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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 253 records · Page 14Linked to original sources

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.

Animals↗

Difference between the effects of atrial natriuretic peptide and calcium antagonist on cytosolic free calcium in cultured vascular smooth muscle cells.

The effect of atrial natriuretic peptide (ANP) on cytosolic free calcium ([Ca2+]i) was studied in monolayers of cultured vascular smooth muscle (VSM) cells loaded with a fluorescent calcium indicator, fura-2. ANP (atriopeptin III, 10(-8) M) decreased the resting level of [Ca2+]i and sustained rises in [Ca2+]i following peak levels induced by vasoconstrictive hormones (angiotensin II or vasopressin). ANP also decreased a rise in [Ca2+]i induced by high potassium (high K+) depolarization. The initial rise in [Ca2+]i induced by vasopressin was not inhibited by ANP. On the other hand, calcium antagonists (nicardipine or nifedipine) inhibited the high K+-induced rise in [Ca2+]i, whereas there was no effect on rises in [Ca2+]i induced by vasopressin. These results suggest that calcium antagonists inhibit voltage-dependent calcium channels, while ANP can decrease [Ca2+]i presumably through a stimulation of calcium-extrusion active transports in vascular smooth muscle cells.

Animals↗

Inhibitory effect of cicletanine on vascular smooth muscle cell proliferation.

We investigated the effect of cicletanine on vascular smooth muscle cell proliferation. In cultured vascular smooth muscle cells from rat mesenteric artery, cicletanine (10(-5) to 10(-4) M) increased prostacyclin synthesis (measured as 6-keto-PGF1 alpha by radioimmunoassay) dose-dependently. When added to cells in which mitogenesis was activated by 10% fetal bovine serum, cicletanine (3.3 x 10(-5) to 10(-4) M) inhibited [3H] thymidine incorporation up to 31% of the control level. Inhibitory effect of cicletanine on mitogenesis was also confirmed at 48 h by cell counts (control: 18965 +/- 629, cicletanine 10(-4) M: 14840 +/- 430, n = 6). The effect of cicletanine on platelet-derived growth factor (PDGF)-stimulated [3H] thymidine incorporation was not abolished by prostaglandin synthesis inhibition with aspirin, but the prostacyclin analogue OP-41483 (125-1000 ng/ml) inhibited it dose-dependently. Calcium entry blockers, nifedipine (3.3 x 10(-6) M) and diltiazem (10(-4) M), inhibited both [3H] thymidine incorporation and cell proliferation, while furosemide did not affect it. Cicletanine also inhibited PDGF-stimulated [3H] thymidine incorporation in cultured glomerular mesangial cells. We conclude that cicletanine stimulates prostacyclin synthesis and inhibits cell proliferation in cultured vascular smooth muscle cells, which may possibly be related to the intracellular calcium mobilization. Such a property might be contributory to the antihypertensive activity of cicletanine.

Animals↗

[Report of a case of Herpes zoster].

Herpes Zoster is a viral disease of the skin and mucosa characterized by grouped vesicula eruptions and neuralgic pain along a peripheral nerve. A case of Herpes Zoster in the right region along the second and third trigeminal nerve branches of a 24-year-old male was reported. The first disorder appeared as a grouped vesicular eruption in the center of the lower lip. This was followed by a cutaneous lesion in the area of the right second trigeminal nerve branch. From the first day of hospitalization, the patient began receiving a daily dose of 2500mg of immunoglobulin. The administration of immunoglobulin, cured the oral and cutaneous lesion.

Adult↗

[Exploration on the reconstruction of lung image and the estimation of lung tissue volume by single photon emission computed tomography (SPECT)].

We studied the use of single photon emission computed tomography (SPECT) for evaluating lung image and measuring lung tissue volume, in a lung phantom and healthy volunteers. Three conditions of image processing were tested using the phantom, and found out a backprojection method with using a Shepp-Logan filter and a pre-reconstruction smoothing of 3 X 3 pixels to be suited. A lung tissue volume was estimated from the summation of voxels in the region where the SPECT value was greater than an arbitrary threshold level. We changed phantom lung density from 0.34 g/cm3 to 0.58 g/cm3, but there was no significant effect in the estimated volume by the density change. Changes in the lung SPECT images and lung tissue volumes in healthy subjects were studied, after changing the lung volume by applying either continuous negative body-surface pressure (CNP) to the thorax or positive end-expiratory pressure (PEEP). Difference of the lung expansion in the two methods was visualized by the SPECT images. The lung tissue volumes obtained by SPECT were correlated with the functional residual capacity by Helium dilution method (r = 0.91, p less than 0.001). We concluded that lung SPECT could be used clinically to display the distribution of a tracer radio-isotope in the lungs and also used to estimate the lung tissue volume.

Adult↗

[Estimation of lung volume and pulmonary blood volume from radioisotopic images].

