Association of a missense Glu298Asp mutation of the endothelial nitric oxide synthase gene with end stage renal disease.
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Age Factors↗
Biomedical subjects
S Kikuchi
Publications and source records attributed to S Kikuchi.
[Diagnostic criteria for Parkinson's disease].
Diagnostic criteria for Parkinson's disease is used in all clinical studies concerning this disease. For supplying meaningful data to the evidence-based medicine, the diagnostic criteria must be clearly defined in such studies. In the setting and usage of diagnostic criteria, it is indispensable to clarify the aim and the population for which the criteria is used. Then, as for the contents of the criteria, 1) additional criteria, 2) exclusion criteria, and 3) levels of confidence must be considered. For the future re-evaluation, diagnostic criteria must be logic. Final references are also necessary for judging the accuracy of the criteria.
Confidence Intervals↗
Clinicopathologic prognostic factors in patients with Borrmann type 4 gastric cancer: univariate and multivariate analyses.
BACKGROUND: Advanced gastric cancer is classified into four Borrmann types, types 1 to 4. Type 4 is a relatively undifferentiated carcinoma with little or no gland-forming capability. Despite recent advances in the diagnosis and surgical management of gastric cancer, most tumors of Borrmann type 4 are not detected at an early stage and the prognosis remains poor; the five-year survival rate after gastric resection ranges from 10 to 20 percent. We evaluated the affects of several clinicopathologic variables on the 5-year survival rate after resection of Borrmann type 4 gastric cancer. METHODS: Data on clinical characteristics were obtained from the records of patients who underwent gastric resection between 1985 and 1995 at the Department of Surgery, Sendai National Hospital, and follow-up data were obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. The relationship between clinicopathologic variables and 5-year survival rate was estimated by the Kaplan-Meier survival curve and the logrank test. Multivariate Cox's proportional hazards regression analysis was then performed to determine which variables were independent prognostic factors. RESULTS: Eighty-seven patients with Borrmann type 4 gastric cancer underwent a resection during the study period at our hospital. The overall 5-year survival rate was 14.8%. The relationship between clinicopathologic variables and 5-year survival rate was determined by constructing a Kaplan-Meier survival curve. Tumor location (upper, middle and distal vs whole stomach, p=0.0214), lymph node metastasis, capillary microinvasion, and peritonitis carcinomatosa (absent vs present, p<0.05) significantly influenced survival. When multivariate analysis using Cox's proportional hazards regression of 5-year survival was performed, capillary microinvasion, peritonitis carcinomatosa (absent vs present) and tumor location (distal vs whole stomach) emerged as the statistically significant independent prognostic factors associated with long-term survival. CONCLUSION: Capillary microinvasion and the presence or absence of peritonitis carcinomatosa are more powerful predictors of 5-year survival than is lymph node metastasis. Patients with gastric cancer of the whole stomach have a poorer prognosis than do those with carcinoma in the antrum of the stomach.
Adult↗
CTLA-4 gene polymorphism may modulate disease in Japanese multiple sclerosis patients.
Multiple sclerosis (MS) is widely believed to have a T-cell-mediated autoimmune etiology. The CTLA-4 gene is a strong candidate for involvement in autoimmune diseases because it plays an important role in the termination of T-cell activation. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed the CTLA-4 gene exon 1 A/G polymorphism in 74 Japanese MS patients and 93 controls. We also investigated the possible interactions of the CTLA-4 gene polymorphism with clinical course and severity, with MRI findings, with another genetic marker-HLA antigens, and with oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). The CTLA-4 exon 1 polymorphism was similar between MS patients and controls. Conversely, clinical disability was significantly more severe in AA homozygous patients than in the other patients, and the allele frequency and the phenotype frequency of the A allele were significantly higher in patients with severe-grade MRI findings of cerebral white matter than in patients with mild-grade MRI findings. The allele frequency and the phenotype frequency of the A allele were significantly higher in patients with OCB than in patients without. This CTLA-4 polymorphism may modulate the prognosis of patients with MS and may be relevant to generation of OCB in the CSF.
Abatacept↗
In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems.
