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Biomedical subjects

T Ashida

Publications and source records attributed to T Ashida.

At least 91 records · Page 5Linked to original sources
PubMed1993

[Successful oral administration of etoposide therapy for refractory malignant lymphoma treated with frequent combination chemotherapy].

A 67-year-old man was diagnosed as non-Hodgkin lymphoma (diffuse, mixed cell type, B cell) with clinical stage IV in March 1989. He had been treated many times with salvage chemotherapy on admission including CHOP-etoposide and ProMACE-Cyta BOM. Recurrence, however, occurred in two or three months after any therapy. He had a therapeutic history of chronic daily administration of etoposide. In November 1991, recurrence was found in the peripheral lymph node and the colon. A new regimen of oral administration of etoposide, 50 mg/day four times a week, was employed. Two months later, the peripheral lymph node swelling disappeared. Seven months later, the patient showed no signs of recurrence by Ga-scintigraphy. This therapy is being continued. It is suggested that anti-neoplastic activity of etoposide is dependent on the schedule of administration. This regimen is suggested to be effective in the treatment of patients with refractory malignant lymphoma.

Administration, Oral↗
PubMed1993

Mucin-producing tumor of the pancreas: natural history and serial pancreatogram changes.

The clinical features and changes of the pancreatic duct system in nine patients with mucin-producing tumor of the pancreas were serially studied to clarify the natural history and evolution of pancreatograms. The observation periods ranged from 6 to 50 months (mean, 30 months), and all patients were examined by endoscopic retrograde pancreatography two or more times. Four of the nine cases exhibited obvious progression of pancreatic duct dilation in association with increased amounts of mucin in the dilated duct, whereas five did not show apparent progression of ductal changes. Changes in the pancreatograms of mucin-producing tumor occurred when mucin secretion by the tumor became prominent, and such cases frequently presented with abdominal pain and pancreatitis. In contrast, most of the branch duct type remained unchanged; all three cases of main duct type showed progression of pancreatograms. There was no apparent relationship between degree and progression of ductal changes and the tumor malignancy.

Aged↗
PubMed1992

Effects of dietary salt on sodium-calcium exchange and ATP-driven calcium pump in arterial smooth muscle of Dahl rats.

AIM: To compare the effects of dietary salt on sodium-calcium exchange and the ATP-driven calcium pump in arterial smooth muscle between Dahl salt-sensitive (DS) and salt-resistant (DR) rats. METHODS: Aortic rings freshly excised from 16 DS rats and 16 DR rats on a low- (0.3%) or high- (8%) NaCl diet for 4 weeks were superfused with physiological saline and isometric tension was measured. In the presence of 10 mumol/l phentolamine, 10 mumol/l verapamil and 5 mmol/l caffeine, relaxation of a low-Na+ contraction was promoted by external calcium removal. RESULTS: On the high-salt diet, the rate of relaxation at 1.2 mmol/l extracellular sodium (calcium extrusion by calcium ATPase) was significantly lower in aortic rings from DS rats than from DR rats. The increase in the rates of relaxation from 1.2 mmol/l to normal (139.2 mmol/l) extracellular sodium (calcium extrusion by sodium-calcium exchange) was significantly greater with the high-salt diet than with the low-salt diet in rings from DR rats, but it was not different between the high- and low-salt diets in DS rats. The rate of increase in tonic tension by reducing extracellular Na+ from normal to 1.2 mmol/l in the presence of verapamil, caffeine and phentolamine (calcium entry by sodium-calcium exchange) was significantly lower in rings from DS rats than in those from DR rats on the high-salt diet. CONCLUSIONS: These observations suggest that the effects of dietary salt on the sodium-calcium exchange system in arterial smooth muscle differ between DS and DR rats and that calcium extrusion by the calcium pump is decreased in DS rats compared with DR rats. The lack of an increase in sodium-calcium exchange in salt-fed DS rats might lead to an elevation in cellular calcium and contribute to the mechanism of hypertension.

Adenosine Triphosphate↗
PubMed1992

Sodium and noradrenaline in cerebrospinal fluid and blood in salt-sensitive and non-salt-sensitive essential hypertension.

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.

Adult↗
PubMed1992

Acute depressor effect of alcohol in patients with essential hypertension.

To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers.

Adult↗
PubMed1992

Vascular responsiveness to angiotensin II and phenylephrine, the tubular function and the prostaglandin, renin-angiotensin system in a patient with Bartter's syndrome.

