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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Age-related differences in postural control in humans in response to a sudden deceleration generated by postural disturbance.

Age-related differences in postural control in response to a relatively large deceleration resulting from postural disturbance were investigated in eight normal elderly men (age range 67-72 years) and eight young men as controls (age range 19-22 years) using a moving platform. Data were obtained for the hip, knee and ankle angles, position of the centre of foot pressure (CFP), head acceleration, and muscle activity of the leg muscles. The elderly subjects had slower and larger ankle and hip joint movements, and CFP displacement in response to the disturbance compared to the young controls. The elderly subjects also had a delayed occurrence, and greater magnitude of peak acceleration of head rotation than did the young subjects. For the elderly subjects, the CFP was closely related to angular changes in the hip joint movement, but not to those of the ankle and knee joint movements. For the young subjects, on the other hand, the CFP was significantly correlated with angular change in the ankle joint. Cocontraction of the tibialis anterior and gastrocnemius muscles was observed in the elderly subjects. The results indicated that a movement pattern for postural correction in the elderly adults was different from that of the young adults. The elderly relied more on hip movements while the young controls relied on ankle movements to control postural stability.

Adult↗
PubMed2001

Relationship between fear of falling and balancing ability during abrupt deceleration in aged women having similar habitual physical activities.

The purpose of this study was to evaluate the influence of fear of falling on balancing ability during abrupt deceleration in aged women. The subjects were 20 women aged between 67 and 75 years. They were classified into two groups, one having a fear of falling (group FF, n = 10) and another without this fear (group NFF, n = 10). The two groups had similar daily physical activities. Changes in the centre of foot pressure (CFP) were measured during postural sway following horizontal deceleration of the force platform on which they were standing, and the response time and CFP displacement were evaluated. In addition, the electromyogram (EMG) onset in the tibialis anterior muscle and medial gastrocnemius muscle during abrupt deceleration, and its difference between the two muscles were measured. and the relative level of co-contraction of antagonistic muscles (the co-contraction index, CCI) in the lower extremity muscle group was calculated. The response time and CFP displacement immediately after abrupt deceleration were significantly higher in group FF than in NFF (P < 0.05). The EMG onset in the two muscles did not significantly differ between the two groups. The difference in EMG onset between the two muscles was significantly lower in group FF than in NFF (P < 0.05). The CCI was significantly higher in group FF than in NFF (P < 0.05). These results suggest that there were negative effects of a fear of falling on the balancing ability immediately after abrupt deceleration. This may be because a fear of falling increases the co-contraction of antagonist muscles in the lower extremity muscle group.

Aged↗
PubMed2001

Hypophosphatemic rickets accompanying McCune-Albright syndrome: evidence that a humoral factor causes hypophosphatemia.

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.

Adolescent↗
PubMed2001

Correlation of genetic etiology with response to beta-adrenergic blockade among symptomatic patients with familial long-QT syndrome.

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

Adolescent↗
PubMed2001

A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia.

Autosomal dominant hypocalcemia can be caused by activating mutations of the calcium-sensing receptor (CaSR) gene. We experienced two patients (proband and her daughter) with hypocalcemia caused by a missense mutation of the CaSR gene. The proband, aged 25, showed hypocalcemia and hypoparathyroidism from infancy. She had been diagnosed as having idiopathic hypoparathyroidism and had been treated with calcitriol. She gave birth to a female infant at age 24 years. Her daughter was found to have hypocalcemia (Ca, 6.6mg/dl), without seizure or tetany, when she was 7 months old. DNA analysis of their CaSR genes showed a novel heterozygous mutation at codon 129 (TGC-to-AGC) with substitution of cysteine for serine (C129S). Familial examination revealed that this mutation had occurred de-novo in the proband. Wild-type and niutant (C129S) CaSR cDNA were transfected into HEK293 cells, and intracellular calcium concentrations were measured with a fluorescent calcium indicator. HEK cells transfected with the C129S mutant CaSR gene showed a larger increase in intracellular calcium concentration in response to the change in the extracellular calcium concentration than HEK cells transfected with the wild-type receptor. We conclude that the C129S mutation in the CaSR gene observed in these patients causes autosomal dominant hypocalcemia.

