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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 19 recordsLinked to original sources
PubMed1992

Phenytoin partially antagonized L-type Ca2+ current in glucagon-secreting tumor cells (ITC-1).

Transmembrane Ca2+ currents were investigated by means of a whole-cell clamp technique in a hamster glucagon-secreting tumor cell line (ITC-1). Two types of Ca2+ current were identified in ITC-1 cells. The low-threshold and transient (T-type) current became detectable above the potential level around -60 mV and decayed rapidly with an inactivation time constant of 95 ms (at -40 mV and 23 degrees C), while the high-threshold and long-lasting (L-type) one was activated by depolarization more positive to -30 mV with non-inactivating kinetics. The voltage dependence and kinetics of these currents were identical to those reported in guinea-pig pancreatic alpha 2 cells. Both currents were augmented by equimolar substitution of Ca2+ with Ba2+ and completely abolished by adding 1 microM La3+. Phenytoin, a well known anti-epileptic drug and a postulated T-type specific Ca2+ current antagonist, surprisingly blocked the L-type current without affecting the T-type current in ITC-1 cells. While phenytoin antagonized the L-type Ba2+ current selectively, 60% of the current remained even in supramaximal concentration range over 500 microM. The residual component of the L-type current was completely abolished by adding nifedipine.

Animals↗
PubMed1992

Influence of chest background on pulmonary 99mTc-DTPA clearance in interstitial lung disease.

We examined the effect of chest extracellular 99mTc-diethylenetriamine pentaacetate (DTPA) as a background in the measurement of pulmonary 99mTc-DTPA clearance in patients with interstitial lung disease (ILD). Eight healthy nonsmokers (HN) and eight patients with ILD were studied. We monitored changes in gamma counts after the inhalation of 99mTc-DTPA aerosol by using a gamma camera placed over the anterior chest. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was assessed by calculating the slope of the decrease in the gamma counts. The chest background, estimated by 99mTc-DTPA intravenous injection, was subtracted from the original data to obtain the corrected DTPA clearance (kc; %/min). In patients with ILD, k was significantly greater [2.19 +/- 1.03 (SD) %/min; n = 8] compared with HN (0.86 +/- 0.17%/min; n = 8; P < 0.01). In patients with ILD, kc was also greater (2.80 +/- 1.15%/min; n = 8; P < 0.01) compared with HN (1.20 +/- 0.12%/min; n = 8). There was no difference in percent underestimation of k between the two groups (29.1 +/- 8.8% for HN, 22.5 +/- 7.9% for patients with ILD). There was a significant correlation between k and kc among all subjects (r = 0.987, P < 0.01). We conclude that background causes significant underestimation of pulmonary 99mTc-DTPA clearance.

Adult↗
PubMed1992

Endothelin-1 augments pressor response to angiotensin II infusion in rats.

To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control.

Angiotensin II↗
PubMed1992

Granulocyte colony-stimulating factor does not enhance endotoxin-induced acute lung injury in guinea pigs.

We studied recombinant human granulocyte colony-stimulating factor (G-CSF) in terms of its hematopoietic and neutrophil-activating effects on acute lung injury induced by endotoxin. Guinea pigs were divided into four groups: (1) saline control animals, (2) endotoxin alone, (3) cyclophosphamide (CPA)+endotoxin, and (4) G-CSF+endotoxin. A G-CSF dose of 20 micrograms/kg was given subcutaneously twice a day for 5 days. Animals were observed for 4 h after intravenously administered endotoxin (0.02 and 2.0 mg/kg) with serial measurements of complete blood counts and hemodynamics. Lung extravascular water, [125I]albumin leakage in lung tissue, and histopathologic features were examined at death. The endotoxin-alone group showed peripheral leukopenia, transient hypotension, excess lung water, increased albumin leakage, PMN accumulation in lung tissue, and gross histopathologic edema. G-CSF-treated animals showed attenuated responses in peripheral leukopenia, excess lung water, and albumin leakage in comparison with the endotoxin-alone group. No augmented responses were seen in the G-CSF group. The CPA+endotoxin group also had attenuated lung injury, which was similar to that in the G-CSF group. In conclusion, pretreatment with G-CSF tended to attenuate rather than enhance neutrophil-dependent acute lung responses to endotoxin.

Animals↗
PubMed1992

The role of recombinant human tissue-type plasminogen activator in the treatment of acute pulmonary thromboembolism.

