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Biomedical subjects

Y Nomoto

Publications and source records attributed to Y Nomoto.

At least 55 records · Page 3Linked to original sources
PubMed1996

Altered synthesis of interferon-gamma and expression of interferon-gamma receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis.

Previously we reported disease-specific interaction between interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon-gamma (IFN-gamma) and expression of IFN-gamma receptor (IFN-gamma R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN-gamma concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-gamma R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-gamma R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4+ T cells, CD8+ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN-gamma or IFN-gamma R mRNA expression by the semiquantitative RT-PCR method. In vitro IFN-gamma synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-gamma R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN-gamma system might be involved in the development of CGN.

Antigens, CD↗
PubMed1996

Increase of HLA-DR-positive natural killer cells in peripheral blood from patients with IgA nephropathy.

Previous in vivo and in vitro studies have presented various abnormalities of cellular immunity in patients with IgA nephropathy (IgAN). In the present study, we described increased expression of HLA-DR antigens on peripheral natural killer cells (NK cells) in relation to altered cytokine interactions. The numbers of HLA-DR expressing NK cells were enumerated by two-color flow cytometry and found to be significantly increased in patients with IgAN. Peripheral blood mononuclear cells were then fractionated into pure NK cells by a magnetic cell-sorting system and analyzed concerning expression of messages of interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Among the four cytokines, only the IFN-gamma message was significantly increased in patients' NK cells. Furthermore, intensity of the IFN-gamma message in NK cells showed positive correlation with the percentage of HLA-DR-positive NK cells from the same patient. Then we assayed serum levels of IL-2, IL-12, and IFN-gamma by enzyme-linked immunosorbent assay (ELISA) and the levels of IL-12 and IFN-gamma showed positive correlations with HLA-DR expression on NK cells. Creatinine clearance of the patients was reevaluated 36 months later, and patients with high HLA-DR on NK cells tended to show faster deterioration of renal function than patients with lower HLA-Dr expression. On the basis of these findings, we suggested that HLA-DR-positive NK cells in patients with IgAN form an "activated" population that produces IFN-gamma, and this unique cell population may be maintained by multiple factors and be involved in the development and progression of IgAN.

Adult↗
PubMed1996

Superoxide dismutase activity in human glomerulonephritis.

Superoxide dismutase (SOD) in renal tissue biopsy specimens obtained from patients with immunoglobulin A nephropathy (13 cases) and non-immunoglobulin A mesangial proliferative glomerulonephritis (nine cases) was studied at the protein level by an enzyme-linked immunosorbent assay method and at the mRNA level by the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Total SOD activity in the tissue supernatant was measured by applying an electron paramagnetic resonance/spin trapping method. Normal renal tissues obtained from kidneys removed for malignancies (six cases) were included as healthy controls. The copper and zinc form of SOD (Cu,Zn-SOD) activity at both the protein and mRNA levels was lower in the moderately or severely damaged tissues compared with that in the normal or mildly damaged tissues. On the other hand, manganese SOD (Mn-SOD) values at either the protein level or the mRNA level did not differ significantly between control and patient samples. In the histochemical study using a polyclonal rabbit anti-Cu,Zn-SOD antibody, the staining intensity for Cu,Zn-SOD antigen was lower in the areas with advanced histologic damage than in the intact tissues. A follow-up study showed that renal function deterioration was proportionately slower in patients whose SOD activity was within the range of healthy tissue levels at the time of biopsy. Our data suggest that a lower level of SOD activity, whether as a cause or a consequence of the disease process, might induce a decrease in the scavenger reaction of superoxide (O2-) thus causing the tissue to become more vulnerable to oxidative stress.

Adult↗
PubMed1996

Sclerosing encapsulating peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: a report of the Japanese Sclerosing Encapsulating Peritonitis Study Group.

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed sclerosing encapsulating peritonitis (SEP) were retrospectively studied in 130 centers in Japan. Among 6,923 patients undergoing CAPD between 1980 and 1994 only 62 (0.9%) given CAPD developed SEP. There were 38 men and 24 women, ranging in age from 20 to 87 years (average age, 48.3 years). These 62 patients developed SEP 10 to 138 months (average, 65.4 months) after starting CAPD. The average frequency of peritonitis before developing SEP was 3.3 times. Five of the 62 patients with SEP had no history of peritonitis, and 27 (43.5%) of them died of various causes in the study period. The major causes of death were almost invariably related to problems concerning bowel obstruction or complications of surgery, such as malnutrition or septicemia. It was concluded that SEP is one of the most serious complications of CAPD, and constant surveillance is necessary to detect SEP in patients during CAPD.

Adult↗
PubMed1996

Expression of inducible-NOS in human glomerulonephritis: the possible source is infiltrating monocytes/macrophages.

