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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 181 records · Page 10Linked to original sources

Granulocyte colony-stimulating factor exacerbates acute lung injury induced by intratracheal endotoxin in guinea pigs.

The effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on the lung injury induced by intratracheal endotoxin were studied using guinea pigs. Animals were divided into four groups: (1) saline control, (2) endotoxin alone, (3) cyclophosphamide (CPA)+endotoxin, and (4) CPA+rG-CSF+endotoxin. CPA was injected intraperitoneally to suppress hematopoietic function 7 d before the study. rG-CSF at a dose of 100 micrograms/kg was administered subcutaneously twice a day for 5 consecutive d beginning 2 d after the CPA pretreatment. Saline or 0.2 mg/kg of endotoxin was administered via the airway, and the animals were observed for 4 h. 99mTc-labeled macroaggregated albumin was mixed with saline or endotoxin to obtain a lobar distribution. Lung injury was assessed by the concentration ratio of 125I-labeled albumin in lung tissue to plasma (T/P) and lung wet-dry weight ratio (W/D). We also counted the number of neutrophils in bronchoalveolar lavage (BAL) fluid and fixed lung tissues. T/P, but not W/D, increased in endotoxin-alone and CPA+endotoxin groups compared with the saline control group (p < 0.01). Both T/P and W/D of the CPA+rG-CSF+endotoxin group were significantly higher than those of the endotoxin-alone and CPA+endotoxin groups (p < 0.01). In the CPA+rG-CSF+endotoxin group, histopathologic examination of the lung sections showed neutrophil recruitment into the lung, and neutrophil counts in BAL fluid were elevated. In conclusion, pretreatment with rG-CSF increased sequestration of neutrophils into the lung and exacerbated the lung injury induced by intratracheal endotoxin in CPA-treated guinea pigs.

Acute Disease↗

Lung cancer with skin metastasis.

We describe findings in 34 cases of lung cancer with skin metastases. In 24 men and 10 women, ages ranged from 32 to 85 years (mean, 61 years). In five, a skin lesion was the first manifestation of the underlying cancer; in another four, it was found coincidentally with detection of the lung mass. Pathologic findings included adenocarcinoma in 18 patients, large-cell carcinoma in 9, squamous cell carcinoma in 5, and small-cell carcinoma in 2. Among 87 patients with large-cell carcinoma, 9 (10.3 percent) developed cutaneous metastases. A review of 510 autopsies of primary lung cancer at Keio University from 1958 to 1992 showed 25 cases with skin metastases (4.9 percent), adenocarcinoma in 13 cases, large-cell carcinoma in 6, squamous cell carcinoma in 4, and small-cell carcinoma in 2. Skin metastases were proven in 15.4 percent of autopsy cases of large-cell carcinoma of the lung. Mean survival time from diagnosis of lung cancer was 10.3 months and that from diagnosis of skin metastasis was 4.9 months. The prognosis for patients having lung cancer with skin metastasis is thus very poor. In the review of 34 patients and 25 autopsies of lung cancer with skin metastasis, we conclude that the incidence of cutaneous metastasis is high for large-cell carcinoma and low for squamous and small-cell carcinoma.

Adult↗

Toxic epidermal necrolysis with tracheobronchial and pulmonary complications.

A 55-year-old man developed multiple erythematous skin lesions after surgery for acoustic neurinoma. Necrosis and detachment of the epidermis developed and a diagnosis of toxic epidermal necrolysis (TEN) was made. Progressive dyspnea was evident two days after the onset of the skin lesions. Chest X-ray revealed diffuse interstitial shadows in both lung fields. On bronchoscopic examination, erosion, vesicle formation, necrosis and desquamation of the epidermis were seen in the tracheobronchial mucosa. Therapy, including prednisolone, improved the skin lesions as well as the chest X-ray and bronchoscopic findings. Tracheobronchial and pulmonary lesions were followed before, during and after treatment of TEN.

Bronchi↗

Pulmonary infection due to Mycobacterium xenopi.

