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Biomedical subjects

M Endoh

Publications and source records attributed to M Endoh.

At least 271 records · Page 15Linked to original sources
PubMed1990

Susceptibility to proteolipid apoprotein and its encephalitogenic determinants in mice.

We investigated in mice strain differences in induction of experimental allergic encephalomyelitis by proteolipid apoprotein and studied encephalitogenic determinants. SJL/J, C3H/He, CBA/J and A/J mice were high responders, BALB/c and AKR/J mice were moderately susceptible, and DBA/2, B6 and congenic strains of B10 background were low responders. Synthetic peptide 136-150 was encephalitogenic for SJL/J mice, and 215-232 was encephalitogenic for C3H/He mice. These encephalitogenic derterminants are present in the extracellular portion of proteolipid apoprotein in myelin.

Animals↗
PubMed1990

Effect of iodopyracet on renal excretion of sulfamethizole in rabbits.

To predict quantitatively drug interaction kinetics from the single-drug clearance studies, we examined the effect of iodopyracet (IOD) on sulfamethizole (SMZ) excretion in rabbits. Even though the decline of systemic IOD plasma concentration was linear, the renal clearance of SMZ decreased significantly in the presence of IOD. The results could be described by a perfusion model incorporated with the competitive inhibition for tubular secretion. For IOD with a high extraction ratio, it was suggested that a heavy load of the drug was supplied to the sites of secretion and caused the saturation of transport systems, even though the renal excretion kinetics were apparently linear in respect to the systemic circulation. These facts indicated that a linear relationship between the concentrations in the systemic circulation and at the sites of tubular secretion can not always be presumed. Consequently, SMZ-IOD interaction study stressed the importance of the drug concentrations at the sites of interaction for quantitative elucidation of drug-drug interactions.

Animals↗
PubMed1990

Kinetic studies on drug disposition in rabbits. I. Renal excretion of iodopyracet and sulfamethizole.

In order to quantify the renal handling of iodopyracet (IOD) and sulfamethizole (SMZ), single-drug clearance studies in rabbits were performed under quasi-steady state conditions with stepwise increasing the infusion rate of IOD or SMZ. Although concentration dependence of plasma protein binding was observed for both drugs, the urinary excretion rate of IOD was proportional to its total plasma concentration at low total plasma concentrations of 0.05-0.8 mM. On the other hand, the relationship between urinary excretion rate and total plasma concentration of SMZ was a concave-ascending curve at low plasma concentrations and the renal clearance of SMZ was sensitive to changes in plasma protein binding. However, renal clearances referenced to unbound plasma concentration at total plasma concentrations of 0.05 mM for IOD and SMZ were 9.5 and 38 l/h, respectively. Those values were much greater than the effective plasma flow in rabbits. These facts indicated that the intrinsic clearances at the sites of tubular secretion were high and that the rates of secretion were fully or partially limited by the renal plasma flow. Furthermore it was suggested that unbound drug was liberated from plasma protein at the sites of tubular secretion. The data obtained at high plasma concentrations indicated that the tubular secretion of IOD had capacity limited characteristics and that the urinary excretion of SMZ involved tubular reabsorption as well as saturable tubular secretion. From the data obtained, a perfusion-limited pharmacokinetic model was constructed characterizing the excretory processes, namely, glomerular filtration, passive tubular reabsorption, saturable tubular secretion and reequilibrium between bound and unbound drugs in plasma. For both drugs, the estimates for bulk flow rate were reasonable values of effective renal plasma flow and the dissociation constants for tubular secretion agreed well with those for in vitro renal cortex accumulation, suggesting that the kinetic model based on physiological concepts was useful for the understanding of the drug elimination processes.

Animals↗
PubMed1990

Effects of a new cardiotonic agent 1,2-dihydro-6-methyl-2-oxo-5-[imidazo (1,2-a) pyridin-6-yl]-3-pyridine carbonitrile hydrochloride monohydrate (E-1020) on contractile force and cyclic AMP metabolism in canine ventricular muscle.

