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T Ashida

Publications and source records attributed to T Ashida.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Functional and structural analysis of the Lyb-2 system].

The Lyb-2 system of the mouse is a B cell-specific cell surface molecule encoded by a gene on chromosome 4. We have previously reported that Lyb-2 is involved in an early phase of B cell differentiation, specifically a process mediated by B cell stimulatory factor-1 (BSF-1) or-interleukin 4. It is thus very important to define the functional role and structural features of Lyb-2 molecule for the understanding of the regulatory mechanisms of B cell activation initiated by BSF-1. In our attempt to resolve these issues, we found that Lyb-2 antibody inhibits activation processes mediated by BSF-1 such as induction of Ia antigen on the B cell surface and of IgG1 production in lipopolysaccharide-activated B cells, suggesting that Lyb-2 molecule participates in a signaling event triggered by the binding of BSF-1 to its receptor. In the structural analysis, we found that in contrast to previous reports, Lyb-2 is not a monomer of 45 kilodaltons (kDa) but is composed of two components with molecular weight of 45 kDa and 105 kDa. Reduced and nonreduced two-dimensional electrophoresis analysis further revealed that Lyb-2 molecules are present on the B cell surface in two forms, a disulfide-bonded heterodimer of 45 kDa and 105 kDa chains and a 45 kDa homatrimer. How the structural uniqueness of Lyb-2 is related to its functional expression remains to be determined.

Animals↗
PubMed1988

Differential regulation by Ly-5 and Lyb-2 of IgG production induced by lipopolysaccharide and B cell stimulatory factor-1 (IL-4).

We have previously shown that mAb Ly-5 which on B cells recognizes a 220,000-Da (B220) molecule, inhibits LPS-induced IgG responses without affecting IgM or proliferative responses, whereas mAb Lyb-2 which modulates B cell activation processes induced by B cell stimulatory factor-1 (BSF-1) or IL-4, has no effect on LPS-induced B cell responses. In this report we further examined the cellular mechanisms of Ly-5 antibody action and the effect of Lyb-2 antibody in IgG responses induced by LPS and BSF-1. The results presented demonstrated that the inhibitory effect of Ly-5 antibody seems to be restricted to the IgG class and is observed in all IgG subclasses induced by LPS. Limiting dilution analysis showed that the Ly-5 antibody reduces primarily the precursor frequency of IgG-secreting cells and that the effect on the clone size is partial. Lyb-2 antibody, on the other hand, greatly inhibited IgG1 induction initiated by LPS and BSF-1 by the action on processes triggered by BSF-1, although it could not reverse the reduced IgG2b or IgG3 responses. Limiting dilution analysis revealed that Lyb-2 antibody reduces the precursor frequency but not the clone size of BSF-1-induced IgG1-producing cells, supporting our previous proposition that Lyb-2 plays a critical role in the B cell differentiation mediated by BSF-1. Taken together, these results indicate that both Ly-5 and Lyb-2 are important molecules in IgG subclass regulation, each acting on a distinct activation step.

Animals↗
PubMed1988

Antihypertensive drugs and sodium restriction. Analysis of their interaction based on pressure-natriuresis relationship.

The hypotensive effects of some antihypertensive drugs are augmented under sodium restriction, while those of others are not. The mechanisms of these interactions were theoretically analyzed based on the arterial pressure-natriuresis relationship. Four-week studies were performed in 24 patients with essential hypertension who were given a regular sodium diet (12-15 g of NaCl/d) in the first and third weeks and a sodium-restricted diet (1-3 g/d) in the second and fourth weeks. One of three antihypertensive drugs, 60 mg/d of nicardipine (Ca-antagonist), 120 mg/d of propranolol (beta-blocker) or 150 mg/d of captopril (converting-enzyme inhibitor) was administered in the third and fourth weeks. The mean arterial pressure and urinary sodium excretion were measured on the last three days of each week. The degree of interaction between the antihypertensive drugs and sodium restriction was statistically compared. The hypotensive effect of nicardipine and propranolol did not differ with the change in sodium intake, whereas that of captopril was greater under sodium restriction than under the regular sodium diet. Urinary sodium excretion was plotted on the ordinate as a function of arterial pressure before and after administration of the antihypertensive drugs. The pressure-natriuresis curve was shifted left, without a change in the slope, by nicardipine and propranolol and also left, but with a decrease in the slope, by captopril. The hypotensive effect of nicardipine and propranolol, being independent of the amount of sodium intake, was based on the leftward shift of the pressure-natriuresis curve that was probably due to the decrease in renal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1988

Pancreatic secretory trypsin inhibitor as a marker for early detection of rejection in canine pancreas allotransplantation.

