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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 199 records · Page 11Linked to original sources
PubMed1993

Urinary active kallikrein excretion and diabetic renal impairments in streptozotocin-treated rats.

To assess possible roles of the renal kallikrein-kinin system in the development of renal impairments in diabetes mellitus, we determined daily excretion of urinary total and active kallikrein in uninephrectomized Wistar-Kyoto rats made diabetic by streptozotocin (45 mg/kg) as a bolus injection. We also evaluated the effect of captopril (50 mg/kg/day) administered orally on the development of diabetic renal impairments in the streptozotocin-treated rats. Active kallikrein was determined by its kininogenase activity, and generated kinins were radioimmunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in streptozotocin-treated rats whereas urinary total kallikrein excretion was unchanged, resulting in the decreased ratio of active to total kallikrein compared to that in the controls. These reductions were preceded by the increased excretion of urine protein measured as an index of renal impairments. The administration of captopril for 12 weeks attenuated the development of diabetic renal impairments evaluated by urine protein excretion in streptozotocin-treated rats, although it did not induce significant changes in urinary total and active kallikrein excretion, and the ratio of active to total kallikrein. Thus the results of this study indicate that the renal kallikrein-kinin system might not play major roles in the development of diabetic renal impairments in the rat, although the pathophysiological relevance of impaired activation of renal kallikrein system to the development of diabetic renal impairments remains to be determined. In addition, they suggest that the renoprotective effects of captopril may be independent of the activation of renal kallikrein system in streptozotocin-treated rats.

Animals↗
PubMed1993

[Measurement of myeloperoxidase and thiobarbituric acid-reactive material in plasma and bronchoalveolar lavage in E. coli-induced acute lung injury].

Myeloperoxidase (MPO), which is exclusively contained in neutrophils, is released on their activation. Therefore, MPO may possibly be used as a parameter of neutrophil activation. Thiobarbituric acid-reactive material (TBARM) reflects lipid peroxidation and is a parameter of oxygen radical-mediated cell membrane damage. Using our guinea pig model of septic lung injury we measured MPO and TBARM in the setting of acute lung injury. The two experimental groups were saline controls (n = 8) and an E. coli septic group to which 2 x 10(9) live E. coli were administered intravenously (n = 8). Lung damage was assessed by measuring wet to dry lung weight ratio (W/D) and lung tissue to plasma accumulation of 125I-albumin (AL: albumin leakage). We measured MPO and TBARM in plasma and BAL fluid. Increased W/D and AL were observed in the E. coli group suggesting the development of acute lung injury. In the E. coli group, plasma MPO increased and MPO in BAL fluid was significantly increased as compared with the saline control group. There was no difference in plasma TBARM between the two groups, while TBARM in BAL fluid of the E. coli group was greater than in that of controls. Although BAL fluid TBARM correlated with both W/D and AL, there was no relation between BAL fluid MPO and either of these parameters. We conclude that TBARM in BAL fluid may be useful for assessing E. coli-induced acute lung injury in guinea pigs.

Animals↗
PubMed1993

[A case of congenital antithrombin III deficiency with pulmonary thromboembolism and cerebellar infarction].

A 41-year old woman was admitted to a local hospital because of leg pain, chest pain and dyspnea after taking estrogen for two months for irregular menstruation. On admission to the hospital, her lung scintigram showed multiple segmental perfusion defects in the right lung. Pulmonary angiography showed several thrombi in the proximal pulmonary artery. A diagnosis of pulmonary thromboembolism was made. AT-III activity was found to be only 50% of normal value, indicating that the pulmonary thromboemboli were due to AT-III deficiency. The patient was then put on anticoagulants for two years. When she was 43-year-old, she was admitted to Keio University Hospital because of worsening of dyspnea. After admission her dyspnea had got better due to bed rest. Her brain CT, which was performed because of her gait disturbance, indicated past right cerebellar infarction. We gave her 2 mg of warfarin and maintained a thrombotest of about 30%. The investigation of her family revealed that her son also showed decrease AT-III activity, indicating a congenital abnormality. 26 families with this disease have been reported in Japan. Most had venous thromboemboli, but only a few cases had brain infarction as well. In addition, it is suggested that an estrogen therapy for irregular menstruation may have contributed, in this particular case, to the onset of thromboemboli.

