Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 37 records · Page 2Linked to original sources

PubMed2003

The antibody responses to adult-worm antigens of Schistosoma haematobium, among infected and resistant individuals from an endemic community in southern Ghana.

Antibody responses to antigens from adult Schistosoma haematobium were investigated in an endemic community in Ghana, using microplate-ELISA. The results of a survey of egg output in urine and of a questionnaire-based investigation of water-contact activities were used to select 'endemic normal' (EN) and patently infected (PI) individuals as subjects. The plasma levels of antibodies reacting with the adult-worm antigens were determined and compared and the correlations between these levels and the age, water-contact index and egg output of each subject were evaluated. Compared with the EN subjects, the PI generally had higher levels of anti-worm IgG and IgE but lower levels of anti-worm IgA. When the data for the EN and PI groups were combined, the levels of anti-worm IgG and IgE were found to be positively correlated with egg output and with each other. Whichever the antibody class considered, levels of anti-worm antibodies were never negatively correlated with egg output. These results indicate that anti-worm IgE and IgG could be used as markers to reflect current infection intensity, and that anti-worm antibodies may not act as protective antibodies in the natural course of urinary schistosomiasis.

Adult↗

PubMed2003

Effects of transdermal and oral estrogen supplementation on endothelial function, inflammation and cellular redox state.

The incidence of ischemic heart disease shows a sharp rise after menopause. However, the effects of hormone replacement therapy (HRT) on cardiovascular disease are still controversial. Not only oxidative stress, but also inflammation has been suggested to play an important role in the pathogenesis of cardiovascular events. We compared the effects of HRT on endothelial function, cellular antioxidant system and inflammation between oral and transdermal administration in mild hypercholesterolemic postmenopausal women. Transdermal estradiol replacement was administrated to 12 patients (mean age 53 years) for 12 weeks, and oral conjugated equine estrogen was administrated to 12 patients (mean age 54 years) for 12 weeks. The flow-mediated endothelium-dependent dilation of the brachial artery, serum levels of thioredoxin as a marker of the cytoprotective antioxidant system, and high-sensitivity C-reactive protein (hs-CRP) were measured every 4 weeks. The flow-mediated vasodilation increased with HRT (oral, baseline 4.9 +/- 0.5, 4-week 8.9 +/- 0.7*, 8-week 9.9 +/- 0.6*, 12-week 9.4 +/- 0.7*; transdermal, 4.7 +/- 0.6, 8.3 +/- 0.7*, 9.1 +/- 0.8*, 8.9 +/- 0.9%*, * = p < 0.01 versus baseline). The thioredoxin levels decreased with HRT (oral, 26.1 +/- 7.2, 24.1 +/- 8.2, 22.1 +/- 7.8, 19.1 +/- 7.0*; transdermal, 26.9 +/- 7.4, 23.4 +/- 8.7, 21.1 +/- 7.9, 19.2 +/- 7.2 ng/ml*, * = p < 0.01 versus baseline). There were no differences in the variation of the flow-mediated vasodilation or thioredoxin concentrations between the 2 groups. The hs-CRP levels increased with oral HRT (0.32 +/- 0.12, 0.72 +/- 0.17*, 0.86 +/- 0.23*, 0.88 +/- 0.21 mg/dl*, * = p < 0.01 versus baseline), while transdermal HRT did not elicit any changes (0.35 +/- 0.15, 0.34 +/- 0.17, 0.38 +/- 0.20, 0.36 +/- 0.22 mg/dl). The differences of hs-CRP concentrations between the 2 groups analyzed by 2-way ANOVA were significant (p < 0.01). Oral HRT instigated inflammation, but transdermal did not. Both oral and transdermal HRT, however, improved endothelial function and decreased oxidative stress through affecting the cellular redox state. These differentials in the effects caused by the course of administration may affect the future cardiovascular events.

Administration, Cutaneous↗

PubMed2003

Mapping soil-transmitted helminths in Southeast Asia and implications for parasite control.