We describe two cases of pulmonary infection due to Mycobacterium xenopi (M. xenopi). Both cases were men, ages 61 and 54 yr. In the first patient, lung infection due to M. xenopi occurred after gastrectomy. The second patient had an inactive M. tuberculosis infection. Both had pulmonary symptoms including cough, sputum and fever. Each chest X-ray showed an infiltrative shadow with a cavity in a unilateral, upper lobe. Isolates from both patients were studied not only by microbiological characteristics but also by DNA-DNA hybridization. All isolates were susceptible to streptomycin and kanamycin. In the first case, the patient had initially received rifampicin, isoniazid and ethambutol despite in vitro susceptibility patterns, however, there was no response and a new infiltrative shadow appeared in the contralateral lobe. With a multiple drug regimen based on in vitro susceptibility, clinical and roentgenographic improvements were achieved. The second patient showed a favorable response to the initial chemotherapy. Pulmonary infection due to M. xenopi can generally be successfully treated with drugs to which the organisms show in vitro sensitivity. We also reviewed the other two cases reported in Japan.

Bacterial Typing Techniques↗

[Radiological approach to the pleura and pleural cavity with CT and MRI].

We discuss the efficacy and limitations of CT and MRI in the assessment of the pleura and pleural cavity. With CT and MRI findings from 610 patients, we address six topics: 1) Normal anatomy of the pleural cavity, 2) Pleural effusion, 3) Pleural tumors, 4) Pyothorax, 5) Lung cancer, and 6) The pleura as a mirror of systemic diseases. CT showed specific findings of acute bleeding. MRI was sensitive enough for the diagnosis of subacute bleeding and chylothorax. In the evaluation of pleural tumors, CT and MRI revealed specific evidence of pedunculated localized fibrous tumors and lipomas. In long-standing pyothorax, it is important to detect any associated secondary malignancies. CT and MRI show as a mass penetrating the bony thorax. B-cell non-Hodgkin malignant lymphoma is the most commonly associated malignancy. The sensitivities for diagnosis of pleural extension of bronchogenic carcinoma are 80% with CT and 86% with MRI. The specificities are 89% with CT and 75% with MRI. To study the pleura as a mirror of systemic diseases, we used high resolution CT to examine 104 patients without evidence of the diseases mentioned above. Eighteen of those 104 patients were found to have pleural thickening, and all 18 were smokers. Of the 24 non-smokers, none had pleural thickening. The difference in the occurrence of pleural thickening between smokers and non-smokers was significant (p < 0.01).

Humans↗

[Mycobacterium kansasii lung infection associated with myelofibrosis--a case refractory to treatment with antitubercular agents].

A case of Mycobacterium kanasasii lung infection associated with myelofibrosis is reported. A 32-year-old woman was admitted to Keio University Hospital because of fever. One year before admission, a diagnosis of myelofibrosis was made at another hospital. The initial chest X-ray film showed bilateral diffuse infiltrative shadows and right hilar enlargement. Sputum cultures yielded Mycobacterium kansasii on 3 occasions. A fever of 38 degrees C or higher persisted for about 4 months despite the use of antitubercular agents, including INH, RFP, SM, and PZA. During the course of treatment, the hilar and mediastinal lymph node enlargement became more severe, and this was followed by calcification of the nodes. The fever and chest X-ray findings improved in response to the addition of treatment with EB, Ofloxacin, TH, and an increase in the doses of INH (from 300 to 500 mg/day) and RFP (from 450 to 600 mg/day). The patient was discharged 14 months after admission. It is rare especially in Japan for a Mycobacterium kansasii lung infection (not disseminated) to persist in spite of treatment with antitubercular drugs, including RFP or TH. The response to treatment may have been impaired by an immunological disorder associated with the myelofibrosis.

Adult↗

[Hodgkin's disease with a giant thymic cyst].

An asymptomatic 26-year-old male was admitted to our hospital for examination of an abnormal mediastinal shadow on chest X-ray. Chest CT showed a large mass in the anterior mediastinum with marked para-aortic lymph node enlargement. The mass consisted mostly of multiloculated low-density areas surrounded by a rim of enhancing parenchymal tissue. Both the cystic tumor and surrounding lymph nodes were resected. The tumor measured 18 x 10 x 2 cm and contained about 450 ml of straw colored fluid. Pathological examination revealed a thymic cyst, the wall of which was composed of Hodgkin's lymphoma cells and nodular sclerotic lesions containing many lacunar cells and Reed-Sternberg cells.