The effect of intravenous recombinant human tissue-type plasminogen activator (tPA) on arterial blood gases was compared with the effect of heparin treatment in acute pulmonary thromboembolism. Fifteen patients received heparin alone (group A), 5 cases were treated with 7.7 x 10(6) I.U. of tPA (group B) and 10 cases with 15 x 10(6) I.U. of tPA (group C) combined with heparin treatment. Arterial oxygen tension before treatment was not significantly different among the three groups. PaO2 was dramatically improved on the 1st day in group C. By the 7th day, PaO2 of group B had improved to the level of group C. However, the PaO2 of group A on the 7th day was not significantly different compared to the pre-treatment value. In group C, post-treatment perfusion lung scintigrams were improved compared to the pre-treatment images, but this was not the case in group B. Treatment with tPA is more effective for acute pulmonary thromboembolism than heparin alone and a high dose of tPA (15 x 10(6) I.U.) leads to rapid improvement in arterial blood gases and lung perfusion images.

Acute Disease↗
PubMed1992

[Measurements of plasmin-alpha 2 plasmin inhibitor complex and FDP.D dimer levels in the fibrinolytic therapy of acute pulmonary thromboembolism].

The key enzyme for fibrinolysis is plasmin, which is converted from plasminogen by plasminogen activator. Activated plasmin lyses fibrinogen and fibrin to make fibrin degradation products(FDPs) and plasmin is inactivated immediately by alpha 2 plasmin inhibitor. As FDP.D dimer is derived solely from insoluble fibrin, FDP.D dimer is thought of as an index for clot lysis. We measured plasmin-alpha 2 plasmin inhibitor complex(PIC) and FDP.D dimer plasma levels in 3 patients with acute pulmonary thromboembolism treated with recombinant tissue plasminogen activator(tPA). Fifteen million units of tPA(TD-2061) were infused in one hour on the first, second and third hospital days. PIC and FDP.D dimer before tPA infusion showed slightly elevated values as compared to normal ranges. They increased markedly after tPA infusion. These findings suggest that the fibrinolytic system is slightly activated in the acute phase of pulmonary thromboembolism and also strongly activated by tPA infusion. Increased FDP D dimer suggests that fibrin clots are dissolved by activated plasmin. Improvement of arterial oxygen tension was observed after tPA infusion. As sustained higher FDP.D dimer means the existence of fibrin clots, heparin treatment should be continued for prevention of clot formation as long as FDP.D dimer shows higher value. In conclusion, PIC and FDP.D dimer are useful indices not only to detect the activated state of the fibrinolytic system but also to know clot lysis in tPA treatment.

Acute Disease↗
PubMed1992

[Left ventricular-right atrial communication with a residual ventricular septal defect: a case report of successful VSD patch closure with tricuspid valvuloplasty using folded patch].

A 18-year-old woman with combination of left ventricular right atrial communication (LV-RA communication) and residual ventricular septal defect (VSD) was presented. She underwent the radical operation of atrial septal defect, VSD and infundibular pulmonary stenosis at the age 11 years. Surgery was performed under the diagnosis of LV-RA communication and residual VSD. Two small defect were existed at the septal leaflet of the tricuspid valve, which communicated to left ventricle. The part of patch being used as closure of VSD at the previous operation, including perforated part of the septal leaflet was resected. A folded patch was used to reinforce the residual VSD and valvuloplasty was made using the remaining intact tricuspid tissues. Post-operative clinical course was uneventful. Shunt flow from LV to RA was not demonstrated in the postoperative left ventricular angiocardiography.

Adolescent↗
PubMed1992

Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer.

In order to evaluate quality-of-life (QOL) questionnaires, we studied the reliability and validity of the self-rating forms: A, comprising 16 questions; B, comprising 39 questions (Table II and III), in a special study supported by the Ministry of Health and Welfare. Sixty-four patients with inoperable lung cancer and 50 patients with chronic, non-malignant disease were entered into the study. Form A was translated and modified to Japanese culture from Schipper's Functional Living Index-Cancer, and Form B was of our own design. The internal consistency of the forms was examined by Cronbach's alpha coefficient. Both forms except for aspects of physical and social concern on form B, had alpha values greater than 0.65. A concurrent validity with performance status was shown over all aspects of concern (Pearson's correlation, r greater than 0.27, P less than 0.05) except for social (forms A and B) and psychological (form B). Analysis of variance of the QOL scores revealed significantly lower scores for the cancer patients than for the non-malignant-disease patients, except for the social aspect of concern (P less than 0.001). Factor analysis, using the principal component method, identified four major factors to account for 60 and 42% of the total variance on forms A and B, respectively. The factors were: patient's mood, anxiety over disease and treatment, relationships with other people, physical capability. In conclusion, this has been the first feasible study to show that QOL forms from the West could be used in Japan with some modifications. We are at present studying successive changes in QOL for advanced lung cancer patients in clinical trials.

Adult↗
PubMed1992

Localization and characterization of neutral metalloendopeptidase (EC 3.4.24.11), the degradative enzyme for atrial natriuretic peptide, in rat kidney using a radioiodinated neutral metalloendopeptidase inhibitor.

