Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 145 records · Page 8Linked to original sources

PubMed1996

[K-ras gene mutations in adenomas from familial adenomatous polyposis].

A 18-year-old woman underwent total colectomy for familial adenomatous polyposis. In order to clarify the significance of K-ras mutations in early colorectal carcinogenesis, K-ras mutations were analyzed in multiple adenomas by PCR-SSCP method. A total of 256 adenomas were found throughout the entire colon and rectum, and the distribution was a sparse type. The correlation between K-ras gene and clinicopathological factors was examined in 90 adenomas. There was no correlation among K-ras mutations and anatomical distribution, or morphological classification, but K-ras mutation was more frequent in severe compared with slight atypia. We investigated the correlation between the size of adenoma in the horizontal and vertical directions and K-ras mutation. K-ras mutation was more frequent in the horizontal size greater than 6 mm in diameter, and also more frequent in vertical size greater than 20 mm in height. It was concluded that the adenomas detecting K-ras mutations might have proliferating potential, and would be applied to determine polypectomy.

Adenoma↗

PubMed1996

[Effects of intravenous 2-chloroadenosine on endotoxin-induced acute lung injury].

To assess the effects of 2-chloroadenosine (2CA) on acute lung injury caused by endotoxin (lipopolysaccharide), guinea pigs were given 2CA intravenously. Three groups were used: saline control, endotoxin control and 2CA+ endotoxin. In the endotoxin and 2CA+ endotoxin groups, neutrophils accumulated in bronchoalveolar lavage fluid and in lung tissue. However, neutrophil accumulation did not differ significantly between the endotoxin and the 2CA+ endotoxin groups. The number of macrophages in bronchoalveolar lavage fluid was significantly higher in the endotoxin group than in the saline control group, but the difference between the saline control and the 2CA+ endotoxin groups was not significant. The lung wet-dry weight ratio and 125I-albumin lung tissue-plasma ratio, which were used to measure acute lung injury, were significantly higher in the endotoxin group than in the 2CA+ endotoxin and the saline control groups. However, these ratios did not differ between the 2CA+ endotoxin and the saline control groups. These results suggest that 2CA attenuated endotoxin induced acute lung injury in guinea pigs.

2-Chloroadenosine↗

PubMed1996

Therapeutic advantages of angiotensin converting enzyme inhibitors in chronic renal disease.

More than other drugs, angiotension converting enzyme (ACE) inhibitors have been shown to provide better control of glomerular hypertension and improved preservation of renal function. Long-term treatment with captopril slows the progression of renal impairment in diabetic nephropathy; however, the data are inconclusive for non-diabetic nephropathies. ACE inhibitors such as captopril, enalapril, alacepril delapril cilazapril, and lisinopril were equally effective in reducing blood pressure in multicenter clinical trials focusing on renal hypertension in Japan. We studied the influence of ambulatory blood pressure (ABP) and the effects of hypertension therapy in 104 patients with chronic renal glomerulonephritis as diagnosed by renal biopsy. Patients were subdivided into hypertensive, normotensive and hypotensive groups according to ABP and ages. Hypotensive subjects showed an improvement, while normotensive subjects showed a slower rate of progression of renal function loss than hypertensive patients. This suggests that the adequate ABP levels were 100 to 125/55 to 75 in those who were less than 40 years old, 100 to 135/60 to 80 mm Hg in patients aged 40 to 60, and 105 to 140/60 to 85 mm Hg in those over 60 years old. The renal protective effects of calcium antagonists and ACE inhibitors were associated with a reduction in blood pressure, but not with the hypotensive action.

Adult↗

PubMed1996

[High concentrations of interleukin-8 in bronchoalveolar lavage fluid from a patient with adult respiratory distress syndrome].