STUDY DESIGN: In vivo intradiscal pressure measurement in different postures in healthy individuals and in those with ongoing back problems. OBJECTIVES: With the most recent technique, 1) to analyze the influence of degeneration on the intradiscal pressure, 2) to calculate the spinal load on the L4-L5 intervertebral discs, and 3) to assess the relation between the spinal load and movement of the intervertebral motion segment. SUMMARY OF BACKGROUND DATA: Almost all the data on intradiscal pressure are from the studies by Nachemson. The results from these pioneering studies have formed the basis for current knowledge about the in vivo loading conditions of the human spine. Although performed already during the 1960s and 1970s with the technique available at that time, virtually no other similar studies have been performed to corroborate the findings. METHODS: The intradiscal pressure (vertical and horizontal) was measured using an advanced pressure sensor in 8 healthy volunteers and 28 patients with ongoing low back pain, sciatica, or both at L4-L5. Among other calculations, the actual loading conditions in various body positions were calculated in relation to the angle between the two vertebrae of the studied motion segments. RESULTS: The effect of respiration on intradiscal pressure was shown as a continuously periodic fluctuation in the healthy prone individual. The intradiscal pressure was significantly reduced according to the degree of disc degeneration as estimated by magnetic resonance imaging. There possibly was a difference between the vertical and horizontal pressures in the degenerated and nondegenerated discs because the nucleus pulposus was pressure-tropic property. The spinal load increased in the following order of body positions: prone, 144 N; lateral, 240 N; upright standing, 800 N; and upright sitting, 996N (P < 0.0001). In the standing and sitting body positions, the spinal load increased not only with forward bending, but also with backward bending. The spinal load was highly dependent on the angulation in the motion segment. The movements of the spine from a flexed to an extended position made the load of the spine change in a curvilinear fashion, fitting a squared equation in the standing body position. There was a correlation between the spinal load and the angle of the motion segment in the standing but not in the sitting body position. CONCLUSIONS: The spinal load was highly dependent on the angle of the motion segment in normal discs in vivo. The intradiscal pressure in degenerated discs was significantly reduced compared with that of normal discs. However, further studies on the effect of respiratory movement on intradiscal pressure, the difference between vertical and the horizontal pressures, and the difference in the spinal load between standing and the sitting body positions are necessary. The data obtained from the current study are fundamental to understanding the pathomechanisms and biomechanical problems of disc disease.
Adult↗
Presence and distribution of antigen-antibody complexes in the herniated nucleus pulposus.
STUDY DESIGN: Herniated tissue was studied by immunohistochemistry in eight patients with lumbar disc herniation. The results were compared with those of control subjects. OBJECTIVE: To assess the presence and distribution of possible antigen-antibody complexes in herniated disc tissue. SUMMARY OF BACKGROUND DATA: It has been suggested that the nucleus pulposus may be recognized as a foreign-body by the immune system and that this will lead to secondary nerve root disturbance. Such immunologic events should be initiated by binding of antibodies to a specific antigen in the disc tissue. However, the presence of antigen-antibody complexes in the herniated disc tissue has not been assessed. METHODS: Amplification of the peroxidase reaction produced in avidin-biotin-peroxidase complex immunostaining by diaminobenzidine was used to visualize antigen-antibody complexes in the herniated tissue. The authors used herniated tissue from eight patients with lumbar disc herniation and nucleus pulposus from five control subjects with nonlumbar disc herniation. Thin paraffin sections, prefixed in 4% paraformaldehyde, were incubated with anti-human IgG antibody to allow visualization of antigen-antibody complexes in the specimens. RESULTS: A brown deposit, indicating antigen-antibody complexes, could be observed in the pericellular capsule in herniated disc tissue but not in control discs or in the residual discs of the herniation patients. CONCLUSION: Antigen-antibody complexes seem to be commonly present in herniated disc tissue, but not in healthy discs. However, the pathophysiologic and clinical significance of this observation has to be elucidated further.
Adult↗
Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases.
In this study, we investigate the neurotoxicity of glycation, particularly early-stage glycation, and its mechanisms, which are possibly synergized with oxidative stress. Methylglyoxal (MG) and 3-deoxyglucosone (3DG), intermediate products of glycation, are known to further accelerate glycation and advanced glycation endproducts (AGEs) formation. Both compounds showed neurotoxicity on cultured cortical neurons and these effects were associated with reactive oxygen species production followed by neuronal apoptosis. Pretreatment with N-acetylcysteine induced neuroprotection against MG and 3DG. Cotreatment, but not pretreatment, with aminoguanidine protected neurons against the neurotoxicities of both compounds. The present study provides the first evidence that MG and 3DG are neurotoxic to cortical neurons in culture. Interference with the process by which glycation and AGEs formation occur may provide new therapeutic opportunities to reduce the pathophysiological changes associated with neurodegeneration, if, as indicated here, the participation of glycoxidation in the pathogenesis of neurodegenerative diseases is essential.
