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Biomedical subjects

A Morita

Publications and source records attributed to A Morita.

At least 19 recordsLinked to original sources

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

INTRODUCTION: The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established. METHODS: We followed 1,283 women aged 15-79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine. RESULTS: Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association. CONCLUSION: Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.

Adolescent↗

Differential expression of two fructokinases in Oryza sativa seedlings grown under aerobic and anaerobic conditions.

Fructokinases (EC 2.7.1.4) may play an important role in carbohydrate metabolism of Oryza sativa L. (rice) seedlings under anoxia. We present here the molecular and biochemical characterizations of two rice fructokinases, namely OsFK1 and OsFK2. The results show that, at both a transcriptional and a transductional level, OsFK1 is preferentially expressed under aerobic conditions, whereas OsFK2 is induced under anoxia. Substrate inhibition was demonstrated for OsFK1, while OsFK2 appears to be largely unaffected by fructose concentrations up to 10 mM. Sugar modulation of anoxia-induced proteins has been proposed, but our results on rice calli treated with or without glucose (10, 30 or 90 mM) for different time indicate that neither OsFK1 nor OsFK2 are sugar-regulated. We propose that OsFK2 plays a major role in fructose phosphorylation under anoxic conditions.

Aerobiosis↗

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53.

We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

Apoptosis↗

Involvement of tenascin-C and PG-M/versican in flexor tenosynovial pathology of idiopathic carpal tunnel syndrome.

Increased intra-carpal-tunnel pressure due to swelling of the flexor tenosynovium is the most probable pathological mechanism of idiopathic carpal tunnel syndrome (CTS). To clarify the role of tenascin-C and PG-M/versican, which have often been found to be involved in tissue remodeling and vascular stenosis in the pathogenesis of CTS, we histologically and biochemically examined the production of extracellular matrix in the flexor tenosynovium from 40 idiopathic CTS patients. Tenascin-C was temporarily expressed in the vessel wall, synovial lining and fibrous tissue, with expression regulated differently in each tissue. Tenascin-C expression by vessels correlated with disease duration and appeared to be involved in vascular lesion pathology. Morphometric analysis showed that tenascin-C expression by small arteries is correlated with PG-M/versican expression in surrounding connective tissue. PG-M/versican was also present at the neointima of severely narrowed vessels. Although tenascin-C expression by synovial lining and connective tissue shows marked regional variation and seems inconsistent, in vitro examination suggested that tenascin-C production by these tissues is regulated in response to mechanical strain on the flexor tenosynovium.

Adult↗

Effects of the Cdx-2 polymorphism of the vitamin D receptor gene and lifestyle factors on bone mineral density in a representative sample of Japanese women: the Japanese Population-based Osteoporosis (JPOS) Study.

Using a large-scale representative sample of the Japanese female population, we examined the effects of a single nucleotide polymorphism within a binding site of Cdx-2 in the promoter region of the vitamin D receptor gene on bone mineral density (BMD), and the interactions between this polymorphism and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15-79 years) in each of three chosen municipalities as a part of the Japanese Population-based Osteoporosis Study. BMD at the lumbar spine, hip, and distal forearm was measured using dual-energy X-ray absorptiometry at baseline and again in a follow-up study conducted 3 years later. Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The G-to-A polymorphism within the Cdx-2 binding site was determined by a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. The baseline BMD in the ultradistal forearm in premenopausal women with the GG genotype was significantly lower than in those with other genotypes. There was no association between the Cdx-2 genotype and the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites but only in subjects with the GG genotype. In conclusion, the Cdx-2 polymorphism alone did not have a substantial effect on BMD in Japanese women. However, this polymorphism might have some effect in women with low calcium intake.

Absorptiometry, Photon↗

Nested polymerase chain reaction for assessing the clinical course of tuberculous meningitis.

The authors examined the usefulness of nested PCR (N-PCR) to detect Mycobacterium tuberculosis (MTB) DNA in CSF for assessing the clinical course of tuberculous meningitis (TBM). N-PCR successfully detected MTB DNA in all nine CSF samples from patients with suspected TBM. During anti-tuberculosis treatments, N-PCR results converted from positive to negative, correlating with the improvement of the patient's clinical condition.

Adult↗

Subfrontal schwannoma.

Subfrontal schwannoma is a rare disease, which can be mis-diagnosed as an olfactory meningioma or a neuroblastoma, because of similar clinical symptoms and signs and neuroradiological features. Especially for young subjects, olfactory neuroblastoma should be carefully differentiated, since the management strategies for those lesions are significantly different. The craniofacial approach is often needed for the resection of a neuroblastoma. We report a case of 14-year old boy in which olfactory neuroblastoma was suspected prior to surgery, but turned out to be a schwannoma histologically. Molecular genetic examination revealed neither NF2 gene mutation nor loss of heterozygosity of chromosome 22q, unlike common schwannomas.

Adolescent↗

Spinal intramedullary ependymal cyst: a case report and review of the literature.