Adult↗

[Activity and localization of neutral metalloendopeptidase (EC 3.4.24.11) (NEP), the degradative enzyme for atrial natriuretic peptide (ANP), in rat kidney].

Atrial natriuretic peptide (ANP) is degraded by neutral metalloendopeptidase (EC 3.4.24.11) (NEP), and the kidney is the major site of ANP clearance. The regional distribution of NEP in rat kidney was investigated by an enzymatic method and by in vitro autoradiography. The activity of NEP, measured with an enzymatic fluorimetric method employing N-dansy 1-D-alanyl-glycy 1-L-4-nitrophenylalany 1-glycine as a synthetic substrate, was 18 times higher in the outer stripe and 8 times higher in the inner cortex than in the outer cortex. Low concentrations of NEP were found in the outer cortex, in the inner stripe and in the inner medulla. NEP activity in rat kidney was inhibited by specific NEP inhibitors (phosphoramidon, thiorphan, SCH39370, SCH47896 and SCH48446) at micromolar concentrations. SCH47896 is a phenolic derivative of SCH39370 which can be radioiodinated with 125I. SCH48446 is a di-iodo analog of SCH47896. Thus, [125I]SCH47896 retains the full enzymatic inhibitory activity and full biological potency to bind to the active site of NEP. Autoradiographs using [125I]SCH47896 demonstrated maximal bind to regions of the outer stripe of the outer medulla and to the inner cortex, which was consistent with binding to the deep proximal tubules. These bindings were displaced in a dose-dependent manner by NEP inhibitors. Enalaprilat did not displace [125I]SCH47896 binding. EDTA inhibited these bindings by 90%. The present result suggests that degradation of ANP by NEP occurs mainly in the deep proximal tubules, and that the proximal convoluted tubule in the outer cortex is not a major site of location of NEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of intermittent coronary sinus retroperfusion on global and regional ventricular function during acute coronary occlusion in dogs].

We hypothesized that intermittent coronary sinus retroperfusion (ICSR) would improve cardiac function after an in situ ischemic insult. To test this, we analyzed the global and regional ventricular function of anesthetized open-chest dogs. The left anterior descending coronary artery (LAD) was occluded for 135 minutes before the animals were killed. ICSR was performed for the 120 minutes (from 5 minutes to 135 minutes after ligation of the LAD) using balloon catheter which is placed at the coronary sinus via right atrium artery. Measurements were performed before, and seven specific times after occlusion of the LAD. Values were expressed as 100% at 15 minutes after LAD ligation. We found that percent recovery of the max volume of the instantaneous pressure-volume ratio (Emax) demonstrated a significant change between the ICSR group (n = 7) and the control group (n = 7) at 60 minutes after the beginning of ICSR (ICSR group: 126.6 +/- 23, control group: 84.5 +/- 40, p < 0.05). Also left ventricular systolic pressure and maximum negative dp/dt improved in ICSR group compared with control group 75 minutes after LAD occlusion (p < 0.01). Other cardiac functions were a trend toward improvement by ICSR though there was no significant difference between any groups. However in the control group, cardiac function was worse after occlusion. We concluded that retrograde perfusion with ICSO improved both global and regional cardiac functions in the acute myocardial infarction.

Animals↗

[Clinical significance of flow cytometric DNA analysis in metastatic lymph node of colorectal cancer].

Significance of flow cytometric DNA analysis in metastatic lymph nodes for assessing malignant potential of colorectal cancer was investigated using paraffin-embedded materials of primary lesions and metastatic lymph nodes from 65 patients who had been treated between 1975 and 1990. The DNA ploidy patterns of metastatic nodes were identical in 61.5% with those of primary lesions. Diploid cancers were significantly more frequent in metastatic nodes than in primary lesions. There were significantly more aneuploid cancers in proximal nodes than in distant nodes. There was no relation between ploidy patterns in primary lesions and survival. However, a significant relation was found between ploidy patterns in metastatic nodes and survival. Diploid cancer in metastatic nodes had a significantly better survival than aneuploid cancer, in all patients as well as those with curative resection. In patients with stage III and in those with the same depth of invasion, the survival rate of diploid cancer in metastatic nodes was significantly higher. There was no correlation between ploidy patterns in metastatic nodes and clinicopathological variables in primary lesions, such as histological type, depth of invasion, nodal involvement, peritoneal or hepatic involvement and stage. These results suggest that nuclear DNA content in metastatic lymph nodes may be a prognostic indicator in colorectal cancer with nodal involvement.

