical developmental periods are known to change levels of biogenic amines in the brain. In fact, maternal stress has been shown to decrease the levels of serotonin and the density of synapses in the hippocampus of the offspring, and they showed developmental disabilities in the spatial learning and memory. A cascade appears to exist from either the child neurological disorders or the environmental factors to mental retardation and developmental disabilities by decreases in the levels of biogenic amines and synaptic density.

Animals↗
PubMed2001

Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells.

E7070 is a novel sulfonamide antitumor agent that exhibits potent antitumor activity in vitro and in vivo. This compound affects cell cycle progression in human tumor cells. To elucidate the mechanisms by which E7070 inhibits tumor cell growth, we established and characterized an E7070-resistant subline, A549/ER, from a human non-small cell lung cancer cell line A549. Flow cytometric analyses demonstrated an increase in G0/G1 and a decrease in S phase populations in cells treated with E7070 at 20 or 100 microg/ml for 24 h. Longer exposure to E7070, i.e. 48 and 72 h, increased the G2/M phase fraction in A549 cells. These inhibitory actions of E7070 on cell cycle progression were not observed in A549/ER cells. E7070 inhibited the phosphorylation of pRb, decreased expressions of cyclin A, B1, CDK2, and CDC2 proteins, and suppressed CDK2 catalytic activity with the induction of p53 and p21 proteins in A549 cells but not in A549/ER cells. Taken together, these results suggest that E7070 exerts its antitumor effects by disturbing the cell cycle at multiple points, including both the G1/S and the G2/M transition, in human lung cancer cells.

Antineoplastic Agents↗
PubMed2001

The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery.

BACKGROUND: Although candidates for lung reduction surgery (LRS) include malnourished patients with severe chronic obstructive pulmonary disease (COPD), the impact of preoperative nutritional status on surgical outcome has not been clearly elucidated. METHODS: We investigated the relationship between preoperative nutritional status and postoperative morbidity in 23 consecutive patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were measured using a bioelectrical impedance analyzer. FFM and FM were expressed as height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin were also determined. RESULTS: 8 patients had major complications. Preoperative %IBW and FFMI were significantly lower among patients with major complications, while no significant differences were observed in pulmonary function, FMI or serum protein. The complication rate was significantly higher among patients with low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results suggest that FFM depletion is an excellent predictor of unacceptable postoperative complication following LRS.

Aged↗
PubMed2001

[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

Adolescent↗
PubMed2001

[Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method].

We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non-contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens.

Adolescent↗
PubMed2001

Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer.

We have previously reported that long-term treatment with clarithromycin (CAM) increased the median survival of patients with non-small cell lung cancer, and improved various clinical parameters in these patients. In the present study, CAM was administered to 33 patients with unresectable primary non-small cell lung cancer, who had received chemotherapy, radiotherapy or both (basic cancer therapy). Patients with clinical backgrounds matched to the CAM group, who did not receive CAM treatment, were included into this study as a control group (non-CAM group). CAM treatment was initiated 4 weeks after the basic cancer therapy. The non-CAM group did not receive a placebo. Before and after the 3-month treatment with CAM, body weight, serum levels of interleukin-6 (IL-6, a cytokine which, together with TNF-alpha, plays a crucial role in the development of cancer cachexia), total protein, albumin, cholinesterase and hemoglobin were measured for the evaluation of the patients' clinical status. There were no statistically significant differences in serum levels of IL-6 between the CAM group before the treatment and the non-CAM group. After 3 months of CAM treatment, serum levels of IL-6 significantly decreased. In contrast, body weight, cholinesterase, and hemoglobin increased to a significant extent. Among these four parameters, however, the decrease in serum IL-6 levels was only statistically correlated with the increase in body weight, but not with that in other parameters. Furthermore, CAM-treated patients whose serum IL-6 levels were decreased after 3 months of treatment survived longer: there was a statistically significant correlation between the decrease in serum IL-6 and survival time. In contrast, in the non-CAM group, these parameters did not change significantly during the study. These results suggest that CAM may reduce the progression of cancer-associated cachexia.

Aged↗
PubMed2001

Distribution of muscle mass and maximal exercise performance in patients with COPD.

