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Biomedical subjects

S Watanabe

Publications and source records attributed to S Watanabe.

At least 379 records · Page 21Linked to original sources

The somatosensory evoked magnetic fields.

Averaged magnetoencephalography (MEG) following somatosensory stimulation, somatosensory evoked magnetic field(s) (SEF), in humans are reviewed. The equivalent current dipole(s) (ECD) of the primary and the following middle-latency components of SEF following electrical stimulation within 80-100 ms are estimated in area 3b of the primary somatosensory cortex (SI), the posterior bank of the central sulcus, in the hemisphere contralateral to the stimulated site. Their sites are generally compatible with the homunculus which was reported by Penfield using direct cortical stimulation during surgery. SEF to passive finger movement is generated in area 3a or 2 of SI, unlike with electrical stimulation. Long-latency components with peaks of approximately 80-120 ms are recorded in the bilateral hemispheres and their ECD are estimated in the secondary somatosensory cortex (SII) in the bilateral hemispheres. We also summarized (1) the gating effects on SEF by interference tactile stimulation or movement applied to the stimulus site, (2) clinical applications of SEF in the fields of neurosurgery and neurology and (3) cortical plasticity (reorganization) of the SI. SEF specific to painful stimulation is also recorded following painful stimulation by CO(2) laser beam. Pain-specific components are recorded over 150 ms after the stimulus and their ECD are estimated in the bilateral SII and the limbic system. We introduced a newly-developed multi (12)-channel gradiometer system with the smallest and highest quality superconducting quantum interference device (micro-SQUID) available to non-invasively detect the magnetic fields of a human peripheral nerve. Clear nerve action fields (NAFs) were consistently recorded from all subjects.

Brain Mapping↗

Ganglioside GD1a enhances immunoglobulin production by human peripheral blood mononuclear cells.

We previously reported that ganglioside GD1a greatly enhanced spontaneous immunoglobulin (Ig) production by human peripheral blood mononuclear cells (PBMC) in vitro. We herein examined the mechanism for the stimulatory effect of GD1a.PBMC from healthy volunteers were cultured with GD1a. The amounts of IgG, IgM, and IgA and cytokine activity in the culture supernatants were measured by enzyme-linked immunosorbent assays. Proliferation was determined by [3H] thymidine uptake.GD1a at 10(-6) M increased IgG, IgM, and IgA production by PBMC 2.10-fold, 2.10-fold, and 2.23-fold above the control values, respectively. GD1a did not affect the proliferation and viability of PBMC. GD1a did not alter Ig production of B cells alone. Anti-interleukin-6 (IL-6) or anti-IL-10 antibody each partially blocked the GD1a-induced enhancement of Ig production by PBMC, and the addition of both antibodies completely blocked the enhancement. GD1a increased IL-6 and IL-10 production of monocytes without altering those of T cells or B cells. The supernatant from GD1a-treated monocytes enhanced B cell Ig production to a greater extent than that from medium-treated monocytes. The supernatant-mediated effect of GD1a was partially blocked by anti-IL-6 or anti-IL-10 antibody, and the addition of both antibodies completely blocked the GD1a effect. GD1a-induced increases of IL-6 and IL-10 production in monocytes were both blocked by Ca(2)+/calmodulin (CaM)-dependent phosphodiesterase (PDE) inhibitors, 8-methoxymethyl-3-isobutyl-1-methylxanthine and vinpocetin, but not by other signal-transducing enzyme inhibitors. The culture with GD1a enhanced Ca(2)+/CaM-dependent PDE activity in monocytes. These results suggest that GD1a may indirectly enhance B cell Ig production in whole PBMC by increasing IL-6 and IL-10 production of monocytes via promoting Ca(2)+/CaM-dependent PDE activity.

1-Methyl-3-isobutylxanthine↗

Divergence of glyceraldehyde-3-phosphate dehydrogenase isozymes in Saccharomyces cerevisiae complex.

Although sake yeasts are placed in Saccharomyces cerevisiae, we have been interested in their difference from the other subgroups of the species, and examined their proteins. When SDS-PAGE patterns of their soluble proteins were compared, specific differences between subgroups were found in their 36,000 Da regions. Proteins isolated therefrom were found to be subunits of three isomers of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from their N-terminal amino acid sequences and identified with anti-GAPDH serum. Therefore, comparison of zymogram was carried out by a modified method: denatured monomers were observed and the enzyme activity of their oligomers was not considered. SDS-PAGE patterns of all the sake yeasts differed from those of the other strains of S. cerevisiae. Strains of Saccharomyces bayanus showed uniform patterns which are different from the above two groups. Saccharomyces pastorianus strains resembled S. bayanus and were partly similar to S. cerevisiae in their patterns, in agreement with the hypothesis that S. pastorianus is a hybrid between these two species. Patterns of S. paradoxus appeared to be rather similar to those of sake yeasts. Results on the other species of the genus and on the preliminary experiments on PAGE of native isozymes are also described.

