Biomedical subjects

K Nakashima

Publications and source records attributed to K Nakashima.

At least 19 recordsLinked to original sources

PubMed2006

Unloading-induced bone loss was suppressed in gold-thioglucose treated mice.

Loss of mechanical stress causes bone loss. However, the mechanisms underlying the unloading-induced bone loss are largely unknown. Here, we examined the effects of gold-thioglucose (GTG) treatment, which destroys ventromedial hypothalamus (VMH), on unloading-induced bone loss. Unloading reduced bone volume in control (saline-treated) mice. Treatment with GTG-reduced bone mass and in these GTG-treated mice, unloading-induced reduction in bone mass levels was not observed. Unloading reduced the levels of bone formation rate (BFR) and mineral apposition rate (MAR). GTG treatment also reduced these parameters and under this condition, unloading did not further reduce the levels of BFR and MAR. Unloading increased the levels of osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS). GTG treatment did not alter the basal levels of these bone resorption parameters. In contrast to control, GTG treatment suppressed unloading-induced increase in the levels of Oc.N/BS and Oc.S/BS. Unloading reduced the levels of mRNA expression of the genes encoding osteocalcin, type I collagen and Cbfa1 in bone. In contrast, GTG treatment suppressed such unloading-induced reduction of mRNA expression. Unloading also enhanced the levels of fat mass in bone marrow and mRNA expression of the genes encoding PPARgamma2, C/EBPalpha, and C/EBPbeta in bone. In GTG-treated mice, unloading did not increase fat mass and the levels of fat-related mRNA expression. These results indicated that GTG treatment suppressed unloading-induced alteration in bone loss.

Adipocytes↗

PubMed2006

Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha-ketoisocaproate.

We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study, we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration) in chicks while D-leucine and alpha-KIC were much more effective. We also examined the expression of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles. Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to alpha-KIC.

Animals↗

PubMed2006

Association between ADAM33 polymorphisms and adult asthma in the Japanese population.

BACKGROUND: ADAM33, a member of the ADAM (a disintegrin and metalloprotease) family, is a putative asthma susceptibility gene recently identified by positional cloning. It is important to know whether the association exists in ethnically diverse populations. OBJECTIVE: To assess whether genetic functional variants of ADAM33 relate to the susceptibility or some phenotypes in adult patients with bronchial asthma in a Japanese population. METHODS: We searched for single nucleotide polymorphisms (SNPs) in ADAM33 by PCR-directed sequencing and identified 48 SNPs. Fourteen SNPs were selected with regard to the LD pattern, and genotyped by Taq-Man and PCR-RFLP methods. We conducted an association study of ADAM33 with 504 adult asthmatic patients and 651 controls, and haplotype analyses of related variants were performed. RESULTS: Significant associations with asthma were found for the SNPs T1 (Met764Thr), T2 (Pro774Ser), S2 and V-3 (with the lowest P-value for T1, P = 0.0015; OR 0.63). We analysed the haplotype using these four polymorphisms, and found a positive association with haplotype CCTG (P = 0.0024). CONCLUSION: Our results replicate associations reported recently in other ethnic populations, and suggest that the ADAM33 gene is involved in the development of asthma through genetic polymorphisms.

ADAM Proteins↗

PubMed2005

Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.

To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle action potential were pronounced in nonresponders of IVIg. Male gender, longer disease duration, and slow progression of symptoms were also associated with IVIg unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP.

Adult↗

PubMed2005

Random amplified polymorphic DNA-PCR based cloning of markers to identify the beer-spoilage strains of Lactobacillus brevis, Pediococcus damnosus, Lactobacillus collinoides and Lactobacillus coryniformis.

AIMS: Beer-spoilage ability of lactic acid bacteria such as Lactobacillus brevis is a strain-dependent phenomenon in which the mechanism has not yet been completely clarified. In order to systematically identify genes that contribute to beer-spoilage, large-scale random amplified polymorphic DNA (RAPD)-based cloning methods was carried out. METHODS AND RESULTS: A systematic RAPD polymerase chain reaction (PCR) analysis using 600 primers was performed on beer-spoilage and on nonspoilage strains of L. brevis. Among 600 primers, three were found to amplify a single locus highly specific to beer-spoilage strains. DNA sequencing of this locus revealed a three-part operon encoding a putative glycosyl transferase, membrane protein and teichoic acid glycosylation protein. PCR analysis of typical beer-spoilage lactic acid bacteria suggested that this locus is highly specific to beer-spoilage strains. CONCLUSION: The cloned markers are highly specific to identify the beer-spoilage strains not only in L. brevis but also in Pediococcus damnosus, Lactobacillus collinoides and Lactobacillus coryniformis. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper proves that RAPD-PCR is an efficient method for cloning the strain-specific genes from bacteria. The markers described here is one of the most useful tools to identify the beer-spoilage strains of lactic acid bacteria.

