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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 127 records · Page 7Linked to original sources
PubMed1996

Serum MIP-1 alpha and IL-8 in septic patients.

UNLABELLED: We studied blood MIP-1 alpha and IL-8 in 38 septic patients and 5 healthy volunteers. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and Il-8 in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in septic patients with disseminated intravascular coagulation, central nervous system (CNS) dysfunction or renal failure, and the mortality rate was higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05). In conclusion, the production of both MIP-1 alpha and IL-8 was increased and initially detectable levels of circulating IL-8 predicted high mortality in sepsis. OBJECTIVE: To determine the significance of the C-C chemokine MIP-1 alpha and the C-X-C chemokine IL-8 in sepsis. DESIGN: Prospective study. SETTING: Clinical investigation, emergency department and general intensive care unit of university hospital. PATIENTS AND PARTICIPANTS: 38 septic patients and 5 healthy volunteers were studied. Sepsis was diagnosed following the criteria formulated by ACCP/SCCM. INTERVENTIONS: 10-20 ml of blood was drawn from each patient at the time of initial diagnosis of sepsis. MEASUREMENTS AND RESULTS: MIP-1 alpha and IL-8 were determined by sandwich ELISA. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and IL-8 was detected in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in patients with disseminated intravascular coagulation (DIC) (p < 0.05), central nervous system (CNS) dysfunction (p < 0.05), renal failure (p < 0.01) and the mortality rates were higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05). CONCLUSIONS: The production of MIP-1 alpha and IL-8 was increased in sepsis. Furthermore, an initially detectable level of circulating IL-8, but not MIP-1 alpha, predicted a high mortality in sepsis diagnosed according to the ACCP/SCCM criteria.

Biomarkers↗
PubMed1996

Linear and angular measurements of the mandible during maximal mouth opening.

PURPOSE: There are numerous reports of the translatory movement of the condyle in maximal mouth opening; however, the rotatory movement is less well understood. The purpose of this study was to investigate the rotatory condylar movement and the factors associated with it in normal subjects. PATIENTS AND METHODS: To study the role of facial morphology in maximal mouth opening, linear and angular measurements of the mandible in both the closed and maximal open positions were made by means of cephalometry. Dental students, 29 men and 31 women with no functional disorders of the masticatory system, were investigated. RESULTS: When the mouth was fully opened, the linear measurement of condylar movement was 20.5 +/- 4.0 mm in men and 18.1 +/- 2.5 mm in women, and the angular measurements of the rotation of the mandibular ramus were 39.1 +/- 5.9 degrees in men and 36.3 +/- 4.3 degrees in women. These differences were statistically significant (P < .01). CONCLUSIONS: During condylar movement and rotation of the mandible, mandibular length and the inclination of the mandibular ramus in the former, and the inclination of the mandibular ramus, the mandibular angle and the position of the condyle in the latter, were important factors.

Adult↗
PubMed1996

Cardiomegaly and vasoactive hormones in rats with chronic myocardial infarction: long-term effects of chlorothiazide.

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day-1 kg-1) in their drinking water or drinking water alone. 2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged. 3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy. 4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin-angiotensin system.

Animals↗
PubMed1996

Augmentation of endotoxin-induced pulmonary responses by mononuclear cell phagocytosis in the reticuloendothelial system.