Alcoholic Beverages↗

Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease.

OBJECTIVES: This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans. BACKGROUND: The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the KATP channel in the PC effect in humans are still unclear. METHODS: Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 microg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 microg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined. RESULTS: In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST. CONCLUSION: In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a KATP channel opener with a nitrate-like effect but not ISDN. This suggests that the opening of KATP channels plays an important role in the protecting effect of NC.

Angina Pectoris↗

Absence of somatic RET gene mutation in sporadic parathyroid tumors and hyperplasia secondary to uremia, and absence of somatic Men1 gene mutation in MEN2A-associated hyperplasia.

Germline mutations of the MEN1 gene are found in more than 85% of multiple endocrine neoplasia type 1 (MEN 1) patients, and germline mutations of the RET gene are found in more than 95% of multiple endocrine neoplasia type 2 (MEN2) patients. Parathyroid hyperplasia is seen in more than 90% of MEN 1 and about 15% of MEN2A patients. To date, somatic MEN1 mutations are reported in about 20% of sporadic parathyroid tumors. To elucidate the genetic basis of parathyroid tumor development, we examined somatic RET gene mutations in sporadic parathyroid tumors and hyperplasia secondary to uremia, and somatic MEN1 gene mutations in parathyroid hyperplasia from MEN2A patients. A total of 145 parathyroid tumors comprising 129 sporadic parathyroid tumors, 14 hyperplastic lesions secondary to uremia, and two hyperplastic lesions from MEN2A patients were examined. DNA was extracted from fresh frozen parathyroid tissue. Exons 2-10 of the MEN1 gene and exons 10 and 11 of the RET gene were sequenced. No somatic RET gene mutations were found in the 129 sporadic parathyroid tumors or 14 parathyroid hyperplastic lesions secondary to uremia. No somatic MEN1 gene mutations were found in the two parathyroid hyperplasia from MEN2A patients. These data suggest that RET gene mutation may not be involved in the development of sporadic parathyroid tumors and hyperplasia secondary to uremia and that MEN1 gene mutation may not be or is rarely associated with development of parathyroid hyperplasia in MEN2A patients.

Aged↗

Usefulness of quick intraoperative measurements of intact parathyroid hormone in the surgical management of hyperparathyroidism.

We investigated the use of quick measurement of intraoperative intact parathyroid hormone (I-PTH) to predict the outcome of parathyroidectomy. We examined intraoperative monitoring of I-PTH in 34 consecutive primary hyperparathyroidism (pHPT) patients operated on between April and December 1999. The average patient age was 56 +/- 13 years, and all but one were women. Four had a history of thyroidectomy. Blood samples were drawn before excision of enlarged parathyroid gland(s) and at 2, 5, 10, and 15 minutes afterward. Plasma I-PTH was measured by a two-site immunochemiluminometric assay. Twenty-three patients were shown to have single gland disease, and ten had multiglandular disease. All patients, except one, underwent successful parathyroidectomies. The plasma I-PTH value 15 minutes after removal of enlarged gland(s) had dropped to 26 +/- 10% of pre-excision I-PTH value. In one patient with a previous history of thyroidectomy for thyroid papillary cancer, no gland enlargement was found in the area where the lesion had been suggested by both ultrasonography and 99mTc sestamibi scanning. In this case, intraoperative measurements of I-PTH in the bilateral internal jugular veins identified an ectopic parathyroid tumor, which was successfully removed. We conclude that quick measurement of intraoperative I-PTH is a valuable tool for decision-making, especially for reoperative parathyroid surgery, for patients with previous history of thyroidectomy, and for patients in whom unilateral neck exploration or a single-gland approach is scheduled based upon preoperative localization.

Female↗

Recent onset of abdominal pain in a patient with advanced breast cancer.

Abdominal pain is a frequent complaint heard in medical practice. For palliative care patients, there are numerous causes of abdominal pain. Because of the non-invasive nature of palliative care practice, emphasis is made on minimal investigations. We present a case of a 49-year old patient who developed progressive abdominal pain and was found to have gangrenous appendicitis. The patient underwent surgery and was able to be discharged home. Our findings suggest that any new pain in a cancer patient must be carefully evaluated. Because of the presence of opioid analgesics and corticosteroids, symptoms can be less severe and related to diagnosis in palliative care patients.

