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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 73 records · Page 4Linked to original sources
PubMed2001

Alteration of endothelin-1 concentration in STZ-induced diabetic rat nephropathy. Effects of a PGI(2) derivative.

BACKGROUND: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. METHODS: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I(2) derivative to investigate the effect of PGI(2) in diabetic vascular disturbance. RESULTS: Renal weight, urinary albumin, urinary N-acetyl-beta,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI(2) derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI(2) derivative is effective in diabetic nephropathy. As the PGI(2) derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. CONCLUSION: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI(2) derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI(2) derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.

Albuminuria↗
PubMed2001

Eosinophil transmigration across VCAM-1-expressing endothelial cells is upregulated by antigen-stimulated mononuclear cells.

BACKGROUND: Adhesion to and transmigration across endothelial cells expressing vascular cell adhesion molecule 1 (VCAM-1) may be key steps in the development of selective eosinophil accumulation at the allergic inflammation sites. There is evidence that cytokines/chemokines produced by CD4+ T cells play a prominent role in these processes. OBJECTIVE: The objective of this study was to evaluate whether eosinophil migration across human pulmonary microvascular endothelial cells (HPMEC) expressing VCAM-1 is modulated by the supernatants of antigen-stimulated mononuclear cells obtained from atopic asthmatics. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from Dermatophagoides farinae (Df)-sensitive asthmatic subjects and cultured for 96 h at 37 degrees C in the presence or absence of 1 microg/ml Df antigen. Eosinophils were isolated from blood of healthy subjects and placed on the HPMEC monolayers cultured on a transwell filter (3-microm pore size) stimulated with IL-4 plus TNF-alpha (both at 100 pM, 24 h) The supernatants of PBMC were then applied to the lower compartment and the transmigration of eosinophils was examined. RESULTS: The supernatants of PBMC stimulated with Df significantly enhanced the eosinophil transmigration across VCAM-1-expressing HPMEC (% migration: 7.6 +/- 0.6 by the supernatants of PBMC cultured without Df vs. 12.3 +/- 1.2 by the PBMC cultured with Df, p < 0.01, n = 8). The enhanced migration, but not spontaneous migration, was blocked by the anti-alpha4 integrin antibody. Moreover, the enhanced transmigration was blocked by anti-CCR3 antibody. CONCLUSION: The antigen-stimulated PBMC from atopic asthmatics produce an activity to induce eosinophil migration across VCAM-1-expressing endothelial cells. This activity appears to involve CCR3 as an essential molecule.

Antibodies↗
PubMed2001

Dexamethasone does not modulate eosinophil adhesion to endothelial cells.

BACKGROUND: Glucocorticoids are representative agents in the anti-inflammatory treatment of allergic airway diseases. Although they reduce the number of tissue eosinophils, its exact mechanism has not been completely established. OBJECTIVE: The present study was undertaken to evaluate whether dexamethasone modulates the adhesive property of eosinophils. The effect on the expression of endothelial adhesion molecules was also evaluated. METHODS: Blood eosinophils from healthy subjects were incubated in the presence or absence of 0.1-1 microM of dexamethasone for 6 h at 37 degrees C. Eosinophil chemotaxis and adhesion to paraformaldehyde-fixed human pulmonary vascular endothelial cells (HPMEC) were then examined. The effects of dexamethasone on the expression of VCAM-1 and ICAM-1 on HPMEC were examined by cell ELISA. RESULTS: 1 microM dexamethasone significantly inhibited the chemotactic response of eosinophils to 1 microM formyl-methionyl-leucyl-phenylalanine (FMLP). On the other hand, dexamethasone did not modify either the spontaneous or FMLP-stimulated adhesion of eosinophils to resting HPMEC. Similarly, dexamethasone did not alter either the spontaneous adhesion of eosinophils to or the expression of VCAM-1 or ICAM-1 on HPMEC stimulated with IL-4 + TNF-alpha. CONCLUSION: Dexamethasone does not modify the adhesive property of eosinophils or the expression of adhesion molecules on endothelial cells. Thus, it is unlikely that glucocorticoids directly modulate the adhesive interaction between eosinophils and endothelial cells.

Adult↗
PubMed2001

Effect of experimental renal failure on the pharmacodynamics of cefoselis-induced seizures in rats.