OBJECTIVE: To test the hypothesis that the effects of intravenous injection of latex particles would demonstrate the contribution of phagocytosis by mononuclear phagocytes to the development of Escherichia coli-induced acute lung injury in neutropenic guinea pigs. DESIGN: Prospective, controlled, experimental study. Intravenously injected the latex particles into 41 guinea pigs to investigate the contribution of the phagocytosis in acute lung injury. SUBJECTS: Forty-one guinea pigs. INTERVENTIONS: Forty-one guinea pigs were divided into five experimental groups: a saline group (n=9); an endotoxin group (n=10) receiving 2 mg/kg of intravenous E. coli endotoxin; a latex group (n=7) receiving 2 x 10(9)/kg of intravenous polystyrene latex (mean diameter 3.19 micrometers); an endotoxin + latex group (n=8); and an E. coli group (n=7) receiving 2 x 10(9) live E. coli/kg. MEASUREMENTS AND MAIN RESULTS: The lung wet/dry ratio was increased in the live E. coli-treated guinea pigs (6.71 +/- 0.16 [SEM], p < .01) as compared with the saline control (5.40 +/- 0.16, whereas the ratio was not increased in the endotoxin (5.52 +/- 0.14) or latex (5.58 +/- 0.20) groups. However, the lung wet/dry ratio was greater in the endotoxin + latex group (6.11 +/- 0.16, p < .05) than in the saline control. The 125I albumin lung tissue/plasma ratio was greater in the E. coli (2.00 +/- 0.29, p < .01) and endotoxin + latex (0.84 +/- 0.12, p < .05) groups than in the saline group (0.18 +/- 0.07), whereas no increases were observed in the endotoxin group (0.22 +/- 0.10) and the latex (0.34 +/- 0.13) group. More than 40% of the injected radiolabeled latex was observed to have accumulated in the reticuloendothelial system (liver and spleen), in both the saline control (40.1 +/- 2.3%, n=4) and endotoxin (57.3 +/- 6.8%, n=5) groups, with 2.6 +/- 1.5% and 3.1 +/- 1.7% in the lungs for the saline control and the endotoxin groups, respectively. The percent deposition of radiolabeled latex in the liver was greater in the endotoxin group (51.7 +/- 3.8%, p < .05) than in the saline group (37.6 +/- 5.9%). CONCLUSIONS: These findings suggest that, in neutropenic guinea pigs: a) the combination of endotoxin and latex particles induces acute lung injury; and b) the phagocytic properties of mononuclear phagocytes in the reticuloendothelial system augment endotoxin-induced pulmonary responses and may play a role in the development of live E. coli-induced acute lung injury.

Animals↗
PubMed1996

Effects of benidipine, a calcium antagonist, on urinary kallikrein excretion and renal impairment in experimental diabetes.

OBJECTIVE: To assess the long-term effects of different antihypertensive agents on urinary protein excretion and kallikrein excretion in diabetic rats with renal impairment. METHODS: Uninephrectomized streptozotocin diabetic Wistar-Kyoto rats were randomly assigned to receive vehicle, a calcium antagonist (benidipine) or an angiotensin converting enzyme inhibitor (captopril) for up to 12 weeks. Active kallikrein was determined by its kininogenase activity, and generated kinins were measured by radioimmunoassay. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin. RESULTS: Urinary protein excretion increased significantly in diabetic rats compared with non-diabetic rats. Urinary active kallikrein excretion was significantly reduced in diabetic rats, whereas urinary total kallikrein excretion was unchanged, resulting in a reduced percentage of active to total kallikrein compared with that in non-diabetic rats. Benidipine and captopril reduced blood pressure and attenuated the development of diabetic renal impairment in a similar manner. However, only benidipine attenuated the decreases in urinary active kallikrein excretion and the ratio of active to total kallikrein in diabetic rats. CONCLUSIONS: Although pathophysiological relevance of impaired urinary kallikrein activation to the development of diabetic renal impairment remains to be determined, our result might suggest a new mechanism by which calcium antagonists protect the kidney from diabetic renal impairment.

Analysis of Variance↗
PubMed1996

The relationship between maximal jaw opening and size of skeleton: a cephalometric study.

The purpose of this study was to investigate the correlation between maximal mouth opening and size of the skeleton. The subjects were dental students at the Dental School of the Health Sciences University of Hokkaido with no functional disorders of the masticatory system. The stature and maximal mouth opening were recorded in 29 males and 31 females. These subjects agreed to have a lateral cephalogram taken at the closed and maximal mouth opening positions. The correlations between the maximal mouth opening and the body height, mandibular length and mandibular angle were significant. The correlation between the maximal mouth opening and the movement of the condyle was also significant.

Adult↗
PubMed1996

Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury.

Because excessive neutrophil elastase (NE) activity is involved in the pathogenesis of acute lung injury, we speculated that administering anti-NE might prevent lung injury. In a guinea pig model of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]), we investigated the effect of ONO-5046, a low-molecular-weight and specific inhibitor of NE. ONO-5046 produced concentration-dependent inhibition of guinea pig NE, whereas there were no inhibitory effects on neutrophil chemotaxis or the expression of adhesion molecules in endothelial cells. Detectable NE activity in bronchoalveolar lavage (BAL) fluid was present in the LPS-alone group. No NE activity in BAL fluid was detected in the LPS+ONO-5046 groups. Neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio, and the lung tissue or BAL fluid to plasma ratio of 125I-albumin were increased in the LPS-alone group as compared with the saline group (p < 0.05). In the LPS+ONO-5046 group, neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio and BAL fluid to plasma ratio of 125I-albumin were decreased as compared with the LPS-alone group (p < 0.05). These data suggest that ONO-5046 can attenuate LPS-induced acute lung injury.

