Biomedical subjects

Y Kobayashi

Publications and source records attributed to Y Kobayashi.

At least 199 records · Page 11Linked to original sources

PubMed2001

Facilitation of saccade initiation by brainstem cholinergic system.

It is well known that the intermediate layer (SGI) of the mammalian superior colliculus (SC) receives cholinergic inputs originating from the pedunculopontine tegmental nucleus (PPTN). The action of the cholinergic input on the SGI neurons was investigated using whole-cell patch-clamp recording technique in slice preparations obtained from rats. Application of acetylcholine (ACh) induced fast inward currents mediated by nicotinic ACh receptors in the SGI neurons. Depolarization induced by nicotine enhanced the N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potential component and lowered the threshold of bursting response in the SGI neurons to stimulation of the superficial layer. Thus, the cholinergic input to the SGI facilitates the signal transmission through the direct visuomotor pathway in the SC. The behavioral correlate of this observation was explored by microinjection of nicotine into the SC of awake monkeys during visually guided saccade task; injection of nicotine increased frequency of express saccades, the saccades with extremely short reaction times (<120 ms). Analysis of single unit activity of the PPTN neurons revealed that a population of the PPTN neurons increased firing preceding saccades in a particular direction and also during the GAP period between the offset of fixation point and onset of the saccade target. Thus, PPTN neurons may be involved in execution and preparation of saccades. All these results explain the mechanisms of how the brainstem cholinergic system facilitates initiation of saccades presumably depending on attention or vigilance level of the animal.

Acetylcholine↗

PubMed2001

Long-term vessel response to a self-expanding coronary stent: a serial volumetric intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent Ultrasound Remodeling Evaluation.

OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND: Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS: Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS: At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Adult↗

PubMed2001

Serum eosinophil derived neurotoxin may reflect more strongly disease severity in childhood atopic dermatitis than eosinophil cationic protein.

Serum levels of eosinophil cationic protein (ECP) have been shown to be a good parameter of the disease severity of patients with atopic dermatitis (AD). However, the relationship between the disease severity and the eosinophil derived neurotoxin (EDN) has not been established in AD patients. The purpose of this study is to examine serum ECP and EDN levels in relation to the disease severity in AD children. Serum ECP and EDN levels were assessed in relation to the skin scores in 34 AD children (18 boys and 16 girls; age 0.6 to 7years: mean+/-S.D. 2.2+/-1.9) and six non-atopic control children (three boys and three girls; age 1 to 3years: mean+/-S.D. 1.7+/-0.9). Serum ECP and EDN levels of the patients with AD were significantly increased compared with the non-atopic controls. Serum EDN levels of the patients were also related to the disease severity. The skin scores were more significantly correlated with serum EDN levels than ECP levels. We concluded that serum EDN may reflect more strongly disease severity as eosinophilic activation in AD children than serum ECP.

Biomarkers↗

PubMed2001

Ruptured epidermoid cyst and haematoma of spleen: a diagnostic clue of high levels of serum carcinoembryonic antigen, carbohydrate antigen 19-9 and Sialyl Lewis x.

Splenic epidermoid cyst is a rare disease and that with haematoma is even more rare. The case of epidermoid cyst of the spleen is described, in a 36-year-old Japanese female, manifesting as left hypochondralgia and rupture of the cyst. Clinical features were splenic lesion 14 cm in diameter and consisting of round-hypovascular and crescent-hypervascular sublesions. Extravasation of cystic fluid was detected in abdominal cavity Preoperative diagnosis was difficult due to such uncommon features, however high levels of serum tumour markers (carcinoembryonic antigen, carbohydrate antigen 19-9, Sialyl Lewis x) strongly suggested epidermoid cyst. Laparotomic splenectomy and cholecystectomy were performed for splenic lesion and gallstones, and serum tumour markers decreased following surgery. Pathological diagnosis of the round-hypovascular lesion was epidermoid cyst and crescent-hypervascular lesion was haemorrhage (haematoma).