A 75-year-old man was admitted to the hospital due to acute onset of a dry cough and dyspnea on exertion. Arterial blood gas analysis showed hypoxemia (PaO2 = 63 Torr) on room air. Chest radiography and computed tomography showed diffuse bilateral infiltrates. Adult respiratory distress syndrome was diagnosed from the findings described above and from the lack of evidence of left heart failure. Diffuse alveolar damage was confirmed at autopsy. During the course of his illness, the patient underwent bronchoalveolar lavage five times. The recovered fluid had high concentrations of interleukin-8 (IL-8), with a maximum of 6260 pg/ml and a minimum of 190 pg/ml, and these values correlated with the number of polymorphonuclear cells in the fluid. Levels of leukotriene B4, another chemotactic factor for PMN, in the lavage fluid were not high. We conclude that IL-8 was a major chemoattractant for PMN in the alveoli of this patient.

Aged↗

PubMed1996

[Pneumonia caused by varicella-zoster virus in a patient with rheumatoid arthritis].

A 56-year-old woman suffering from rheumatoid arthritis, was admitted to our hospital for evaluation of fever and dyspnea. A month before admission, she had been given a diagnosis of herpes zoster and was treated with an antiviral agent. However, a perineal eruption persisted. A chest X-ray film and a chest CT scan showed many diffuse nodular shadows in both lung fields. With conservative treatment, the shadows regressed along with the skin eruption and other symptoms. Pneumonia caused by varicella-zoster virus was diagnosed from the clinical course, chest roentgenographic and CT scan findings, and serological data. The risk of mortality in varicella-zoster pneumonia is high in adults, especially in immunosuppressed patients. Early diagnosis and effective treatment are, therefore, essential in the management of this disease. Though varicella-zoster pneumonia is rare, chest roentgenographic and CT scan findings are characteristic and suggestive. This case may serve as a reminder of the features of varicella-zoster pneumonia: many nodular shadows on the chest X-ray film and CT scan.

Aged↗

PubMed1996

[Roles of inflammatory cells in the pathogenesis of acute lung injury in guinea pigs exposed to heat-killed bacteria].

To study the contribution of polymorphonuclear (PMN) and mononuclear (MN) phagocytes to the development of acute lung injury, we studied lung injury after intratracheal instillation of lipopolysaccharide (0.02 mg/kg) in guinea pigs previously exposed to heat-killed Corynebacterium parvum. In on group, cyclophosphamide was given to deplete peripheral PMNs. In another group, gadolinium chloride (GdCl3) was injected to suppress the function of MNs. Four hours after instillation of lippoly soccharide, the animals were killed, bronchoalveolar lavage was done, and the lungs were examined histopathologically. 125I-labeled albumin was injected to estimate the endothelial damage, and 131I-labeled albumin was injected to correct for blood contamination in the samples. In the group given cyclophosphamide, lung injury was no less than in the control group. In contrast, lung injury was less sever in the group given GdCl3 than in the control group. These findings suggest that MN are important in the pathogenesis of lung injury, especially in individuals who are immunologically primed by infection.

Acute Disease↗

PubMed1996

[Role of adhesion molecules in an animal model of endotoxin-induced acute lung injury].

We studied the role of adhesion molecules in acute lung injury caused by lipopolysaccharide (LPS). Forty-eight female guinea pigs were divided into three groups: saline (n = 12); B464, an LPS antagonist, (0.2 mg/kg i.v.) (n = 12); LPS (0.02 mg/kg i.v.) (n = 12); and LPS + B464 (n = 12). The numbers of polymorphonuclear cells (PMN) in blood sampled over 4 hours were counted. Accumulation of PMNs in the lungs was determined by counting the number of PMNs in lung-tissue samples fixed for light-microscopic examination. The lung wet-to-dry weight ratio and the 125I-albumin tissue-to-plasma ratio were used to assess lung injury. Human umbilical-vein endothelial cells were treated with B464 and then stimulated with either LPS or tumor necrosis factor. Expression of ICAM-1 and ELAM-1 was estimated by enzyme-linked immunosorbent assay. After LPS injection, light microscopy revealed decreases in peripheral PMN counts, and accumulation of PMNs in the lungs. Increases in the two indices of lung injury were also observed. These changes were attenuated by prior treatment with B464. The LPS-induced increases in ICAM-1 and ELAM-1 expression were dose-dependently suppressed by B464. These results suggest that pulmonary accumulation of activated PMNs plays an important role in LPS-induced lung injury.