We report a rare case of spinal intramedullary ependymal cyst in a 44-year-old female and reviewed 12 cases reported in the literature. The patient presented with slowly progressive lower limb paresis. She underwent biopsy of the cyst wall and placement of a cysto-subarachnoid shunt with complete recovery at the follow-up examination 18 months after surgery. This is a benign lesion and appropriate management should be performed at an early stage of the disease.

Adult↗

Resolution of spinal epidural haematoma without surgery in a haemophilic infant.

Non-traumatic spinal epidural haematoma is a rare complication of haemophilia. We report a seven-month-old boy who presented with symptomatic spinal epidural haematoma. He was found to have a hemophilia B trait, and after factor IX replacement, his neurological signs were stabilized and follow-up MRI demonstrated rapid resolution of the haematoma. This illustrative case suggests that surgical intervention can be deferred as the first step in treating spinal epidural haematoma in a haemophilic infant.

Factor IX↗

Diffusion property following functional hemispherectomy in hemimegalencephaly.

Diffusion-tensor imaging (DTI), a unique magnetic resonance technique for analysis of diffusion-anisotropy of the brain, can identify subtle white matter changes in vivo. To investigate changes of truncated neurofibers, DTI was conducted prior to and following functional hemispherectomy in a female infant for refractory epilepsy associated with hemimegalencephaly. Anisotropy of the amputated pyramidal tract decreased relative to the unaffected side after surgery, which reflects secondary degeneration in neurofibers. In DTI applied to infants, differentiation between developmental changes and changes associated with the current phenomenon must be evaluated cautiously. Standardization of diffusion-tensor analysis of developmental change is desirable.

Adult↗

Energetic protons from a few-micron metallic foil evaporated by an intense laser pulse.

With detailed experimental studies and hydrodynamics and particle-in-cell simulations we investigate the role of the prepulse in laser proton acceleration. The prepulse or pedestal (amplified spontaneous emission) can completely evaporate the irradiated region of a sufficiently thin foil; therefore, the main part of the laser pulse interacts with an underdense plasma. The multiparametric particle-in-cell simulations demonstrate that the main pulse generates the quasistatic magnetic field, which in its turn produces the long-lived charge separation electrostatic field, accelerating the ions.

Journal Article↗

TRPV1 activation and induction of nociceptive response by a non-pungent capsaicin-like compound, capsiate.

Capsiate is a capsaicin-like ingredient of a non-pungent cultivar of red pepper, CH-19 sweet. To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1). In patch-clamp experiments, capsiate was found to activate TRPV1 expressed transiently in HEK293 cells with a similar potency as capsaicin. Capsiate induced nociceptive responses in mice when injected subcutaneously into their hindpaws with a similar dose dependency as capsaicin. These data indicate that the non-pungent capsiate is an agonist for TRPV1 and could excite peripheral nociceptors. In contrast to this, capsiate did not induce any significant responses when applied to the skin surface, eye or oral cavity of mice, suggesting that capsiate requires direct access to nerve endings to exhibit its effects. Capsiate was proved to have high lipophilicity and to be easily broken down in normal aqueous conditions, leading to less accessibility to nociceptors. Another highly lipophilic capsaicin analogue, olvanil, was similar to capsiate in that it did not produce irritant responses when applied to the skin surface, although it could activate TRPV1. Taken together, high lipophilicity and instability might be critical determinants for pungency and so help in understanding the effects of capsaicin-related compounds.

Animals↗

Difference in the heat sensitivity of DNA-dependent protein kinase activity among mouse, hamster and human cells.

PURPOSE: To examine the heat sensitivity of DNA-dependent protein kinase (DNA-PK) activity in a variety of cultured mouse, hamster and human cell lines. MATERIALS AND METHODS: Eight cell lines, which have been routinely used in our laboratory, were examined. Cells were heated at 44.0 +/- 0.05 degrees C and DNA-PK activity was measured by a DNA-pull-down assay followed by gel-electrophoresis. Cellular sensitivity to hyperthermia and/or X-ray was evaluated by a colony formation assay. RESULTS: In mouse FSA1233 and FM3A cells, DNA-PK activity dropped to 15-16% of unheated control after 20 min of heating. In Chinese hamster V79 and CHO-K1 cells, kinase activity did not change appreciably after 20 min treatment but decreased to 60-70 and 22-23% after 40 or 60 min treatment, respectively. However, even after 180 min treatment, DNA-PK activity remained almost intact in human MOLT-4, MKN45 and A7 cells, and decreased only slightly in U937 cells. Hyperthermic radiosensitization was seen even in human cells but, as a trend, it was small compared with rodent cells. CONCLUSIONS: The heat sensitivity of DNA-PK was clearly different among mouse, hamster and human cells. The results suggested a possibility that the role of DNA-PK inactivation in hyperthermic radiosensitization might be variable, depending on cells, and would reinforce the warning that the direct extrapolation of data from rodent cells might lead to overestimation of the effectiveness of hyperthermia on human cancer.

Animals↗

Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukaemia cell line MOLT-4.