In a 39-yr-old female patient with Bartter's syndrome, vascular responsiveness to angiotensin II and phenylephrine was studied. Pressor responses to angiotensin II and to phenylephrine were markedly decreased prior to treatment and were improved by administration of indomethacin, dextran, KCl, captopril, propranolol or pindolol. Moreover, the responses of total peripheral vascular resistance to angiotensin II and phenylephrine were markedly decreased before treatment and were improved by the treatment. A relatively low fractional distal chloride reabsorption was found, and that was not changed after the administration of KCl or indomethacin. The results of this patient were compatible with the primary cause of Bartter's syndrome, defective chloride reabsorption at the loop of Henle, but the possibility of an abnormality in the vascular wall could not be denied.

Adult↗
PubMed1992

Effect of manidipine, a new calcium antagonist, on intrarenal hemodynamics in essential hypertension.

The effect of manidipine, a new Ca2+ antagonist, on intrarenal hemodynamics was assessed in essential hypertension and compared with nicardipine, a previously studied Ca2+ antagonist. Identical 2-week studies were repeated before and during the administration of manidipine (10 mg once daily, 2 weeks) in 3 patients with essential hypertension who were given regular- and sodium-restricted diets for 1 week each. The renal function curve (pressure-natriuresis relationship) was drawn by plotting the urinary sodium excretion rate on the y-axis as a function of the systemic mean arterial pressure (MAP) on the x-axis. Assuming that the difference between MAP and the extrapolated x-intercept of the renal function curve represents the effective filtration pressure across the glomerular capillary walls, the intrarenal hemodynamics were calculated (e.g., afferent arteriolar resistance (RA), efferent arteriolar resistance (RE), and glomerular pressure (PG)). During the regular sodium diet, MAP was lowered from 100 +/- 7 to 93 +/- 5 mmHg (p < 0.04) and the effective filtration pressure was lowered from 20 +/- 2 to 10 +/- 3 mmHg (p < 0.05); the renal plasma flow rate (pre: 560 +/- 74 vs. post: 627 +/- 108 mL/min) and glomerular filtration rate (82 +/- 10 vs. 78 +/- 5 mL/min) were not altered. RA remained unchanged (3,800 +/- 700 vs. 3,400 +/- 300 dyn.sec.cm-5; % reduction: 4 +/- 16%) whereas RE was reduced from 4,300 +/- 700 to 3,300 +/- 800 dyn.sec.cm-5 (19 +/- 15%). Thus, PG was lowered from 58 +/- 2 to 50 +/- 2 mmHg (13 +/- 3%), which parallels with the reduction in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

The association between salt sensitivity of blood pressure and family history of hypertension.

1. The salt sensitivity index (SSI) and family history of hypertension were studied in 140 hospitalized patients with essential hypertension to clarify whether salt sensitivity of blood pressure is related to familial disposition to hypertension. 2. SSI was calculated by dividing the change of mean blood pressure by that of urinary sodium excretion when salt intake was restricted from 15 to less than 3 g/day. 3. Family history of hypertension was classified into three groups depending on the presence or absence of hypertension in the father, mother and siblings. 4. The group without a family history of hypertension showed a significantly lower SSI value than other groups. 5. In multiple regression analysis undertaken within each gender, SSI showed significant partial correlations with blood pressure and family history of hypertension in the female group (r = 0.402 and 0.265, respectively), whereas in the male group it showed a positive correlation only with blood pressure (r = 0.501). These results indicate that salt sensitivity of blood pressure is related to familial disposition to hypertension. This association was more apparent in the female than male group and its gender difference can be partially attributed to the fact that blood pressure in the female group is more sensitive to salt.

Blood Pressure↗
PubMed1992

[Analysis of coagulation factor XIII in Crohn's disease--establishment of a novel monoclonal anti-coagulation factor XIII antibody].

A novel monoclonal anti-human coagulation factor XIII (F. XIII) antibody (2C3 antibody) raised in BALB/c mice was established by Kohler and Milstein methods. The monoclonal antibody recognized F. XIII of 85 KD demonstrated by western blotting analysis. Plasma F. XIII-IR levels measured by ELISA with 2C3 antibody were significantly lower in active disease than in quiescent disease in a total of 21 Crohn's disease (CD) patients. Plasma F. XIII levels were significantly lower on admission in CD with fistulas than in CD without fistulas. Relationships between activities of CD and plasma F. XIII levels were shown. No significant relationships, however, were observed between F. XIII-IR levels and nutritional states assessed by TP, ALB, TF, PA, RBP, %IBW. Low levels of F. XIII in active CD patients with fistulas may occur regardless of hyponutrition. By using 2C3 antibody, global functions of F. XIII will become clarified as well as pathologic and diagnostic roles of plasma F. XIII in CD.

Adolescent↗
PubMed1992

A gender difference in the association between salt sensitivity and family history of hypertension.