Breast Neoplasms↗

Effect of imidapril on myocardial remodeling in L-NAME-induced hypertensive rats is associated with gene expression of NOS and ACE mRNA.

Chronically administered N(omega)nitro-L-arginine methyl ester (L-NAME) produces vascular structural changes and fibrosis of the left ventricle (LV). However, very few studies have evaluated whether the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on these myocardial remodelings are associated with local gene expression of nitric oxide synthase (NOS) and ACE mRNA in the LV. Effects of long term treatment with imidapril, an ACE inhibitor, on gene expression of endothelial-cell NOS (eNOS) and ACE mRNA in the LV and its relation to myocardial remodeling in L-NAME-induced hypertensive rats were evaluated. Fifteen male Sprague-Dawley rats were given L-NAME (60 mg/ kg/day) in drinking water for 6 weeks to induce hypertension, and then treated with imidapril (L-NAME-I, n = 8, 1 mg/kg/day, subdepressor dose), or a vehicle (L-NAME-V, n = 7) for 4 weeks. Age-matched rats (C, n = 7) served as a control group. Blood pressure in L-NAME-V and L-NAME-I was similar and significantly higher than that in C. The level of eNOS mRNA in the LV was significantly decreased in L-NAME-V compared with C, and was significantly increased in L-NAME-I compared with C and L-NAME-V. The ACE mRNA and type I collagen mRNA expression levels were significantly increased in L-NAME-V compared with C, and significantly suppressed in L-NAME-I compared with L-NAME-V. L-NAME-V demonstrated a significant increase in wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These changes in the microvasculature were improved significantly by imidapril. Myocardial remodeling in L-NAME-induced hypertensive rats was significantly ameliorated by a subdepressor dose of imidapril, which may be due to an increase in local eNOS mRNA expression and a decrease in angiotensin II in the LV.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of distraction on pain-related somatosensory evoked magnetic fields and potentials following painful electrical stimulation.

We aimed to compare the effects of distraction on pain-related somatosensory evoked magnetic fields (pain SEF) following painful electrical stimulation with simultaneous recordings of evoked potentials (pain SEP). Painful electrical stimuli were applied to the right index finger of eleven healthy subjects. A table with 25 random two-digit numbers was shown to the subjects, who were asked to add 5 numbers of each line in their mind (calculation task) or to memorize the numbers (memorization task) during the recording. In the SEF recording, 3 short-latency components within 50 ms of the stimulation were generated in the primary sensory cortex (SI) of the hemisphere contralateral to the stimulated finger. Middle-latency components between 100 and 250 ms after the stimuli were recorded from the secondary somatosensory cortex (SII) in the bilateral hemispheres or the cingulate cortex. No SEF components were significantly affected by either task. In the SEP recording, the middle-latency components (N140 and P230) were identified as being maximal around the vertex. Amplitudes of the N140 and P230 were not affected by each task, but the peak-to-peak amplitude (N140-P230) was significantly decreased by both the calculation and memorization tasks, particularly by the former. Subjective pain rating was decreased in both the calculation and memorization tasks, particularly in the former. We concluded that distraction tasks reduced activities in the limbic system, in which the middle-latency EEG component probably generated, while neither the short-latency SEF components generated in SI nor the primary pain-related SEF components generated in SII-insula are affected.

Adult↗

Characterization of the physicochemical properties of the micelles by the novel platelet activating factor receptor antagonist E5880.

E5880, a novel platelet activating factor receptor antagonist, was dispersed in the buffer solution (4.8 mM citric acid, 10% lactose, pH 2.8) for the preparation of an injectable formulation and the physicochemical properties of the micelles were characterized. The critical micelle concentration of E5880 was 0.12 mM. Using the area per molecule results, the critical packing parameter was calculated and showed that the structure was spherical and the number of molecules in the aggregates was 46. The diameter of the micelle was 5.6 nm. The micropolarity around the hydrocarbon region of the micelle was similar to that of isobutanol.

Algorithms↗

Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines.

