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Biomedical subjects

K Seki

Publications and source records attributed to K Seki.

At least 19 recordsLinked to original sources

Inhibition of interleukin-8 production in human endothelial cells by Staphylococcus aureus supernatant.

Recent reports have shown that Staphylococcus aureus infection increases the expression of cytokines and cell adhesion molecules in endothelial cells and enhances leucocyte migration, thereby resulting in bacterial elimination. In this study, we analysed the production of the chemokine interleukin (IL)-8 in human umbilical vein endothelial cells (HUVEC) infected with several S. aureus strains by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We found that the avirulent strains (00-51 and 00-62) increased IL-8 production but the virulent strains (A17 and A151) decreased it at both the mRNA and protein levels. We considered that the inhibition of IL-8 production depended on certain inhibitory factor(s) secreted by bacteria. This was because S. aureus also abolished IL-8 expression in HUVEC treated with cytochalasin D, and the addition of culture supernatants of strains A17 and A151 decreased IL-8 production in HUVEC. This factor(s) in the bacterial culture supernatant inhibited both basal and tumour necrosis factor (TNF)-alpha-induced IL-8 production. In contrast, no inhibitory effect was observed on monocyte chemotactic protein-1 (MCP-1) production. These results indicate that S. aureus can down-regulate IL-8 release in endothelial cells through the secretion of inhibitory factor(s), and this may result in decreased neutrophil recruitment, thus interfering with the host immune response to bacterial infection.

Bacteriological Techniques↗

Long-term mobility of fallout 90Sr in ploughed soil, and 90Sr uptake by wheat grain.

In this study, we evaluated the mobility of 90Sr in ploughed upland soil, which affects the residual amount in the soil and plant uptake on the basis of long-term monitoring data. Paired samples of soil and wheat grain were taken annually from 1961 to 1995 from 8 agricultural fields in Japan, and the concentrations of exchangeable 90Sr in soil and total 90Sr in wheat grain were determined. The concentration of exchangeable 90Sr in ploughed soil decreased exponentially with time. The environmental factor responsible for the decrease of exchangeable 90Sr in the ploughed layer, lambda(e), was determined from the monitoring data of exchangeable 90Sr in the ploughed soil and the amount of fallout-derived deposition. The lambda(e) was larger from 1970 to 1980 than it was from 1980 to 1995, suggesting that an easily removable fraction of 90Sr in soil was preferentially lost from ploughed soil. Among various soil properties that we investigated, the main factor controlling the long-term mobility of 90Sr from ploughed upland soil and 90Sr uptake by wheat grain was the cation-exchange capacity (CEC) of soil. Our experimental results indicate that the entrapment of 90Sr on a cation-exchange site retards the downward migration and wheat uptake of 90Sr from ploughed soil. The empirical parameters that we obtained based on the long-term observation of a wheat-cultivated upland field in Japan could be used as reference data in order to roughly estimate the mobility of 90Sr in ploughed soil and soil-borne 90Sr transfer to wheat grain in the humid Japanese climate.

Agriculture↗

Terrestrial nitrogen and noble gases in lunar soils.

The nitrogen in lunar soils is correlated to the surface and therefore clearly implanted from outside. The straightforward interpretation is that the nitrogen is implanted by the solar wind, but this explanation has difficulties accounting for both the abundance of nitrogen and a variation of the order of 30 per cent in the 15N/14N ratio. Here we propose that most of the nitrogen and some of the other volatile elements in lunar soils may actually have come from the Earth's atmosphere rather than the solar wind. We infer that this hypothesis is quantitatively reasonable if the escape of atmospheric gases, and implantation into lunar soil grains, occurred at a time when the Earth had essentially no geomagnetic field. Thus, evidence preserved in lunar soils might be useful in constraining when the geomagnetic field first appeared. This hypothesis could be tested by examination of lunar farside soils, which should lack the terrestrial component.

Atmosphere↗

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women.

OBJECTIVES: Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. METHODS: Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group (n=16), hypertensive control group (n=15), normotensive HRT group (n=16) and normotensive control group (n=15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 microl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). RESULTS: CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. CONCLUSIONS: CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Aged↗

Severity of oral mucositis correlates with the response of oral cancer to preoperative radiochemotherapy.

Oral mucositis is a dose-limiting toxic effect of radiotherapy and chemotherapy on oral cancer. The purpose of the present study is to assess the relationship between tumor response and oral mucositis in preoperative radiochemotherapy for oral cancer retrospectively. Fifty-four cases of oral squamous cell carcinoma were treated with concurrent radiochemotherapy prior to surgery. When oral mucositis was evaluated with the WHO scale, severe oral mucositis (Grades 3 and 4) developed in 22 cases (41%). A more than 50% reduction in tumor size was clinically observed in 38 cases (70%). From histopathological analysis of the surgical specimens all tumor cells observed appeared to be non-viable in 16 cases (29%). The cases with Grade 1, Grade 2, Grade 3 and Grade 4 oral mucositis included 33%, 62%, 85% and 89% of clinical good-response cases and 0%, 24%, 31% and 55% of histopathological good-response cases, respectively. This retrospective study suggests that severe oral mucositis promises a good response of oral squamous cell carcinoma to radiochemotherapy.