Adult↗
PubMed2001

Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester.

Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.

Apolipoproteins E↗
PubMed2001

Effects of the acyl chain composition of phosphatidylcholines on the stability of freeze-dried small liposomes in the presence of maltose.

The effects of the acyl chain composition of phosphatidylcholines (PCs) on the stability of small unilamellar vesicles during freeze-drying and rehydration in the presence of maltose were studied by monitoring the retention of a trapped marker, calcein, in the internal liposome compartment. In dipalmitoyl PC, beta-oleoyl-gamma-palmitoyl-PC and egg yolk PC liposomes, good or fair retentions (>50%) were observed in the presence of maltose, but maltose was ineffective in preserving retention in the dioleoyl PC (DOPC) liposomes (<10%). The extremely low retention in the DOPC liposome was ascribed to neither a formation of the inverted hexagonal phase of the liposomal membrane nor the fusion/aggregation of the liposomes in the drying-rehydration process. Differential scanning calorimetry measurements suggested that interactions of maltose with PC headgroups were essential to stabilizing the dry liposomes. These interactions were significant in the saturated or mixed chain liposomes but were markedly reduced in the DOPC liposomes.

Calorimetry, Differential Scanning↗
PubMed2001

Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome.

Rett syndrome (RTT) is one of the most common neurodevelopmental disorders in females. Recently, this disease was found to be linked with mutations in the methyl-CpG-binding protein 2 gene (MECP2) and various mutations have been reported. To explore the spectrum of phenotypes resulting from MECP2 mutations, we searched for mutations in the MECP2 of 20 Japanese patients who had more than five of the criteria necessary for RTT diagnosis proposed in 1988 (The Rett Syndrome Diagnostic Criteria Work Group, Ann Neurol 23 (1988) 425) and compared the phenotype between patients with and without mutation by giving a score to each diagnostic criterion. We found four missense mutations (T158M, R133C, Y120D, and R306C), two nonsense mutations (R168X and R270X), one frameshift (726delAAAG) mutation, and one polymorphism (A201V) in ten patients (50%). This included two novel mutations (726delAAAG and Y120D). All mutations were found in the highly conserved methyl-binding and transcription repression domains. Comparison of the mean total diagnostic criterion score of the groups with and without mutation did not reveal any statistically significantly difference (P=0.28). The only difference between the groups, which was of borderline significance (P=0.051), was the sum of the scores for diagnostic criteria 2 (apparently normal psychomotor development through the first 6 months) and 5 (loss of acquired purposeful hand skills between the ages of 6 and 30 months). From these results, it is suggested that the clinical phenotype of RTT is variable and it is important to investigate the MECP2 genotype for patients having more than five criteria and not only in those who exhibit all RTT diagnostic criteria. The diagnosis of RTT is clinically difficult before 3 years of age, especially in atypical cases, but molecular analysis of the MECP2 will assist diagnosis in some patients.

Adolescent↗
PubMed2001

Growth hormone receptor antagonists: discovery and potential uses.

Serum levels of growth hormone (GH) in the human body vary and can influence the levels of insulin-like growth factor I (IGF-1). Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly, and also have been implicated in diabetic eye and kidney damage. Additionally, it has been postulated that the GH-IGF-I system can be involved in several types of cancers. Overall, both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago a new class of drug, a GH antagonist, was discovered. It is now being tested for its ability to combat the effects of high circulating levels of GH. In this review, we will discuss some of the detrimental actions of GH and how a GH antagonist may be used to combat these effects.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Analysis of gene expression of aldose reductase and sorbitol dehydrogenase in rat Schwann cells by competitive RT-PCR method using non-homologous DNA standards.

