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Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 19 recordsLinked to original sources
PubMed2006

Heat capacity, Raman, and Brillouin scattering studies of M2O-MgO-WO3-P2O5 glasses (M=K,Rb).

The authors report the results of temperature-dependent Brillouin scattering from both transverse and longitudinal acoustic waves, heat capacity studies as well as room temperature Raman scattering studies on M2O-MgO-WO3-P2O5 glasses (M=K,Rb). These results were used to obtain information about structure and various properties of the studied glasses such as fragility, elastic moduli, ratio of photoelastic constants, and elastic anharmonicity. They have found that both glasses have similar properties but replacement of K+ ions by Rb+ ions in the glass network leads to decrease of elastic parameters and P44 photoelastic constant due to increase of fragility. Based on Brillouin spectroscopy they show that a linear correlation between longitudinal and shear elastic moduli holds over a large temperature range. This result supports the literature data that the Cauchy-type relation represents a general rule for amorphous solids. An analysis of the Boson peak revealed that the form of the frequency distribution of the excess density of states is in agreement with the Euclidean random matrix theory. The reason of the observed shift of the maximum frequency of the Boson peak when K+ ions are substituted for Rb+ ions is also briefly discussed.

Journal Article↗
PubMed2006

Ikaros is a mutational target for lymphomagenesis in Mlh1-deficient mice.

Deficiencies in DNA mismatch repair (MMR) result in replication errors within key tumor suppressor genes or oncogenes, and cause hereditary nonpolyposis colorectal cancer (HNPCC). Hematological malignancy with microsatellite instability is also associated with defective MMR, but little is known about the target genes for MMR. Here we identified Ikaros, a master transcription factor of lymphoid lineage commitment and differentiation, as a mutational target in spontaneous and radiation-induced T-cell lymphomas in Mlh1-deficient mice. Three quarters of lymphomas lacked Ikaros protein expression, which resulted from a frameshift mutation that created a stop codon. Mononucleotide repeat sequences at 1029-1034(C)6 and 1567-1572(G)6 in Ikaros were mutational hot spots with a one-base deletion occurring with a frequency of 45 and 50%, respectively. Point mutations and splicing alterations were also observed. In total, 85% of the lymphomas showed aberrations in Ikaros. The characteristic of Mlh1-deficient lymphomas is harboring of multiple mutations simultaneously in the same tumor, displaying a combination of two frameshift mutations at different repeats, frameshift and point mutations, and/or deletion mutations. This is the first report of Ikaros mutations coupled with Mlh1 deficiency in lymphomagenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effects of mitiglinide on glucose-induced insulin release into the portal vein and fat-induced triglyceride elevation in prediabetic and diabetic OLETF rats.

OBJECTIVE: The effect of single-dose mitiglinide on glucose and lipid metabolism was examined in OLETF rats with spontaneous type 2 diabetes in which the early insulin response following glucose challenge is known to diminish over time and become lost with aging. METHODS: (1) With catheters inserted into the portal veins, 12-wk-old prediabetic OLETF rats were given an OGTT of 1 g/kg after 17 h of fasting. Eight rats each were orally given mitiglinide 1 mg/kg, nateglinide 50 mg/kg, or glibenclamide 1 mg/kg, vs 0.5% carboxymethylcellulose (CMC) as control, and were given an OGTT immediately afterward. Following oral administration of mitiglinide, nateglinide, glibenclamide, or 0.5% CMC, the 24-wk-old overt-diabetic OLETF rats were immediately given an OGTT of 1g/kg. (2) After 17 h of fasting, 24-wk-old OLETF rats were subjected to a fat-loading test. Eight rats each were given mitiglinide 3 mg/kg, glibenclamide 1 mg/kg, or glimepiride 1 mg/kg, vs 0.5% CMC, and were given soy oil 2 g/kg immediately afterward. They were also given mitiglinide orally and examined for LPL mRNA expression in their adipose tissue. RESULTS: (1) After OGTT, mitiglinide produced a significant increase in portal insulin levels 15 min after its administration, as well as a significant decrease in peripheral glucose levels 15-120 min after its administration in the OLETF rats. Likewise, nateglinide produced an increase in portal insulin levels and a decrease in peripheral glucose levels shortly after its administration in these rats. Glibenclamide increased portal insulin levels for an extended time after its administration, and significantly decreased peripheral glucose levels in the rats 120-300 min after its administration in the rats. In contrast, as in the 12-wk-old rats, a precipitous rise in insulin secretion was seen in the portal vein of 24-wk-old rats given mitiglinide, which peaked 15 min after mitiglinide administration, but the insulin levels continued to increase for 120 min or longer in the 24-wk-old rats given glibenclamide. In addition, as in the 12-wk-old rats, a significant decrease in glucose levels in peripheral blood was noted 30 and 60 min after mitiglinide administration and 300 min after glibenclamide administration in the 24-wk-old rats. (2) Mitiglinide increased LPL mRNA expression 120 min after its administration, and significantly decreased peripheral TG and chylomicron- TG levels after fat challenge in the 24-wk-old OLETF rats. CONCLUSION: Mitiglinide exhibited fast-onset and short-acting insulin-secretagogic effects, inhibiting post-glucose challenge increases in glucose levels and post-fat challenge increases in TG levels.