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). In this paper, we have studied the expression of the inducible NO synthase (iNOS) in the tissues of the human kidney at the mRNA level by RT-PCR assay and at the protein level by an immunohistochemistry technique using a specific anti-macrophage NOS monoclonal antibody. Biopsied renal tissues from patients with IgA nephropathy (IgAN; 28 cases) and with non-IgA mesangial proliferative glomerulonephritis (PGN;12 cases), and normal renal tissues obtained from kidneys removed for malignancies (11 cases) were included in this experiment. iNOS message was present in about 73% tissues from IgAN and PGN patients, which was supported by histochemical findings and the iNOS positive cells were predominantly in the tubulointerstitial areas where infiltration of monocytes/macrophages was abundant. The iNOS positive tissues were also strongly positive for CD14, INF-gamma and TNF-alpha mRNA expression. In our in vitro study, iNOS expression was found only in cytokines (INF-gamma and TNF-alpha) stimulated monocytes/macrophages but not in lymphocytes and neutrophils. Normal renal tissues did not show any iNOS expression either at the mRNA level or at the protein level in this study. Clinical and histological data showed that decreased renal function and tubulointerstitial damage were greater in the iNOS expressing patients. This study demonstrates that there is some in vivo induction for iNOS expression, likely to be mediated by cytokines, for local NO production that might be involved in the initiation and/or progression of mesangial proliferative glomerulonephritis.

Base Sequence↗
PubMed1996

Localization of glycated proteins in the glomeruli of patients with diabetic nephropathy.

Glycation of proteins is regarded as one of the major causes of the development and progression of diabetic nephropathy. Based on the numerous reports on experimental models and on our own newly developed techniques, we planned to localize Amadori products and advanced glycation end-products (AGEs), as well as the mRNA expression of cytokines, enzymes and their inhibitors, which are responsible for the expansion of the mesangial areas of the glomeruli. Ten patients with diabetic nephropathy were examined. Patients with immunoglobulin (Ig) A nephropathy and normal portions of the surgically removed kidneys served as controls. Amadori products and AGEs in biopsy specimens were stained by specific monoclonal antibodies, and mRNA expression of the above substances was detected by in situ hybridization. There was a parallel progression in the degree of staining with anti-Amadori product antibody or anti-AGE antibody with the severity of tissue damage in patients with diabetic nephropathy. Patients with IgA nephropathy and normal renal tissues did not show any positive staining with these antibodies. The expression of transforming growth factor beta 1, stromelysin and tissue inhibitor of matrix proteinase 1 in the glomeruli was decreased in diabetic patients with advanced tissue damage, but they were progressively expressed in the advanced stage of IgA nephropathy. It is concluded that Amadori products and of AGEs were formed in parallel in diabetic kidneys. The decrease in the expression of the cytokine and enzymes might be due to altered protein formation associated with glycation.

Case-Control Studies↗
PubMed1996

Involvement of interleukin-4 and soluble CD23 in hypersynthesis of immunoglobulins A and E in patients with IgA nephropathy.

To determine the cytokines responsible for the increase in production of IgA in patients with IgA nephropathy (IgAN), the roles of interleukin-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from 24 patients with IgAN and 14 patients with non-IgA proliferative glomerulonephritis. Twenty healthy adults served as controls. Concentrations of IgA and IgE in 10-day culture supernatants of PBMCs were measured by the sandwich ELISA method. Levels of sCD23 and activities of IL-4 in 4-day (96-hour) culture supernatants and serum were measured by ELISA and bioassay, respectively. Activities of IL-4 both in culture supernatants and serum were significantly elevated in patients with IgAN compared with controls (1.26 +/- 0.53 vs. 0.68 +/- 0.37 U/ml in culture supernatants, p < 0.05; 1.35 +/- 1.34 vs. 0.89 +/- 0.82 U/ml in serum, p < 0.05). Levels of sCD23 in IgAN patients' serum were also significantly elevated (521.7 +/- 514.9 vs. 173.0 +/- 166.2 U/ml, p < 0.01). In vitro IgA and IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb) only when the antibody was added on the day when the culture was started (day 0). No suppression of IgA or IgE synthesis was observed when the antibody was added on day 4. IgE but not IgA synthesis was suppressed by anti-CD23 mAb when added on both days 0 and 4. Serum levels of IgE showed positive correlations with serum activities of IL-4 and with levels of serum sCD23. It is concluded that IL-4 and sCD23 might play decisive roles in in vitro and in vivo hyperproduction of IgA and IgE in patients with IgAN, and that sCD23 seemed to control IgE but not IgA synthesis through a unique pathway.

Adult↗
PubMed1996

Plasma glutathione peroxidase deficiency caused by renal dysfunction.