We investigated the effect of infusion rate and experimental renal failure on the pharmacodynamics of cefoselis (CFSL)-induced seizures. As an animal model of CFSL-induced seizures, male Wistar rats received an intravenous infusion of CFSL at one of three different rates (1.4-5.8 g/h/rat) until the onset of maximal seizures (which occurred after 8.0 to 36.0 min of infusion). Samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately after stopping infusion of CSFL. The serum concentration of CFSL at the onset of seizures increased with increasing infusion rate, but brain and CSF concentrations of CFSL at the onset of seizures were not affected by the infusion rate. Ureter-ligated (UL) and control rats received an intravenous infusion of CFSL at 1.4 g/h/rat until the onset of seizures. Then the same procedure as used to determine the effect of infusion rate on the concentrations of CFSL was carried out. Renal failure was associated with a significant decrease in the amount of CFSL required to induce seizures. Serum, brain, and CSF concentrations of CFSL in UL rats were significantly lower than those in control rats. These results indicate that the experimental strategy and animal model in this investigation would be useful to assess the effects of diseases and other variables on the pharmacodynamics of CFSL-induced seizures and that renal failure is one of the risk factors for neurotoxicity of CFSL.

Acute Kidney Injury↗
PubMed2001

Systolic dysfunction and blood pressure responses to supine exercise in patients with hypertrophic cardiomyopathy.

Left ventricular function and blood pressure responses were evaluated in 56 patients with non-obstructive hypertrophic cardiomyopathy (HCM) and 12 control subjects by using a radionuclide ventricular function monitor during supine ergometer exercise. Patients with HCM were divided into 2 groups: (i) group A had no decrease in ejection fraction (EF) during exercise; and (ii) group B had a decrease in EF during exercise. During exercise, the change in end-diastolic volume did not differ between the 3 groups. In contrast, the change in end-systolic volume differed between the 3 groups (p<0.0001). The change in systolic blood pressure (SBP) also differed significantly between the 3 groups. The change in SBP in group B was smaller than that in the control group and group A, and changes in the EF and changes in the SBP between rest and peak exercise showed a significant correlation (p<0.005). These results suggest that exercise-induced systolic dysfunction in patients with non-obstructive HCM may contribute to abnormal blood pressure response in those patients.

Adult↗
PubMed2001

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features.

OBJECTIVE: The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A population of 735 IgAN patients whom we were able to observe for more than two years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. CONCLUSION: These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.

Adolescent↗
PubMed2001

Effects of long-term acidification of extracellular pH on ATP-induced calcium mobilization in rabbit lens epithelial cells.

ATP-induced calcium (Ca2+) mobilization was investigated in rabbit lens epithelial cells that had been cultured in a medium with pH of 7.4 (group 1), 7.2 (group 2), or 7.0 (group 3) for 10 to 21 d. Intracellular free Ca2+ ([Ca2+]i and pH (pHi) were measured by using fluorescent dyes, fura-2 and BCECF, respectively. The long-term acidification decreased the pHi to 7.15 +/- 0.01, from 7.22 +/- 0.01, in group 2 and to 7.09 +/- 0.01 in group 3. The administration of 10 micromol/l ATP produced an initial peak followed by a sustained increase in [Ca2+]i in the lens cells of group 1. Both the initial peak and the sustained increase in [Ca2+]i were enhanced in groups 2 and 3. The initial peak was abolished by pretreatment with 1 micromol/l thapsigargin, an ER Ca2+ pump inhibitor, but was not affected by the removal of extracellular Ca2+. On the other hand, the sustained increase was suppressed either by the thapsigargin treatment or by the Ca2+ removal. Treatment with only thapsigargin caused a sustained increase in [Ca2+]i that was greater in group 3 than in group 1. These results suggest that (1) the ATP-induced initial peak in [Ca2+]i is due to Ca2+ release from the intracellular stores, (2) the sustained increase in [Ca2+]i is mediated through either Ca2+ influx from the extracellular space or Ca2+ release from the store triggered by the Ca2+ influx, and (3) long-term, moderate acidification enhances both the initial peak and the sustained increase in [Ca2+)]i in rabbit lens epithelial cells. One possible mechanism of the ATP-induced Ca2+ influx seems to be a capacitative Ca2+ entry pathway.

Adenosine Triphosphate↗
PubMed2001

[Clinical result of thermochemoradiotherapy for advanced head and neck cancer].