Establishing the current status and distribution of soil-transmitted helminths is essential for developing and implementing parasite control. Although Southeast Asia is known to have a high prevalence of infection, a precise estimate of the total disease burden has not been fully described. Here, we use Geographical Information Systems (GIS) to collate and map recent published surveys on soil-transmitted helminth epidemiology and distribution for this region. Distinct geographical variation was observed, which is suggested to reflect climatic variation, as well as behavioral differences. However, for much of the region few data are available, and therefore it proved necessary to generate predictions of the distribution of soil-transmitted helminths using remotely sensed (RS) satellite sensor environmental variables. A significant finding was the importance of land surface temperature in influencing the distribution of Ascaris lumbricoides and Trichuris trichiura. Spatial analyses using RS satellite sensor data were then used to generate predictive maps of infection risk. This information provided the basis for an estimate of the population at risk of infection and the numbers requiring treatment. These applications of GIS and remote sensing provide a good basis for developing control of soil-transmitted helminths in the region.

Animals↗

PubMed2002

Claudin 5 is transiently expressed during the development of the retinal pigment epithelium.

During the development of chick retinal pigment epithelium (RPE), the permeability and selectivity of the epithelium's tight junctions are continuously modulated. Overall paracellular permeability decreases, but selectivity increases. Because the claudin family of transmembrane proteins appears to provide the structural basis for selectivity, we examined the expression of claudins as a function of development in chick RPE. Degenerate primers were used with the reverse transcriptase-polymerase chain reaction (RT-PCR) to obtain complete sequences of chick claudins 3 and 5. Northern blotting and semi-quantitative RT-PCR demonstrated that claudin 5 was expressed in RPE, but claudin 3 was expressed only in the choroid layer of the eye. Northern blotting, semiquantitative RT-PCR and immunoblotting demonstrated that the expression of claudin 5 was transient, with peak levels of expression between embryonic days 10 and 14. Primary cultures were used to demonstrate that factors secreted by the neural retina induced the expression of claudin 5 nearly 3-fold if RPE was isolated from embryonic day 7 embryos. There was little effect if RPE was isolated from embryonic day 14. The upregulation of claudin 5 correlates with permeability changes that occur during the intermediate stage of RPE development. Interestingly, claudin 5 must be replaced during the late stage of development when the number and complexity of tight junctional strands increases. This would imply more changes in selectivity.

Amino Acid Sequence↗

PubMed2002

Expression of tegument protein pp65 of human cytomegalovirus (CMV) and its application to the analysis of viral-specific cellular immunity in CMV-infected individuals.

Investigations into human cytomegalovirus (CMV)-specific cellular immunity are important to better understand and manage CMV infections. CMV phosphoprotein pp65 is thought to be a major antigen for CMV-specific cellular immunity. We newly synthesized protein pp65 with a baculovirus expression system and purified it via metal affinity chromatography in a soluble form. The recombinant protein pp65 was antigenic in an enzyme immuno-linked assay for pp65-specific IgG in sera from 196 children. Traditional lymphoproliferation assays have shown that pp65 protein promotes specific lymphoproliferation in CMV-seropositive donors. Using an intracellular cytokine detection system, we showed that this recombinant protein stimulated CD4-positive T cells to express interferon-gamma. The results of these assays using protein pp65 were comparable with the use of CMV whole antigen. pp65- and CMV-specific cellular immunity, and CMV DNA load were also compared in four recipients of unrelated cord blood transplantation. The delay in re-constitution in CMV-specific cellular immunity was associated with reactivation of CMV. These results indicated that the recombinant protein pp65 can be used to study specific immunity in CMV infections.

Adolescent↗

PubMed2002

Radioiodination of glycoprotein-conjugated liposomes by using the Bolton-Hunter reagent and biodistribution in tumor-bearing mice.