Acetylcysteine↗
Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active form of vitamin D, exerts an immunosuppressive effect and can completely prevent experimental autoimmune encephalomyelitis (EAE). 1,25(OH)2D3 exerts most of its actions only after it has bound to its specific nuclear receptors. To investigate the possible role of vitamin D receptor gene (VDRG) polymorphism in susceptibility to or disease-modulation of MS, we evaluated 77 Japanese patients with 'conventional' MS and 95 controls. A VDRG allelic polymorphism was assessed by Bsm1 endonuclease restriction after specific PCR amplification. Genotypic polymorphism was clearly defined as BB (absence of restriction site on both alleles), bb (presence of restriction site on both alleles), or Bb (heterozygous). We found overexpression of the b allele (92.9 vs. 84.2%: P=0.0138) and homozygote bb (85.7 vs. 71.6%; P=0.0263) in MS patients compared with controls. The results indicate for the first time an association of MS with VDRG polymorphism, which may be involved in pathogenesis of MS, or in the linkage disequilibrium of VDRG to another pathogenic gene loci. The role of VDR gene polymorphism should be further studied in other populations, and the distribution of other polymorphism, such as Apa I, Taq I, should be also analyzed to confirm another susceptibility gene for MS and to obtain more adequate strategies for treatment of MS.
Adolescent↗
Involvement of a chloroplast homologue of the signal recognition particle receptor protein, FtsY, in protein targeting to thylakoids.
We isolated an Arabidopsis thaliana cDNA whose translated product shows sequence similarity to the FtsY, a bacterial homologue of SRP receptor protein. The Arabidopsis FtsY homologue contains a typical chloroplast transit peptide. The in vitro-synthesized 37 kDa FtsY homologue was imported into chloroplasts, and the processed 32 kDa polypeptide bound peripherally on the outer surface of thylakoids. Antibodies raised against the FtsY homologue also reacted with a thylakoid-bound 32 kDa protein. The antibodies inhibited the cpSRP-dependent insertion of the light-harvesting chlorophyll alb-binding protein into thylakoid membranes suggesting that the chloroplast FtsY homologue is involved in the cpSRP-dependent protein targeting to the thylakoid membranes.
Amino Acid Sequence↗
Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin.
Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis factor (TNF) release followed by liver injury were investigated. Intraperitoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) challenge of lipopolysaccharide significantly reduced serum TNF levels in a dose-dependent manner and was the most effective when administered 60 min prior to lipopolysaccharide challenge. Treatment with naringin 3 h prior to lipopolysaccharide challenge resulted in complete protection from lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated mice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase, responsible for lipopolysaccharide-induced liver injury, blocked by naringin administration and the levels were nearly to the normal level. These results indicate that action of naringin is mediated through suppression of lipopolysaccharide-induced TNF production.
Alanine Transaminase↗
Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons.
Pretreatments with TNF-alpha and lower concentrations of C2-ceramide protected cultured mesencephalic neurons from excitotoxicity in a dose-dependent manner. These protective effects are reduced by cotreatment with N,N-dimethylsphingosine (DMS), an inhibitor of sphingosine kinase. Since the pretreatment with sphingosine-1-phosphate (SPP) showed a neuroprotective effect, our data suggest that protective effects of TNF and C2-ceramide could be attributable to their further metabolism to SPP.
Animals↗
Altered expression levels of G protein subclass mRNAs in various seizure stages of the kindling model.
The expressions of mRNAs encoding G protein alpha subunits were analyzed in the cerebral cortex of amygdaloid kindled rats. A remarkable increase in Gsalpha mRNA were observed on the bilateral cerebral cortex at 24 h after the last generalized seizure and persisted 3 weeks on the unstimulated side. Gi2alpha mRNA level was also increased on the stimulated side at 24 h and persisted 3 weeks. These result suggest that dysfunction of Gs and Gi2 might relate to the basic mechanisms of seizure generation and the maintenance of epileptogenesis.