Acute Disease↗

PubMed1995

A subfamily 2 homo-dimeric glutathione S-transferase mYrs-mYrs of class theta in mouse liver cytosol.

A homo-dimeric subfamily 2 glutathione (GSH) S-transferase (GST) mYrs-mYrs of the class theta was isolated from mouse liver cytosol and purified to homogeneity. The first 28 N-terminal amino acid sequence of the GST was completely identical to that of rat subfamily 2 GST Yrs-Yrs of the class theta. GST mYrs-mYrs cross-reacted with anti-rat GST Yrs-anti-sera but not with anti-sera raised against rat GSTs Ya-Ya (alpha), Yb1-Yb1 (mu), and Yp-Yp (pi) and represented more than 95% of the mouse liver cytosolic GST activity to scavenge the reactive sulfate ester 5-sulfoxymethylchrysene of the potent carcinogen 5-hydroxymethylchrysene. The mouse class theta GST had little activity toward 1-chloro-2,4-dinitrobenzene and was unretainable on GSH and an S-hexyl-GSH affinity columns. GST mYrs-mYrs had a much higher GSH peroxidase activity toward fatty acid hydroperoxides than did the other classes of mouse GSTs.

Amino Acid Sequence↗

PubMed1995

Immunohistochemical analysis of rat and human respiratory cilia with anti-dynein antibody: comparison between normal cilia and pathological cilia in primary ciliary dyskinesia.

Wistar Imamichi rat and human respiratory cilia were examined with anti-dynein antibody (AD2), which is specific for sea urchin sperm flagellar dynein. AD2-labelled fresh-frozen normal rat and human cilia stained clearly by immunofluorescence and the peroxidase-antiperoxidase (PAP) technique. On immunoelectron microscopy, AD2 labelled the outer dynein arms of normal human cilia. Paraffin-embedded normal human cilia also stained by immunofluorescence, although not always clearly. Neither the cilia of WIC-Hyd male rats, an animal model of Kartagener's syndrome, nor human cilia from patients with primary ciliary dyskinesia (PCD) reacted positively by the immunofluorescence or PAP technique. Western blots of normal rat cilia yielded a single band of about 450 kDa. In conclusion, AD2 recognizes the outer arm dynein heavy chains of healthy cilia and may be useful in diagnosing and classifying PCD light microscopically especially when only paraffin-embedded specimens are available. This approach may be of potential use for better defining and classifying PCD.

Adolescent↗

PubMed1995

Venous invasion as a prognostic factor in colorectal cancer.

Venous invasion as a prognostic factor was evaluated in 124 patients with colorectal cancer. By classifying the patients as having either negative to mild invasion or moderate to marked invasion, a significant correlation was found between the degree of venous invasion and clinicopathological variables such as lymphatic invasion, lymph node metastasis, liver metastasis, and DNA ploidy. Significantly more favorable survival was seen in those with a lower degree of vascular invasion; however, of the six prognosticators analyzed by Cox's proportional hazard model, the only significant factors were depth of invasion and DNA ploidy. Although venous invasion showed no significance, it is still considered a valuable prognostic indicator that is easy and economical to perform.

Adenocarcinoma↗

PubMed1995

Effects of recombinant human erythropoietin on blood pressure and renal function in SHR with chronic renal failure.

1. The effects of chronic administration of erythropoietin (EPO) on blood pressure and renal function in rats with ablation of renal mass were assessed. 2. Spontaneously hypertensive rat were subjected to 5/6 nephrectomy (5/6Nx). Four weeks after the operation, the rats were randomly allocated to vehicle, EPO 20IU/kg i.p., or EPO 100 IU/kg i.p. (both given twice a week) for 4 weeks. 3. Marked anaemia was noted in SHR-5/6Nx. EPO caused a significant increase in haematocrit at a high dose but not at a low dose. A dose dependent relationship was noted in the EPO-induced rise in the systolic blood pressure. 4. EPO dose-dependently increased urinary protein excretion. It also increased blood urea nitrogen and serum creatinine levels. 5. These results suggest that EPO ameliorates anaemia and severely accelerates renal failure in SHR-5/6Nx. They also suggest that anaemia can be a haemodynamically favorable adaptation to chronic renal disease and that its correction may have adverse renal haemodynamic and structural consequences.