E-1020, a newly synthesized imidazopyridinylpyridine or imidazopyridine derivative (structurally closely related to the bipyridine derivative milrinone) increased the force of contraction and cyclic AMP levels in a concentration-dependent manner in the isolated canine ventricular trabeculae electrically driven at 0.5 Hz at 37 degrees C. The concentration-response curve for the increase in force of contraction by E-1020 was biphasic. The maximal positive inotropic effect (PIE) of E-1020 is comparable to that of milrinone, and its potency is 3-fold less than that of milrinone, but 10-fold higher than that of amrinone. The time course of increases in force of contraction induced by E-1020 was coincident with that of cyclic AMP accumulation. The concentration-response curve for the PIE of E-1020 was superimposable to that of cyclic AMP accumulation. A beta-adrenoceptor antagonist, (+/-)-bupranolol (3 X 10(-7) mol/l), did not affect the PIE of E-1020. The increase in the force of contraction and accumulation of cyclic AMP produced by E-1020 were inhibited by a muscarinic receptor agonist, carbachol. The relationship between the force of contraction and cyclic AMP levels in the presence of E-1020 was not modified by addition of carbachol or isoproterenol. E-1020 shifted the concentration-response curve for isoproterenol to the left. E-1020 shortened the total duration of contraction and relaxation time of isometric contractions. These findings indicate that cyclic AMP is essentially involved in the PIE of E-1020 on the canine ventricular muscle, although the possible involvement of a cyclic AMP-independent mechanism can not be excluded.

Amrinone↗
PubMed1990

Effect of thymic hormones on induction of experimental allergic encephalomyelitis in old mice.

This study was aimed at restoring decreased T-cell functions and reduced susceptibility to proteolipid apoprotein (PLP) induced-experimental allergic encephalomyelitis (EAE) in old mice with thymic hormones. Thymosin fraction 5 (TF-5) and serum thymic factor (FTS) had no significant in vitro and in vivo effect on proliferative responses to PLP and concanavalin A (Con A), and on EAE induction in young and old mice. These results suggest that decreased T-cell functions cannot be restored by these thymic hormones tested.

Aging↗
PubMed1990

Retrograde thrombosis of feeding arteries after removal of arteriovenous malformations.

Five cases of retrograde thrombosis of former feeding arteries after removal of an arteriovenous malformation (AVM) are reported. The clinical features of these patients were studied and compared to those of 71 patients without this complication. The following characteristics were found to correlate with retrograde thrombosis: 1) advancing age of the patient; 2) large AVM size; and 3) markedly dilated and elongated feeders. It is suggested that the slow flow in the former feeding arteries that was observed immediately after AVM removal and pathological changes in these vessels due to long-standing hemodynamic stresses contributed to the development of retrograde thrombosis. Neurological manifestations related to retrograde thrombosis were noted in three of the five cases. Although infrequent, this complication should be considered as a serious possibility following removal of an AVM.

Adolescent↗
PubMed1990

Influenza antibody titers after vaccination of chronic renal failure patients; before and during hemodialysis, or on continuous ambulatory peritoneal dialysis.

Anti-influenza antibody (Ab) titers were measured in order to elucidate whether there are any disturbances in Ab production in chronic renal failure (CRF) patients. A total of 55 CRF patients plus 15 normal individuals were vaccinated with influenza vaccine twice, 4 weeks apart of the 55 CRF patients, 15 were not on dialysis, 10 were undergoing hemodialysis (HD), and 30 were on continuous ambulatory peritoneal dialysis (CAPD). Of the 30 CAPD patients, 14 had peritonitis. Serum Ab titers were measured by complement fixation (CF) and hemagglutination inhibition (HI) tests, and IgG and IgM class specific antibodies by ELISA. All groups responded to immunization, but CAPD patients with peritonitis and CRF patients not yet on dialysis did not show a significant elevation in IgM class Ab titers. The number of CAPD patients with peritonitis who achieved positive titers was significantly lower in HI (p less than 0.01) and IgG class antibodies (p less than 0.05) compared with normal controls. Two patients with frequent peritonitis did not show any response to vaccination. It was concluded that patients with renal dysfunction have some abnormalities in Ab production against influenza vaccine, the effects of which were more pronounced in the CAPD patients with frequent peritonitis.