Adenosine Diphosphate Ribose↗
The protective effect of good physical fitness when young on the risk of impaired glucose tolerance when old.
BACKGROUND: The role of physical activity or fitness on preventing impaired glucose tolerance (IGT) has not been widely investigated. The present case-control study examined the relationship between the occurrence of IGT in men in their 50s and the level of their physical fitness while in their 30s. METHODS: The subjects consisted of 38 male Japan Self-Defense Forces officials in their 50s who had IGT, as diagnosed by the 75-g oral glucose tolerance test, and 60 control individuals. Nine diabetics were included in the IGT cases. As an indicator of physical fitness between the ages of 30 and 39 years, we selected the best time recorded for each individual during that decade of life for the 1,500-m physical fitness test run. We calculated the odds ratio for IGT in relation to selected risk factors (including physical fitness), and a logistic regression analysis was used to adjust for possible confounding variables. RESULTS: The odds ratio (95% confidence interval, P value) for IGT with physical fitness in their 30s was 0.25 (0.11-0.58, P < 0.05). With adjustment for a parental history of diabetes and body mass index in both their 30s and their 50s, the odds ratio was 0.31 (0.11-0.86, P < 0.05). CONCLUSIONS: We concluded that the occurrence of IGT, including diabetes, in men in their 50s can be reduced by maintaining a high level of physical fitness while in their 30s.
Adult↗
Cross-sectional study on the relationship between smoking or smoking cessation and trait anxiety.
OBJECTIVE: The relationships between trait anxiety, or anxiety proneness, and smoking and between trait anxiety and smoking cessation, among an adult population were investigated. METHODS: The subjects were 2,669 male Japanese personnel working for a Japanese government agency. Participants completed a self-administered questionnaire on smoking and smoking cessation status and other habits. Trait anxiety was evaluated with the trait anxiety part of the standardized Japanese version of the Spielberger State-Trait Anxiety Inventory. Trait anxiety is regarded as the long-term, more endogenous general type of anxiety. Odds ratios of the single 2 x 2 table were calculated and a logistic regression analysis was used to adjust for age. RESULTS: After adjusting for age, high trait anxiety did not increase the risk of smoking and was not related to success in abstaining from smoking. More subjects with high trait anxiety had planned to stop smoking (adjusted odds ratio: 1.39, P = 0.01) but did not actually succeed in doing so. CONCLUSION: The present study did not support the hypothesis that high trait anxiety increased the risk of having a smoking habit and that high trait anxiety increased the chance of abstaining from smoking. However, the study did show that high trait anxiety was related to the planning of smoking cessation, but not to actually giving up the smoking habit.
Adult↗
Successful treatment of tracheomalacia associated with esophageal atresia without a tracheoesophageal fistula by aortopexy: report of a case.
Tracheomalacia (TM) is well known as a complication associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF); however, the occurrence of TM requiring surgical treatment in a patient having EA without a tracheoesophageal fistula has never been reported. We describe herein a rare case of TM associated with EA without TEF. Respiratory distress was caused by compression of the trachea by a severely dilated upper esophageal pouch with weakness of the tracheal wall. Aortopexy was performed, and an excellent postoperative result was achieved.
Aorta↗
Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21waf1.
Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cell proliferation and migration. Recently, tranilast, an anti-allergic drug, has been used for the prevention of restenosis after PTCA. To determine the molecular mechanism involved, the effect of tranilast on the proliferation of human coronary smooth muscle cells (SMCs) was investigated. Tranilast arrested the proliferation of human coronary SMCs at the G0/G1 phase of the cell cycle. In association with this inhibitory effect, tranilast increased p21waf1 and p53 tumor suppressor factor, and decreased cyclin-dependent kinase 2 (CDK2) activity. These results suggest that tranilast inhibits the proliferation of human coronary SMCs during restenosis after PTCA via an induction of p21waf1 and p53. Tranilast may thus allow us to prevent restenosis after PTCA by interfering with this mechanism.
Anti-Allergic Agents↗
Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions.
Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.
Cells, Cultured↗
Epstein-Barr virus-associated lymphoid hyperplasia of the eyelid characterized by intramuscular infiltration.
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Adolescent↗