Aldose reductase (AR) and sorbitol dehydrogenase (SDH) are the enzymes constituting the polyol pathway, an alternate route of glucose metabolism. A wealth of experimental data has indicated the involvement of the polyol pathway in the pathogenesis of diabetic complications. However, there has been surprisingly little research on the relative abundance of SDH to AR in the tissues affected in diabetes. We therefore developed a competitive RT-PCR system to simultaneously determine the mRNA levels of these two enzymes in small amounts of samples, and studied their expression in Schwann cells isolated from adult rat sciatic nerves. Although both AR and SDH mRNA were expressed in the Schwann cells, the levels of SDH cDNA were much lower than those of AR cDNA. The induction of AR mRNA expression in the Schwann cells under hyperosmotic conditions was similarly detected by Northern blot analysis and our competitive RT-PCR method. The RT-PCR system developed in this study may be a useful tool in ascertaining the relative contributions of AR and SDH to the metabolic derangements resulting from the acceleration of polyol pathway activity in the target organ of diabetic complications.

Aldehyde Reductase↗
PubMed2001

Biological effects of growth hormone and its antagonist.

Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and has been implicated in diabetic eye and kidney damage. Additionally the GH/IGF-1 system has been postulated as a risk factor for several types of cancers. Thus both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago the first drug of a new class, a GH antagonist, was discovered. This molecule is now being tested for its ability to combat the effects of high circulating levels of GH. Here, we discuss some of the detrimental actions of GH, and how a GH antagonist can be used to combat these effects.

Aging↗
PubMed2001

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications.

To assess the involvement of vascular endothelial cell activation and damage in stem cell transplantation (SCT)-related complications, such as acute and chronic GVHD and thrombotic microangiopathy (TMA), we investigated the changes in serum levels of soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) in SCT. The soluble form of intercellular adhesion molecule-1 (sICAM-1) was also analyzed. In patients with acute GVHD (grades II-IV), serum levels of sE-selectin and sICAM-1 increased around onset of GVHD (day 30). While the increase of sE-selectin levels was transient, sICAM-1 levels remained high until day 60. In patients with extensive chronic GVHD, sVCAM-1 as well as sE-selectin levels significantly increased. The appearance of clinical symptoms was preceded by elevations of sVCAM-1 and sE-selectin levels on day 60, and sICAM-1 levels on days 30 and 60. For the analysis of TMA, to exclude the influence of GVHD, serum levels were measured in auto-SCT patients. Around the onset of TMA, sVCAM-1 and sE-selectin levels significantly increased in patients with TMA without an increase of sICAM-1 levels. These findings support the notion that activation and injury of endothelium are commonly involved in the pathogenesis of acute and chronic GVHD and TMA.

Adolescent↗
PubMed2001

Inverse relationship between human herpesvirus-6 and -7 detection after allogeneic and autologous stem cell transplantation.

Human herpesvirus-6 (HHV-6) and -7 were analyzed in 25 and 18 patients with allogeneic (allo) and autologous (auto) stem cell transplantation (SCT), respectively, by weekly examination of viral DNA in peripheral mononuclear cells using semiquantitative PCR and serologic tests up to 12 weeks after SCT. HHV-6 DNA was detected in 29.6% and 27.9% of samples after allo- and auto-SCT, respectively. The proportions of HHV-6-DNA-positive samples increased in week 3 and 4 after allo-SCT, and in week 1 to 3 after auto-SCT. The frequency of HHV-7 DNA detection, however, was higher after auto-SCT (24.7%) than allo-SCT (12.8%) (P 10(2) copies of HHV-6 DNA (/10(5) cells) on two consecutive occasions were allo-SCT recipients and three showed clinical episodes. Conversely, three of five patients with continuous reactivation of HHV-7 were auto-SCT recipients. Thus, the frequencies of HHV-6 and -7 DNA detection showed an inverse relationship comparing allo- and auto-SCT, suggesting a different mechanism may regulate HHV-6 and -7 reactivation.