Anemia↗

PubMed1995

Do kinins mediate cardioprotective and renoprotective effects of cilazapril in spontaneously hypertensive rats with renal ablation?

1. We assessed the potential of the kallikrein-kinin system in mediating the cardioprotective and renoprotective effects of an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (CIL) in rats with renal ablation. 2. Eight week old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy. One week after the operation, the rats were divided into 5 groups: (i) vehicle; (ii) CIL 1 mg/kg per day per os (p.o.); (iii) Hoe140 (HOE) 70 mu g/kg per day given intraperitoneally (i.p.); (iv) CIL 1 mg/kg per day p.o. plus HOE 7 mu g/kg per day i.p.; (v) CIL 1 mg/kg per day p.o. plus HOE 70 mu g/kg per day i.p. The treatment lasted for 4 weeks. 3. CIL alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine level. HOE alone did not induce any significant changes in these parameters. CIL in combination with HOE (7 or 70 mu g/kg per day) did not induce any changes in these parameters, in addition to those associated with the effects of CIL alone. 4. These results indicate that the kallikrein-kinin system might not play a major role in the cardioprotective and renoprotective effects of ACE inhibitors in the rat remnant kidney model of chronic renal failure.

Adrenergic beta-Antagonists↗

PubMed1995

Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.

1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Long-term course of bronchiectasis and bronchiolitis obliterans as late complication of smoke inhalation.

We describe the long-term course of a patient with bronchiectasis and bronchiolitis obliterans, both of which developed as late complications of a smoke inhalation injury. Sequential chest X-rays obtained during the observation period showed gradual progression of bronchiectasis from the saccular to the cystic type. Symptoms, spirometry and blood gas analysis, however, remained stable for 15 years. We believe that symptoms and physiological derangement were due mainly to bronchiolitis obliterans, and that once the pathophysiological condition had been established following the initial injury, it could be maintained by conservative medical management.

Adult↗

PubMed1995

Soluble form of P-selectin in plasma is elevated in acute lung injury.

A number of adhesion molecules on neutrophils and the pulmonary capillary endothelium mediate the neutrophil accumulation in the lungs at the onset of adult respiratory distress syndrome or acute lung injury (ALI). P-selectin, located on both vascular endothelial cells and platelets, has been shown to be one of these neutrophil-endothelial cell adhesion molecules. In this study, we measured the soluble form of P-selectin in plasma (PPS) from 19 patients (surviving, 11; deceased, 8) with ALI due to various causes and assessed the clinical significance of this measurement. Twelve healthy subjects and 29 patients with other pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 5), pneumonia (n = 8), and sepsis without ALI (n = 8) were also studied for comparison. PPS in patients with ALI (474.5 +/- 366.8 ng/ml, mean +/- SD) were significantly higher than those in control subjects (98.8 +/- 39.7, p < 0.01) and in patients with IPF (210.4 +/- 76.6, p < 0.05), sarcoidosis (135.2 +/- 71.5, p < 0.05), pneumonia (225.3 +/- 81.0, p < 0.05), and sepsis without ALI (271.8 +/- 46.5, p < 0.05). There was no significant difference in PPS levels between seven patients with and 12 patients without multiple organ failure. Lung injury scores correlated significantly with the PPS level (r = 0.605, p < 0.05). PPS levels of deceased patients with ALI (841.0 +/- 252.4) were significantly higher than those of surviving patients with ALI (208.0 +/- 109.2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Effect of external negative pressure on pulmonary 99mTc-DTPA clearance in humans.