Glutathione peroxidase (GPx) activity was determined in the plasma of 118 healthy persons, 18 nondialyzed patients with chronic renal failure (CRF), 20 patients on maintenance hemodialysis (HD), and 58 patients on continuous ambulatory peritoneal dialysis (CAPD). Serum creatinine levels in the nondialyzed CRF patients revealed a highly significant negative correlation (r = -0.71, p < 0.001) with plasma GPx activity. Immunoblot analysis revealed that the plasma (extracellular) GPx protein was reduced or undetectable in patients with low plasma GPx activity. Plasma GPx activities in the HD and CAPD patients were reduced to 44 and 23% (female), and to 70 and 45% (male) of the sex-matched control values, respectively. In contrast, erythrocyte (cellular) GPx activity was not decreased in the nondialyzed CRF patients and the dialyzed patients. Plasma selenium concentrations were within the normal range in these patient groups. These results indicate that the plasma GPx activity largely depends on renal function.

Aged↗
PubMed1996

P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis.

The tumor suppressor p53 protein is a transcription factor that plays a central role in the cellular response to DNA damage, and it can cause either G1 arrest or apoptosis. Recently, it was shown to induce the tumor suppressor p21Waf1/Cip1/Sdi1 (p21), which inhibits cyclin-CDK complex kinase activity. Although the etiology of idiopathic pulmonary fibrosis (IPF) is still uncertain, it is postulated that IPF begins with an initial inflammatory lesion localized to the alveolus and progresses on to chronic inflammation with alveolitis. We examined whether p53 and p21 are upregulated in association with chronic DNA damage in the bronchial and alveolar epithelial cells in patients with IPF in an attempt to repair the injury. We performed in situ detection of DNA strand breaks or apoptosis (TUNEL) in the tissues as well as immunohistochemistry (IHC) for p53 and p21. Positive signals by TUNEL were detected mainly in the bronchiolar and alveolar epithelial cells in 10 of 14 lung specimens from patients with IPF. On the other hand, no positive signal by TUNEL was detected in normal lung parenchyma or in specimens of pulmonary emphysema. The IHC demonstrated that p53 and p21 were expressed especially in hyperplastic bronchial and alveolar epithelial cells of lung tissues from all patients with IPF, except five specimens for p21. These results are consistent with those obtained by TUNEL. In normal lung parenchyma and specimens of pulmonary emphysema, p53 and p21 were not detected except in scattered alveolar macrophages and in the epithelial cells within localized fibrotic regions. These results suggest that p53 and p21 are upregulated in association with chronic DNA damage, resulting in either G1 arrest or apoptosis so that the DNA damage can be repaired in IPF. We speculate that chronic DNA damage and repair may lead to mutation of the p53 gene and tumorigenesis in IPF.

Aged↗
PubMed1996

Intraglomerular C3 synthesis in human kidney detected by in situ hybridization.

Complements 3 and 4 are known to be synthesized in diseased renal tissue and the mRNA of these complements has been demonstrated, using polymerase chain reaction, in renal biopsies from nephritic patients. However, the types of cells producing the complements in intact renal tissue have not been defined. To identify the renal cellular components involved in complement synthesis, we analyzed the expression of C3 mRNA in renal tissues from patients with immune-complex glomerulonephritis by a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide. Renal tissues from 15 patients with immunoglobulin (Ig) A nephropathy (IgAN), five with lupus nephritis (LN), and five with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidney with tumors served as normal controls. C3 mRNA was detected in mesangial cells, glomerular epithelial cells, and Bowman's capsule in IgAN and LN. In the interstitium, some tubules and some infiltrating mononuclear cells were positively stained for C3 mRNA. C3 mRNA was not detected in MCNS and control tissues. Our results confirm that the glomerular resident cells can synthesize C3 in immune-mediated glomerulonephritis and suggest that locally synthesized complement may be involved in tissue injury in glomerulonephritis.

Biopsy↗
PubMed1996

Empyema following the percutaneous instillation of antifungal agents in patients with aspergillosis.

We report two cases of empyema as a complication of the percutaneous instillation of antifungal drugs for pulmonary and pleural aspergillosis. Case 1 underwent percutaneous administration of amphotericin B and fluconazole for 2 months. Six months later, the patient was found to have an Aspergillus empyema with a bronchopleural fistula. Case 2 with pulmonary and pleural aspergillosis underwent percutaneous administration of amphotericin B for one month. Four months later, the patient underwent pleural drainage due to empyema. Pleural biopsy revealed pleural aspergillosis. In both cases, it was suggested that the preceding Aspergillus infection and percutaneous instillation of antifungals resulted in the development of empyema.

Aged↗
PubMed1996

Monocyte superoxide generation and its IgA-receptor in IgA nephropathy.