Acute Disease↗
PubMed1996

Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs.

Corynebacterium parvum (CP) is known to increase susceptibility to endotoxin, which is associated with increased production of tumor necrosis factor (TNF). We investigated the effect of CP-priming on the pathogenesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into four groups: (1) control (n=6), (2) CP-alone (n=6), (3) LPS-alone (n=6) and (4) CP + LPS (n=6). A CP dose of 4 mg/kg was injected intraperitoneally 7 d before the study. Animals were observed for 4 h after intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to-dry weight ratio (W/D), [125I] albumin concentration ratio of lung tissue to plasma (T/P) and of bronchoalveolar lavage (BAL) fluid to plasma (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leakage was observed. The CP + LPS group showed increased lung water and albumin leakage as compared with the other three groups (p<0.05). We also observed increased cell counts in BAL fluid (p<0.05), in the CP + LPS group. The spleen weight was increased in guinea pigs pretreated with CP, indicating reticuloendothelial system (RES) activation. In the CP + LPS group, the TNF level was increased in both plasma and BAL fluid. We conclude that pretreatment with CP enhances LPS-induced acute lung injury in parallel with increasing TNF production, which suggests that the activation of mononuclear phagocytes contributes to increased susceptibility to intratracheal endotoxin in guinea pigs.

Administration, Topical↗
PubMed1996

Local Pseudomonas instillation induces contralateral lung injury and plasma cytokines.

We investigated whether local bacterial instillation leads to lung injury in noninstilled lung regions and examined local and systemic cytokine accumulation. Rats were challenged by intrabroncheal instillation of Pseudomonas aeruginosa, 10(7) colony-forming units (CFU) (HD group, n = 11), 4 x 10(6) CFU (LD group, n = 10), or saline (control group, n = 12). 99mTc-labeled macroaggregated albumin was added to the P. aeruginosa or saline solution for later documentation of the instilled area. At 4 h the right lung, including instilled segment, and the left lung were sampled. Lung injury was assessed by lung tissue to plasma 125I-labeled albumin (T/P) and lung wet-dry (W/D) ratios. We measured plasma and bronchoalveolar lavage fluid (BALF) levels of tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC). HD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation in BALF (p < 0.05) associated with increased T/P (p < 0.005) and W/D (p < 0.05) ratios in both instilled and the noninstilled lungs as compared with the saline-instilled and noninstilled controls. LD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation only in the instilled lung (p < 0.05), and not in the noninstilled lung, and did not increase the T/P or W/D ratio. Plasma levels of TNF and CINC were increased in the HD, but not the LD, group when compared with the saline controls (p < 0.05). These data indicate that, when the dose is high enough to cause an excess inflammatory response, local bacterial instillation leads to neutrophil sequestration, lung injury, and cytokine elevation in the noninstilled lung associated with systemic cytokine release.

Albumins↗
PubMed1996

Protective effect of B464, a lipid A analog, on endotoxin-induced cellular responses and acute lung injury.

B464 is a novel synthetic analog of lipid A, a toxic component of endotoxin (LPS; lipopolysaccharide). We investigated the effects of B464 on both LPS-induced cellular responses in vitro and acute lung injury in vivo. In the in vitro study, B464 inhibited tumor necrosis factor-alpha (TNF-alpha) production from human monocytes, priming and stiffening of neutrophils, and expression of adhesion molecules on endothelial cells induced by LPS. We then studied the effects of B464 pretreatment on acute lung injury elicited by intravenous LPS administration in vivo. Guinea pigs were divided into saline control, B464 alone, LPS alone, and LPS + B464 groups. Animals were observed for 4 h after LPS administration, and lung injury was evaluated by extravascular lung water, 125I-albumin leakage in lung tissue, and lung neutrophil accumulation. In the LPS alone group, rapid and sustained peripheral neutropenia (p < 0.001 versus saline at 15 min and at 1, 2, and 4 h), an increased plasma TNF-alpha concentration (p < 0.005 at 1 h), and increases in lung injury parameters (p < 0.05) were observed. In the LPS + B464 group, no changes were observed in either plasma TNF-alpha or lung injury parameters. Transient peripheral neutropenia and subsequent rapid recovery (p > 0.05, p < 0.001, p < 0.01, and p > 0.05 at 15 min and 1, 2, and 4 h, respectively) were observed in the LPS + B464 group. These in vivo data, together with in vitro evidence of suppressed cellular responses, suggest that B464 (1) inhibits neutrophil accumulation in lung tissue, and (2) attenuates the development of acute lung injury by blocking the activation of neutrophils and mononuclear cells as well as the interaction between neutrophils and endothelial cells.