We studied the mechanisms by which pulmonary solute clearance is affected by lung inflation. We examined the pulmonary clearance of inhaled technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) together with changes in lung volumes in healthy men after applying graded levels of continuous external negative pressure (CNP) and positive end-expiratory pressure (PEEP). The 99mTc-DTPA clearance increased from the baseline during -15 cm H2O CNP (p < 0.005) and during -20 cm H2O CNP (p < 0.001). The 99mTc-DTPA clearance increased during +15 cm H2O PEEP (p < 0.001). However, the changes during both -10 cm H2O CNP and +10 cm H2O PEEP did not differ from the baseline, indicating a threshold effect. On the other hand, changes in FRC during CNP were proportional to the applied pressures and were similar to those during PEEP with corresponding pressures. These results suggest that pulmonary vascular recruitment induced by CNP does not affect pulmonary 99mTc-DTPA clearance. This threshold effect suggests that the increased clearance is due to changes in membrane permeability rather than in the area of the alveolar-capillary interface or the lining layer thickness. We concluded that the effect of lung inflation on solute clearance may be mediated by the changes in membrane permeability.

Adult↗

PubMed1995

Neutrophil-induced lung protection and injury are dependent on the amount of Pseudomonas aeruginosa administered via airways in guinea pigs.

We investigated the roles of neutrophils in mediating both the protective effect against bacterial infection and the harmful effect of lung injury induced after the intratracheal instillation of live bacteria. We examined the mortality rate, lung injury, and bacterial clearance following the intratracheal instillation of Pseudomonas aeruginosa in low (10(4) colony-forming units [CFU]) and high doses (10(8) CFU) in normal (control) guinea pigs, others made neutropenic with cyclophosphamide (CPA), and guinea pigs made neutrophilic with recombinant granulocyte colony-stimulating factor (rG-CSF). Lung injury was assessed by the ratio of the concentration of 125I-labeled albumin in lung tissue to that in plasma (T/P) and the animals' lung weight-to-body weight (LW/BW) ratio. With 10(4) CFU, the CPA group showed an increased T/P ratio of 0.22 +/- 0.03 versus 0.14 +/- 0.01 in the control and 0.11 +/- 0.01 (mean +/- SEM) in the rG-CSF groups (p < 0.01). Viable bacteria were recovered from bronchoalveolar lavage fluid (BALF) in the CPA group. Neutrophil recruitment was observed in the lungs of animals in the control and rG-CSF groups. With 10(8) CFU, the mortality rate was increased in the rG-CSF group (7 of 10) as compared with the control (0 of 9) and CPA groups (1 of 9) (p < 0.05), which reflected an increased LW/BW (g/kg) ratio (16 +/- 2 versus 12 +/- 1) in the CPA group (p < 0.05). We conclude that neutrophils protect against lung injury during low-level bacterial challenge, but enhance lung injury and contribute to mortality during high-level bacterial challenge.

Animals↗

PubMed1995

Neutrophils activated by granulocyte colony-stimulating factor suppress tumor necrosis factor-alpha release from monocytes stimulated by endotoxin.

We investigated the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on tumor necrosis factor-alpha (TNF-alpha) release from monocytes. Peripheral blood monocytes and neutrophils were obtained from healthy donors (n = 8). Neutrophils alone, neutrophils plus monocytes, and monocytes alone were incubated with and without G-CSF (10 ng/ml) and were studied for TNF-alpha release; monocytes subsequently were stimulated by endotoxin (lipopolysaccharide [LPS] at 10 and 1,000 ng/ml). Neutrophils alone did not produce TNF-alpha after LPS stimulation irrespective of G-CSF treatment. TNF-alpha release from monocytes was suppressed significantly by pretreatment with G-CSF in the presence of neutrophils (P < 0.01). Suppression of TNF-alpha release after LPS was not observed when monocytes were preincubated with G-CSF in the absence of neutrophils. TNF-alpha release from monocytes stimulated by LPS was not inhibited when monocytes were incubated with the supernatant from G-CSF-activated neutrophils. Pretreatment with G-CSF inhibited intracellular TNF-alpha production, as measured by flow cytometry, of monocytes stimulated by LPS (P < 0.05). These data suggest that neutrophils activated by G-CSF directly suppress TNF-alpha release from monocytes stimulated by LPS.

Adult↗