Millimolar concentrations of chlorogenic acid (CGA) showed higher cytotoxic activity against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines, as compared with that against human gingival fibroblast (HGF). The cytotoxic activity of CGA was significantly reduced by catalase or CoCl2, but not affected by FeCl3 or CuCl2. ESR spectroscopy showed that higher (millimolar) concentrations of CGA produced radicals under alkaline conditions, acting as a prooxidant, whereas lower concentrations of CGA scavenged superoxide and hydroxyl radical. CGA produced large DNA fragments (as identified by slightly faster migrating band of DNA on agarose gel electrophoresis) and nuclear condensation (as demonstrated by Hoechst (No. 33258) staining) in tumor cell lines. Activation of caspase was demonstrated by staining with M30 monoclonal antibody, which reacts with degradation products of cytokeratin 18. Contact with CGA for at least 6 h was necessary for irreversible cytotoxicity induction. Pretreatment of the cells with caspase 3 inhibitor partially inhibited the cytotoxic action of CGA. These date suggest that CGA induces cytotoxicity in oral tumor cell lines, possibly by hydrogen peroxide-mediated oxidation mechanism.

Anticarcinogenic Agents↗

Serum alpha-glutathione S-transferase: a new marker of hepatocellular damage associated with hepatectomy.

Serum concentrations of alpha-glutathione S-transferase (alphaGST) were determined before and after hepatectomy to examine the clinical usefulness of alphaGST as a marker of hepatocellular damage compared with the conventional liver function tests. Prior to hepatectomy, serum alphaGST concentrations correlated significantly with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In patients who had a good postoperative course, serum alphaGST concentrations rose significantly to a peak immediately after surgery, followed by a rapid fall to the normal range within 1 week, yielding a monophasic pattern. Serum alphaGST concentrations reached a peak earlier than other parameters of liver function, and peak serum alphaGST concentrations correlated with peak serum concentrations of AST and ALT. The mean decrease rate of serum alphaGST concentration from peak values was significantly more rapid than that of serum AST and ALT, indicating an early return of alphaGST concentrations to the normal range. These findings suggest that serum alphaGST may be a more sensitive marker of hepatocellular damage than transaminases and may therefore be useful for rapid monitoring of the extent and persistence of liver injury after hepatectomy.

Journal Article↗

Development of an enzyme-linked immunosorbent assay for the fungicide imazalil in citrus fruits.

Imazalil has been widely used in citrus fruits such as lemons, oranges, and grapefruits. A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the detection of residual imazalil in citrus fruits. A monoclonal antibody (MoAb) generated to the synthetic imazalil hapten (EIT-0073)-protein conjugate was used. This assay was applied to lemon, orange, and grapefruit matrices for an imazalil analysis. The acceptable residue level for lemons, oranges, and grapefruits in Japan is 5 ppm. The matrix interference was minimized by direct dilution of the sample homogenate. No further cleanup was needed. The detection limit for imazalil in these citrus fruits was 0.1 ng/mL. The recovery of each fortified citrus fruit sample was >81.0%. The imazalil recovery measured by the proposed ELISA was compared to the recovery determined by a conventional HPLC. A good correlation was observed between the proposed ELISA and the HPLC. This proposed ELISA would be useful for monitoring for residual imazalil.

Antibodies, Monoclonal↗

Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acid-perfusion model in rats.

One of the important problems in experimentally induced small intestinal lesions is that there is no reproducible model of diffuse and stable mucosal lesion. In this paper, we studied in detail the effects of continuous perfusion of various concentrations of acetic acid on the rat small intestinal mucosa. In order to evaluate its applicability for screening of the preventive effect of drugs on gut damage, we also evaluated the efficacy of corticosteroid pretreatment in preventing acetic acid-induced mucosal lesion. Male Sprague-Dawley rats were fasted for 12 hr, and the small intestinal lumen was perfused with 1%, 1.5%, 2.5%, 3%, 3.75% (pH 2.4-2.6) acetic acid or saline (control) at 1 ml/min for 15 min. In separate experiments, the effect of preadministration of budesonide (0.5 or 0.75 mg/kg/day) and prednisone (0.75 mg/kg/day) on 1.5% acetic acid-induced mucosal damage was investigated. Macroscopic and microscopic lesions occurred diffusely in a concentration-dependent fashion. Histological findings revealed signs of transmural inflammation characterized by mucosal-submucosal edema, ulceration, and neutrophil infiltration. Mucosal-submucosal height had an inverse relation with the acetic acid concentrations perfused. Myeloperoxidase activity levels increased several-fold in the acetic acid-perfused groups. Corticosteroid pretreatment prevented microscopic damage and was associated with reduction of MPO activity levels in 1.5% acetic acid-perfused rats. We conclude that this simple and reproducible model could be applied for the screening of new drugs in the gastrointestinal tract in which large numbers of animals are taken into account.

Acetic Acid↗

Specific preinduction of 60-kDa heat shock protein (chaperonin homolog) by TRH does not protect colonic mucosa against acetic acid-induced lesion in rats.

