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Biomedical subjects

R Maeda

Publications and source records attributed to R Maeda.

At least 19 recordsLinked to original sources

[A case of schistosomiasis suspected by circumoval precipitin test and diagnosed by rectal biopsy].

A forty-year-old female from Brazil was admitted to Teikyo Hospital because of easy fatigability, fullness of the abdomen and left hyochondralgia. She was anxious about Schistosoma mansoni infection, because three of her relatives died of the infection. Physical examinations revealed a tenderness at the left hypochondrium. Laboratory data showed no abnormal finding. No egg of S. mansoni was found in the stool. A circumoval precipitin test (COPT) with the serum showed a deposite around the egg. Enzyme-linked immunosorbent assay (ELISA) revealed the presence of antibody against S. mansoni in the serum. A colonoscopy showed no abnormal finding macroscopically. The rectal biopsy showed the existence of mild procitis. The diagnosis was made by finding the characteristic lateral-spined eggs in the biopsy specimens from the rectum. Treatment of 3 g of prazicantel per day for three days was started. She complained of mild nausea at the first dosing. A month later, another three-day-treatment was given. In the case where there are no eggs found in the stool, COPT and ELISA are usefull in detecting the disease, and colonoscopy is recommended in diagnosing the disease.

Adult

Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of determinants of alpha-conotoxin M1 selectivity.

The acetylcholine receptor from vertebrate skeletal muscle is a pentamer of homologous subunits with composition alpha 2 beta gamma delta. Its two ligand binding sites, formed at alpha-gamma and alpha-delta interfaces, differ in their affinities for agonists and competitive antagonists, owing to different contributions of the gamma and delta subunits. To identify portions of the gamma and delta subunits that contribute to the binding sites, the experiments described here use gamma-delta subunit chimeras and site-specific mutants to determine the basis of the 10,000-fold selectivity of conotoxin M1 for the sites. Three distinct regions of the extracellular domain were found to contribute to conotoxin M1 selectivity, each containing a single residue responsible for the contribution of that region. Residues K34, S111, and F172 of the gamma subunit confer low affinity to the alpha-gamma binding site, whereas the corresponding residues of the delta subunit, S36, Y113, and I178, confer high affinity to the alpha-delta site. Identification of three separate determinants of ligand selectivity suggests a limited model of the folding pattern of the extracellular domain of the subunits.

Amino Acid Sequence

Endoscopic polypectomy for pacemaker patients.

Endoscopic polypectomy using high frequency voltage is contraindicated in patients with cardiac pacemakers. Recently, highly advanced pacemakers have enabled us to perform endoscopic polypectomy on these patients by taking appropriate cautions. We successfully removed 10 colonic polyps and one gastric polyp in patients with pacemakers by endoscopic polypectomy. No complication and dysfunction of the pacemaker occurred before, during or after the polypectomy.

Aged

Expression and ligand specificity of acetylcholinesterase and the nicotinic receptor: a tale of two cholinergic sites.

The functional design of the nAChR and AChE rather than their recognition capacities requires divergence in structure of the two binding sites. The receptor requires co-operativity to link ligand occupation to the response, rapid conformational transitions of activation, and slower transitions of desensitization. Hence, its binding sites have evolved at subunit interfaces. By contrast, AChE functions with a large kcat and a comparatively large Km. To do so, it must force acetylcholine through a low-energy transition site that features tetrahedral rather than the ground-state, trigonal conformation around the carbonyl carbon. This requires a high affinity (KD approximately 10(-17) M) for the enzyme complex of the transient transition state. Interestingly, the three-finger peptide toxins (alpha-bungarotoxin and fasciculin), though closely homologous, use different interaction sites on the receptor (the agonist recognition site) and AChE (a peripheral site). Finally, although the two proteins show co-ordinated expression during muscle differentiation, the receptor relies primarily on transcriptional control while AChE expression is post-transcriptional, being controlled by mRNA stability.

Acetylcholinesterase

Phosphatidylserine suppresses myelin-induced experimental allergic neuritis (EAN) in Lewis rats.

Phosphatidylserine administered as an aqueous dispersion to myelin-induced experimental allergic neuritis rats had a significant effect on disease course. Intraperitoneal injections of 30 mg/kg were given daily beginning at the onset of disease and continued for 14 days. Clinical severity and mortality were markedly reduced by this treatment as compared to saline controls. Improved clinical outcome was associated with a reduction in peripheral nerve pathology. A possible mechanism involving tumor necrosis factor is discussed.

Animals

Abnormal regulation of ribosomal protein S6 kinase by insulin in skeletal muscle of insulin-resistant humans.