Aged↗

An attempt to integrate Western and Chinese medicine: rationale for applying Chinese medicine as chronotherapy against cancer.

Current Western medical treatment lays its main emphasis on evidence-based medicine (EBM) and cure is assessed by quantifying the effects of treatment statistically. In contrast, in Chinese medicine, cure is generally assessed by evaluating the patient's "pattern" (Zheng) [cf. Glossary] and medicines are prescribed according to this. We believe that traditional Chinese medicine (TCM) cannot be evaluated precisely according to Western principles, in which a constant amount of the same medicine is given to a group of patients to be evaluated. When assessing cure using TCM, Zheng is more important than the determination of medical effects. This means that quantitative evaluation of TCM treatment can be very difficult. In this paper, we focused on the Yin-Yang [cf. Glossary]balance to determine Zheng, and at the same time attempted to determine the treatment effects by applying the concept of regulation of Yin-Yang according to chronotherapeutic principles. According to Zheng, advanced cancer patients generally lack both Yin and Yang. Chinese medical treatment therefore seeks to supplement both Yin and Yang. However, we divided patients into two groups and compared them with respect to survival. One group was administered a predominantly Yang (Qi) [cf. Glossary] tonic herbal treatment during the daytime, while the other group was administered Yin (Blood) [cf. Glossary] tonics during night time. A comparison of the results of treatment showed that the patients in the group receiving Yang (Qi) replenishment during the daytime lived longer than patients receiving Yin (Blood) nourishment during the night. Moreover, the patients in the daytime Yang (Qi) replenishment group also fared significantly better than patients treated solely by Western methods.

Adult↗

Phenotypic characterisation of flagellin and flagella of urease-positive thermophilic campylobacters.

In this study, flagellin is purified biochemically from eight urease-positive thermophilic camplylobacters (UPTC) isolated from river water, sea water and mussels, and purified also from two isolates of Campylobacter jejuni and C. coli and fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results showed that no flagellin components were detected in the two Japanese UPTC isolates (CF89-12 and CF89-14) and the two UPTC NCTC strains (NCTC12893 and NCTC12894). Flagellin components, each consisting of a single peptide, with a heterogeneous molecular mass of approximately 52-63 kDa were demonstrated in the other four UPTC isolates (NCTC12892, NCTC12895, NCTC12896 and NI15F [from Northern Ireland]) and the two Japanese isolates of C. jejuni (JCM2013 and C. coli 27). The approximate molecular mass of flagellin from the flagellin-positive UPTC isolates was smaller than those of C. jejuni and C. coli. Flagella were not detected by electron microscopy in the four flagellin-negative UPTC isolates but they were detected in the four flagellin-positive UPTC isolates and the two isolates of C. jejuni and C. coli. Thus, significant phenotypic diversity for flagellin, which must be due to genotypic variations, was demonstrated among the UPTC isolates.

Campylobacter↗

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Drug Evaluation, Preclinical↗

Detection of Epstein-Barr virus in saliva by real-time PCR.

The purpose of this investigation was to assess the salivary levels of Epstein-Barr virus (EBV) in patients with periodontitis using real-time PCR. EBV was detected in 16 out of 33 (48.5%) periodontitis patients and in 3 out of 20(15%) healthy subjects. The baseline mean values for bleeding on probing in EBV-positive patients were significantly higher than those in EBV-negative patients. A significant decrease in EBV levels was observed after initial periodontal treatment. Our findings indicate that levels of EBV in saliva may reflect the status of periodontal inflammation.

Adult↗

Characteristics of a newly developed dentomaxillofacial X-ray cone beam CT scanner (CB MercuRay): system configuration and physical properties.

OBJECTIVE: The purpose of this paper is to present the system configuration and physical properties of a new dentomaxillofacial X-ray cone beam CT system (CB MercuRay) being developed. METHODS: The system consists of an image intensifier and a cone beam X-ray source. There are two different models of this system, each with a different size image intensifier, 9" or 12". Each system has three field of view (FOV) modes. The 12" system has facial (F), panoramic (P) and implant (I) FOV modes. The 9" system has P, I and dental (D) modes. Images produced by these systems consist of 512 x 512 x 512 isotropic voxels. Physical properties such as resolution, noise and distortion of the images were evaluated in this study. Modulation transfer function (MTF) was measured using Boone's method. Image noise was measured as the standard deviation of the CT value in water. Circularity of the axial images yielded by the two models was measured using an 8 mm diameter acrylic pipe phantom. RESULTS: The resolving power at a MTF of 0.1 in the D mode was over 2.0 lp mm(-1), suggesting that this system yields images of high resolution. The standard deviation of the CT value in water was approximately 80, which is thought to be greater than that of conventional CT. The circularity of images of the pipe phantom was 99% of the ideal value. CONCLUSION: This study shows that our newly developed cone beam CT system produces high resolution three-dimensional volumetric images that will be useful for the examination of dentomaxillofacial disorders.