We have developed a suitable radiolabeling method for our new type of glycoprotein-liposome conjugate (GCL), in order to investigate its potential utility as a drug carrier that can target the cellular functions of carbohydrate-binding proteins. In order to obtain radiolabeled GCL with high labeling efficiency, we introduced p-hydroxyphenylpropyl groups into the liposome membrane through the amine moiety of a constitutive phospholipid, dipalmitoylphosphatidylethanolamine (DPPE) by using Bolton-Hunter reagent (BHR). Radioiodination of the introduced tyrosyl groups was performed by the Chloramine-T method. The labeling efficiency of the BHR-treated liposome conjugate was high in comparison with that of the BHR-untreated liposome conjugate. An in vitro inhibition study showed that the binding affinity of 125I-labeled BHR-treated GCL (125I-F3S-BH) with lectin was twice as high as that of untreated conjugate (125I-F3S). The biodistribution of 125I-F3S-BH in mice was considerably different from that of 125I-F3S. 125I-F3S-BH was more rapidly taken up by the liver and was more rapidly excreted from the liver than 125I-F3S. Moreover, 125I-F3S-BH accumulated more rapidly into the kidneys, which resulted a lower radioactivity in the blood circulation at an earlier time point than in the case of 125I-F3S. The characteristics of tumor accumulation of 125I-F3S-BH and 125I-F3S were similar to those in blood. If F3S is to be employed as an in vivo targeting ligand in biodistribution studies, BHR would be a suitable tool for radiolabeling because it allows GCL to retain the biological activity and characteristics of the unmodified conjugate.

Animals↗

PubMed2002

Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group.

Prognostic factors of juvenile myelomonocytic leukemia (JMML) have not been clarified because of its very low incidence and inaccuracy in the diagnosis. The purpose of this study was to evaluate children with JMML given an allogeneic hematopoietic stem cell transplantation (SCT) and the role of different variables potentially influencing outcome in a nationwide survey in Japan based on the newly proposed criteria by the International JMML Working Group. The study patients were 27 children who underwent SCT among 55 JMML patients retrospectively collected in the survey. The source of grafts was HLA-identical siblings in 12 cases, HLA-matched unrelated individuals in 10 and others in five. Total body irradiation was used in 18 cases. Event-free and overall survival (OS) at 4 years after SCT were 54.2 +/- 11.2% (s.e.) and 57.9 +/- 11.0% (s.e.), respectively. Six patients died of relapse and three of complications. Patients with abnormal karyotypes showed a significantly lower OS than those with normal karyotypes (P < 0.001). Patients below 1 year of age showed a significantly higher OS than those of 1 year of age or more (P = 0.02). Patients with grade 0-1 acute graft-versus-host disease (GVHD) or chronic GVHD had a more favorable OS than those without them, although they were not statistically significant (P > 0.05). Other variables studied were not associated with OS. A multivariate analysis of these factors yielded the abnormal karyotype as the only significant risk factor for lower OS (risk ratio: 11.0; 95% CI: 2.7-45.1).

Adolescent↗

PubMed2002

Donor selection in Japan: a trial of new criteria with predonation haemoglobin testing.

BACKGROUND AND OBJECTIVES: In Japan, eligibility for blood donation depends on blood specific gravity, which does not directly measure blood haemoglobin. Additionally, the criteria are not based on normal values. Therefore, we investigated the feasibility of predonation screening by using actual haemoglobin levels, and adopted a new criterion based on the normal range for men. MATERIALS AND METHODS: Using a portable device, we measured haemoglobin in 1032 prospective blood donors, then applied this method to all blood donations. The criterion for men was set at the 95th percentile of haemoglobin distribution, namely 13.0 g/dl and 13.5 g/dl, respectively, for 200-ml and 400-ml donations. That for women remained unchanged. RESULTS: The percentage of men ineligible by these criteria increased from 0.6 to 1.5%, while that of women decreased from 16.5 to 14.6%. Donors with abnormal haemoglobin levels were referred to hospitals. CONCLUSION: Predonation measurement of haemoglobin concentration, combined with the referral of those with abnormal values, provided a health benefit to that population.

Adult↗

PubMed2002

Wide distribution of Plasmodium ovale in Myanmar.

