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Biomedical subjects

R Maeda

Publications and source records attributed to R Maeda.

At least 73 records · Page 4Linked to original sources
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1986

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats.

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly reduced portal pressures (24 +/- 1 vs 32 +/- 1 cm saline), macroscopic mucosal damage (24 +/- 1 vs 39 +/- 4% of mucosa), and histologic deep necrosis (36 +/- 2 vs 61 +/- 4% of mucosal length). Increased dosage of propranolol to 4 mg did not produce any further reduction of portal pressure or mucosal damage. Central venous and systemic arterial pressures were not significantly altered by propranolol. The extent of mucosal damage correlated with levels of portal pressure (P less than 0.01) in portal hypertensive rats. Sham-operated normotensive rats had less macroscopic mucosal damage (26 +/- 4%) than portal hypertensive rats, and propranolol did not affect the extent of ethanol-induced damage or portal pressures in these animals. We conclude: (1) Propranolol is effective in reducing extent of ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in sham-operated controls; (2) this effect correlates with reduction of portal pressure; and (3) our study supports the clinical impression that reducing portal pressure may be one approach for the prevention and therapy of gastric mucosal damage in portal hypertension.

Animals↗
PubMed1986

An electron microscopic study on digestive tract amyloidosis in ferric nitrilotriacetate (Fe-NTA)-induced "F1 amyloidosis" mice.

The histological distribution and ultrastructural findings were investigated in 52 amyloid-positive cases obtained from 80 F1 mice (32 males and 48 females) receiving 126 to 502 daily intraperitoneal injections of ferric nitrilotriacetic acid (Fe-NTA) resulting from reciprocal crossing of 20 parental mice receiving daily intraperitoneal injections of Fe-NTA for 5 months. Of 52 amyloidotic F1 mice 49 (94%) developed a moderate degree of amyloid deposits in the gastrointestinal tract. Moderate amounts of amyloid deposits were sporadically discernible in the lamina propria of the stomach pars glandularis, the duodenal mucosa, and to a lesser extent in that of the rectal mucosa. Electron microscopic observation revealed that macrophages adjacent to amyloid mass were radiating outward abundant bundles of non-branching amyloid fibrils from the cytoplasmic invaginations. In the cytoplasm of the macrophages there were occasionally acid phosphatase-positive lysosomes including amyloid fibrils measuring approximately 100 A in width. Moreover, it is discussed whether fibroblasts or fibroblast-like interstitial cells are involved in amyloid formation.

Amyloid↗
PubMed1986

An electron microscopical and histochemical study on ferric nitrilotriacetate-induced "F1 amyloidosis".

Of a total of 80 offspring obtained by reciprocal crossing of ICR/JCL strain of mice of both sexes receiving 84-140 injections of Fe-NTA over 98-163 days before crossing, 52 (65%) showed severe generalized amyloidosis after 93-502 injections of Fe-NTA over 115-522 days, but not "hemochromatosis", which was a striking contrast to the findings of "hemochromatosis" without amyloidosis observed in the parent mice. Electron microscopic examinations revealed numerous bundles of non-branching, well-oriented amyloid fibrils radiated outward from the surface of cytoplasmic invaginations of the Kupffer cells or splenic reticuloendothelial cells of the F1 mice with amyloidosis, and close contact frequently observed between "amyloid-forming cells" and adjacent lymphocytes in the amyloid-laden liver and spleen of the F1 mice. Since the above findings in the F1 mice were not found in the parent mice treated with multiple Fe-NTA injections, the present authors assumed that the immunological memory for the Fe-NTA conjugate transmitted via the placenta to the fetus from the mother that received multiple Fe-NTA injections might be involved in the development of generalized amyloidosis in the F1 mice, although the possible mechanism by which Fe-NTA-induced "F1 amyloidosis" has been developed remains yet undetermined.

Amyloidosis↗
PubMed1986

[Functional significance of left ventricular distortion in patients with right ventricular volume or pressure overloading].

To evaluate the effects of left ventricular (LV) distortion on its pump function, the LV cavity shape was analyzed by two-dimensional echocardiography in normal subjects and in patients with right ventricular (RV) volume or pressure overload. The functional significance of LV distortion in the short-axis sections was evaluated by an index of the efficiency of ejection (E) of endocardial circumferential fiber length (ECL) shortening in reducing LV cavity area during systole; E = measured systolic area reduction/ideal systolic area reduction X 100 (%), where an ideal area at end-diastole or end-systole was computed for the measured ECL, assuming its shape to be perfectly circular (ideal area = ECL2/4 pi), and then an ideal systolic area reduction was determined. E at the chordal level was termed Ech. In patients with atrial septal defect (ASD), the LV cavity was distorted at end-diastole and became more circular at end-systole. Since this characteristic change during systole diminished the E, and the values of E at the chordal level (Ech) were significantly lower in ASD than those in normal subjects (89.4 +/- 4.4% vs 98.3 +/- 0.8%, p less than 0.001), strongly suggesting impairment of the efficiency of LV pump function in ASD. In patients with pulmonary hypertension, the LV cavity was more distorted at systole, and a decrease in cavity area at end-systole with the distorted LV contributed to increased systolic area reduction. Thus, the values of Ech in this group exceeded 100% in five of nine patients (103.8 +/- 12.3%). In other words, when marked RV systolic overload exists, an increase in LV systolic area reduction due to progressive LV compression will occur against LV systolic pressure. This phenomenon suggests the existence of "cardiac massage on the LV by the RV with elevated pressure". In conclusion, it was strongly suggested that the efficiency of LV pump function is modulated by RV overload through dynamic changes in the LV shape.

Adolescent↗