Insulin resistance in Pima Indians appears to result from a post-receptor impairment of insulin signal transduction that affects only some responses to insulin. To identify the primary lesion responsible for insulin resistance, we investigated the influence of insulin on ribosomal protein S6 kinase activities in skeletal muscle of insulin-sensitive and insulin-resistant nondiabetic Pima Indians during a 2-h hyperinsulinemic, euglycemic clamp. In sensitive subjects, S6 kinase activity was transiently activated fivefold over basal activity by 45 min of insulin infusion. Although basal activities in the two groups were similar, the response to insulin was delayed and restricted to about threefold over basal in subjects resistant to insulin. Two major S6 kinase activities in extracts of human muscle were resolved by chromatography on Mono Q. Peak 1, which accounted for basal activity owes to an enzyme antigenically related to the 90-kD S6 kinase II, a member of the rsk gene family. The major insulin-stimulated S6 kinase eluted as peak 2 and is antigenically related to a 70-kD S6 kinase. Our results show that insulin resistance impairs signaling to the 70-kD S6 kinase.

Adult

Basic studies on visible light-cured resin as a denture base. Part 17. Transverse and tensile strengths of repaired denture base resin using a trial repair resin.

Trial production of a visible light-cured repair resin (powder/liquid type, TPL) as a denture base resin was carried out using cyclophosphazene monomer, and then the transverse and tensile strengths of the repaired specimens were examined. As a control, Triad Gel (TRI) was used. In the transverse strength test, TPL showed values of 507-470 kgf/cm2, which were about double those of TRI. As for tensile strength, TPL showed values of 329-268 kgf/cm2, and higher values were obtained in comparison with TRI, especially after 30 days of water immersion, when the values were doubled. The durability of TPL was favorable in comparison with TRI.

Composite Resins

A case report of epithelioid leiomyosarcoma of transverse mesocolon: diagnosis and treatment.

A case of epithelioid leiomyosarcoma of the transverse mesocolon in a 45-year-old man was reported. The patient had a rapidly growing mass in the left upper quadrant. Ultrasonography, gastrointestinography, and abdominal computed tomography showed that the mass was separated from the pancreas, the gastrointestinal tract, and the retroperitoneal organs. Preoperatively the primary origin of this tumor was related to the transverse mesocolon. On laparotomy the tumor of 5cm by 6cm by 3cm in size was found in the anterior left of the transverse mesocolon and the mass was resected entirely. The patient is well 18 months after surgical treatment with no evidence of recurrence.

Humans

Diagnostic difficulty in a case of heterotopic pancreatic tissue of the ileum.

We describe a case of heterotopic pancreatic tissue of the ileum causing acute gastrointestinal tract bleeding. It was initially clearly demonstrated as an ileal polyp preoperatively by radiologic means. Exploratory surgery was performed, and the segment of ileum containing the mass was resected. Histopathologic examination of the lesion revealed heterotopic pancreatic tissue of Heinrich type II. There was no histological evidence of acute or chronic pancreatitis, but erosion was confirmed at the tip of the mass. Even symptomatic heterotopic pancreatic tissue of the ileum may give difficult diagnostic problems. The present case is reported to show the possibility of diagnosing rare abnormalities of the ileum.

Choristoma

Defective insulin response of phosphorylase phosphatase in insulin-resistant humans.

Insulin-stimulated glycogen synthase activity in human muscle is reduced in insulin-resistant subjects. Insulin regulation of human muscle glycogen synthase may require activation of a type-1 protein phosphatase (PP-1). We investigated the change of phosphorylase phosphatase and glycogen synthase activities in muscle biopsies obtained during a 2-h hyperinsulinemic euglycemic clamp in 12 insulin-sensitive (group S) and 8 insulin-resistant (group R) subjects. Fasting phosphorylase phosphatase activity was lower in group R than in group S, and did not increase significantly with insulin infusion in group R until 20 min. In group S, phosphorylase phosphatase was significantly stimulated by 10 min, remaining significantly higher than in group R at all time points. The insulin-mediated changes in phosphatase activities were not decreased by 3 nM okadaic acid but were completely inhibited by 1 microM okadaic acid, thereby verifying that insulin-stimulated phosphorylase phosphatase is accounted for by a PP-1. Subcellular fractionation demonstrated reduced fasting PP-1 activities in both the glycogen and cytosolic fractions of muscle obtained from subjects in group R compared to those in group S. These results suggest that insulin activation of PP-1 could contribute to the stimulation of glycogen synthase by this hormone in human muscle. Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin-stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects.

Adult

Induction of demyelination by intraneural injection of antibodies against sulfoglucuronyl paragloboside.

Sulfoglucuronyl glycolipids (SGGLs) carry the glucuronyl 3-sulfate (HNK-1) epitope which is recognized by monoclonal IgM paraproteins from patients with demyelinating polyneuropathy. We report that intraneural injections of rat anti-SGGL antibodies induce demyelination in rat sciatic nerve, along with mild to moderate clinical symptoms. Morphologically, vesiculation and loosening of the myelin sheath were observed 3 h postinjection, followed by extensive demyelination and macrophage infiltration after 4 days. Since the anti-SGGL antibodies showed no cross-reactivity with other components in rat sciatic nerve, these results indicate that SGGLs alone can serve as the target antigens in demyelinating neuropathy.

Animals

Activation of skeletal muscle casein kinase II by insulin is not diminished in subjects with insulin resistance.