Atrial natriuretic peptide (ANP) is rapidly degraded by neutral metalloendopeptidase (EC 3.4.24.11, NEP), with the kidney being a major site of ANP clearance. NEP has been anatomically localized in the rat kidney by in vitro autoradiography and the active site studied by a radioinhibitor binding assay (RIBA) using a newly developed radioinhibitor as a radioligand. SCH47896 is a phenolic derivative of SCH39370, a potent specific inhibitor of NEP, which can be radioiodinated with 125I. NEP catalytic activity in the rat kidney was inhibited by SCH47896 and its di-iodo analog SCH48446. Specific binding of [125I]SCH47896 to renal plasma membranes fitted a single-site model with Kd = 43.3 nM and maximal binding site density = 13.8 pmol/mg protein. Thus, [125I]SCH47896 retains full enzymatic inhibitory activity and full binding to the active site of the NEP. Autoradiographs using [125I]SCH47896 demonstrated maximal binding to deep proximal renal tubules. This binding was displaced in a dose-dependent manner by NEP inhibitors. Renal NEP was inhibited by SCH39370. Inhibition of ANP degradation by NEP in the kidney by the new NEP or atriopeptidase inhibitors may explain their natriuretic and diuretic effect in the absence of changes in plasma ANP levels. These studies will allow investigation of the regulation of NEP and the role inhibition of tissue NEP plays in the actions of the new atriopeptidase inhibitors. Furthermore, this method of radioinhibitor binding is applicable to any enzyme, provided a suitable radioligand can be constructed.

Animals↗
PubMed1992

[Clinical significance of gallium-67 scintigraphy in assessing pulmonary lesions of sarcoidosis and idiopathic pulmonary fibrosis].

To evaluate whether one can predict the course and prognosis of interstitial lung diseases from lung gallium-67 (67Ga) uptake, we studied 31 subjects with sarcoidosis and 28 with idiopathic pulmonary fibrosis (IPF) retrospectively. We quantified the lung 67Ga uptake using posterior scans by Line's method, and calculated a visual index (VI). The normal range of 67Ga uptake was defined as less than 65 VI values, obtained from the 95 percent confidence interval of the control subjects. All subjects with stage I sarcoidosis, having only bilateral hilar lymphadenopathy (BHL) on chest X-ray, revealed normal lung 67Ga uptake. Fifty percent of patients with stage II sarcoidosis, with both BHL and pulmonary involvement on chest X-ray, showed increased lung 67Ga uptake. The patients with increased lung 67Ga uptake showed decreased percent vital capacity and increased alveolar-arterial oxygen tension difference, but none of them showed clinical deterioration during the follow-up period of more than 6 months. Fifty-four percent of subjects with IPF showed increased lung 67Ga uptake. But there was no difference between the subgroups with normal and increased lung 67Ga uptake with respect to the severity of dyspnea, percent vital capacity, arterial oxygen tension, or alveolar-arterial oxygen tension difference. There was also no difference between the two subgroups of IPF in the cumulative percent survival after either the onset of symptoms or the 67Ga scintigram. We conclude that lung 67Ga uptake was not able to predict the clinical course or the prognosis of patients with sarcoidosis and IPF.

Adult↗
PubMed1992

[Corrected transposition of the great arteries with associated tricuspid valve incompetence--report of a case of successful tricuspid valve replacement].

A 36-year-old woman with corrected transposition (C-TGA) of great arteries with associated systemic atrioventricular valve (A-V valve) regurgitation was presented. Cineangiography revealed that the right sided ventricle was morphologic left ventricle, and left sided ventricle was morphologic right ventricle. In addition, severe systemic A-V valvular regurgitation (Sellers IV) was demonstrated. Under the diagnosis of C-TGA with associated A-V valvular regurgitation, left sided atrioventricular valve replacement was performed using 29 mm SJM valve. Left sided atrioventricular valve was tricuspid valve (TV). A part of the anterior tricuspid leaflet and two pieces of papillary muscle was resected. Postoperative course was uneventful. The pathological findings indicated that valvular tissue had myxomatous degeneration.

Adult↗
PubMed1992

[Usefulness of vitamin A binding protein as a marker for capillary endothelial permeability].

We performed a preliminary study to assess the usefulness of Vitamin A binding protein (VABP) as a gamma-camera marker for capillary endothelial permeability. We used a guinea pig model of endotoxin (LPS) induced acute lung injury. We calculated the concentration ratio of either 125I-albumin or 125I-VABP in lung tissue to that in plasma (tissue plasma ratio; T/P) as a parameter of capillary endothelial permeability. 99mTc-diethylene triamine pentaacetic acid (DTPA) was used as a marker for pulmonary interstitial volume. We estimated wet to dry lung weight ratio as a parameter of lung water accumulation (W/D). LPS increased the T/P of 125I-albumin and W/D, suggesting the development of permeability edema. The T/P for 125I-VABP was also increased, indicating that 125I-VABP can be used to detect elevated capillary endothelial permeability. In both groups, LPS and saline, the T/P was higher for 125I-VABP than for 125I-albumin. These data suggest that the pulmonary capillary endothelium is more permeable to VABP than albumin.