The presence of Plasmodium ovale has never been previously reported in Myanmar. Using blood samples obtained in many villages across the country between 1996 and 2000, molecular diagnosis of Plasmodium species was made with semi- or full-nested polymerase chain reaction (PCR) with species-specific primers, followed by agarose gel electrophoresis to detect amplification products. The presence of P. ovale was also confirmed with the another PCR-based diagnosis, the microtiterplate hybridization (MPH) method using species-specific probes. Both methods target the A type of the small subunit ribosomal RNA gene of the four human malaria parasites. Plasmodium ovale DNA was amplified in samples from 65 (4.9%) of 1323 PCR-positive patients, with perfect agreement between results obtained by nested PCR and MPH. Only four P. ovale-infected patients had single-species infection; all others were coinfected with P. falciparum, P. vivax and/or P. malariae. Quadruple infections were observed in six subjects. Parasites with typical P. ovale morphology were found in only 19 patients by conventional microscopy of Giemsa-stained thin smears or fluorescence microscopy of acridine orange-stained thin smears. Plasmodium ovale infections were found in villages situated in the southern, central and western regions of Myanmar, suggesting that P. ovale may be widely distributed in this country.

Adolescent↗

PubMed2002

Kinetics of the nucleoside triphosphate hydrolase of Toxoplasma gondii in mice with acute and chronic toxoplasmosis.

The kinetics of the nucleoside triphosphate hydrolase (NTPase) of Toxoplasma gondii was examined using an avidin-biotin sandwich-ELISA (ABS-ELISA) based on an anti-NTPase monoclonal antibody, 6C6. The RH and ME49 strains of the parasite were used to produce acute and chronic infections in mice, respectively. In the acute model, detectable serum concentrations of NTPase were observed from day 1 post-infection and gradually increased until the death of the mice. They were associated with parasitaemia (as estimated by bioassay). No anti-T. gondii antibody could be detected at any time. In the chronic model, in which 20 T. gondii ME49 cysts were given to each mouse per os, the NTPase concentration generally increased from day 3, peaked between days 7 and 14 and then declined. However, one of the four mice used still had a high serum concentration of NTPase on day 35. Again, detectable NTPase concentrations occurred when the mice had parasitaemias. Antibody to T. gondii was detected from day 7 (IgM) or 10 (IgG) and brain cysts were observed from day 14. Since detectable serum concentrations of NTPase appear to be associated with parasitaemia in both acute and chronic toxoplasmosis, the ABS-ELISA of the enzyme may make a useful diagnostic tool.

Acid Anhydride Hydrolases↗

PubMed2002

A cross-sectional study of intestinal parasitic infections among schoolchildren in Nan Province, Northern Thailand.

A cross-sectional study of the prevalence of intestinal parasitic infections at eight schools in Bo Klau district and four schools in Chalerm Prakiet district, Nan Province, in January and February, 2001. A total of 1,010 fecal samples were examined using the formalin-ether sedimentation technique. Results revealed that the rate of helminthic infection was 60.0%, while protozoa accounted for 36.2% of infections; mixed infections were common, resulting in a total prevalence of both parasites of 68.1%. Helminthic parasites, listed by frequency of infections, were Ascaris lumbricoides (21.7%), hookworm (18.5%), Trichuris trichiura (16.3%), Opisthorchis viverrini (1.7%), Strongyloides stercoralis (0.9%) and Enterobius vermicularis (0.9%). The protozoal infections were Entamoeba coli (25.8%), Giardia lamblia (5.3%), Endolimax nana (2.5%), Entamoeba histolytica (1.4%), Blastocystis hominis (0.8%), Chilomastix mesnili (0.3%) and Iodamoeba bütschlii (0.1%). This study emphasizes the need for improved environmental hygiene ie clean water supplies and enhanced sanitation, in affected communities. Health promotion, by means of a school-based educational approach is recommended; regular check-ups should be implemented, and a continuos program of treatment should be considered.

Child↗

PubMed2001

The influence of moving auditory stimuli on standing balance in healthy young adults and the elderly.