Adolescent↗
PubMed1990

[A case report of successful surgical removal of a lipoma in the left ventricle].

A 63-year-old man with anterior chest oppression was diagnosed as an acute myocardial infarction. The two-dimensional echocardiogram revealed a mass which bulged into the left ventricular cavity. Subsequently, the computed tomographic findings of the mass lesion demonstrated the attenuation values of -49 Hounsfield units, which corresponded to that of fatty tissues. From these findings the left ventricular lipoma was highly suspected. The tumor existed at the base of the anterior papillary muscle. It was successfully resected and mitral valve replacement was performed concomitantly. The tumor was yellowish and sized by 25 X 20 mm. On histological examination of the specimen, the tumor was composed of mature fatty cells. CT scanning was very useful for the preoperative evaluation of lipoma.

Echocardiography↗
PubMed1989

Preponderance of beta- over alpha-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium.

[3H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (Kd = 0.25 nmol/l and Bmax = 27 fmol/mg protein in the right ventricle). [3H]CGP-12177, a beta-adrenoceptor ligand, bound to the membrane fraction with a Kd value of 0.29 nmol/l and a Bmax of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37 degrees C, phenylephrine elicited a concentration-dependent positive inotropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 mumol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 mumol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both alpha- and beta-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, beta-adrenoceptors predominate over alpha-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of beta-adrenoceptors is not especially high when compared with other species.

Adrenergic beta-Antagonists↗
PubMed1989

Regulation of force and intracellular calcium transients by cyclic AMP generated by forskolin, MDL 17,043 and isoprenaline, and its modulation by muscarinic receptor agents: a novel mechanism for accentuated antagonism.

The relation of changes in intracellular calcium transients and force of isometric contractions in response to an elevation or reduction of cyclic AMP levels was investigated in isolated dog ventricular trabeculae and rabbit papillary muscles, in which multiple superficial cells have been microinjected with the calcium sensitive bioluminescent protein aequorin. Forskolin, MDL 17,043 and isoprenaline elevated the tissue cyclic AMP level, increased consistently the peak aequorin signals and force, and abbreviated the duration of both signals in a concentration-dependent manner. When the effect of isoprenaline was compared with that of alteration of extracellular calcium concentration [( Ca2+]0), the increase in force by isoprenaline was associated with higher peak aequorin signals than that by alteration of [Ca2+]0 for a given increase in force, indicating the decrease in calcium sensitivity of myofibrils by cyclic AMP generated by beta-adrenoceptor stimulation. Carbachol, which did not affect significantly the basal force and cyclic AMP levels, lowered the cyclic AMP levels elevated previously by forskolin, MDL 17,043 or isoprenaline in the isolated dog ventricular trabeculae. It antagonized the increase in peak aequorin signals and force caused by these agents in a concentration-dependent manner. When carbachol had been administered prior to isoprenaline and the concentration-response curve for isoprenaline was determined in the presence of carbachol, the relation of force peak aequorin signals was not modified by carbachol in the rabbit papillary muscle. Carbachol, when administered during induction of the positive inotropic action by forskolin, MDL 17,043 and isoprenaline, decreased the force more than peak aequorin signals in a concentration-dependent manner in the dog ventricular trabeculae. Therefore, the relation of force to peak aequorin signals was shifted downwards during the carbachol-induced inhibition, indicating a further decrease of calcium sensitivity of myofibrils by carbachol. This effect of carbachol appears to be specific to the cyclic AMP-mediated positive inotropic action, since the alpha-adrenoceptor-mediated (cyclic AMP-independent) action was unaffected by carbachol. This mechanism may play an important role for "accentuated antagonism" in the mammalian ventricular myocardium.