In order to study the cytoprotective function of colonic heat shock proteins (HSPs) in vivo, the effect of specific preinduction of HSP60 by thyrotropin-releasing hormone (TRH) administration on the development of acetic acid-induced colonic mucosal lesion was investigated. Expression of 60-kDa, 72-kDa, and 90-kDa heat shock proteins (HSP60, HSP72, and HSP90, respectively) in rat colonic mucosa was investigated by western blot and immunohistochemical analyses before and after TRH administration. Following pretreatment with or without TRH administration, the rats received intrarectal infusion of 5% acetic acid. The colonic mucosal damage was macroscopically evaluated 24 hr after the intrarectal infusion of acetic acid. Expression of HSP60 was significantly increased by TRH administration in the colonic mucosa, whereas HSP72 and HSP90 did not increase. Immunohistochemical study also showed a significant increase in HSP60 in colonic mucosal cells, especially at the surface of the colonic mucosa after TRH administration. No histopathologic alteration was observed in the colonic mucosa after TRH administration. The colonic mucosal damage caused by intrarectal infusion of 5% acetic acid was not prevented by preinduction of HSP60. We demonstrated that specific preinduction of HSP60 by TRH administration did not show cytoprotective function in the colonic mucosa, although this protein plays a crucial role for cytoprotection in the pancreatic acinar cells. Our results indicate that the role of HSP60 may be different in each organ with respect to cytoprotection.

Acetic Acid↗

Implications of mechanical stretch on wound repair of gastric smooth muscle cells in vitro.

Gastric smooth muscle cells continually receive repetitive physical stretching by food storage, peristalsis and fasting contraction; therefore mechanical stretch can not be disregarded in gastric events. The aim of this study was to clarify the effects of mechanical stretch on wound repair using a rabbit gastric smooth muscle cell sheet. Mechanical stretch was imposed on adherent cells on a flexible membrane in order to increase elongation by an average of 5% and 10%, respectively, at 5 cycles per minute after artificial wounding. Adherent cells not subjected to mechanical stretch served as controls. The restoration process was monitored by measuring wound size for 48 h. Proliferation was assessed by BrdU staining and the influence on the cytoskeletal system was assessed by actin staining. The speed of restoration was highest in controls and lowest in the 10% stretch groups. Proliferation was almost equal to that of controls in the stretch groups. Under the condition of mechanical stretch, stress fibers appeared weakened and the direction of fibers was not consistent but random. In conclusion, mechanical stretch inhibited the migration of gastric smooth muscle cells, leading to cytoskeletal dysfunction. It is suggested that physical stretch, such as mechanical stretch, might be an important factor in the process of gastric wound repair.

Animals↗

Interactions of a didomain fragment of the Drosophila sex-lethal protein with single-stranded uridine-rich oligoribonucleotides derived from the transformer and Sex-lethal messenger RNA precursors: NMR with residue-selective [5-2H]uridine substitutions.

Proteins that contain two or more copies of the RNA-binding domain [ribonucleoprotein (RNP) domain or RNA recognition motif (RRM)] are considered to be involved in the recognition of single-stranded RNA, but the mechanisms of this recognition are poorly understood at the molecular level. For an NMR analysis of a single-stranded RNA complexed with a multi-RBD protein, residue-selective stable-isotope labeling techniques are necessary, rather than common assignment methods based on the secondary structure of RNA. In the present study, we analyzed the interaction of a Drosophila Sex-lethal (Sx1) protein fragment, consisting of two RBDs (RBD1-RBD2), with two distinct target RNAs derived from the tra and Sxl mRNA precursors with guanosine and adenosine, respectively, in a position near the 5'-terminus of a uridine stretch. First, we prepared a [5-2H]uridine phosphoramidite, and synthesized a series of 2H-labeled RNAs, in which all of the uridine residues except one were replaced by [5-2H]uridine in the target sequence, GU8C. By observing the H5-H6 TOCSY cross peaks of the series of 2H-labeled RNAs complexed with the Sx1 RBDI-RBD2, all of the base H5-H6 proton resonances of the target RNA were unambiguously assigned. Then, the H5-H6 cross peaks of other target RNAs, GU2GU8, AU8, and UAU8, were assigned by comparison with those of GU8C. We found that the uridine residue prior to the G or A residue is essential for proper interaction with the protein, and that the interaction is tighter for A than for G. Moreover, the H1' resonance assignments were achieved from the H5-H6 assignments. The results revealed that all of the protein-bound nucleotide residues, except for only two, are in the unusual C2'-endo ribose conformation in the complex.

Animals↗