Serum pancreatic secretory trypsin inhibitor (PSTI)* was measured in the course of canine segmental pancreas allotransplantation without immunosuppression. Serum PSTI concentrations showed two distinct elevations: the first elevation was on the first day and the onset of the second elevation was the sixth day after operation. The first postoperative elevation of the serum PSTI level is thought to be related to the operative procedures, because the first elevation was observed after both autotransplantation and allotransplantation, and biopsies of the autograft and allograft at the first day after the operations showed nonspecific neutrophilic infiltration and no perivascular lymphoid infiltrates. The second postoperative elevation of the serum PSTI level is thought to reflect a rejection process because this elevation was not seen after autotransplantation, and biopsies of allografts at the sixth day after the operation showed typical perivascular lymphoid infiltrates and cellular rejection of the exocrine tissue. In addition, the onset of the second elevation of serum PSTI level preceded by about three days the onset of the elevation of blood sugar at the ninth day after the operation. The results suggest that serum PSTI can be used as a marker for diagnosis of early pancreatic allograft rejection.

Animals↗
PubMed1988

Role of sarcoplasmic reticulum in arterial contraction: comparison of ryanodines's effect in a conduit and a muscular artery.

Ryanodine interferes with sarcoplasmic reticulum function in various types of muscle; in vascular smooth muscle, it can inhibit contractions that depend on sarcoplasmic reticulum calcium release, probably by depleting the sarcoplasmic reticulum calcium store. We tested ryanodine and calcium channel blockers (verapamil, diltiazem, and nitrendipine) on small rings of rat thoracic aorta (RA) and bovine tail artery (BTA) to determine the relative contributions of sarcoplasmic reticulum calcium release and gated calcium entry to contractions induced by norepinephrine, caffeine, and 100 mM K depolarization. Ryanodine blocked caffeine contractions in both tissues and attenuated norepinephrine responses (by 52% in RA, 14% in BTA) but minimally altered potassium contractions. Calcium channel blockers almost completely abolished potassium contractions and reduced norepinephrine contractions (by 45% in RA, 82% in BTA) but hardly affected caffeine responses. The blocking effects of ryanodine and calcium channel antagonists on the norepinephrine responses were additive. Ryanodine had no effect on baseline tension in the standard media; however, when calcium extrusion via Na-Ca exchange was inhibited by low external sodium (0-calcium, low-sodium solution), tension increased progressively after introduction of ryanodine. This indicates that the sarcoplasmic reticulum calcium released by ryanodine then accumulated in the cytosol and activated contraction; restoration of external sodium caused prompt relaxation. The smaller effects of caffeine and ryanodine in BTA indicate that sarcoplasmic reticulum plays a less important role in calcium control in this tissue, with gated calcium entry dominating. These functional findings are correlated with electron-microscopic evidence that BTA has about 60% less sarcoplasmic reticulum than does RA. Ryanodine appears to be a useful tool for determining the functional relevance of sarcoplasmic reticulum for contraction in different arterial smooth muscles.

Alkaloids↗
PubMed1988

Pressor response to vasopressin and norepinephrine in DOC-salt hypertensive and prehypertensive rats.

Pressor responses to arginine-vasopressin (AVP) and norepinephrine (NE) were studied in deoxycorticosterone (DOC)-salt hypertensive and prehypertensive rats. DOC-salt rats received weekly subcutaneous injection of DOC acetate (30 mg/kg) and given 1% saline for drinking. Salt and control rats received injections of sesame oil and given 1% saline or tap water, respectively. On the 5th day (prehypertensive stage) and at 6th week (hypertensive stage) after treatment had started, pressor responses were studied by measuring changes in mean arterial pressure recorded from the iliac artery in response to i.v. injections of AVP or NE under urethane anesthesia. Pressor response to AVP was enhanced both in DOC-salt hypertensive and prehypertensive rats compared with that in salt and control rats. Pressor response to NE tended to be enhanced in DOC-salt hypertensive rats, however, the enhancement was not observed in the rats in prehypertensive stage. Enhanced pressor response to AVP in DOC-salt prehypertensive rats was not due to the structural change of vascular beds, because peripheral resistance in isolated hindlimb preparations was similar in the three groups. Thus, pressor response to AVP was enhanced even in the prehypertensive stage in DOC-salt rats and the enhancement might be involved in the pathogenesis of hypertension in DOC-salt rats.

Animals↗
PubMed1988

Atrial natriuretic peptide, angiotensin, norepinephrine and electrolyte in cerebrospinal fluid of essential hypertension.