Adult↗

PubMed2001

Case report: pulmonary embolism from thrombosis in a duplicated inferior vena cava developing after an electrophysiologic procedure.

Duplicated inferior cava (IVC) is an anomaly we rarely encounter during electrophysiologic procedures. We report a case with duplicated IVC who developed thrombosis of the left IVC following an electrophysiologic procedure, which resulted in an asymptomatic pulmonary embolism. It is speculated that several catheters placed in the torturous route through the left IVC caused either endothelial damage to the vessel wall, or hemostasis in the relatively narrow portion of the vessel, resulting in thrombus formation. Since the prevalence and characteristics of thrombo-embolic complications during electrophysiologic procedures in patients with a duplicated IVC remain unknown, we believe this case should be reported.

Electrophysiologic Techniques, Cardiac↗

PubMed2001

Infiltration of neutrophils following injection of apoptotic cells into the peritoneal cavity.

It has been assumed that apoptosis leads to no production of pro-inflammatory cytokines or the production of anti-inflammatory cytokines in vivo, although the response of macrophages following phagocytosis of apoptotic cells in vivo has not been examined. In this study we therefore examined the response to apoptotic cells in vivo. Injection of apoptotic cells into the peritoneal cavity of mice led to transient neutrophil infiltration and concomitant production of MIP-2, a mouse homologue of IL-8. Apoptotic cells were phagocytosed by macrophages, as revealed on two-color flow cytometric analysis and microscopic observation. When the mice were depleted of macrophages by pretreatment with liposome-encapsulated dichloromethylene bisphosphonate, both neutrophil infiltration and MIP-2 production were significantly suppressed, suggesting that macrophages are required for MIP-2 production in this in vivo response. These results support the hypothesis that extensive apoptosis occurring rapidly may induce an inflammatory response in vivo.

Animals↗

PubMed2001

Secondary structure prediction and folding of globular protein: refolding of ferredoxin.

The physicochemical mechanism of protein folding has been elucidated by the island model, describing a growth type of folding. The folding pathway is closely related with nucleation on the polypeptide chain and thus the formation of small local structures or secondary structures at the earliest stage of folding is essential to all following steps. The island model is applicable to any protein, but a high precision of secondary structure prediction is indispensable to folding simulation. The secondary structures formed at the earliest stage of folding are supposed to be of standard form, but they are usually deformed during the folding process, especially at the last stage, although the degree of deformation is different for each protein. Ferredoxin is an example of a protein having this property. According to X-ray investigation (1FDX), ferredoxin is not supposed to have secondary structures. However, if we assumed that in ferredoxin all the residues are in a coil state, we could not attain the correct structure similar to the native one. Further, we found that some parts of the chain are not flexible, suggesting the presence of secondary structures, in agreement with the recent PDB data (1DUR). Assuming standard secondary structures (alpha-helices and beta-strands) at the nonflexible parts at the early stage of folding, and deforming these at the final stage, a structure similar to the native one was obtained. Another peculiarity of ferredoxin is the absence of disulfide bonds, in spite of its having eight cysteines. The reason cysteines do not form disulfide bonds became clear by applying the lampshade criterion, but more importantly, the two groups of cysteines are ready to make iron complexes, respectively, at a rather later stage of folding. The reason for poor prediction accuracy of secondary structure with conventional methods is discussed.

Animals↗

PubMed2001

In vivo gene electroporation of glial cell line-derived neurotrophic factor (GDNF) into skeletal muscle of SOD1 mutant mice.

Motor neurons degenerate with intracellular vacuolar change and eventually disappear in spinal cords of SOD1 mutant mice, resembling human amyotrophic lateral sclerosis (ALS). The GDNF gene was electroporatically transferred into the leg muscles of SOD1 mutant mice and expressed in muscle cells. This gene therapy with GDNF delayed the deterioration of motor performance, being retrogradely transported into spinal motor neurons. However, the number of the motor neurons and survival of the mutant mice were not improved by GDNF treatment. These results indicate that in vivo gene electroporation of GDNF into muscles could be an appropriate therapeutic approach to ameliorate an early dysfunction of motor neurons in SOD1 mutant mice, but further improvement is needed to use this gene transfer as an effective treatment of ALS.