Lung volume and pulmonary blood volume in man were estimated from the radioisotopic image using single photon emission computed tomography (SPECT). Six healthy volunteers were studied in a supine position with normal and altered lung volumes by applying continuous negative body-surface pressure (CNP) and by positive end-expiratory pressure (PEEP). 99mTc labeled human serum albumin was administered as an aerosol to image the lungs. The CNP caused the diaphragm to be lowered and it increased the mean lung tissue volume obtained by SPECT from 3.09 +/- 0.49 l for baseline to 3.67 +/- 0.62 l for 10 cmH2O (p less than 0.01), and to 4.20 +/- 0.67 l for 20 cmH2O (p less than 0.01 as compared with 10 cmH2O), respectively. The PEEP also increased the lung tissue volume to 3.68 +/- 0.68 l for 10 cmH2O as compared with the baseline (p less than 0.05), but there was no further increase in the volume after applying 15 cmH2O PEEP. The lung tissue volume obtained by SPECT showed a positive correlation with functional residual capacity measured by the He dilution method (r = 0.91, p less than 0.001). Pulmonary blood volume was estimated by taking the ratio of gamma-counts in the lung field to those in the intracardiac space (L/H ratio) after the equilibration of intravascular 99mTc-labeled red blood cells. The L/H ratio decreased after either the CNP or PEEP, suggesting a decrease in the blood volume per unit lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The effect of airway deposition on the assessment of lung injury by 99mTc-DTPA clearance--lung injury in interstitial lung diseases assessed by using the duplicated 99mTc-DTPA aerosol inhalation method].

The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearance curve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung diseases (2.52 +/- 0.72%/min, n = 8; p less than 0.01) was significantly greater than that in healthy nonsmokers (0.92 +/- 0.20%/min, n = 4). The alveolar-peripheral airway deposition was similar in both healthy nonsmokers and interstitial lung diseases (73.5 +/- 7.8% and 75.5 +/- 9.2%, respectively). The mean k corrected for alveolar-peripheral airway deposition (corrected k; kc) was higher in patients with interstitial lung diseases (4.08 +/- 1.63%/min; p less than 0.01) as compared with healthy nonsmokers (1.36 +/- 0.47%/min). The mean k was significantly greater than the mean kc in both groups (p less than 0.01, p less than 0.01). However, there was a significant correlation between the k and kc obtained among the subjects (r = 0.951; p less than 0.01). We, therefore, conclude that correction for alveolar-peripheral airway deposition was not necessary to distinguish the patients with interstitial lung diseases from the healthy nonsmokers using 99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects.

Adult↗

[A case of gastric carcinoid with transient features of tubular adenocarcinoma].

A 51-year-old male sought a medical advice because of gastric lesion that had been detected by a mass screening though the man felt no symptoms. Gastrofiberscopy revealed a superficially elevated, depressed lesion on the lesser curvature of the antrum. Biopsy specimens showed a moderately differentiated adenocarcinoma, and surgically obtained material, about 1.5 cm in diameter, revealed a carcinoid and tubular adenocarcinoma. The tumor consisted mainly of carcinoid tissue while the surface of the tumor manifested, histologically, an adenocarcinoma, though the margins of the two histologies were unclear. The carcinoid tissue revealed a positive Grimerius-staining and a negative Fontana-Silver staining. Fifteen patients having a gastric lesion containing a carcinoid and a carcinoma have been reported in Japan. Five of these 15 cases were pointed out as having existing transient features between the cancer and carcinoid.

Adenocarcinoma↗

[Permeability changes in bronchiolo-alveolar epithelium].

The pathophysiology in the bronchiolo-alveolar region in healthy smokers and patients with interstitial lung diseases was assessed in terms of changes in epithelial permeability. The pulmonary epithelial permeability was estimated by the rate constant (referred to as "kep") of inhaled 99mTc-DTPA (diethylene triamine penta acetate) clearance from the lungs. Healthy nonsmokers had a mean kep value of 0.82 +/- 0.26%/min, and their kep values were constant irrespective of age or sex. Of healthy smokers 53% showed increased permeability. Young smoking males, whose lung injury was supposed to be limited mainly to respiratory bronchioles, showed increased permeability. This increase was correlated with their cigarette consumption per day and was reversible after stopping smoking. The patients with interstitial lung diseases also showed increased permeability as compared with healthy non-smokers. We believe that the method is a sensitive test to detect inflammatory changes in the bronchiolo-alveolar epithelium.

Adult↗

[Surgical treatment of the malignant mediastinal tumors--with special reference to prosthetic reconstruction of superior vena cava].