Adipose Tissue↗
PubMed2006

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure.

Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.

Acylation↗
PubMed2005

Ocular blood flow changes after dynamic exercise in humans.

PURPOSE: To investigate control mechanisms for ocular blood flow changes after dynamic exercise using two different methods. METHODS: Changes over time in the tissue blood flow in the retina and choroid-retina of healthy volunteers were determined after dynamic exercise (Master's double two-step test), using scanning laser Doppler flowmetry (SLDF) and laser speckle flowgraphy (LSFG). Changes in intraocular pressure (IOP), blood pressure, plasma CO(2) gas concentration (pCO(2)), and levels of nitric oxide (NO) metabolites were examined. RESULTS: Retinal blood flow measured by SLDF increased significantly only at 15 min after exercise. In contrast, normalized blur (NB) values in the choroid-retina, obtained by LSFG, increased significantly up to 60 min after exercise. Ocular perfusion pressure (OPP), calculated from IOP and blood pressure, increased significantly immediately and 15 min after exercise. The plasma NO metabolite levels increased significantly, although pCO(2) levels were unchanged. CONCLUSIONS: Dynamic exercise changes OPP and produces increased tissue blood flow in the retina in the immediate postexercise period, while blood flow increases more persistently in the choroid-retina. Difference in control of blood flow in these two regions may be related to stronger autoregulatory mechanism of blood flow in the retina. Nitric oxide may play a role in the regulation of blood flow.

Adult↗
PubMed2005

Therapy-related myelodysplastic syndrome in childhood: a retrospective study of 36 patients in Japan.

We report here a retrospective analysis of 36 children with therapy-related myelodysplastic syndrome (t-MDS) diagnosed between 1990 and 1999 in Japan. Their median age was 7.7 years and the median latency period for the development of t-MDS was 38.5 months. The primary tumors were hematologic in 15 of the cases and nonhematologic in 21. Chromosomal abnormalities were detected in 32/34(94%) patients: abnormalities of chromosomes 5and/or 7 in 41% and notably, 11q23 abnormalities in 31%. The prognosis of children with t-MDS was very poor as compared to children with primary MDS (5 year survival: 16% versus 54%, p<0.0001).

Adolescent↗
PubMed2005

Recovery patterns and long term prognosis for axonal Guillain-Barré syndrome.

BACKGROUND: Little is known about the long term prognosis for patients the severe acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS), unlike those with acute inflammatory demyelinating neuropathy (AIDP). OBJECTIVE: To clarify the long term prognosis for patients with AMAN. METHODS: Clinical recovery and outcome in 97 consecutive GBS patients were reviewed. RESULTS: Electrodiagnostic criteria showed that 44 patients (45%) had AMAN, 33 (34%) had AIDP, and 20 (21%) were unclassified. Most of the severely affected patients had received plasmapheresis or immunoglobulin therapy. Slow recovery (inability to walk independently at six months after onset) was found in six of the AMAN patients (14%) and in two of the AIDP patients (6%). Of the six AMAN patients, four could walk independently one year after the onset, and the other two could walk independently at 28 and 57 months after onset. Of the two AIDP patients, one could walk at nine months after the onset while the other died of pneumonia seven months after onset. CONCLUSIONS: AMAN electrodiagnosis is not always a marker of poor recovery. Almost all the severe AMAN patients who had slow recoveries over the first six months could eventually walk independently, although some required several years.

Adolescent↗
PubMed2004

Predicting the timing of second praziquantel treatment and its effect on reduction of egg counts in southern Ghana.

Schistosoma haematobium infection could be associated with morbidity. Generally, the cost of schistosomiasis control is high and it becomes a burden for governments or non-governmental organisations to repeat control programs so as to reduce morbidity. There is therefore, the need to optimise the available meagre resources for its control. From 1993 to 1997 the Noguchi Memorial Institute for Medical Research of the University of Ghana carried out a schistosomiasis control program in southern Ghana. Using the generated data, an attempt is made to determine the timing of the second praziquantel treatment and the period needed after the second chemotherapy to have egg counts reduced to low levels in southern Ghana. It was revealed that the second praziquantel treatment in areas 1, 2, and 3 should be administered latest at 13.8, 11.8 and 13.2 months, respectively after the first one. Most importantly, it takes 24.4 months to bring egg counts to zero in area 3 while in area 1, it takes about 29 months after the second praziquantel treatment. Egg counts were not reduced to zero in area 2 after the second chemotherapy. At least passive health education and continuous safe water supply should support the chemotherapy in addition to weed removal at the water contact sites.