Adult↗

Roles of primate spinal interneurons in preparation and execution of voluntary hand movement.

To study the contribution of primate cervical interneurons (INs) to preparation and execution of normal voluntary hand movement we investigated their activity and correlational linkages to muscles in monkeys performing tracking tasks. During ramp-and-hold flexion-extension torques about the wrist most task-related spinal INs exhibited some activity during both flexion and extension, in unexpected contrast to the strictly unidirectional activity of corticomotoneuronal (CM) cells and motoneurons. Most INs increased their activity more in one of these two directions; response patterns in their preferred direction were typically tonic or phasic-tonic. Spike-triggered averages of EMG detected significant features in muscle activity for many task-related INs. Premotor INs (PreM-INs) were identified by post-spike facilitation or suppression with appropriate onset latencies after the trigger spike. Muscle fields of PreM-INs were smaller than those of supraspinal PreM cells in cortex and red nucleus, and rarely involved reciprocal effects on antagonist muscles. To investigate the relation of spinal INs to a repertoire of different muscle synergies, activity of INs was recorded from a macaque performing a multidirectional wrist task. The monkey generated isometric torques in flexion/extension, radial/ulnar deviation, pronation/supination, and executed a power grip that co-contracted wrist flexor and extensor muscles. Many INs showing task-modulated activity had preferred directions in this multidirectional space, typically with broadly tuned activation. The role of spinal INs in preparation for voluntary movement was revealed in monkeys performing instructed delay tasks. During the delay between a transient visual cue and a go signal a third of the tested INs showed significant delay modulation (SDM) of firing rate relative to the pre-cue rate. The SDM responses often differed from the INs' responses during the subsequent active torque period. In a monkey instructed by either visual or proprioceptive cues the delay period activity for many INs was similar in visual and perturbation trials, although other INs exhibited different SDM for visually and proprioceptively cued trials. These results suggest that spinal INs are involved, with cortex, in the earliest stages of movement preparation. The sensory input to INs could be identified in transient responses to the torque pulse, which showed two predominant patterns, consistent with inputs from cutaneous or proprioceptive receptors. We also investigated the task-dependent modulation of neural responses to peripheral input in a monkey performing wrist flexion/extension movements in a visually cued instructed delay task. Monosynaptic responses evoked by electrical stimulation of the superficial radial nerve through a cuff electrode were suppressed or abolished during the dynamic movement phase. Since task-related activity of the INs increased at the same time, the suppression was mediated by presynaptic rather than postsynaptic inhibition. These observations indicate that under normal behavioral conditions many spinal INs have response properties comparable to those previously documented for cortical neurons in behaving animals.

Animals↗

High-rate methane fermentation of lipid-rich food wastes by a high-solids co-digestion process.

This paper presents an experimental study on anaerobic degradation of lipids-rich food wastes by using the high solids co-digestion process. The experiments were conducted under mesophilic (35 degrees C) and thermophilic (55 degrees C) condition, respectively, by using a semi-continuous flow completely mixed reactor. The influent TS level was controlled at around 10%, while the hydraulic retention time (HRT) was changed from 15 days to 7.5 days. The lipids (fats or oil and grease) content in the influent TS was changed from 8% to 40% by adding salad oil (vegetable) and lard (animal) to the food wastes. The result of this study showed that the food wastes containing high lipids content was effectively degraded by the high solids co-digestion process and over 85% of lipid was degraded to biogas with 60-65% of methane. In addition, thermophilic methane fermentation was more effective for reducing lipids and had more higher loading capacity compared with mesophilic condition.

Bacteria, Anaerobic↗

Impact of maintenance chemotherapy on disease-free survival in patients with stage Ic and II epithelial ovarian cancer.