Colorectal Neoplasms↗

Protein phosphatase inhibitor calyculin A induces hyperphosphorylation of cytokeratins and inhibits amylase exocytosis in the rat parotid acini.

Calyculin A, a protein phosphatase inhibitor with a chemical structure completely different from that of okadaic acid, reproduced the inhibitory effect of okadaic acid on cyclic AMP-mediated amylase release from rat parotid acinar cells. Calyculin A markedly enhanced phosphorylation of cytokeratins in the cytoskeletal fraction of the cells, whereas cAMP had apparently no effect on the phosphorylation. Microscopic observations showed that parotid acini incubated with 100 nM calyculin A for 15 min had large vacuoles in the cytoplasm and conspicuous blebs on the basal plasma membrane. K252a, a nonselective protein kinase inhibitor, clearly reduced calyclin A-induced phosphorylation of cytokeratins, and it markedly blocked the inhibition of amylase release and morphological changes evoked by calyculin A. These results suggest that hyperphosphorylation of cytokeratins profoundly affects the morphology and secretory activity of parotid acinar cells.

Amylases↗

Modification of regional myocardial performance caused by blood withdrawal and infusion in acute ischaemic canine heart.

The effect of changes in preload on regional myocardial motion in acute ischaemia was examined by miniature ultrasonic gauges after left anterior descending coronary artery occlusion in eight open chest dogs with the pericardium preserved. Left ventricular end-diastolic pressure was varied by blood withdrawal and infusion. When preload changed, isovolumetric shortening in the non-ischaemic region was inversely related to that in the ischaemic region. When preload decreased, stroke volume decreased and was accompanied by a decrease in end-diastolic length and ejection shortening in the non-ischaemic region together with an increase in isovolumetric bulging in the ischaemic region. When preload increased, these variables changed in opposite directions. These results indicate that in acute ischaemia: (1) changes in isovolumetric shortening in the non-ischaemic and ischaemic regions were related with each other when the level of volume expansion varied, and suggest that; (2) stroke volume is affected by end-diastolic length, ejection shortening in the non-ischaemic region and isovolumetric bulging in the ischemic region.

Animals↗

Effects of valinomycin on osmotic lysis of zymogen granules and amylase exocytosis from parotid acini.

The role of osmotic swelling of the secretory granules in adenosine 3',5'-cyclic monophosphate (cAMP)-mediated amylase exocytosis was evaluated by use of isolated zymogen granules and saponin-permeabilized acini of the rat parotid gland. The osmotic lysis of the isolated granules was markedly enhanced by the addition of valinomycin (> 10(-9) M) in the presence of isosmotic KSCN or KI medium. However, valinomycin (up to 10(-5) M) did not increase the granule lysis in KCl medium, although the granules were slightly less stable in KCl medium than in K2SO4 or potassium gluconate medium. Guanosine 5'-O-(3-thiotriphosphate) did not affect the granule lysis. Valinomycin alone had no effect on amylase release from saponin-permeabilized parotid acini incubated in KCl medium, but completely abolished cAMP-mediated amylase release in all K+ media used. The inhibition was clearly detected at 0.1 microM valinomycin in KCl medium, not blocked by the addition of 1 mM MgATP to the medium, and was greatly reduced in NaCl medium. cAMP-evoked amylase release was completely inhibited by SCN- and I- (permeant anions), the mean inhibitory dosages of which were approximately 25 and 50 mM, respectively. These results suggest that 1) the membrane of parotid zymogen granules has no detectable Cl- channels responsible for osmotic swelling of the granules, and 2) increase in K+ or anion conductance of the granule does not enhance but inhibits cAMP-mediated amylase exocytosis from parotid acini.

Amylases↗

Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.