PURPOSE: To investigate the possible involvement of c-Myc and ceramide-c-Jun N-terminal kinase (JNK) pathway in X-ray-induced apoptotic cell death of MOLT-4 cells. MATERIALS AND METHODS: The expressions of c-Myc protein and c-myc mRNA after X-irradiation were analysed by Western blotting and RT-PCR between radiosensitive MOLT-4 and radioresistant variant Rh-1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c-Myc inhibitor peptides (Int-H1-S6A, F8A) on the amount of c-Myc protein and on the induction of apoptosis was investigated, respectively. RESULTS: In X-irradiated MOLT-4 cells, amounts of both c-myc mRNA and c-Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c-Myc protein was observed in X-irradiated Rh-1a cells with accompanying higher cell viability. Exposure of MOLT-4 and Rh-1a cells to c-Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c-Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c-Myc protein, causing cell death in MOLT-4 cells. On the other hand, Rh-1a cells were more resistant to anisomycin than parental MOLT-4 cells, showing less JNK activation and a delayed decrease of c-Myc protein. CONCLUSION: A decrease of c-Myc protein was considered important in X-ray-induced apoptotic cell death of MOLT-4 cells; activation of the JNK pathway caused reduction in the amounts of c-myc mRNA and c-Myc protein, and finally induced apoptotic cell death.

Anisomycin↗

Age-specific values and cutoff levels for the diagnosis of osteoporosis in quantitative ultrasound measurements at the calcaneus with SAHARA in healthy Japanese women: Japanese population-based osteoporosis (JPOS) study.

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.

Adult↗

Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent protein kinase activity.

Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins including DNA polymerases, and inhibit their functions. In the present study, we report inhibition of DNA-dependent protein kinase activity by phosphorothioate oligonucleotides, suramin and heparin. Inhibitory effect of phosphorothioate oligonucleotides on DNA-dependent protein kinase activity was increased with length and reached a plateau at 36-mer. The base composition of phosphorothioate oligonucleotides did not affect the inhibitory effect. The inhibitory effect by phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was also observed with purified DNA-dependent protein kinase, which suggests direct interaction between DNA-dependent protein kinase and phosphorothioate oligonucleotides. DNA-dependent protein kinase will have different binding positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer because they were not competitive in DNA-dependent protein kinase activation. Suramin and heparin inhibited DNA-dependent protein kinase activity with IC(50) of 1.7 microM and 0.27 microg ml(-1) respectively. DNA-dependent protein kinase activities and DNA double-stranded breaks repair in cultured cells were significantly suppressed by the treatment with suramin in vivo. Our present observations suggest that suramin may possibly result in sensitisation of cells to ionising radiation by inactivation of DNA-dependent protein kinase and the impairment of double-stranded breaks repair.

Antineoplastic Agents↗

Increased levels of a TH2-type CC chemokine thymus and activation-regulated chemokine (TARC) in serum and induced sputum of asthmatics.

BACKGROUND: Cytokines liberated by TH2 cells play crucial roles in the pathogenesis of bronchial asthma. Recent studies have demonstrated that CC chemokine receptor (CCR)4 is preferentially expressed by TH2 cells. These facts suggest possible involvement of two CCR4-specific ligands i.e., thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), in the pathogenesis of bronchial asthma via recruitment of TH2 cells to inflammatory sites. We investigated the levels of TARC and MDC in the serum and induced sputum of asthmatics. METHODS: The levels of TARC in the serum (46 asthmatics and 26 healthy subjects) and induced sputum (30 asthmatics and 6 healthy subjects) were measured using a highly sensitive ELISA system. The levels of eotaxin and MDC were also measured by ELISA. RESULTS: TARC, but not MDC, was significantly increased in asthmatic sera (P<0.001). Although MDC was undetectable in the sputum of most cases by our assay system, sputum TARC was significantly increased (P=0.027). CONCLUSIONS: The elevated TARC levels in asthmatics might be involved in the pathophysiology of asthma.

Adult↗

Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus.

The pathogenesis of uraemic pruritus is unclear, although there is some evidence that an increased number of skin-infiltrating mast cells may play a role. Ultraviolet B reduces itchy sensation of uraemic patients by leading to depletion of cutaneous mast cells. This study presents data that both broad-band and narrow-band ultraviolet B irradiation are able to induce apoptosis in transformed mast cells (murine mastocytoma cell line P815) in a dose-dependent manner at a time point of 24 hours. The positive apoptotic rates were as follows: sham-exposed cells (controls) -- 13.3% +/- 0.6%; with broad-band ultraviolet B irradiation -24.5% +/- 1.1% with 10mJ/cm(2), 57.9% +/- 4.6% with 20mJ/cm(2) and 70.9% +/- 4.5% with 30mJ/cm(2); with narrow-band ultraviolet B irradiation -- 29.6% +/- 2.3% with 100mJ/cm(2), 57.3% +/- 4.1% with 200mJ/cm(2) and 81.5% +/- 1.9% with 300mJ/cm(2). The difference between the number of apoptotic cells in all groups of ultraviolet B-irradiated cells and sham-exposed cells was highly significant (P<0.001). Based on these findings, it is hypothesized that ultraviolet B induced mast cell apoptosis could be an important factor in phototherapy for the diseases dependent on increased number of cutaneous mast cells, including uraemic pruritus.

Animals↗