Adolescent↗
PubMed2001

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis after stem cell transplantation: effective monitoring of CMV infection by quantitative analysis of CMV mRNA.

We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.

Adolescent↗
PubMed2001

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia.

To determine the clinical relevance of in vitro drug chemoresistance in childhood acute myeloid leukemia, we used an MTT assay to test leukemic cells from 132 newly diagnosed children. Patients were diagnosed according to the French-American-British (FAB) classification as follows: M0 (n = 12), M1 (n = 16), M2 (n = 53), M4 (n = 17), M5 (n = 19) and M7 (n = 15). The results revealed that, compared to leukemic cells from complete-responders (n = 107), those from non-responders who failed induction therapy (n = 17) were 1.4 to 5.0 times more resistant in vitro to cytarabine (P = 0.005), melphalan (P = 0.003), etoposide (P = 0.011), L-asparaginase (P = 0.017), aclarubicin (P = 0.026) and dexamethasone (P = 0.039). For seven other drugs tested, the median lethal dose of 70% and leukemic cell survival of non-responders were higher than those of complete-responders, but the difference was not statistically significant. We sought correlations between FAB subtypes and in vitro drug resistance. Leukemias of the FAB M4 and M5 subtype were more sensitive to L-asparaginase (P = 0.01, P = 0.0036) than those of the FAB M2 subtype. FAB M5 leukemia was more sensitive to etoposide than were the FAB M2, M4 and M7 subtypes (P = 0.001, P = 0.034, P = 0.023, respectively). By contrast, FAB M5 leukemia was significantly more resistant to prednisolone and dexamethasone than were the FAB M0, M1, M2, M4 and M7 subtypes. We sought correlations between in vitro drug resistance and long-term clinical outcome, but found no associations in this case. These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy. Selecting an appropriate anti-cancer drug according to the FAB classification together with drug sensitivity testing may contribute to improved prognoses in childhood acute myeloid leukemia.

Acute Disease↗
PubMed2001

Host and geographical factors influence the thermal niche of enteric bacteria isolated from native Australian mammals.

The thermal profiles of 118 bacterial strains, representing six species of the family Enterobacteriaceae, isolated from a variety of native Australian mammals were determined under in vitro conditions. Each of the bacterial species had a unique thermal profile and differed in their minimum or maximum temperature for growth and in their response to changing temperatures. The taxonomic classification of the host from which the bacterial strains were isolated explained a significant amount of the variation in thermal profile among strains of a species. Host effects were detected at all taxonomic levels: order, family, genus, and species. The locality (State or Territory) or climate zone from which the strain was collected explained a significant amount of the variation in the thermal profile of Citrobacter freundii, Enterobacter cloacae and Klebsiella pneumoniae strains. Genetically similar strains, as determined by allozyme profiles, had similar thermal profiles for the bacterial species Hafnia alvei and Escherichia coli. The results of this study indicate that there are potentially many aspects of host biology that may determine the thermal profile of these bacteria.

Adaptation, Physiological↗
PubMed2001

In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A.

Epstein-Barr virus (EBV)-associated nasal T/natural killer (NK) cell lymphoma has often been reported in Asian countries and has been recently confirmed as a novel clinicopathological entity. The prognosis of advanced stage disease is quite poor and an effective chemotherapeutic modality is strongly advocated. We have established the novel cell line NK-YS, which preserves the original characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using this cell line, we investigated the induction of apoptosis by apoptosis-inducing agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp but not p53. To overcome this drug resistance, we added cyclosporine A (CsA) and these agents to culture media as a P-gp antagonist. The combination of CsA and etoposide or CsA and doxorubicin induced apoptotic cell death. These results indicated that P-gp-mediated drug resistance is an essential mechanism of drug resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer agents with CsA may have an important place in the establishment of a curative therapy for disseminated nasal angiocentric NK cell lymphoma.

ATP Binding Cassette Transporter, Subfamily B↗