Since 1986, we have applied thermochemo (CDDP) therapy combined with radiotherapy to 18 patients with 25 advanced and/or recurrent head and neck cancers (thermochemoradiotherapy: TCR). In this report, the effects of TCR were compared with those of radiochemotherapy (RC) without hyperthermia for 22 patients with 27 cancers before 1985 in our department. Thermochemotherapy was performed twice a week, for a total of 8.8 times on average. Three kinds of heating system were used: a radiofrequency system, a microwave system, and a RF interstitial system. In the TCR group, 11 lesions (44.0%) showed a complete response (CR), 12 lesions (48.0%) a partial response (PR), and 2 lesions (8.0%) no change (NC). Therefore, the total response rate was 92.0%. After treatment with only RC, 5 lesions (18.5%) showed a CR, 12 lesions (44.5%) a PR, and 10 lesions (37.0%) NC, giving a total response rate of 63.0%. There was a significant difference in the CR and total response rate between these two groups. Furthermore, the 5-year cumulative local control and survival rates in the TCR group were 68.2% and 44.4%, and in the RC group were 22.2% and 18.2%, respectively. There was a significant difference in the local control rate between these two groups. In conclusion, thermochemoradiotherapy is an effective strategy for patients with advanced head and neck cancers.

Adult↗
PubMed2001

C-reactive protein frequently localizes in the kidney in glomerular diseases.

AIM: In recent reports, C-reactive protein (CRP) has emerged as a component that may play important roles in atherogenesis. Based on the analogies set out in a previous report between focal-segmental sclerosis and atherosclerosis, we hypothesized that CRP contributes to the pathogenesis of glomerular diseases. To our knowledge, no immunohistochemical study of CRP localization in the kidneys has been previously reported. PATIENTS AND METHODS: In the present study, we investigated 106 kidney biopsy specimens from children with various types of glomerular diseases and minor glomerular abnormalities. Of the 106 cases, 74 were proliferative diseases, 17 were non-proliferative diseases, and 15 were minimal-change nephrotic syndrome (MCNS). Immunohistochemical staining was performed using monoclonal antibody to CRP. RESULTS: CRP immunoreactivity was found in 48 of 106 (45.3%) specimens. CRP deposition was encountered more often in patients with proliferative diseases (56.8%) than in those with non-proliferative diseases (23.5%) (p < 0.01). CRP deposition, most frequently observed along the capillary walls of glomeruli, was found in 33 of 46 (71.7%) cases with positive expression of CRP. CRP was also located in the peritubular capillary walls and small vessels in the interstitium in 13 of 46 cases (28.3%). CRP deposition was also found in 2 of 15 cases of MCNS. The two MCNS specimens showing positive CRP immunoreactivity were both from patients who had undergone cyclosporin therapy. CRP deposition was not shown in any cases treated with steroids or cyclophosphamide. The cases of patients who had undergone renal biopsies within 6 months after onset revealed a tendency toward positive CRP deposition. The clinical outcomes at the latest follow-up were quite similar between the groups of patients with and without CRP deposition. CONCLUSIONS: We surmise that circulating CRP may deposit at the site of endothelial injury, and may not be relevant to the progression of renal lesions.

Adolescent↗
PubMed2001

[Immunological properties of S-1090, cefmatilen hydrochloride hydrate].

S-1090, a cefmatilen hydrochloride hydrate, is being developed as a cephalosporin antibiotic for oral use. Immunogenicity, hypersensitivity-eliciting antigenicity and immunological cross-reactivity with other antibiotics were evaluated by active systemic anaphylaxis (ASA) test, passive cutaneous anaphylaxis (PCA) test and enzyme-linked immunosorbent assay (ELISA) using guinea pigs and mice/rats. In addition, in vitro direct Coombs' test was also performed to examine the possibility of hemolytic anemia in clinical use. Immunogenicity of S-1090 was not observed in guinea pigs after repeated immunization with S-1090 by ASA or PCA tests. Even in ELISA, only weak antibody production against S-1090 was found in some guinea pigs from the intraperitoneal groups showing the antibody titers only 10(1) to 10(2). When the sera collected from C3H/He mice and C57BL/6J mice immunized with S-1090 were tested for immunogenicity, rat PCA was elicited in a C3H/He mouse serum by S-1090 and antibodies against S-1090 were detected in a C57BL/6J mouse serum by ELISA. When adjuvant was used in mice and guinea pigs, the production of antibody against S-1090 was less frequent in comparison with other antibiotics such as cefmetazole (CMZ) and cefotiam (CTM). When hypersensitivity-eliciting antigenicity of S-1090 was examined using S-1090 as an eliciting antigen in ASA and PCA tests, positive ASA and PCA were observed in guinea pigs and positive PCA in a C3H/He mouse. Hypersensitivity-eliciting antigenicity was also observed in other reference antibiotics, i.e. cephalothin (CET), CMZ and CTM. Immunological cross-reactivity among S-1090, penicillin G (PCG), CET, CMZ and CTM was tested by ASA and PCA tests. S-1090 was found to immunologically cross-react only with CET in guinea pigs. In the present study, immunological cross-reactivities were also noted between PCG and CET, PCG and CMZ, PCG and CTM, and between CET and CMZ. In in vitro direct Coombs' test using human red blood cells, S-1090.Na, PCG and CET gave positive reactions at the final concentrations of 40 mg/mL, 20 to 40 mg/mL and 2.5 to 10 mg/mL, respectively.