We examined 174 subjects (82 men and 92 women) with essential hypertension to determine whether gender played an important role in the association of blood pressure (BP) familial disposition, and hypertension. To evaluate the salt sensitivity of BP, we measured changes in blood pressure after restricting salt intake from about 15 g/day to less than 3 g/day. The familial disposition to hypertension was categorized into four groups according to the presence or absence of hypertension in the father, mother, and siblings. If none, one, two, or three family members had hypertension, they were assigned the FH(-), FH(+), FH(++), and FH( ) groups, respectively. Only in women did the FH(-) group show a significantly smaller blood pressure reduction than that of the other groups. The mean BP reduction in the four groups was 4.1 +/- 1.9, 8.5 +/- 1.1, 10.1 +/- 1.5, and 11.2 +/- 2.8 mm Hg (mean +/- SEM), respectively. This difference in BP reduction was not observed in men. Multiple regression analysis, using percent changes in mean BP as the dependent variable and other factors as independent variables, also showed a significant partial correlation coefficient for familial disposition to hypertension only in women. Thus, the relationship between salt sensitivity and familial disposition to hypertension differed according to gender. This difference may provide an important insight into the hereditary nature of hypertension.

Adult↗
PubMed1991

Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in essential hypertension.

The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG. This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Diet, Sodium-Restricted↗
PubMed1991

Crystal structure of Streptomyces erythraeus trypsin at 2.7 A resolution.

The crystal structure of Streptomyces erythraeus trypsin (abbreviated as SET) has been determined in order to clarify the precise structure of the vicinity of the active site of serine protease and to understand its structure-function relationship. Crystals of SET were prepared at its active pH range (pH 5-10) without any inhibitors which might have affected the circumstances around the active sites. The structure model of SET was made based on the electron density map obtained by the multiple isomorphous replacement method at 3.5 A resolution, and refined by the restrained least-squares method. The current model yields a crystallographic R-factor of 0.272 for 4,968 reflections between 8 and 2.7 A resolution. Though the sequence homology among SET, Streptomyces griseus trypsin and bovine trypsin, 32-37%, is not so high, their overall structures are similar to each other. Comparison of the three molecular structures shows that: 1) the folding of the main chains of the three proteins is essentially the same though there are significant differences on the molecular surface; 2) the spatial arrangements of the catalytic triads in the three proteins are similar to each other; 3) in SET and S. griseus trypsin a short stretch of 3(10)-helix is found through Ala56 to Thr59; His57 in this segment is one important amino acid residue involved in the active sites.

Amino Acid Sequence↗
PubMed1991

Effects of ouabain and verapamil on endothelin-1-induced contraction of mesenteric artery in young spontaneously hypertensive rats.

We studied the effects of ouabain and verapamil on endothelin-1(ET-1)-induced contraction of the mesenteric artery in prehypertensive spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. Rings of mesenteric artery of SHRs and WKY rats aged 4 weeks were superfused with physiological saline solution and isometric tension was measured. ET-1 (10(-9) or 10(-8) M)-induced contractions were significantly larger in WKY rats than in SHRs. ET-1 (10(-7) M)-induced contractions were not significantly different between SHRs and WKY rats. Verapamil markedly inhibited ET-1 (10(-7) M)-induced contractions both in SHRs and in WKY rats. Although the percent inhibition tended to be larger in SHRs than in WKY rats, the difference was not significant. Ouabain significantly increased ET-1 (10(-7) M)-induced contraction in the presence of verapamil both in SHRs and in WKY rats. The increase was significantly greater in SHRs than in WKY rats. As a result, ET-1 (10(-7) M)-induced contractions were significantly greater in SHRs than in WKY rats in the presence of verapamil and ouabain. These results suggest that in ET-1-induced arterial contraction, [Na+]i-mediated [Ca2+]i regulation such as the Na+/Ca2+ exchange system might be greater in SHRs than in WKY rats, and that this might be, at least in part, involved in the pathogenesis or maintenance of hypertension in SHRs.

Animals↗
PubMed1991

Differential effects of endothelin-1 and big endothelin on canine kidneys.

Renal effects of endothelin-1 (ET-1, human, 1-21) and the equivalent molar concentration of big ET (human, 1-38) and the contributions of prostaglandins and endothelium-derived relaxing factor to these actions were examined. Intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, decreased renal blood flow (RBF), glomerular filtration rate (GFR), and urine output (V) to 62, 70, and 45% of control values, respectively. Additional aspirin-DL-lysine (ASP) treatment (25 mg/kg) caused marked decreases in RBF, GFR, and V to 20, 14, and 9% of control values, respectively. During ET-1 infusion, intrarenal infusion of NG-monomethyl-L-arginine (L-NMMA, 1 mumol/min) caused decreases in RBF, GFR, and V. In another group, intrarenal infusion of big ET at a dose equivalent to that of ET-1 did not significantly affect RBF, GFR, or urine output, which were 95, 107, and 84% of control values, respectively. Additional ASP treatment decreased these values to 78, 69, and 52% of control values, respectively. L-NMMA infusion during big ET infusion showed little effect on renal function. Our study demonstrated that intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, caused significant hemodynamic and functional changes in the canine kidney compared with an equivalent molar concentration of big ET.