PURPOSE OF INVESTIGATION: To evaluate the impact on disease free survival (DFS) with maintenance chemotherapy following complete surgery and adjuvant chemotherapy in patients with stage Ic and II epithelial ovarian cancer by a retrospective study. METHODS: One hundred and forty patients with stage Ic and stage II epithelial ovarian cancer were classified into three groups according to the modality of maintenance chemotherapy (no therapy, oral or intravenous administration of anti-cancer drugs). DFS was compared among the three groups, and independent predictive factors for relapse were analyzed. RESULTS: There were no statistically significant differences in DFS among the three groups for either stage Ic or II cancers, stage Ic and stage II. Multivariate analysis revealed that independent predictive factors for relapse were stage II (p = 0.004) in all patients and less than three cycles of adjuvant chemotherapy in stage II patients (p = 0.015). CONCLUSION: Maintenance chemotherapy had no impact on DFS in patients with stage Ic or II epithelial ovarian cancer.

Adenocarcinoma, Clear Cell↗

Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine.

The immunohistochemical localization of connexin (Cx) 43 and Cx 45 in the musculature of the rat small intestine was studied at the ultrastructural level, with special reference to the interstitial cells of Cajal in the deep muscular plexus region (ICC-DMP). Cx 43 was localized at gap junctions formed between every group of cells, i.e., smooth muscle cell~smooth muscle cell, smooth muscle cell--ICC-DMP and ICC-DMP--ICC-DMP. In contrast, Cx 45 immunoreactivity was only detected at gap junctions between ICC-DMP--ICC-DMP. Since different types of Cx molecules have different properties for electrical and chemical coupling of cells, it is suggested that the homotypic network of ICC-DMP connected with Cx 45 gap junctions may function as an independent compartment segregated from the whole cellular network including the smooth muscle cells connected with Cx 43 gap junctions. It is further speculated that the ICC-DMP of the rat small intestine communicate with each other and with smooth muscle cells via the passage of messenger molecules through Cx 43, but they may use an additional mechanism, as yet unknown, for communications restricted to other ICC-DMP.

Animals↗

Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation.

Impaired immune responses in cancer patients have been associated with oxidative stress. Increased levels of reactive oxygen species released from activated, tumor-infiltrating macrophages or granulocytes may therefore constitute a hurdle for effective immunotherapy against cancer. In this study, we investigated functional consequences and molecular events in T cells exposed to low levels of oxidative stress. We observed that cytokine production of human PBMC, upon stimulation with an HLA-A*0201-restricted influenza peptide and nonspecific receptor cross-linking, was reduced after exposure to micromolar levels of H2O2. Functional impairment as measured by IFN-gamma release occurred earlier and at lower doses of exogenously added H2O2 than required to induce apoptosis. This suggests that there is a dose window of oxidative stress leading to T cell unresponsiveness in the absence of apoptosis. The reduction of Th1 cytokines, induced by H2O2, was predominantly observed in memory/effector (CD45RO(+)) T cells and correlated with a block in NF-kappaB activation. IL-10 production was more profoundly influenced by low doses of H2O2 than IFN-gamma, TNF-alpha, and IL-2. The influence of H2O2 on production of IL-10 was not significantly different between memory/activated and naive T cells. These observations suggest that Th1 and Th2 cytokines are differently regulated under conditions of oxidative stress. Taken together, these findings may explain why Ag-experienced, CD45RO(+), T cells found in the tumor milieu are functionally suppressed.

Apoptosis↗

Tumor necrosis factor-alpha induces coordinated changes in major histocompatibility class I presentation pathway, resulting in increased stability of class I complexes at the cell surface.

It is demonstrated that similar to interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) induces coordinated changes at different steps of the major histocompatibility complex (MHC) class I processing and presentation pathway in nonprofessional antigen-presenting cells (APCs). TNF-alpha up-regulates the expression of 3 catalytic immunoproteasome subunits--LMP2, LMP7, and MECL-1--the immunomodulatory proteasome activator PA28 alpha, the TAP1/TAP2 heterodimer, and the total pool of MHC class I heavy chain. It was also found that in TNF-alpha--treated cells, MHC class I molecules reconstitute more rapidly and have an increased average half-life at the cell surface. Biochemical changes induced by TNF-alpha in the MHC class I pathway were translated into increased sensitivity of TNF-alpha--treated targets to lysis by CD8(+) cytotoxic T cells, demonstrating improved presentation of at least certain endogenously processed MHC class I--restricted peptide epitopes. Significantly, it was demonstrated that the effects of TNF-alpha observed in this experimental system were not mediated through the induction of IFN-gamma. It appears to be likely that TNF-alpha--mediated effects on MHC class I processing and presentation do not involve any intermediate messengers. Collectively, these data demonstrate the existence of yet another biologic activity exerted by TNF-alpha, namely its capacity to act as a coordinated multi-step modulator of the MHC class I pathway of antigen processing and presentation. These results suggest that TNF-alpha may be useful when a concerted up-regulation of the MHC class I presentation machinery is required but cannot be achieved by IFN-gamma. (Blood. 2001;98:1108-1115)

ATP Binding Cassette Transporter, Subfamily B, Mem↗