We determined concentrations of atrial natriuretic peptide (ANP), angiotensin (Ang), norepinephrine (NE) and electrolyte in plasma and cerebrospinal fluid (CSF) to study possible roles of these substances within the brain in human hypertension. Blood and CSF samples were obtained from 10 patients with mild to moderate essential hypertension (EHT) aged 40-65 y and 10 age-matched normotensive subjects (NT) on a regular salt diet (8 g/day). Levels of ANP, NE, Na, K, Ca and Cl in CSF and plasma were comparable between EHT and NT. Plasma renin activity, plasma and CSF Ang II were lower in EHT than NT. CSF Ang III tended to be lower in EHT. There was no correlation between CSF and plasma ANP, or between CSF and plasma Ang II. Our results indicate that CSF levels of ANP may not be altered in middle aged patients with mild to moderate hypertension. It is also suggested that Ang II, NE and sodium in the central nervous system may not have important roles in hypertension of those patients.

Adult↗
PubMed1987

Regulation of cell calcium and contractility in mammalian arterial smooth muscle: the role of sodium-calcium exchange.

1. The contraction and relaxation of rings of rat thoracic aorta and bovine tail artery were examined as a function of changes in the Na+ electrochemical gradient in order to determine the role of Na-Ca exchange in the control of contractility. 2. Inhibition of the Na+ pump in rat aorta by K+-free media or a low concentration (5 x 10(-5) M) of strophanthidin reversibly increased the contractile responses to caffeine and noradrenaline. These effects were dependent upon external Ca2+ and were observed even in the presence of a Ca2+ channel blocker (10 microM-verapamil or 10 microM-diltiazem) and an alpha-receptor blocker (10 microM-phentolamine). 3. Reduction of external Na+ concentration, [Na+]o (replaced by N-methylglucamine, tetramethylammonium or Tris), also caused an external Ca2+-dependent increase in tonic tension and, in rat aorta, an increase in the response to caffeine. These effects were also observed in the presence of verapamil and phentolamine. 4. Caffeine relaxed the bovine tail artery, but increased the sensitivity of the rat aorta to reduced [Na+]o. The latter effect was presumably due to block of Ca2+ sequestration in the sarcoplasmic reticulum, so that entering Ca2+ was more effective in raising the intracellular free Ca2+ level, [Ca2+]i. 5. Relaxation from K+-free or low-Na+ contractions, in Ca2+-free media, depended upon [Na+]o. Reduction of [Na+]o to 1.2 or 7.5 mM slowed the relaxation of rat aorta (5 mM-caffeine present) 3- to 5-fold, and the relaxation of bovine tail artery (without caffeine) 5- to 10-fold. These effects were seen in the presence of verapamil and phentolamine. 6. These observations are all consistent with an Na-Ca exchange transport system that can move Ca2+ either into or out of the arterial smooth muscle cells. Ca2+ entry is enhanced by raising [Na+]i (by Na+ pump inhibition) and/or lowering [Na+]o. Ca2+ extrusion from the contracted muscles is largely dependent upon external Na+. The latter observation implies that, when [Ca2+] exceeds the contraction threshold, Ca2+ efflux is mediated primarily by the Na-Ca exchanger, rather than by the sarcolemmal ATP-driven Ca2+ pump. 7. When bovine tail artery was treated with verapamil and phentolamine, and [Na+]o was reduced from 139.2 to 43.9 mM, substitution of K+ for Na+ induced a larger external Ca2+-dependent contraction than did substitution of Tris for Na+. The amplitudes of these contractions were greatly increased when the Na+ pump was inhibited by 5 x 10(-5) M-strophanthidin, presumably because of the rise in [Na+]i.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Renal function curve in patients with secondary forms of hypertension.

The causative mechanisms of hypertension were investigated by studying the renal function (pressure-natriuresis) curve in patients with primary aldosteronism (n = 6) and renovascular hypertension (n = 6). Before and after radical operation (removal of adenoma in primary aldosteronism and percutaneous transluminal angioplasty in renovascular hypertension), dietary NaCl intake was altered from 10 to 13 g/day in Week 1 to 1 to 3 g/day in Week 2. Mean arterial pressure (MAP) and urinary sodium excretion were measured on the last 3 days of each week. By restricting sodium intake before operation, MAP was reduced from 122 +/- 7 to 113 +/- 7 mm Hg (p less than 0.025) in primary aldosteronism but not in renovascular hypertension (130 +/- 6 to 128 +/- 5 mm Hg). The renal function curve was drawn by plotting urinary sodium excretion on the ordinate and MAP on the abscissa before and after operation. The slope of the curve was analyzed between the plotted points, and each curve was extrapolated to zero sodium excretion as an estimate of the degree of shift of the curve along the MAP axis. Before, as compared with after operation, the extrapolated x-intercept of the curve was shifted rightward in both primary aldosteronism (111 +/- 7 vs 87 +/- 4 mm Hg; p less than 0.025) and renovascular hypertension (128 +/- 5 vs 95 +/- 2 mm Hg; p less than 0.025) and the slope was depressed in primary aldosteronism (16 +/- 1 vs 40 +/- 17 [mEq/day]/mm Hg; p less than 0.025) but not in renovascular hypertension (130 +/- 75 vs 40 +/- 13 [mEq/day]/mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Comparison of effects of vegetable protein diet and animal protein diet on the initiation of anemia during vigorous physical training (sports anemia) in dogs and rats.