The maintenance of postural balance depends on effective and efficient feedback from various sensory inputs. The importance of auditory inputs in this respect is not, as yet, fully understood. The purpose of this study was to analyse how the moving auditory stimuli could affect the standing balance in healthy adults of different ages. The participants of the study were 12 healthy volunteers, who were divided into two age categories: the young group (mean = 21.9 years) and the elderly group (mean = 68.9 years). The instrument used for evaluation of standing balance was a force plate for measuring body sway parameters. The toe pressure was measured using the F-scan Tactile Sensor System. The moving auditory stimulus produced a white-noise sound and binaural cue using the Beachtron Affordable 3D Audio system. The moving auditory stimulus conditions were employed by having the sound come from the right to left or vice versa at the height of the participant's ears. Participants were asked to stand on the force plate in the Romberg position for 20 s with either eyes opened or eyes closed for analysing the effect of visual input. Simultaneously, all participants tried to remain in the standing position with and without auditory stimulation that the participants heard from the headphone. In addition, the variables of body sway were measured under four conditions for analysing the effect of decreased tactile sensation of toes and feet soles: standing on the normal surface (NS) or soft surface (SS) with and without auditory stimulation. The participants were asked to stand in a total of eight conditions. The results showed that the lateral body sway of the elderly group was more influenced than that of the young group by the lateral moving auditory stimulation. The analysis of toe pressure indicated that all participants used their left feet more than their right feet to maintain balance. Moreover, the elderly had the tendency to be stabilized mainly by use of their heels. The young group were mainly stabilized by the toes of their feet. The results suggest that the elderly may need a more appropriate stimulus of tactile and auditory sense as a feedback system than the young for maintaining and control of their standing postures.

Acoustic Stimulation↗

PubMed2001

Optical detection of neuromodulatory effects of conditioned taste aversion in the pond snail Lymnaea stagnalis.

Multiple site optical recording was used to analyze the neural activity changes caused by conditioned taste aversion (CTA) training in the pond snail Lymnaea stagnalis. In response to electrical stimulation of the median lip nerve, which transmits chemosensory signals of appetitive taste to the central nervous system, we optically detected large numbers of spikes in several parts of the buccal ganglion. The effects of CTA training on the spike responses were examined in two areas of the ganglion where the most active neural responses occurred. In one area (termed Area I) that included the N1 medial (N1M) cells, a class of central pattern generator interneurons involved in feeding behavior, the number of spikes in a period 1500-2000 ms after median lip nerve stimulation was significantly reduced in conditioned animals compared to control animals. In another area (termed Area II) positioned between buccal motoneurons, the B3 and B4CL (cluster) cells, the evoked spike responses were unaffected by CTA training. These results, taken together with our previous results indicating an enhancement of an inhibitory input to the N1M cells during CTA, suggest that an appetitive taste signal transmitted to the N1M cells through the median lip nerves is suppressed during CTA, resulting in a decrease of the feeding response.

Action Potentials↗

PubMed2001

Conformational change in the stator of the bacterial flagellar motor.

MotA and MotB are integral membrane proteins of Escherichia coli that form the stator of the proton-fueled flagellar rotary motor. The motor contains several MotA/MotB complexes, which function independently to conduct protons across the cytoplasmic membrane and couple proton flow to rotation. MotB contains a conserved aspartic acid residue, Asp32, that is critical for rotation. We have proposed that the protons energizing the motor interact with Asp32 of MotB to induce conformational changes in the stator that drive movement of the rotor. To test for conformational changes, we examined the protease susceptibility of MotA in membrane-bound complexes with either wild-type MotB or MotB mutated at residue 32. Small, uncharged replacements of Asp32 in MotB (D32N, D32A, D32G, D32S, or D32C) caused a significant change in the conformation of MotA, as evidenced by a change in the pattern of proteolytic fragments. The conformational change does not require any flagellar proteins besides MotA and MotB, as it was still seen in a strain that expresses no other flagellar genes. It affects a cytoplasmic domain of MotA that contains residues known to interact with the rotor, consistent with a role in the generation of torque. Influences of key residues of MotA on conformation were also examined. Pro173 of MotA, known to be important for rotation, is a significant determinant of conformation: Dominant Pro173 mutations, but not recessive ones, altered the proteolysis pattern of MotA and also prevented the conformational change induced by Asp32 replacements. Arg90 and Glu98, residues of MotA that engage in electrostatic interactions with the rotor, appear not to be strong determinants of conformation of the MotA/MotB complex in membranes. We note sequence similarity between MotA and ExbB, a cytoplasmic-membrane protein that energizes outer-membrane transport in Gram-negative bacteria. ExbB and associated proteins might also employ a mechanism involving proton-driven conformational change.