Adult↗
PubMed1993

[A case of chronic necrotizing pulmonary aspergillosis treated with itraconazole].

An 84-year-old woman was admitted because of fever, hemoptysis and productive cough with infiltrative shadows in the right lung field on chest X-ray. Chronic necrotizing pulmonary aspergillosis was diagnosed on the basis of her clinical and radiographic features, positive cultures and positive serological tests. Conventional chemotherapy with fluconazole and 5-FC produced only minimal improvement. A course of itraconazole was initiated and proved to be effective.

Administration, Oral↗
PubMed1993

[Pulmonary disease due to Mycobacterium xenopi].

A 54-year old man with pulmonary disease due to Mycobacterium xenopi is described. He had a history of pulmonary tuberculosis at 8 years of age. He was admitted to our hospital in October 1992, complaining of productive cough and fever. A chest X-ray on October 20 showed an infiltrative shadow with a cavity, although chest X-ray picture on October 2 showed only inactive shadow, in the right upper lobe. Acid-fast organisms were seen in his sputum specimens and M. xenopi was identified by culture. The isolates were confirmed to be M. xenopi by the DNA-DNA hybridization method. He was treated with isoniazid, rifampicin and streptomycin. The fever decreased within a week. After two months of therapy, sputum cultures became negative and chest X-ray findings improved. It was concluded that this is a case of rapidly progressed pulmonary disease caused by M. xenopi in the normal host. This patient's condition responded to antituberculosis drugs.

Humans↗
PubMed1993

[Gastric metastasis of primary lung cancer].

A 74-year-old man was admitted to Keio University Hospital because of an abnormal shadow in the right upper lung field on chest roentgenogram. Bronchoscopic examination revealed malignant cells, by which large cell carcinoma of the lung was diagnosed. Systemic survey for metastasis disclosed an ulcerated tumor on the greater curvature of the stomach. Endoscopic examination showed an elevated submucosal tumor suggesting submucosal metastasis of lung cancer to the stomach. A review of 473 autopsies of primary lung cancer at Keio University from 1958 to 1987 showed 16 cases with gastric metastasis (3.4%). Two of 16 cases were detected clinically. Gastric metastases were proven in 15.6% of autopsy cases of large cell carcinoma of the lung. Forty-three cases of primary lung cancer with gastric metastasis were reported in the Japanese literature from 1965 to 1990. Thirteen of these cases had large cell carcinoma.

Aged↗
PubMed1993

[Assessment of pulmonary aerosol deposition and epithelial permeability in 99mTc-DTPA inhalation scintigram].

The degree of lung injury in bronchiolo-alveolar lesions may be quantitated from the pulmonary epithelial permeability estimated by 99mTc-DTPA (diethylene triamine penta acetate) aerosol inhalation scintigram. However, significant aerosol deposition sometimes occurs in the central airways and obscures the permeability change in the lung periphery. The radioaerosol deposition pattern and its effect on assessing the pulmonary epithelial permeability was studied. 99mTc-DTPA aerosol scintigraphy was performed in 47 patients with pulmonary fibrosis (PF), 12 patients with chronic obstructive pulmonary diseases (COPD), and 27 non-smoking and 17 smoking healthy volunteers. The scintigraphic images of the lungs were classified into 4 grades, 0; homogeneous distribution, 1; patchy distribution, 2; hot spots with partial defect, and 3; hot spots with little deposition in the lung field. The rate constant was used as a parameter for the permeability. The smokers and patients with PF showed increased kep values of 2.36 +/- 1.21%/min (mean +/- SD) and 2.49 +/- 1.29%/min as compared with the nonsmokers with 0.94 +/- 0.27%/min, respectively. The nonsmokers, smokers and 36 patients with PF were classified as deposition grade 0 or 1, suggesting good aerosol penetration to the lung periphery. All patients with COPD showed either grade 2 or 3 deposition. Aerosol deposition in the central airways can cause underestimation of the permeability because of the thicker lining layer in the bronchus than in the alveolus. In conclusion, the aerosol deposition pattern should be analyzed when the method is applied clinically to assess the permeability of the bronchiolo-alveolar epithelium.