Animals↗
PubMed1989

Subpopulations of T alpha cells in patients with IgA nephropathy: correlation between T alpha 4 cells and in vitro IgA production.

T cells play important roles in the regulation of the immune system and are divided into subpopulations by various kinds of markers on the membrane surface. T cells with Fc-receptors for IgA are termed T alpha cells, and the properties of this cell population have been revealed in recent years. T alpha cells are increased in patients with IgA nephropathy and possess IgA specific helper activity. T alpha cells consist of two subpopulations, T alpha cells with OKT4 antigen (T alpha 4 cells) and with OKT8 antigen (T alpha 8 cells). To investigate the immunological aberrations in patients with IgA nephropathy, we detected immunoglobulin produced by peripheral blood lymphocytes and enumerated the numbers of T alpha cells (including both T alpha 4 and T alpha 8 cells). The numbers of T alpha 4 cells (but not T alpha 8 cells) and in vitro IgA production were increased in patients with IgA nephropathy (IgA nephropathy, mean 1.9%. Control, mean 0.8%. P = 0.0075). In addition, the numbers of T alpha 4 cells and the amount of IgA in the supernatant of lymphocyte cultures were positively correlated in these patients (P = 0.025. r = 0.3836). From the results in the present study, it was suggested that T alpha 4 cells might be related to immunological aberrations, such as an increase in IgA seen in patients with IgA nephropathy.

Adult↗
PubMed1989

Utilization of therapeutic embolization in haemorrhage caused by carcinoma of the tongue.

Selective transcatheter arterial embolization, using Gelfoam, was performed in 2 patients with bleeding from tongue arteries due to carcinoma. Though the patients were in poor general condition, being in the terminal stage of cancer, there were no complications and the bleeding was successfully controlled. This method was effective in controlling haemorrhage from the tongue due to carcinoma of the tongue.

Carcinoma↗
PubMed1989

Association of IgA nephropathy and myasthenia gravis.

Three patients with IgA nephropathy associated with myasthenia gravis are described. In all 3 cases, myasthenia gravis emerged after the discovery of glomerulonephritis. Myasthenic symptoms were improved by thymectomy in 2 cases, but progression of the renal disease was not improved. Some systemic abnormalities, including immunological aberrations, were observed in these two disorders. It is postulated that T cell abnormalities in IgA nephropathy might be independent of the development of myasthenia gravis.

Adult↗
PubMed1989

Kinetic studies of the pharmacologic response to captopril in rats. I. Role of the renin-angiotensin system.

Pressor response to exogenous angiotensins was investigated in rats. Two-kidney Goldblatt hypertensive rats (GHR) and sodium-deficient normotensive rats (SDR), as well as normal rats, (NR) were used. Various amounts of angiotensin I (Ang I) or angiotensin (Ang II) were administered intravenously by constant infusion, with or without pretreatment with angiotensin converting enzyme (ACE) inhibitor, and the pressor response was determined. Captopril was used as the ACE inhibitor. From the data obtained, a simple kinetic model for the renin-angiotensin system was constructed. The model was based on a linear compartment model with the following assumptions; (a) there are compartments in respect to Ang I and II in the body; (b) in the steady-state condition, Ang I is produced at a constant rate; (c) a part of Ang I is converted to Ang II by a first-order rate process; (d) Ang I and II are eliminated from the respective compartments by first-order rate processes and (e) the relationship between mean arterial blood pressure and the amount of Ang II in the body can be described by Hill's equation with a baseline effect. Then the pressor response to angiotensins in GHR, SDR or NR was fitted to the model. The result indicated that the pressor response to Ang I or Ang II can be described by the present model. The model parameters obtained were consistent with the actual physiological parameters of rats.

Angiotensin I↗