Adolescent↗
PubMed2004

Diurnal variation in microcirculation of ocular fundus and visual field change in normal-tension glaucoma.

PURPOSE: Diurnal variations in microcirculation of the ocular fundus in normal-tension glaucoma (NTG) were examined to compare with the normal control eyes. The correlation between progression of visual field impairment and diurnal variations in ocular circulation was also studied. METHODS: The subjects were 12 patients with NTG and 12 normal controls. Blood pressure (BP), intraocular pressure (IOP), ocular perfusion pressure (OPP), and square blur rate (SBR), an index of microcirculation acquired by the laser speckle method, were measured at 9 a.m. (morning), 3 p.m. (afternoon), and 9 p.m. (night). Diurnal variations in SBR were tested using the Friedman test and Wilcoxon signed ranks test. On the other hand, diurnal variations in BP, IOP, and OPP were tested by the analysis of variance. The visual field was evaluated at the same time as determining diurnal variation and again about 9 months later to calculate the change. The correlation between variation ratio in SBR and the change in visual field was examined by simple regression. RESULTS: A significant decrease (P=0.04) was found in SBR at night, as compared with the morning value, in the optic nerve head (ONH) of NTG, although no significant diurnal variations were found in SBR either in the choroid-retina or in normal control eyes. Other parameters showed no significant diurnal variations. The larger diurnal variation was in SBR of the ONH, and the more exacerbated visual field impairment was (r=0.59, P=0.04). CONCLUSION: These findings suggest that diurnal variations in the microcirculation of the ONH may play a role in the progression of NTG.

Aged↗
PubMed2004

Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale: a simple culture system using tetrameric HLA-peptide complexes.

BACKGROUND: Recipients of allogeneic stem cell transplants (SCT) are at risk of human CMV infection during their immunocompromised period. The increasing number of reports of CMV isolates resistant to ganciclovir after transplantation has led us to attempt to develop alternative strategies for preventing or treating CMV infection. This study describes a system for generating sufficient numbers of CMV-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy after SCT. METHODS: CMV-specific CTL were isolated from a single blood draw of a CMV-seropositive donor using PE-labeled HLA-A*0201/pp65(495-503) tetramers and anti-PE magnetic beads. A mixture of a tetramer-positive population and CD4(+) T lymphocytes was expanded to sufficient numbers for clinical application with IL-2 and immobilized anti-CD3 stimulation. RESULT: Starting from 50 mL of blood, we generated >10(7)/m(2) tetramer-positive CTL within 2 weeks. Flow cytometric analysis of expanded lymphocytes showed that purity of CMV peptide-specific CTL was >75%. Upon stimulation of HLA-A*0201-restricted CMV peptide, expanded CD8 T lymphocytes produced intracellular IFN-gamma. Purified CTL exhibited cytotoxic activity against CMV peptide-pulsed T2 cells and CMV-infected HLA-A*0201-positive fibroblasts, but not against HLA mismatched or uninfected target cells. Alloreactivity could be excluded in MLC. DISCUSSION: This simple, rapid culture system can be useful for adoptive immunotherapy after allogeneic SCT. We are now trying to adapt our laboratory scale study to a clinical scale study under good manufacturing practices (GMP) conditions.

Antigens, Viral↗
PubMed2004

Infant schistosomiasis in Ghana: a survey in an irrigation community.

We used a rapid, visually read, field applicable monoclonal antibody (MoAb)-dipstick assay for specific diagnosis of urinary schistosomiasis together with microscopy to determine the prevalence of infant schistosomiasis in a community in the Awutu-Efutu Senya District in the Central Region of Ghana. The study group consisted of 97 infants (51 males and 46 females) aged 2 months to 5 years. A total of 75 of 97 (77.3%) subjects submitted stool samples; none had Schistosoma mansoni. Three individuals (3.1%) had hookworms but there were no other intestinal helminths. The urinary schistosomiasis prevalence by MoAb-dipstick (30%) was higher (P < 0.05) than that estimated by microscopy (11.2%). However, three of nine (33.3%) microscopically confirmed cases tested MoAb-dipstick positive after pre-treatment of the urine specimen with heat. The youngest infant to be found infected with S. haematobium microscopically was 4 months old. Fifteen of 71 S. haematobium egg negative individuals tested dipstick positive, giving a dipstick specificity of 78.9% as compared with microscopy as gold standard test. The relative sensitivity of the dipstick was 100%.