Animals↗
PubMed2001

[Hypersensitivity pneumonitis caused by a factory humidifier. A case report].

A 64-year-old man was hospitalized for productive cough and dyspnea. Both chest radiographs and CT scans showed areas of ground-glass opacity in the middle and lower lung fields on both sides. The BAL and TBLB findings were compatible with hypersensitivity pneumonitis. The serum was negative for antibodies against Trichosporon species, and the result of a lymphocyte stimulating test for administered drugs including a Chinese medicine was also negative. A humidifier was suspected as the cause because it had been used for more than 10 years in the factory where the patient had been working. An inhalation test using the humidifier fluid successfully provoked dyspnea, fever and fine crackle, and laboratory tests demonstrated hypoxemia, reduction in vital capacity and the elevation of CRP. Agar gel diffusion using the patient's serum showed a precipitating line against Cephalosporium acremonium, but this line did not fuse with any precipitating line formed between the humidifier fluid and the serum, indicating that no Cephalosporium was Present in the humidifier fluid. Since a high level of beta-D glucan was detected in the humidifier fluid, an unidentified fungus was suspected to be the antigen.

Acremonium↗
PubMed2001

[An evaluation of the long-term effect of clustered immunotherapy in house-dust-mite-sensitive adult bronchial asthma].

The optimal treatment period for specific immunotherapy in atopic asthma remains to be established. The present study was undertaken to evaluate the efficacy and the optimal treatment period of immunotherapy in adult asthma patients. Eight house-dust-mite-sensitive asthmatics were initiated by clustered immunotherapy (C-IT) using house-dust (HD) antigen followed by maintenance treatment with 10-fold dilution of HD. The increase in morning peak expiratory flow rate reached a plateau at 16 weeks following C-IT. On the other hand, the maximal improvement in clinical scores was observed at a year following C-IT. Thus, it would be reasonable to determine the clinical response of immunotherapy at a year following maintenance treatment.

Adolescent↗
PubMed2001

[Local staging with magnetic resonance imaging after neoadjuvant hormonal therapy for prostate cancer].

We retrospectively studied the staging accuracy of magnetic resonance (MR) imaging after neoadjuvant hormonal therapy (NAH) for 21 localized prostate cancers. MR imaging was performed using a 1.5-Tesla magnetic resonance system with a pelvic phased array coil. T2-weighted MR images were obtained on axial and coronal planes, and T1-weighted MR images using the dynamic technique with Gd-DTPA bolus enhancement were obtained in axial planes for each patient. On T2-weighted imaging, the signal intensity of the normal tissue in the peripheral zone became lower after NAH. Therefore, it was more difficult to detect residual malignant lesions in many cases than before NAH. The accuracy of T staging for prostate cancer after NAH in MRI was 71%. The accuracy, sensitivity, and specificity of the extracapsular invasion was 76%, 0% and 94%, respectively, and those of the seminal vesicular invasion 85%, 0% and 100%, respectively. While 2 of the 4 patients judged as downstaged cases in MRI showed corresponding pathological findings, 5 of the 21 cases (23.8%) were underdiagnosed. Local staging with only MRI for prostate cancer after NAH seems to have limits in applicability.

Aged↗
PubMed2001

[A case of combined squamous cell carcinoma and aspergilloma arising in a cyst wall].

A 76-year-old man in whom interstitial pneumonia and diabetes mellitus had been diagnosed complained of bloody sputum in August, 1998. Chest radiography disclosed irregular shadows in the left lower lung field. Chest computed tomography (CT) scans revealed a cyst and a small nodular lesion in the left S6 segment. Although primary lung cancer was suspected, we did not detect any malignant cells in the transbronchial lung biopsy specimen. CT scans in January 2000 showed a ball-like shadow in the thick-walled cyst in the left S6 segment. Cytologic examination of the sputum and the bronchial lavage fluid from the left B6 revealed squamous cell carcinoma. Left lower lobectomy and mediastinal lymph node dissection were performed. Pathological examination revealed that moderately differentiated squamous cell carcinoma had extensively invaded the wall of the cyst in the left S6 and S10 segments, and was accompanied with aspergilloma. Abnormal thickening of a cyst wall may in some cases suggest the presence of lung cancer.

Aged↗