Animals↗

PubMed2001

Increased serum nitrate levels in infants with atopic dermatitis.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) is still unknown. A recent study has shown that inducible nitric oxide synthase (iNOS) is expressed in the atopic skin lesion, suggesting the involvement of nitric oxide in the skin inflammation of AD. The purpose of the study was to examine serum nitrate (NO3) levels in relation to the disease severity in children with AD. METHODS: Serum nitrate levels were assessed in relation to the skin scores in 88 patients with atopic dermatitis (AD) (aged 0.4-8 years: mean+/-SD, 2.2+/-1.9, 41 boys and 47 girls) and 12 nonatopic children (aged 0.8-4 years: mean+/-SD, 1.8+/-0.9, seven boys and five girls). RESULTS: Serum nitrate levels of patients with AD were significantly increased as compared to nonatopic controls and were also correlated with the disease severity. The skin scores were significantly correlated with serum nitrate levels as well as peripheral eosinophil counts. CONCLUSION: Our results indicate that nitric oxide may be involved in the pathogenesis of vasodilation and erythema in AD skin.

Administration, Topical↗

PubMed2001

Lack of association between the Met196Arg polymorphism in the TNFR2 gene and autoimmune diseases accompanied by vasculitis including SLE in Japanese.

A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus erythematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese.

Amino Acid Substitution↗

PubMed2001

Telepsychiatry: assessment of televideo psychiatric interview reliability with present- and next-generation internet infrastructures.

OBJECTIVE: We assessed the reliability of remote video psychiatric interviews conducted via the internet using narrow and broad bandwidths. METHOD: Televideo psychiatric interviews conducted with 42 in-patients with chronic schizophrenia using two bandwidths (narrow, 128 kilobits/s; broad, 2 megabits/s) were assessed in terms of agreement with face-to-face interviews in a test-retest fashion. As a control, agreement was assessed between face-to-face interviews. Psychiatric symptoms were rated using the Oxford version of the Brief Psychiatric Rating Scale (BPRS), and agreement between interviews was estimated as the intraclass correlation coefficient (ICC). RESULTS: The ICC was significantly lower in the narrow bandwidth than in the broad bandwidth and the control for both positive symptoms score and total score. CONCLUSION: While reliability of televideo psychiatric interviews is insufficient using the present narrow-band internet infrastructure, the next generation of infrastructure (broad-band) may permit reliable diagnostic interviews.

Analysis of Variance↗

PubMed2001

Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan.

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

Adolescent↗

PubMed2001

Long-term low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.

To evaluate the efficacy of long-term administration of acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started long-term low-dose (400 mg/day) oral administration of acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of long-term prophylaxis with low-dose acyclovir. Resumption of acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose acyclovir should be confirmed prospectively.

Acyclovir↗

PubMed2001

Relationship between total and regional bone mineral density and menopausal state, body composition and life style factors in overweight Japanese women.