The effect of the quality of dietary protein on the initiation of temporary anemia during vigorous physical training (sports anemia) was studied in dogs and rats. In the dog experiment, one group of dogs was fed a crude animal protein (AP) diet and the other a crude vegetable protein (VP) diet. After 6 weeks on the diets in a sedentary state (rest period), all the dogs were forced to run every day for two weeks (exercise period). The rat experiment was carried out using purified nutrient mixtures. Casein (C) was used as AP and gluten (G) as VP. Feeding was done for two weeks in two series with two diet groups of rats. One series was 15% protein feeding (15% C and 15% G) groups and the other 24% protein feeding (24% C and 24% G) groups. In each group, one group remained in a sedentary state (rest group), and the other ran vigorously on a treadmill every day for one week (exercise group). In a sedentary state, there was a slight tendency for the hemoglobin content or erythrocyte count to be reduced, even when the values remained within the normal range, in dogs and rats fed VP. On the other hand, after vigorous running, significant anemia (reduction of hemoglobin) appeared in the VP diet dogs and in all exercise rat groups except the 24% C group. It was confirmed that the anemia was caused by a reduction of erythrocyte resistance to hemolysis, which was closely related to changes in the lipid composition of blood (serum and especially erythrocytes). The change in lipid profile revealed by the experiments was a reduction of free cholesterol in blood associated with an increase of lysolecithin in dogs during the exercise period and in the rat exercise groups. It was suggested that repeated physical exercise increased the activity of LCAT (lecithin-cholesterol-acyltransferase) in the liver, spleen, etc., resulting in the above changes in lipid patterns in the blood. In dogs of AP and rats of 24% C, however, those changes in lipid pattern caused by exercise and sports anemia did not appear significantly. The different effects of the AP diet seemed to be due to the antagonistic effects of lysine, which was present in sufficient amounts in the diet. Thus the theoretical basis for our recommendation of a high amount of AP in the diet to prevent sports anemia was clarified by the present experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia↗
PubMed1987

Sodium metabolism and hypertension: how are they linked?

Some of the critical links between sodium metabolism and vascular smooth muscle (VSM) contraction have been examined in an effort to explain the role of sodium in the etiology of hypertension. We found that the Na electrochemical gradient across the sarcolemma plays a critical role in the control of contractility in rat aorta and bovine tail artery. Reducing external Na and/or increasing internal Na increases vascular reactivity to norepinephrine (NE), to K and (in rat aorta) to caffeine, and slows relaxation; marked reduction in the Na gradient induces contraction. These effects appear to be the results of Ca movements mediated by Na/Ca exchange. Studies with Ca channel blockers and with alpha-adrenoceptor antagonists (except when NE was used) indicate that these effects cannot be attributed to Ca entry through Ca channels or to release of endogenous alpha-agonists. There is increasing evidence that individuals with essential hypertension have kidneys with an impaired ability to excrete Na. The retained Na (Cl) and attendant (slight) volume expansion may be compensated by the secretion of a (natriuretic) hormone which inhibits Na pumps. Inhibition of the Na pump in kidney tubules would be expected to induce a natriuresis (and net negative Na balance). Inhibition of the Na pump in VSM should increase intracellular Na, and thus enhance contractility via Na/Ca exchange. These mechanisms may explain the increased vascular reactivity and vascular tone that are the hallmark of essential hypertension and many other types of hypertension. The direct natriuretic action of the hormone, as well as the pressure natriuresis that results from its action on VSM, may help to protect these hypertensive individuals against the tendency to extracellular fluid volume expansion at the expense of the elevated blood pressure.

Animals↗
PubMed1987

Control of contractility and the role of Na/Ca exchange in arterial smooth muscle.

Pharmacological tools were used to examine the "sources" of Ca for arterial smooth muscle (ASM) contraction. The influence of the transsarcolemmal Na gradient on the regulation of tension was also determined in small rings of rat aorta and bovine tail artery. Ryanodine plus a Ca channel blocker can be used to separate the portions of a contraction that are due respectively, to sarcoplasmic reticulum (SR) Ca release and to Ca entry through Ca channels. Manipulations that reduce the sarcolemmal Na gradient increase basal tone and augment the contractile responses to noradrenaline and caffeine; these manipulations also slow the rate of relaxation, in Ca-free solution, following induction of contractures. When Ca channels, alpha-receptors, and the Na pump are blocked, the contractile responses to K-rich media increase as the ASMs accumulate Na. These data indicate that a voltage-sensitive Na/Ca exchange system helps to regulate cell Ca in ASM.

Animals↗