Animals↗
PubMed1991

Immunoreactive endothelin-1 contents in brain regions from spontaneously hypertensive rats.

To investigate the possible role of brain endothelin-1 (ET-1) in hypertension of spontaneously hypertensive rats (SHRs), we measured immunoreactive (ir) ET-1 contents in brain regions as well as plasma ir-ET-1 levels in SHRs aged 4-5 and 12-14 weeks and age-matched Wistar-Kyoto rats (WKY) with a radioimmunoassay for ET-1. Systolic blood pressures of SHR aged 4-5 and 12-14 weeks were significantly higher than those of corresponding WKY. Significant amounts of ir-ET-1 were detectable throughout the discrete brain regions analyzed in both strains; higher ir-ET-1 contents in structures such as thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum, with the lowest in cerebral cortex, were observed. A reverse-phase high-performance liquid chromatography of the brain extracts revealed the presence of both a major component identical to the elution position of synthetic ET-1 and a minor component possibly corresponding to its oxidized form. When compared, ir-ET-1 contents in all brain regions analyzed were lower in SHRs than in WKY rats. This strain-related change of ir-ET-1 contents was significant in the medulla at 4-5 weeks of age, and in all brain regions except hypothalamus at 12-14 weeks of age. Plasma ir-ET-1 levels, in contrast, were comparable between SHRs and WKY rats. These results suggest that brain ET-1 may be involved in the development and the maintenance of hypertension in SHRs.

Aging↗
PubMed1991

Acute and chronic effects of anti-endothelin-1 antibody on blood pressure in spontaneously hypertensive rats.

To evaluate the significance of endogenous endothelin (ET) in the maintenance of blood pressure in hypertensive and normotensive conditions, we examined the acute and chronic effects of anti-ET-1 antibody in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Immunoglobulin (Ig) solution purified from anti-ET-1 rabbit serum was injected intravenously in conscious rats aged 12-14 weeks (SHR: n = 7, WKY: n = 7). In the control group (SHR: n = 5, WKY: n = 4), Ig prepared from nonimmune rabbit serum was administered. One week after the first injections of Ig, second intravenous injections were given. After the intravenous injections of ET-1 antibody, there were no significant changes in directly measured blood pressure (BP) for up to 60 min in both strains. On the first, third, and seventh days after the first administration of ET-1 antibody, as well as on the first, third, and seventh days after the second injection, there were no appreciable differences in BP between SHR treated with anti-ET-1 antibody and SHR with control Ig. No significant changes in BP were observed throughout the observation period in WKY groups. Plasma levels of immunoreactive ET-1 were similar in SHR and WKY. This study suggests that circulating ET may not play a significant role in the maintenance of hypertension in SHRs or in the regulation of blood pressure in WKY rats.

Animals↗
PubMed1991

Intrarenal hemodynamics in patients with essential hypertension.

Intrarenal hemodynamics were estimated clinically in essential hypertension. Two-week studies were performed in 30 patients with essential hypertension who were given a regular sodium diet in the first week and a sodium-restricted diet in the second week. Intrarenal hemodynamic parameters such as afferent arteriolar (preglomerular) resistance, efferent arteriolar resistance, and glomerular hydrostatic pressure were calculated from renal clearances and plasma total protein concentration measured on the last day of the regular sodium diet. Calculations were based on Gomez's equations with the assumption that the gross filtration coefficient of glomerular capillaries was normal. The increase in afferent arteriolar resistance (8,100 +/- 500 dyne.sec.cm-5) was significantly correlated with an elevation in mean arterial pressure (120 +/- 2 mm Hg), whereas glomerular pressure (56 +/- 1 mm Hg) and efferent arteriolar resistance (2,500 +/- 100 dyne.sec.cm-5) remained normal. The renal function curve (pressure-natriuresis relation) was drawn by plotting urinary sodium excretion on the y axis as a function of mean arterial pressure on the x axis, both of which were measured on the last 3 days of each week. The extrapolated x intercept (107 +/- 2 mm Hg) of the renal function curve was strongly correlated in a 1:1 fashion with the sum of the arterial pressure drop from the aorta to the renal glomeruli plus the opposing pressures against glomerular filtration at glomeruli (r = 0.7, p less than 0.001) on the regular sodium diet, suggesting that the difference between mean arterial pressure on the regular sodium diet and the extrapolated x intercept represented the effective filtration pressure across the glomerular capillaries on the regular sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