Animals↗
PubMed1991

Pathological calcification of the cervico-facial region.

Two rare cases of pathological calcification affecting the face and neck are reported. The first case, a 32-year-old male, developed massive calcification of the lymphoid tissues in the preauricular, submandibular and cervical regions. In the second case, a 56-year-old male, a radiographic diagnosis of bilateral multiple miliary osteomas of the cheeks was made. Although dystrophic calcification of lymph nodes and salivary glands is common, it is important to establish any underlying disease.

Adult↗
PubMed1991

Chronic synergistic effect of endothelin-1 and angiotensin II on blood pressure in conscious rats.

We assessed whether there is an interaction between angiotensin II (Ang II) and endothelin-1 (ET-1) in the regulation of blood pressure and sodium and water metabolism in rats. Male Sprague-Dawley rats were divided into four groups. Group I rats received Ang II at a subpressor dose (400 micrograms/kg/day i.p.) for up to 6 days. Group II rats received ET-1 at a subpressor dose (3 micrograms/kg/day i.v.) for up to 6 days. Group III rats received both the subpressor dose of Ang II and the subpressor dose of ET-1. Group IV rats received vehicle only. There was no significant difference in systolic blood pressure (SBP) among groups I, II, and IV during the study. On day 6, SBP in groups I, II, and IV was 148.0 +/- 3.0, 142.7 +/- 2.9, and 143.5 +/- 3.0 mm Hg, respectively. On the other hand, SBP in group III was higher than those of the other groups on day 2 and remained elevated thereafter. On day 6, SBP in group III rats was 189.0 +/- 12.5 mm Hg. There were no significant differences in body weight, fluid intake, urine volume, urinary sodium excretion, or urinary potassium excretion among the four groups. The present results suggest that Ang II and ET-1 exert their pressor effects synergistically and might play a role in controlling blood pressure. They also suggest the possibility of the existence of a common pathway in the hypertension-producing mechanism of these two peptides.

Angiotensin II↗
PubMed1991

Distribution and inhibition of neutral metalloendopeptidase (NEP) (EC 3.4.24.11), the major degradative enzyme for atrial natriuretic peptide, in the rat kidney.

1. Atrial natriuretic peptide (ANP) is degraded by neutral metalloendopeptidase (NEP) (EC 3.4.24.11) and the kidney is a major site of ANP clearance. 2. The regional distribution of NEP in the rat kidney was investigated. 3. The activity of NEP, measured with an enzymatic fluorimetric method employing N-dansyl-D-alanyl-glycyl-L-4-nitrophenylalanyl-glycine as a synthetic substrate, was 18 times and eight times higher in the outer stripe of the medulla and inner cortex than in the outer cortex (OC). 4. Low concentrations of NEP were found in the OC, inner stripe and inner medulla. 5. NEP activity in the rat kidney was inhibited by the specific NEP inhibitors (SCH39370, phosphoramidon and thiorphan) at micromolar concentrations. 6. The present result suggests that degradation of ANP by NEP occurs mainly in the proximal tubules of the juxtamedullary nephrons, rather than cortical nephrons, and that the convoluted tubule in the OC is not a major site of location of NEP. 7. The relationship between NEP activities in the kidney in vitro and plasma clearance of ANP in vivo remains to be clarified.

Animals↗
PubMed1991

Antihypertensive effect of captopril and enalapril in endothelin-infused rats.

Comparative effects of angiotensin converting enzyme inhibitors and calcium channel blockers were assessed in rats infused chronically with synthetic endothelin. When 50 mg/kg/day of captopril orally or 6 mg/kg/day of enalapril intraperitoneally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 142.7 +/- 5.9 mmHg (p less than 0.05) or 128.7 +/- 6.7 mmHg (p less than 0.05), respectively, compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of captopril or enalapril was sustained for the entire experimental period and was not associated with a significant change in urinary sodium excretion, whereas both drugs induced a significant increase in urine volume. Chronic infusion of angiotensin II intraperitoneally at a subpressor dose (400 micrograms/kg/day) reversed the antihypertensive effect of captopril in endothelin-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine orally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 137.0 +/- 2.4 mmHg (p less than 0.05) or 119.7 +/- 5.9 mmHg (p less than 0.05), respectively, compared to the rise when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. These results indicate that the reduced sensitivity of the peripheral arteries to endothelin may be involved in the mechanism of the hypotensive action of angiotensin converting enzyme inhibitors, dependent on the suppressed angiotensin II formation.

Animals↗