Antibodies, Monoclonal↗
PubMed2004

Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand.

Our previous study showed that in vitro susceptibility of Plasmodium vivax to chloroquine has significantly decreased in Thailand within the past two decades. Thus, the evaluation of alternative antimalarials for treatment of vivax malaria is needed. The aim of this study was to examine parasitological and clinical efficacy of an artemisinin derivative (artesunate) for the treatment of vivax malaria in patients who were admitted to the Bangkok Hospital for Tropical Diseases. We randomly allocated patients aged 12-56 years to receive 3.3mg/kg (adult dose 200 mg) on the first day, and for the next four days each patient was given 1.65 mg/kg orally (adult dose 100 mg), total dose = 600 mg. After the five-day course of artesunate, primaquine was given: a single oral dose of 15mg for 14 days. A total number of 42 patients received treatment. All participants were followed up for 28 days. In all the cases, both parasitemia and fever were resolved rapidly; the mean fever clearance time and parasite clearance time, 14.6 and 36.7 hours, respectively, showed that therapeutic response to artesunate was better than that of chloroquine. The 14-day cure rate was 100%, but reappearance of parasitemia was seen in two patients on days 21 and 25 following treatment, respectively. These two cases of failure rate should be considered as true relapse rather than recrudescence, since the relapse interval in Southeast Asian vivax malaria according to recent findings seems to be 3 weeks after start of treatment, if primaquine is not given or an inadequate amount is given. In conclusion, artesunate might be useful in treatment of vivax malaria, causing a good blood schizontocidal effect. However, to prevent emerging resistance it should never be used alone.

Adolescent↗
PubMed2003

Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric analysis of opiates and metabolites in rat urine after inhalation of opium.

To examine the urinary excretion of opiates and their metabolites following inhalation exposure of rats to opium, analytical procedures for the simultaneous determination of the compounds in opium, the vapor derived by the volatilization of opium and the urine of rats exposed to the opium vapor were developed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). Seven compounds were determined in the opium, namely morphine, codeine, thebaine, noscapine, papaverine, meconic acid and meconin. All seven were extracted with 2.5% acetic acid solution and subjected to LC-APCI-MS analysis. The separation was performed on an ODS column in acetonitrile-50 mM ammonium formate buffer (pH 3.0) using a linear gradient program and quantitative analysis was carried out in the selected ion monitoring mode ([M+H](+)). For the analysis of the volatilization of opium, the opium (1 g) was added to a glass pipe, which was then heated at 300 degrees C for 20 min. Negative pressure (air flow-rate; 300 ml/min) was used to draw the vapor through a series of glass wool and methanol traps. The total amount of each compound in the vapor was estimated by measurement of the compounds trapped in the glass wool and methanol. Wister rats (n=3) were exposed to the vapor derived from the volatilization system and the urinary amounts (0-72 h) of the six opiates and metabolites including morphine-3-grucronide (M3G) and morphine-6-grucronide (M6G) were measured after solid-phase extraction. The calibration curves for those compounds in the rat urine were linear over the concentration range 10-500 ng/ml. The recoveries for each analyte from the rat urine sample spiked with standard solution were generally greater than 80%, and the relative standard deviation for the analytical procedure was less than 8% with the exception of meconin. After inhalation exposure of rats to opium, M3G (5.45-14.38 micro g), morphine (2.27-4.65 micro g), meconin (0.54-1.85 micro g), codeine (0.54-1.85 micro g), noscapine (0.34-0.40 micro g) and papaverine (0.01-0.04 micro g) were detected in the urine over 72 h. However, only trace levels of thebaine were observed despite it being one of the major alkaloids found in the opium. On the other hand, a relatively large amount of meconin was detected in the vapor and the urine as compared with the opium. It is suggested that the presence of meconin in biological fluids could be indicative of opium ingestion by inhalation.

Administration, Inhalation↗
PubMed2003

Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers.

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.

Animals↗
PubMed2003

A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint.

Although excessive mechanical stress is assumed to be one of the factors contributing to pathogenesis of temporomandibular joint (TMJ) osteoarthritis (OA), no pure mechanical-stress-induced OA model has been developed without surgical manipulation or puncture of the joint cavity. The purpose of this study was to establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive, forced jaw-opening, 3 hrs/day for 5 days, was applied with the use of a general anesthesia protocol. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes, and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the repetitive, forced-jaw-opening period. These results suggest that the repetitive, forced-jaw-opening protocol without surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.

Animals↗