Beer↗

PubMed2005

The relationship between bone mineral density and the number of remaining teeth in community-dwelling older adults.

Tooth loss and osteoporosis may share common aetiologic agents which influence the process of both diseases. The purpose of this study was to evaluate the relationship between bone mineral density (BMD) of the os calcis and the number of remaining teeth, controlling the known confounding factors. Among all 70-year-old inhabitants in Niigata City, Japan, 600 people were selected randomly in order to have approximately the same number of each gender. We analysed 460 subjects. We evaluated the BMD of the os calcis using an ultrasound bone densitometer, then we counted the number of remaining teeth excluding the third molars. Stiffness is a clinical index which is calculated by the spread speed of supersonic waves. To monitor the general health condition of the subjects, serum levels of disease markers and smoking habits were also investigated. The mean number of remaining teeth for the osteopenia group (OG) and the no-osteopenia group (NOG) was 15.97+/- 9.98 and 18.31+/- 8.06, respectively in females, and 16.32+/- 9.93 and 18.12+/- 9.33, respectively in males (OG versus NOG, P=0.047 by two-way anova). In addition, stiffness was significantly associated with the number of remaining teeth (CV=-0.157, P=0.005) using linear multiple regression analysis adjusted by four other variables. In this study, there was a significant relationship between the number of remaining teeth and BMD of the os calcis.

Adipose Tissue↗

PubMed2005

Relationship between bleeding on probing and periodontal disease progression in community-dwelling older adults.

OBJECTIVE: The main objective of this study was to determine the relationship between bleeding on probing (BOP) and periodontal disease progression in community-dwelling older adults. METHODS: A 3-year longitudinal study was carried out in 229 non-smoking healthy older adults aged 70 years. Using pressure-controlled periodontal probes, BOP, pocket depth and attachment level at 13,289 sites were measured annually. Periodontal disease progression was defined as an increase in attachment loss of >or=3 mm from the baseline to the final examination. The backward stepwise logistic regression analysis was performed to assess the relationship between the total number of sites with BOP in the four examinations and periodontal progression. RESULTS: Logistic regression analysis showed that the odds ratios of BOP frequency for periodontal disease progression ranged from 1.4 to 6.2 after controlling for pocket depth >or=4 mm at baseline, number of missing teeth, jaw type and tooth site. CONCLUSION: Increasing frequencies of bleeding might increase the probability of periodontal disease progression in community-dwelling older adults.

Aged↗

PubMed2005

Age associated axonal features in HNPP with 17p11.2 deletion in Japan.

OBJECTIVE: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy (HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities. METHODS: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls. RESULTS: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination. CONCLUSIONS: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.

Action Potentials↗

PubMed2004

Morphological change of the micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) induced by binding of sodium dodecyl sulfate.

Morphological change of a micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) (PS-PVP-PEO) polymer was induced by binding sodium dodecyl sulfate (SDS) to the PVP block in acidic aqueous solutions. The change in the size of SDS/PS-PVP-PEO complexes was detected by dynamic light scattering measurements and atomic force microscopy, and the binding of SDS was confirmed by zeta-potential measurements. When the micelle was free from SDS in acidic aqueous solutions, the hydrodynamic diameter of the micelle was 216 nm, reflecting the extended conformation of the PVP block due to the repulsion between protonated pyridine units. As the cationic PVP block was electrically neutralized with anionic SDS, the diameter was gradually reduced concomitant with the decrease in zeta-potential and finally reached 175 nm when the PVP block was completely neutralized. The decrease in the diameter shows the morphological change of the PVP block from extended to shrunken forms. Further addition of SDS did not cause the changes of the diameter nor zeta-potential. This indicates that SDS was not bound to the PS-PVP-PEO polymer after the PVP block was fully neutralized and that the hydrophobic binding of SDS to the polymer was negligible due to the low concentration of SDS.

Journal Article↗

PubMed2004

Mutational analysis of carbamoylphosphate synthetase I deficiency in three Japanese patients.