OBJECTIVE: To investigate whether menopausal state, body composition and lifestyle factors influence total and regional bone mineral density in overweight Japanese women. DESIGN: Cross-sectional study of women who were recruited to the weight reduction program held at community-based health promotion center in Tokyo area. SUBJECTS: A total of 178 women with a mean age of 48 y old (20-69 y) with a clear menstrual history and BMI over 24. MEASUREMENTS: Total, regional and lumbar spine bone mineral density (BMD) and body composition were measured using DXA (Lunar). Menstrual history was taken by a questionnaire and walking steps per day and energy intake were measured. Physical fitness was assessed by cardio-respiratory fitness and leg extension power. Subjects were divided into pre-menopausal and post-menopausal groups. RESULTS: Pre-menopausal group had significantly higher total body BMD as well as regional BMD than post-menopausal group. However, no differences in BMI, percentage fat and fat mass (FM) were seen between the two groups. The multiple regression analysis stepwise method revealed that total and regional BMD correlated with menopausal state and total FM independently. Total and regional BMD did not correlate with total non-fat soft tissue mass (NFSM), energy intake, walking steps or physical fitness levels. Trunk and lower extremities BMD correlated with corresponding regional FM and NFSM, and upper extremities BMD correlated with only corresponding body part NFSM after adjusting menopausal state. CONCLUSION: Total and regional BMD had strong negative correlation with menopausal state rather than total FM in overweight Japanese women. Weight-bearing site BMD correlated with corresponding body part FM and NFSM and non-weight bearing site BMD only correlated with corresponding body part NFSM after adjusting for menopausal state.

Absorptiometry, Photon↗

PubMed2001

Effects of ten year body weight variability on cardiovascular risk factors in Japanese middle-aged men and women.

OBJECTIVE: The purpose of the present study was to determine the effects of weight variability on cardiovascular risk factors (CRF) based on a large sample of community-resident Japanese males and females. METHOD: A total of 3564 men and 1955 women, all Japanese, aged 30-69 y in the baseline year (1987), were followed-up for up to 10 y (end-point in 1996). Height, body weight, systolic and diastolic blood pressure, fasting serum total cholesterol, triglyceride and fasting plasma glucose were measured as an annual health check-up. At least six times in 10 y, body mass index (BMI) mean was calculated as an index of the BMI level of each subject (BMI mean). Direction and magnitude of the change in a subject's BMI was determined by a regression slope of BMI values over time (BMI slope). BMI fluctuation was defined as the root mean square error (BMI RMSE) of a regression line. The slopes of the five CRF were calculated using each regression equation over time. RESULTS: The BMI slope strongly correlated to each CRF slope independent of baseline age, baseline CRF value, smoking habit, BMI mean and BMI RMSE. BMI RMSE did not correlate to any CRF slopes. CONCLUSION: This study indicates that weight gain and weight loss have a much greater effect on CRF change than does weight fluctuation in Japanese middle-aged men and women.

Adult↗

PubMed2001

Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases.

BACKGROUND: T helper-type 2 cytokines, such as interleukin-4 (IL-4) and IL-13, may play a central role in allergic diseases. The protein known as 'signal transducers and activators of transcription 6' (STAT-6) is a key transcription factor involved in both IL-4- and IL-13-mediated biological responses. OBJECTIVE: The objective of this study was to evaluate the possible role of the STAT-6 gene in modulating atopy in the Japanese population. METHODS: We screened all 23 exons of the STAT-6 gene from 10 subjects for mutations by direct polymerase chain reaction (PCR) sequencing. The STAT-6 gene polymorphisms were genotyped by PCR fragment length polymorphism analysis and PCR-SSCP analysis. The IL-4 receptor Q576R polymorphism was also examined by PCR-SSCP analysis. RESULTS: We found a novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene. The genotypes were classified into four groups according to the number of GT repeats present, from 13 to 16. The frequency of the A1 allele (326 bp, containing 13 repeats of GT) was higher in children with allergic diseases (bronchial asthma, atopic dermatitis and/or food-related anaphylaxis) than controls, although this was not statistically significant (P = 0.0158). In addition, a strong association between the A1 and A3 allele (containing 15 repeats of GT) heterozygote and allergic diseases was identified (P = 0.0002). However, the levels of IgE were not related to the GT repeat polymorphism in the allergic subjects. The GT repeat polymorphism was not associated with the polymorphism in the IL-4 receptor a chain gene (Q576R) and there was no association between the G2964A variant and allergic diseases. CONCLUSION: This suggests that genetic variation in the STAT-6 gene may be associated with predisposition to allergic diseases.