Short chain enoyl-CoA hydratase (SCEH) catalyzes the second step of the mitochondrial fatty acid beta-oxidation spiral. We isolated cDNA clones for human SCEH to facilitate investigation of the enzyme structure of the gene and to examine the genetic background of Reye's syndrome and sudden infant death. Oligo(dT)-primed and random primed human liver cDNA libraries in lambda gt11 were screened using the entire sequence of the rat SCEH cDNA as a probe. Three positive clones covered the full-length cDNA sequence with an open reading frame encoding a precursor polypeptide of 290 amino acid residues, and deduced relative molecular mass (31,280) with a putative N-terminal presequence of 29 residues, a 5'-untranslated sequence of 21 bp and a 3'-untranslated sequence of 391 bp. Comparison with the rat SCEH cDNA showed that the deduced amino acid sequence of the human SCEH precursor is 84% identical to that of the rat enzyme precursor. Northern blot analysis gave a single mRNA species of 1.6 kb in the human liver, fibroblast and muscle.

Amino Acid Sequence↗

The augmented blood pressure response to chronic angiotensin II infusion in partially nephrectomized rats.

To assess potential roles of circulating levels of angiotensin II (Ang II) in the regulation of blood pressure in rats with reduced functional renal mass, we studied the blood pressure response to chronic infusion of Ang II at a subpressor dose in partially nephrectomized rats. Male Sprague-Dawley rats were subjected to 1/6, 2/6, 3/6, 4/6 and 5/6 nephrectomy, and sham operation a week before the infusion of Ang II at a rate of 400 micrograms/kg/day delivered intraperitoneally by osmotic minipumps for 14 days, or vehicle alone served as controls. Infusion of Ang II was associated with a slight but significant increase in systolic blood pressure in 1/6 nephrectomized rats (p < 0.05), whereas it did not induce a significant change in systolic blood pressure in sham-operated rats. Hypertension during Ang II infusion was more prominent in 2/6 nephrectomized rats than that in 1/6 nephrectomized rats (p < 0.05). However, there was no significant difference in hypertension during Ang II infusion among groups in 2/6, 3/6, 4/6 and 5/6 nephrectomized rats. Blood urea nitrogen and serum creatinine levels, endogenous creatinine clearance, urinary excretion of protein as indices of renal function, and urinary sodium excretion were not affected by chronic infusion of Ang II in 1/6, 2/6, 3/6, 4/6 and 5/6 nephrectomized, and sham-operated rats. There was also no significant difference in circulating levels of Ang II among Ang II infused-groups in 1/6 and 2/6 nephrectomized rats. These results indicate that elevated levels of circulating Ang II are capable of causing a sustained hypertension in rats with reduced functional renal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Chronic treatment with anti-endothelin antibodies fails to modify the development of hypertension in stroke-prone spontaneously hypertensive rats and DOCA-salt hypertensive rats.

This study was designed to assess whether blocking endogenous endothelin with anti-endothelin antibodies could alter the development of hypertension in stroke-prone spontaneously hypertensive rats (SHR) and DOCA-salt treated rats. Specific anti-endothelin antibodies were produced in rabbits by standard methods. The amount of anti-endothelin antibodies employed in this study blocked the hypertensive effect of endothelin-1, 750 ng/kg, by 55% in conscious rats. Intravenous injection of anti-endothelin antibodies as a bolus twice a week for 3 weeks did not affect the rise in blood pressure of stroke-prone SHR (268 +/- 8 mmHg, n = 8) compared to control stroke-prone SHR (256 +/- 7 mmHg, n = 8) treated with normal rabbit serum. Intravenous administration of anti-endothelin antibodies in a same manner also failed to alter the development of hypertension in DOCA-salt treated rats (160 +/- 6 mmHg in anti-endothelin antibodies-treated group, n = 7 compared to 164 +/- 5 mmHg in normal rabbit serum-treated group, n = 7). The administration of anti-endothelin antibodies did not induce any significant changes in body weight, urine volume and urinary sodium excretion in stroke-prone SHR and DOCA-salt treated rats compared to those treated with normal rabbit serum. These findings suggest that circulating endothelin might not play a major role in the regulation of blood pressure in stroke-prone SHR and DOCA-salt treated rats.

Aging↗