Recent studies indicated that polymorphonuclear leukocytes (PMNL) were primed to produce superoxide (O2-) in various types of glomerulonephritis with a particular importance in IgA nephropathy (IgAN). In this study, we have examined O2- production and receptor expression for the Fc portion of IgA (Fc alpha R) in monocytes to evaluate their incorporation in IgAN, since infiltration of these cells in the glomeruli are more commonly observed than that of PMNL. Similar to PMNL, monocytes obtained from IgA nephropathy (IgAN) seemed to be primed both non-specifically and specifically, as increased O2- generation was observed to N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA), as well as IgA aggregates stimulants, respectively. Monocytes O2- generation to IgA aggregates was comparatively higher in amount than in PMNL, and showed a correlation with the severity of proteinuria in IgAN patients. Flow cytometric assessment showed an increased expression of Fc alpha R on circulating monocytes in IgAN patients which showed a linear correlation with the amount of IgA-induced O2- generation. Comparing with the previous literature on PMNL, inflammation-related substances such as cytokines/immune complexes, particularly IgA immune complexes which present in the circulation of IgAN, can prime the phagocytic cells in the circulation for a burst of O2- generation to a second stimulus. The increased expression of Fc alpha R appears to be associated with the increase in priming and the degree of priming can be reflected in the severity of proteinuria/hematuria, although it can not be defined as a cause or consequence of this disease.

Adult↗
PubMed1996

[DNA strand breaks in epithelial cells from mice with bleomycin induced pulmonary fibrosis].

Bleomycin-induced cytotoxicity is believed to be caused by single- and double-strand DNA breaks. To examine the effect of bleomycin on DNA strand breaks and the role of these breaks in bleomycin induced pulmonary fibrosis in mice, we analyzed DNA strand breaks in situ by TdT-mediated dUTP-biotin nick end labeling (TUNEL), previously described by Gavrieli et al. The nuclei of bronchiolar epithelial cells were strongly stained 1 hr to 12 hr after bleomycin administration, and after that period DNA damage was repaired. Nuclei of alveolar epithelial cells showed positive signals correlated with progression of fibrosis. Although corticosteroids did not block the early DNA damage in bronchiolar epithelial cells, they did inhibit later damage to alveolar epithelial cells and fibrosis. We speculate that the DNA damage in alveolar epithelial cells and the progression of fibrosis in later stages are associated with inflammatory cytokines. These findings show the location and the time course of the DNA damage in bleomycin-induced pneumonitis in mice, and they indicate that the prolongation of DNA damage in alveolar epithelial cells is closely related to fibrinogenesis.

Animals↗
PubMed1996

[Endobronchial brachytherapy with high dose rate 192Ir afterloading technique using a new applicator].

Recently, high dose rate endobronchial brachytherapy has been carried out for the treatment of lung cancer. We devised a new applicator for Ir-192 high dose rate brachytherapy that can position the source in the center of the bronchial lumen, and tried to set up reference points according to bronchial diameter, for optimal dose distribution. Treatment consisted of external beam radiotherapy (40-60 Gy in 4-6 weeks) and endobronchial brachytherapy (6 Gy x 3 fractions for curative intent, 10 Gy x 1 fraction for palliative intent). Reference dose points were 3, 5, 7 and 10 mm from the center of the source according to bronchial diameter. We treated 19 patients with endobronchial brachytherapy and used the new applicator in 13 of them. We could place the applicator in all 13 patients, and no remarkable side effects were observed during the observation period. Our newly designed applicator will help to reduce radiation side effects caused by irradiation overdose due to adherence of the source to the bronchial wall. The reference point should be set according to bronchial diameter not only for curative intent but also palliative intent.

Brachytherapy↗
PubMed1995

Carpal tunnel syndrome in patients undergoing CAPD: a collaborative study in 143 centers.

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

Adult↗
PubMed1995

Differential distribution of type IV collagen chains in patients with diabetic nephropathy in non-insulin-dependent diabetes mellitus.

Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of human diabetic nephropathy. Renal tissues from 15 patients with type II (non-insulin-dependent) diabetes (NIDDM) were studied by immunofluorescence (IF) and immunogold electron microscopy (IEM) for the distribution of 2 type IV collagen peptides [alpha 3(IV) noncollagenous (NC) domain and alpha 4(IV) NC domain] and 2 classical type IV collagen chains [alpha 1(IV) NC domain and alpha 2(IV) domain]. There was intense staining for alpha 3(IV) NC and alpha 4(IV) NC domain in the GBM but not in the mesangial matrix of patients with overt diabetic nephropathy. In contrast, staining with antibodies to alpha 1(IV) NC and alpha 2(IV) NC domain reacted with mesangial matrix but was significantly decreased in the GBM in the patients with overt diabetic nephropathy. IEM confirmed the IF findings. These data suggest that expansion of the mesangial matrix and thickening of GBM in NIDDM involves separate and distinct type IV collagen components and that the site-specific matrix alterations in NIDDM and type I (insulin-dependent) diabetes are parallel.

Adult↗