We describe the results of mutational analysis of the carbamoylphosphate synthetase I (CPSI) gene in three nonconsanguineous patients with CPSI deficiency. Compound heterozygotes of 3422T/G (V1141G) plus 3784C/T (R1262X), 1528delG (510-514 ARQLX) plus 2752T/C (S918P), and 2549G/A (R850H) plus 2797delT (L933X) were identified through genomic analysis; however, the 2797delT (L933X) mutation was not detected in cDNA analysis using biopsied liver, suggesting that mRNA expression rom this mutant allele is absent or markedly low.

Adolescent↗

PubMed2004

Serotonin 2C receptor gene Cys23Ser polymorphism: a candidate genetic risk factor of migraine with aura in Japanese population.

OBJECTIVES: The goal of this study is to clarify the association between migraine and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. MATERIALS AND METHOD: This study included 37 individuals with migraine with aura (MWA), 80 with migraine without aura, 43 with tension type headache (TH) and 360 with controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS: The Ser allele frequency in control subjects is much less than that in Caucasian population. The Ser allele frequency in patients with MWA was higher than that in control subjects. CONCLUSION: The present study provides that 5HTR2c Cys23Ser polymorphism may be associated with MWA in Japanese population.

Adult↗

PubMed2004

Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia patients.

OBJECTIVES: To investigate a possible implication of inflammatory processes in the development of dementia in cerebrovascular disease. PATIENTS AND METHODS: We examined the levels of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 26), ischemic cerebrovascular disease without dementia (CVD) (n = 11), vascular dementia (VD) (n = 11), and other neurological disorders (n = 21) using sensitive enzyme-linked immunosorbent assay. RESULTS: The CSF concentrations of IL-6 were significantly elevated in patients with VD compared with those of patients with AD or CVD. CONCLUSION: The CSF IL-6 levels are increased in patients with VD, suggesting that inflammatory mechanisms may be involved in the development of cognitive decline in some patients with cerebrovascular disease. CSF IL-6 may be a biological marker for dementia in cerebrovascular disease.

Aged↗

PubMed2004

Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli.

OBJECTIVE: To investigate anti-apoptogenic mechanism of transforming growth factor beta1 (TGFbeta1) towards synovial cells. METHODS: Isolated synovial cells, treated or not with TGFbeta1, were cultured in the presence or absence of anti-Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of synovial cells was examined by the presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption of mitochondrial transmembrane potential (DeltaPsim). RESULTS: Activation of caspase-9 and DeltaPsim was found in anti-Fas IgM treated synovial cells. The increment of both hypodiploid DNA(+) cells and TUNEL(+) cells accompanied by the activation of caspase-8 and caspase-3 was also determined in anti-Fas IgM treated synovial cells. These hallmarks for apoptosis induced by anti-Fas IgM were significantly suppressed in TGFbeta1 treated synovial cells. LLL-CHO, etoposide, and C2-ceramide also caused DeltaPsim, the increment of both hypodiploid DNA(+) cells and TUNEL(+) cells, and the activation of both Leu-Glu-His-Asp ase (LEHDase; caspase-9 like activity) and Asp-Glu-Val-Asp ase (DEVDase; caspase-3 like activity) in synovial cells. As determined in anti-Fas IgM treatment, TGFbeta1 significantly reduced apoptotic cell death of synovial cells induced by the above chemicals. CONCLUSIONS: The protective effect of TGFbeta1 for mitochondrial homoeostasis may be important in the anti-apoptogenic function of TGFbeta1 for synovial cells.

Apoptosis↗

PubMed2004

Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease.

OBJECTIVE: To describe a novel missense mutation, Asp678Asn (D678N), in the amyloid precursor protein (APP) gene in a Japanese pedigree of probable familial Alzheimer's disease (FAD). SUBJECT: The proband was a women of 72. Symptoms of dementia that fulfilled the criteria for probable Alzheimer's disease appeared at about 60 years of age, and slowly worsened over more than 10 years without evident cerebrovascular complications, either clinically or neuroradiologically. METHODS: Polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) analysis followed by sequence analysis was used to examine genomic DNA of the proband for mutations in the APP gene exons 16 and 17. RESULTS: Analysis of the APP exon 16 in the proband showed a GAC to AAC nucleotide substitution in codon 678 of the APP gene, causing an amino acid substitution of Asp to Asn (D678N). Heterozygosity of the APP D678N mutation was found in the proband and in the demented elder sister. CONCLUSIONS: The production and accumulation of mutated Abeta (Asn7-Abeta) or the misfunction of D678N mutant APP may have pathogenic properties for the development of Alzheimer's disease in this pedigree.