Agar↗

PubMed2001

Phosphorylation of retinoid X receptor alpha at serine 260 impairs its metabolism and function in human hepatocellular carcinoma.

Retinoids induce apoptosis and differentiation of hepatocellular carcinoma (HCC) cells and are used clinically in the chemoprevention of HCC. We have shown previously that hepatocarcinogenesis is accompanied by accumulation of full-length retinoid X receptor alpha (RXRalpha), although the underlying mechanisms and biological implications have remained unclear. The present studies were based on the finding that the accumulated full-length RXRalpha was phosphorylated at serine/threonine residues both in all human HCC tissues examined and in human HCC-derived HuH7 cells. Phosphorylation at serine 260 of RXRalpha, a consensus site of mitogen-activated protein kinase, was closely linked to its retarded degradation, low transactivating activity, and the promotion of cancer cell growth. There was no genomic mutation in the RXRalpha gene, and abrogation of phosphorylation by mitogen-activated protein kinase-specific inhibitors restored the degradation of RXRalpha in an RXR ligand-dependent manner. These results suggest that phosphorylation of RXRalpha may interfere with its metabolism and signaling in human HCC, which could lead to growth promotion of these tumors.

Carcinoma, Hepatocellular↗

PubMed2001

Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.

Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibitors in which 3-acyltetronic acid is used as a "core" phosphate mimic. A series of novel tetronic acid derivatives were synthesized and evaluated as inhibitors of the dual-specificity protein phosphatases VHR and cdc25B. Several compounds are found to be potent inhibitors of cdc25B, which is a key enzyme for cell-cycle progression. The promising results described herein strongly indicated that this tetronic acid library is potent as a library focused on the PTP/DSP-selective inhibitor.

Cell Cycle Proteins↗

PubMed2001

Cytotoxic T cell activity against the peptide, AYRARALEL, from Yo protein of patients with the HLA A24 or B27 supertype and paraneoplastic cerebellar degeneration.

OBJECTIVE: To determine a peptide that reacts with cytotoxic T cells (CTL) of patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies with either HLA A24 or B27 supertype. METHOD: We studied CTL activity of four patients, three were HLA A24-positive and one did not have HLA A24 but had B27 supertype. After an incubation of mononuclear cells with or without peptide and IL-2, CD8-rich fraction was prepared by treatment with Magnetic Cell Sorting system (MACS) twice. CTL activity was calculated by 51Cr release from transfectant, C1RA*2402 as target cells. The peptide-binding assay was examined by flow cytometry. RESULTS: Two of three HLA A 24-positive patients demonstrated CTL activity against the Yo peptide, AYRARALEL. CTL activity was found to be 19.5% and 11.7% at the effector/target (E/T) ratio of 23:1 and 11:1, respectively. A patient who did not have HLA A24 but had A2 and B27 supertype possessed a CTL activity of 19.4% with 15:1 as E/T ratio. The peptide could bind to HLA A*2402 molecules but not to A*0201. CONCLUSIONS: We showed CTL activity in two of three Japanese patients with HLA A24 by using HLA A*2402 transfectant cells as the target. In addition, we identified the first Japanese patient who had B27 supertype, and suggested that the same peptide, AYRARALEL, could be recognized by CTL in this patient.

Autoantigens↗

PubMed2001

Highly selective one-pot synthesis of spirophosphoranes exhibiting reversed apicophilicity by oxidation of dianions generated from P-H spirophosphorane.

[see reaction]. Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the basis of the procedures, O-cis phosphorane bearing an aryl group (R = 2,4,6-tri-i-propylphenyl) could be isolated for the first time; the procedure is also applicable for alkyl derivatives. Particularly effective was the use of I2 as an oxidizing reagent.

Journal Article↗