STUDY OBJECTIVE: To investigate the distribution of reduction in lean body mass (LBM) and whether LBM in legs (LBMlegs) can be a determinant of maximal exercise performance in COPD patients. METHODS: Thirty-eight male outpatients with COPD (mean +/- SD FEV1, 47.4 +/- 24.0% of predicted) who underwent complete pulmonary function testing were classified into two groups according to FEV1 expressed as a percentage of predicted value. Group A comprised 21 patients with mild-to-moderate airflow limitation (FEV(1) > or =35% predicted), and group B comprised 17 patients with severe airflow limitation (FEV1 < 35% predicted). LBM, which represents skeletal muscle mass, was measured by dual energy x-ray absorptiometry (DXA) and was assessed separately in arms, legs, and trunk. Maximal oxygen uptake VO2max was measured during maximal exercise on a cycle ergometer. RESULTS: LBM in each region was expressed as a percentage of ideal body weight (IBW). LBM in arms (LBMarms)/IBW, LBMlegs/IBW, and LBM in trunk (LBMtrunk)/IBW were significantly depleted in group B compared with group A (p < 0.01). LBMlegs expressed as a percentage of total LBM (LBMlegs/total LBM) was significantly lower in group B (p < 0.05), although there was no significant difference in LBMarms/total LBM and LBMtrunk/total LBM between the two groups. VO2max correlated significantly with LBMlegs/IBW in group A, but not in group B. By stepwise regression analysis, LBMlegs/IBW appeared to be a significant predictor of VO2max in group A, while not in group B. CONCLUSION: LBMlegs was a significant predictor of maximal exercise performance in patients with mild-to-moderate airflow limitation, but not in patients with severe airflow limitation who had disproportional reduction in LBMlegs.

Absorptiometry, Photon↗
PubMed2001

Serotonin transporter gene variation is a risk factor for sudden infant death syndrome in the Japanese population.

OBJECTIVE: Serotonin (5-HT) in the nervous system is a major factor in facilitation of the brain center for respiration. Variations in the promoter region of the 5-HT transporter (5-HTT) gene have been shown to potentially regulate 5-HT activity in the brain. Therefore, we aimed to identify the possibility that specific allele variants of the 5-HTT gene can be found as a genetic background for sudden infant death syndrome (SIDS). METHODS: Polymorphisms in the 5' regulatory region of the 5-HTT gene were determined in genomic DNA obtained from 27 SIDS victims and 115 age-matched health control participants. RESULTS: There were significant differences in genotype distribution and allele frequency of the 5-HTT promoter gene between SIDS victims and age-matched control participants. The L and XL alleles were more frequently found in SIDS victims than in age-matched control participants. CONCLUSION: Efficiency in the transportation of 5-HTT with the L allele is known to be higher than that with the S allele. The excitatory function by 5-HT is considered to be lower in the respiratory center of individuals with the L allele compared with those with S allele. The XL allele variant has shown another novel biological risk factor for SIDS.

Carrier Proteins↗
PubMed2001

[Effective use of camostat mesilate for chronic disseminated intravascular coagulation complicated by thoracoabdominal aortic aneurysm].

A 73-year-old man who had been receiving treatment for hypertension and angina pectoris was admitted to hospital following a transient ischemic attack. He was diagnosed as having chronic disseminated intravascular coagulation (DIC) complicated by a thoracoabdominal aortic aneurysm, and was treated with heparin sodium and a protease inhibitor. Although the DIC was controlled, the patient had to remain hospitalized in order to receive the medication by continuous infusion. Therefore, the heparin sodium and protease inhibitor were replaced by camostat mesilate, a drug suitable for oral administration and widely used for treatment of chronic pancreatitis. The drug proved effective for the chronic DIC, thus allowing the patient to receive regular treatment on an outpatient basis, and improving his quality of life.

Administration, Oral↗
PubMed2001

[Usefulness of three-dimensional color Doppler sonography for the differential diagnosis of subpleural lesions].

The purpose of our investigation was to assess the usefulness of three-dimensional color Doppler sonography (velocity mode and power mode) for the differential diagnosis of subpleural lesions. Thirty lesions (11 pneumonias, 5 lung abscesses, 11 primary lung cancers, 3 metastatic lung cancers) were examined. Three-dimensional images were reconstructed by a maximum intensity projection method. Three-dimensional representations of intralesional blood flow became available for all lesions approximately 11 seconds after scanning. In every case, the entire vasculature of the tumor, the pneumonia, the abscess, or the inflamed region of the lung was appreciated more easily from three-dimensional images than from two-dimensional images. We classified the color flow pattern of subpleural lesions depicted by color flow imaging into seven groups. Color flow was depicted better by the three-dimensional color Doppler power mode than the velocity mode. Three-dimensional color flow patterns observed in power mode, patterns of the pneumonias and the lung cancers differed significantly. Our results suggest that the three-dimensional color Doppler power mode is useful for the differential diagnosis of subpleural lesions.

Adult↗