Adult↗
PubMed1993

[Effects of various doses of endotoxin on physiological and hematological parameters in conscious guinea pigs].

We investigated the effects of various doses (0.2 to 2000 micrograms/kg) of endotoxin on physiological and hematological parameters in our guinea pig model. Bronchoalveolar lavage (BAL) and lung tissue sampling were performed 6 hours after endotoxin injection. Lung damage was assessed by measuring wet to dry lung weight ratio (W/D), lung tissue to plasma accumulation of 125I-albumin (AL: albumin leakage) and BAL fluid to plasma accumulation of 125I-albumin (BALL: bronchoalveolar lavage leakage). Changes in peripheral cell counts were estimated at times 0, 1, 2, 4 and 6 hours after endotoxin injection. Pulmonary cell accumulation was determined by counting the number of cells in BAL fluid and tissue samples fixed for light microscopic examination. Increased W/D and AL were observed only in the high dose endotoxin treatment groups (200 and 2000 micrograms/kg), while BALL increased even in the low dose endotoxin treatment groups (2 micrograms/kg). Decreases in peripheral neutrophil counts at one hour were observed in all endotoxin treated groups. Increase in BAL fluid neutrophils was seen in the 20, 200, and 2000 micrograms/kg groups, while neutrophil accumulation assessed by light microscope was observed in all endotoxin treated groups. We conclude that different amounts of endotoxin are required to affect different parameters of lung injury.

Albumins↗
PubMed1993

[Detection of radiation-induced lung injury by 99mTc-DTPA aerosol inhalation method].

We prospectively monitored pulmonary 99mTc-DTPA (diethylene triamine penta acetate) clearance in patients who received chest radiation therapy, in order to determine whether this method allows us to predict the development of radiation pneumonitis. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was used to assess pulmonary epithelial damage. Fifteen nonsmoking patients who underwent radiation therapy were studied. The subjects included 4 patients who had already developed radiation pneumonitis at the time of study, and 11 in whom we prospectively observed 99mTc-DTPA clearance serially during the course of chest radiation therapy. In the 4 patients with pre-existing radiation pneumonitis, the mean k value obtained from the area with infiltration on the chest X-ray was significantly greater than that from the opposite lung (p < 0.02). In the prospective study, 3 out of 11 patients developed radiation pneumonitis. The mean k of the irradiated lung field in the 8 patients who did not develop radiation pneumonitis was unchanged. The mean k value obtained in the 3 patients who did develop radiation pneumonitis increased just before the onset, and further increased when the disease manifested clinically. We conclude that pulmonary 99mTc-DTPA clearance may be useful for predicting the development of radiation pneumonitis.

Adult↗
PubMed1993

[A case of slowly-growing localized malignant mesothelioma].

We report a case of localized malignant mesothelioma. The patient was a 37-year-old male, admitted to our hospital because of a solitary nodular shadow in the right middle lung field noted on chest X-ray. Five years prior to admission, a solitary nodular shadow had been seen in the same area on chest X-ray, and the diameter of the tumor had gradually increased. A transbronchial biopsy specimen revealed proliferation of spindle-shaped tumor cells, suggesting fibrosarcoma. No other lesions were identified as primary foci, so we made the tentative diagnosis of primary pulmonary sarcoma prior performing right upper lobectomy. The resected specimen revealed that the tumor, which partially touched the pleura, contained a number of large and small cystic spaces, and was composed of numerous spindle-shaped tumor cells. Some of the tumor cells were immunohistochemically positive for cytokeratin and epithelial membrane antigen, and many mitotic figures were noted. Thus, we made the histopathological diagnosis of localized malignant mesothelioma.

Adult↗
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↗