Animals↗
PubMed1996

A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion.

Cationic antimicrobial protein of 18 kD (CAP18) was identified and purified from rabbit granulocytes and shown to inhibit various activities of lipopolysaccharide (LPS). We investigated the effect of a 32-amino-acid C-terminal fragment of CAP18 (CAP18-derived peptide, CDP) on the pathogenesis of acute lung injury caused by intravenous endotoxin. Guinea pigs were divided into six groups: (I) saline control (n = 8), (2) CDP-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5) LPS+CDP10m (n = 8), and (6) LPS+CDP60m (n = 8). A CDP dose of 0.2 mg/kg was injected at various time points after LPS injection. Lung wet-to-dry weight ratio, [125I]albumin leakage in lung tissue and bronchoalveolar lavage (BAL) fluid, differential cell count in BAL fluid, and histopathologic features were examined 4 h after intravenous administration of 0.02 mg/kg of LPS. The LPS+CDP0m and the LPS+CDP10m groups showed significantly attenuated lung injury compared to that seen in the LPS-alone group, however the LPS+CDP60m group revealed no attenuation of lung injury. The accumulation of peripheral white blood cells into pulmonary vasculature was attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups. We examined the effect of CDP on the expression of adhesion molecules using human umbilical vein endothelial cells, the result of which showed that CDP suppressed the LPS-induced expression of adhesion molecules in a dose-dependent manner. We conclude that CDP attenuates inflammatory cell migration into alveoli resulting in the attenuation of lung injury.

Albumins↗
PubMed1996

Flow cytometric detection of cell-associated cytokines in alveolar macrophages.

To elucidate the cytokine-producing capacity of alveolar macrophages (AMs), we have introduced a method of flow cytometry combined with saponin treatment to detect the cell-associated cytokines. We studied bronchoalveolar lavage fluid cells from six patients with sarcoidosis (SAR) and six control (CTL) subjects. Cells were either left uncultured, or cultured with and without lipopolysaccharide (LPS), then treated with paraformaldehyde and saponin and analysed for cell-associated interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) by flow cytometry. Cell-associated IL-1 beta and TNF-alpha were also analysed by immunoassays. The flow cytometric cytokine values were correlated with the immunoreactive cell-associated cytokines (IL-1 beta: r = 0.45, p < 0.05; TNF-alpha: r = 0.82, p < 0.001). The histograms of cell-associated IL-1 beta yielded a single peak both in the patients and controls, whereas the histograms of cell-associated TNF-alpha exhibited two peaks in SAR patients, but just a single peak in the CTL subjects. The mean value of the cell-associated TNF-alpha in LPS+ AMs was higher in the SAR patients than in the CTL subjects (p < 0.001). In conclusion, the flow cytometric method can be applied to the semiquantitative detection of cell-associated cytokines in alveolar macrophages at the single cell level.

Adult↗
PubMed1996

Cardiac angiotensin converting enzyme and endothelin receptor in rats with chronic myocardial infarction.

To ascertain the pathophysiological roles of the renin-angiotensin system and endothelin in heart failure and cardiac hypertrophy, we assessed changes in cardiac angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) receptor using rats in which myocardial infarction was induced by left coronary ligation. The animals were decapitated 1 or 8 months after the operation. Cardiac ACE and ET-1 receptor were quantified by computerized in vitro autoradiography using 125I-MK351A (a lisinopril derivative) and 125I-ET-1. One month after myocardial infarction, cardiac weight and plasma atrial natriuretic peptide had increased in rats with infarction, compared to sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium and plasma renin activity were unchanged. Cardiac ACE increased markedly in the infarcted area and moderately in hypertrophied myocardium without any change in affinity compared to sham-operated rats. On the other hand, there was no change in cardiac ET-1 receptors in infarcted rats. The same results were found even at 8 months after myocardial infarction. The present study indicates that cardiac ACE may participate in tissue repair at the site of myocardial infarction and may also play a role in the pathophysiology of cardiac hypertrophy in rats with chronic heart failure. However, the present results do not reveal whether ET-1 receptor participates in the pathophysiology of cardiac hypertrophy in this model.