Aged↗

PubMed2004

Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation.

BACKGROUND: The MPZ Thr124Met mutation is characterised by a late onset, pupillary abnormality, deafness, normal or moderate decreased motor nerve conduction velocity, and axonal damage in sural nerve biopsy. OBJECTIVE: To investigate the clinical manifestations of the axonal or demyelinating forms of the Japanese MPZ Thr124Met mutation originating in four different areas: Tottori, Nara, Aichi, and Ibaragi. RESULTS: Genotyping with DNA microsatellite markers linked to the MPZ gene on chromosome 1q22-q23 showed shared allelic characteristics between 12.65 cM and revealed a common haplotype in all Tottori families. Aichi and Ibaragi families shared parts of the haplotype around the MPZ gene. However, there was no consistency with a Nara family. CONCLUSIONS: The high frequency of this peculiar genotype in the Tottori CMT population is presumably due to a founder effect, but in Thr124 it might constitute a mutation hotspot in the MPZ gene.

Adult↗

PubMed2004

[Prostacyclin oral internal therapy for severe pulmonary hypertension after total correction of cor triatriatum with partial anomalous pulmonary venous return; report of a case].

A 37-day-old girl having cor triatriatum with partial anomalous pulmonary venous return was found on emergent admission. Echocardiography and angiography revealed severe pulmonary hypertension with anomalous pulmonary venous return to inominate vein. She still was in respiratory failure after emergent surgical repair because of severe pulmonary hypertension following pulmonary venous obstruction. Prostacyclin is the first Food and Drug Administration (FDA)-approved treatment for advanced primary pulmonary hypertension, which has antithrombotic properties related to its effect on platelets and is a potent vasodilator of both the systemic and pulmonary arteries, and has positive inotropic properties. We started prostacyclin oral internal therapy for her and she recovered from respiratory problems very quickly. Prostacyclin might be effective for pulmonary hypertension before and after surgical repair as primary pulmonary hypertension.

Administration, Oral↗

PubMed2003

Protection of trocar sites from gallbladder cancer implantation by sodium hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm) in a murine model [corrected].

BACKGROUND: The risk of port site metastasis in laparoscopic surgery for cancer patients is a problem that has yet to be resolved. We examined the protective effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor cell implantation at laparoscopic trocar sites. METHODS: Four 2-mm trocar sites were created in nude mice, and the peritoneal wounds were covered with different-sized pieces of Seprafilm. The protective effect of Seprafilm on the implantation of GB-d1 (a human gallbladder cancer cell line) at the trocar sites was assessed after 7 days. In addition, the effects of sodium hyaluronate and Seprafilm on the growth and motility of GB-d1 were examined in vitro. RESULTS: Seprafilm significantly decreased the incidence of implantation compared with the control group. Histologically, Seprafilm was observed on days 1 and 3, as a sheet of gel that covered the injured peritoneum and muscle layer. In an invasion assay using Seprafilm, no cells were found to infiltrate through the gel sheet. CONCLUSION: Seprafilm protects peritoneal wounds by physically covering the injured peritoneum. Therefore, if Seprafilm were attached to the injured peritoneum after laparoscopic surgery for cancer patients, it might reduce port site metastasis.

Adenocarcinoma↗

PubMed2003

Characterisation of Fasciola gigantica adult 27-kDa excretory-secretory antigen in human fascioliasis.

The 27-kDa excretory-secretory antigen partially purified from adult Fasciola gigantica adult worms (FG27) has been used as the sensitive and specific antigen for immunodiagnosis of human fascioliasis. Lectin-blot analyses have shown that the FG27 possesses both N - and O -glycans. In two-dimensional electrophoresis, silver staining, lectin blotting and immunoblotting, FG27 displayed at least four antigenic-glycosylated protein spots at the pI values of 4.8, 4.9, 5.2 and 5.4, respectively. After removing glycan moieties from the antigen by alkaline treatment, the molecular mass of the FG27 was reduced to 26.5 kDa as a prominent deglycosylated band. Immunoblotting analysis has revealed that the 26.5-kDa band reacts with the pooled human fascioliasis sera without any loss of antigenicity. These results suggest that the major antigenicity of the FG27 is due to its protein epitopes.

Animals↗