Insulin resistance, which may precede the development of non-insulin-dependent diabetes mellitus in Pima Indians, appears to result from a postreceptor defect in signal transduction in skeletal muscle. To identify the putative postreceptor lesion responsible for insulin resistance in Pima Indians, we investigated the influence of insulin on the activity of casein kinase II (CKII) in skeletal muscle of seven insulin-sensitive, four insulin-resistant, nondiabetic, and five insulin-resistant diabetic Pima Indians during a 2 h hyperinsulinemic, euglycemic clamp. In sensitive subjects, CKII was transiently activated reaching a maximum over basal activity (42%) at 45 min before declining. CKII was also stimulated in resistant (19%) and diabetic (34%) subjects. Basal CKII activity in resistant subjects was 40% higher than in either sensitive or diabetic subjects, although the concentration of CKII protein, as determined by Western blotting, was equal among the three groups. Basal CKII activity was correlated with fasting plasma insulin concentrations, suggesting that the higher activity in resistant subjects resulted from insulin action. Extracts of muscle obtained from all three groups either before or after insulin administration were treated with immobilized alkaline phosphatase, which reduced and equalized CKII activity. These results suggest that insulin stimulates CKII activity in human skeletal muscle by a mechanism involving phosphorylation of either CKII or of an effector molecule, and support the idea that elevated basal activity in resistant subjects results from insulin action. It appears that the ability of insulin to activate CKII in skeletal muscle is not impaired in insulin-resistant Pima Indians, and that the biochemical lesion responsible for insulin resistance occurs either downstream from CKII or in a different pathway of insulin action.

Alkaline Phosphatase

Synthetic studies on diuretics. 5-(3,3-N,S-substituted-2-propenoyl)-2,3-dihydro-2- benzo[b]furancarboxylic acids.

6,7-Dichloro-2,3-dihydro-2-benzo[b]furancarboxylic acid derivatives having a 3,3-N,S-disubstituted-2-propenoyl group at the 5-position were prepared by alkylation of 5-(thiocarbamoyl)acetyl derivatives of the 2,3-dihydro-2-benzo[b]furancarboxylic acid ester or by acetal exchange reaction of 5-[3,3-bis(alkylthio)-2-propenoyl] derivatives. Synthesis of 5-[4 and/or 5-(di)substituted-4-thiazolin-2-ylidene]acetyl-2,3- dihydro-2-benzo[b]furancarboxylic acids was also achieved by the reaction of 2-halo-1-methoxyethyl isothiocyanate with the 5-acetyl derivative in the presence of base or through sulfide contraction of 2-[[6,7-dichloro-2-methoxycarbonyl-2,3-dihydrobenzo[b]furan-5-yl) carbonyl)-methylthio]thiazolium bromide. Some of the compounds which were synthesized showed potent natriuretic activities in rats and mice. The structure-activity relationship is also discussed.

Animals

Basic studies on the laboratory assessment of macrofilaricides using Brugia malayi in the jird, Meriones unguiculatus. 1. Longevity and periodicity of microfilaremia.

The longevity and periodicity of microfilaremia were examined in the jird infected with Brugia malayi to be used for assessing the filaricides. Jirds 4 to 6 weeks old were inoculated subcutaneously with 100 to 200 infective larvae of B. malayi. Microfilariae were present in 75 out of 94 jirds observed over 3 years and high microfilaremia, with 10 mf/microliters or higher, developed in 43 out of 75 jirds. Such a high level of microfilaremia was necessary for narrowing the variation of microfilaria counts among the blood samples. The microfilaria negative jirds, 4 months after inoculation, were abandoned, because in those cases where they became patent later the microfilaria density did not reach an appropriate level. The selected jirds were used for experiment from 6 to 15 months after inoculation when most of them revealed the maximal count of microfilariae. The jirds that failed to develop microfilaremia to the level of 10 mf/microliters by 9 months after inoculation were also abandoned because they did not continue the appropriate level of microfilaremia even when they reached this level later. Although a significant periodicity was observed only in of 10 jirds examined by the Aikat and Das method, the peak hour of microfilaria density was observed in most animals in the afternoon and the time was nearly the same in each animal. Therefore, the blood sampling would be performed preferably in the afternoon.

Animals

Basic studies on the laboratory assessment of macrofilaricides using Brugia malayi in the jird, Meriones unguiculatus. 2. Establishment and evaluation of a new method of macrofilaricide assessment.

Jird infected subcutaneously with infective stage larvae (L3) of Brugia malayi were evaluated as an animal model for assessing macrofilaricides using a method of observing the change in microfilaria (mf) density but not by recovering adult worms. The animals were treated with a test compound followed by diethylcarbamazine (DEC) at 50 mg/kg for 5 consecutive days for clearing the existing mf from the blood stream. A continuous decrease in mf density was observed when jirds were treated with flubendazole. Nevertheless, slow recovery of mf density was observed in the jirds which were given suramin or Mel W, indicating that mf productivity of female worms was continuing after DEC treatment. The results obtained by monitoring microfilaremia corresponded with those obtained by recovery of adult worms at autopsy, suggesting that the system of L3-induced B. malayi jird model is useful for testing macrofilaricides.

Animals