Angiotensin II↗
PubMed1996

Clinical presentation of pulmonary tuberculosis associated with acquired immunodeficiency syndrome in metropolitan Tokyo.

The clinical features of pulmonary tuberculosis associated with acquired immunodeficiency syndrome (AIDS) in Japan were surveyed utilizing questionnaires completed by 48 institutes around the Tokyo metropolitan area. We found 11 Japanese and six foreign patients. The average number of patients per institute was 0.37. The Japanese patients had advanced human immunodeficiency virus (HIV) infection. A middle aged man, with fever and cough, nonspecific chest X-ray infiltrates, decreased lymphocyte counts, and a negative tuberculin skin test was the typical presentation of the Japanese patients. The clinical diagnosis was often difficult. The smear positive rate was high among those from whom smears were obtained, suggesting high communicability. None of the isolates indicated multidrug-resistant tuberculosis at the time of diagnosis. In conclusion, sputum smear and culture remain the keys to diagnosing tuberculosis in patients with AIDS, although the clinical picture may be atypical for pulmonary tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Acute lung injury: clinical concept and experimental approaches to pathogenesis.

Acute lung injury (ALI) was defined recently as a syndrome of inflammation and increased permeability of the lungs that is associated with clinical radiologic, and physiologic abnormalities that can not be explained by left atrial hypertension. ALI has the same clinical spectrum, although in a milder form, as acute respiratory distress syndrome (ARDS). The risk factors, incidence, and prognosis of ALI are described based on the medical literature and data collected at Keio University Hospital. We estimate that 20,000 to 40,000 cases of ALI, half of which also have ARDS, occur annually in Japan. Despite the new diagnostic criteria, the clinical entity of ALI remains to be clarified both physiologically and biochemically because of the lack of direct diagnostic methods. I briefly review the central mediator(s) and their role in the inflammatory cascade of ALI. Experimental studies and pharmacological interventions from our laboratory are also described.

Acute Disease↗
PubMed1996

[Measurement of the common carotid arterial flow during parabolic flight in the anesthetized rat].

To measure the blood flow of a common carotid artery (CCA) during parabolic flight in the rat, we developed an animal double hold box (ADHB) made of styrene expanded form for the anesthetized rat to keep the animal at a proper posture in an aircaft. Twelve anesthetized rats weighing 291-342 g were surgically operated to mount a ultrasound flowmeter probe (1 mm size,1RS:Transonic Systems Inc.) around the right CCA and to insert a catheter into the right axillar artery for blood pressure measurement. These animals were held comfortably in ADHBs which were placed on the rack installed in the aircraft (MU-300). A total of 27 parabolic flights was performed and the blood flow was measured accurately in 9 rats. This special animal holding facility is useful for various types of animal experiments in an aircraft.

Animals↗
PubMed1996

[A case report of small cell carcinoma of the esophagus with remarkable response to neoadjuvant chemotherapy].

A 61-year-old male consulted our hospital with complaints of pain in swallowing. The X-ray Barium studies and upper gastrointestinal (UGI) scope revealed an irregular ulcerated lesion in the middle portion of the esophagus. He was diagnosed as having small cell carcinoma of the esophagus by means of biopsy specimens. Three courses of combined chemotherapy with CDDP, etoposide and 5-FU were used before operation. Following the chemotherapy, according to the UGI scope findings, the tumor of the esophagus disappeared. An esophagectomy through a thoracolaparotomy was performed. The chemotherapy resulted in a Grade 2 response, as ascertained by means of pathological findings for the resected specimen. After an additional course of chemotherapy, the patient was discharged from the hospital. Although we performed the curative resection for this patient, extensive recurrences and distant metastasis to the mediastinal lymph nodes and lung were found in less than a year. It is said that this tumor has a poor prognosis, and the one-year survival rate is about 10% following the treatment. It is necessary to combine surgery with effective chemotherapy and irradiation to obtain a good prognosis after resection of small cell carcinoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