Alleles↗

PubMed2001

Cytotoxic T lymphocyte antigen 4 gene polymorphism confers susceptibility to type 1 diabetes in Japanese children: analysis of association with HLA genotypes and autoantibodies.

OBJECTIVE: Although the polymorphisms of the cytotoxic T lymphocyte antigen 4 (CTLA4) gene have been shown to be associated with Type 1 diabetes in Caucasians, some conflicting results have been reported among subjects of different ethnic backgrounds. We examined a CTLA4 polymorphism and its relationship to human leucocyte antigen (HLA) genotypes and autoantibodies for glutamic acid decarboxylase 65 (GAD65) and IA-2 in Japanese children with Type 1 diabetes. SUBJECTS AND MEASUREMENTS: The study group consisted of 125 childhood-onset Japanese subjects (50 males, 75 females) with Type 1 diabetes. The CTLA4 A/G polymorphism at position 49 was analysed using a PCR-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DRB1 and DQB1 genotypes were defined by DNA analysis using PCR-sequence-specific oligonucleotide (PCR-SSO) probes. The GAD65 autoantibody (GAD65Ab) and IA-2 autoantibody (IA-2Ab) titres were measured using radioimmunoassay. RESULTS: The distribution of genotype frequencies differs between subjects with Type 1 diabetes (GG: 46%, AG: 50%, AA: 5%) and controls (GG: 39%, AG: 44%, AA: 17%) (P < 0.01). The frequency of the G allele is higher in the diabetes group than in the controls (P < 0.05). When the subjects were subdivided according to HLA genotype, the two major HLA high-risk groups, with DR9-DQ9 and DR4-DQ4, that are unique to Japanese populations showed no difference in their CTLA4 polymorphism frequencies. Although no association between the CTLA4 polymorphism and the prevalence of GAD65Ab was found, CTLA4 GG subjects that had been newly diagnosed (< 9 months) had significantly higher levels of autoantibodies than AG subjects (P < 0.01). The prevalence and titres of IA-2Ab were not associated with the CTLA4 polymorphism. CONCLUSIONS: The CTLA4 gene might confer a susceptibility to childhood-onset Type 1 diabetes in the Japanese population. The association between this CTLA4 polymorphism and the HLA genotype was similar for both major groups with HLA high-risk alleles. CTLA4 might contribute to the humoral immune response to GAD in newly diagnosed subjects.

Abatacept↗

PubMed2001

Functional divergence of the TFL1-like gene family in Arabidopsis revealed by characterization of a novel homologue.

BACKGROUND: The TERMINAL FLOWER 1 (TFL1) gene of Arabidopsis plays an important role in regulating flowering time and in maintaining the fate of inflorescence meristem (IM). TFL1 is a homologue of CENTRORADIALIS (CEN) from Antirrhinum, which is only involved in IM maintenance. Recent mutational studies and the genome project revealed that TFL1 belongs to a small gene family in Arabidopsis, in which functional divergence may have occurred among the members. RESULTS: We found a new member of the TFL1 gene family, which is mapped on chromosome 2 of Arabidopsis. The predicted protein sequence encoded by this gene is more closely related to that of CEN than other Arabidopsis TFL1 homologues (and therefore named ATC for Arabidopsis thaliana CENTRORADIALIS homologue). Transgenic plants constitutively expressing the ATC gene (35S:ATC), in either wild-type or tfl1 mutant backgrounds, showed a phenotype similar to that observed in transgenic plants constitutively expressing the TFL1 gene. However, in contrast to TFL1, the expression of ATC was only detected in the hypocotyl of young plants, and not in the IM. In addition, an atc loss-of-function mutant, isolated by screening a T-DNA library, showed no phenotypes that were similar to those of tfl1 mutants. CONCLUSION: The phenotypes of transgenic plants over-expressing ATC suggest that the ATC protein can functionally substitute for TFL1. However, the pattern and level of expression and the loss-of-function phenotype indicate that ATC does not participate in the regulation of IM identity, but rather has a role that is different from that of TFL1.

Amino Acid Sequence↗