Sixteen patients with the malignant mediastinal tumors compromising the superior vena cava (SVC) and brachiocephalic veins (BCV) were treated from April 1974 to March 1987. SVC reconstruction by prosthesis combined with or without tumor resection were performed in 6 cases and removal of the tumor with partial resection of SVC and right BCV in one case. Two patients died within one month and two patients survived over 5 years postoperatively. Tumor resection, removal of the right lung and SVC wall, and patch angioplasty were performed in one patient who died three and one half months postoperatively. Resection of the tumor and left BCV were performed in 4 patients. Segmentally resected left BCV was reconstructed with interposed graft in two, prosthesis was implanted between left BCV and right atrium in one and no venous reconstruction was attempted in one. Three patients are alive and one patient died six and one half years after operation. Exploratory mediastinotomy was carried out in 3 cases and radiation therapy alone in one case. All but one patients died within one year after diagnosis. Though the long term results of the surgical treatment for malignant mediastinal tumor was not satisfactory, extensive resection of the tumor was worth attempting, as the patency rate of the prosthetic venous reconstruction was improved.

Adolescent↗

[Changes of plasma amino acid on the course of septic multiple organ failure].

The changes of plasma amino acid (AA) pattern on the course of septic multiple organ failure (SMOF), and the effect of branched chain amino acid enriched solution (BCAA-S) on the AA pattern were evaluated in thirteen patients who died of SMOF in ICU. The course of ICU was divided into the following three stages. Stage I was a few days after the admission in ICU. Stage II was severe infected state. Stage III was terminal state. Following results were obtained: 1) Total AA value (TAA) of each stage was 2,693 n.mol/ml, 6,666 n.mol/ml and 19,480 n.mol/ml. 2) BCAA/aromatic AA (B/A) of each stage was 1.4, 1.03 and 1.05. Above values were lower than those of normal one (2.44). 3) Most kinds of AA in stage III were exhibited significantly higher than those of stage I as evaluated in absolute value. 4) In the BCAA-S administered group, B/A exhibited higher values than those of control, but, there was no sign of amelioration for SMOF condition in the former group. In severe infected or septic shock state, AA metabolism is deeply deteriorated. So, we can not decide whether BCAA-S given in this condition plays beneficial effect on the course of SMOF or not.

Adult↗

Alteration of insulin and glucagon secretion from the perfused BB rat pancreas before and after the onset of diabetes.

Secretion of insulin and glucagon from perfused BB rat pancreas was examined in rats (5 weeks old; n = 6) before and 2 weeks after (13 weeks old; n = 5) the onset of diabetes mellitus. The secretion of insulin and glucagon was modified by increasing concentrations of glucose in the perfusate from 2.8 mM to 16.5 mM. In 5-week-old BB rats, glucagon secretion was higher at the low glucose concentration (2.8 mM) and insulin secretion lower at the high glucose concentration (16.5 mM) than the corresponding values in age-matched control rats. In 13-week-old BB rats, insulin secretion was undetectable irrespective of glucose concentration. Glucagon secretion was only moderately suppressed by the perfusion of high glucose (16.5 mM) and was significantly higher than that of age-matched controls. The reduction in insulin secretion observed in 5-week-old rats without insulitis indicated that pancreatic B cells of BB rats of this age are somehow injured by humoral factors rather than cell infiltration. Cell function was apparently modified indirectly by the destruction of neighboring B cells.

Aging↗

Papillary collecting tubule responsiveness to vasoactive hormones in spontaneously hypertensive rats.

Renal papillary collecting tubule (RPCT) hormone responsiveness was compared between cultured RPCT cells from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Unstimulated cells from 4-week-old SHR produced less prostaglandin E2 (PGE2) and cyclic (c)AMP than comparable cells from WKY, while cells from both stains synthesized similar amounts of PGE2 after stimulation with arachidonate, A23187 or bradykinin and similar amounts of cAMP after stimulation with vasopressin or PGE2. There was no difference in basal or stimulated levels of cyclic (c)GMP between the strains. In RPCT cells from 16-week-old rats, basal levels of cAMP, cGMP and PGE2 were significantly lower than those from 4-week-old rats, but they did not differ between the strains. These results suggest that RPCT cells of SHR and WKY at the post-weaning period may differ in the metabolism of PGE2 and cAMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.

Age Factors↗

Effects of chronically administered atrial natriuretic factor in aldosterone-infused hypertensive rats.

To assess the pathophysiological role of atrial natriuretic factors in mineralocorticoid hypertension, we studied the effects of chronic infusion of synthetic atrial natriuretic factor on blood pressure and sodium-water excretion in rats with aldosterone salt-induced hypertension. Administration of synthetic atrial natriuretic factor (150 micrograms/kg/day) to rats made hypertensive by 7-day infusion of aldosterone (100 micrograms/kg/day) and sodium loading with 1% NaCl as drinking water returned the blood pressure to control levels, and the antihypertensive effect was not associated with any changes in urine volume and urinary sodium excretion. These results indicate that atrial natriuretic factors may be involved in the regulation of blood pressure in mineralocorticoid hypertension, independent of the renal effects of these substances.

Aldosterone↗