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Biomedical subjects

Y Nomoto

Publications and source records attributed to Y Nomoto.

At least 109 records · Page 6Linked to original sources

Studies on cardiotonic agents. VII. Potent cardiotonic agent KF15232 with myofibrillar Ca2+ sensitizing effect.

A series of novel 4,5-dihydro-5-methyl-6-(2 or 4-substituted 7-quinazolinyl)-3(2H)-pyridazinones was synthesized and examined for cardiotonic activity in anesthetized dogs. The 4-substituted aminoquinazolines generally showed potent and long-lasting inotropic activity. Fall in the activity was observed on the introduction of substituent at the 2-position of the quinazoline ring. The 3-substituted 4 (3H)-quinazolinimines generally exhibited weak activity. Ca2+ sensitizing effect of the 4-substituted amino derivatives was also examined in chemically skinned fiber from papillary muscle of guinea pig. The alkylamino derivatives exhibited small sensitizing effect, while the benzylamino derivatives exhibited large effect. Among them, KF15232 (Ix) was found to have the most potent cardiotonic and Ca2+ sensitizing activities.

Animals↗

No increase in antibodies to six food antigens in Japanese patients with IgA nephropathy.

It has been postulated that mucosa-related antigens are involved in the development of IgA nephropathy. The aim of this study was to elucidate whether food antigens have any relation to IgA nephropathy in Japan. Sera from 15 patients with IgA nephropathy and 15 healthy controls were examined using an enzyme linked immunosorbent assay (ELISA). IgG, IgA, and IgM antibody titers were measured against six food-derived antigens, i.e. rice, soy bean paste, soy sauce, egg yolk, egg white and gluten, all of which are frequently found in the ordinary Japanese diet. No significant differences between patients and controls were found. It was concluded that food antigens appear to have little, if any, relation to IgA nephropathy.

Egg Proteins↗

Molecular cloning of human plasma glutathione peroxidase gene and its expression in the kidney.

A genomic clone containing the human plasma glutathione peroxidase (GSH-Px) gene has been isolated using a rat plasma GSH-Px cDNA as a probe. The partial nucleotide sequence of the clone completely matched the sequence of the human plasma GSH-Px cDNA. The results of Southern blot hybridization indicate that the human plasma GSH-Px gene consists of at least 4 exons and 3 introns, and spans about 12 kb. RNA blot analysis demonstrated that the human plasma GSH-Px gene is expressed in the kidney.

Animals↗

[Preoperative evaluation of patients with disturbed respiratory functions].

It is difficult to predict the occurrence of postoperative pulmonary complications. We analyzed correlation between postoperative pulmonary complications and pre-operative pulmonary functions in patients with severely disturbed respiratory functions; i.e. %VC of under 50% or FEV1% of under 50%, for the past 6 years. Pulmonary complications developed in 15 of the 137 patients studied (10.9%). Of the 108 patients with preoperative %VC of under 50%, pulmonary complications developed in 7 patients (6.5%). Of the 29 patients with preoperative FEV1% under 50%, pulmonary complications developed in 8 patients (27.5%). We found that postoperative pulmonary complications correlate well with preoperative FEV1%.

Aged↗

[Preoperative evaluation of patients with disturbed respiratory functions (II)].

We analyzed correlation between postoperative pulmonary complications and pre-operative pulmonary functions. In patients with severely disturbed respiratory functions; i.e. % VC of under 30% or % FEV1 of under 30%, for the past 6 years. Pulmonary complications developed in 6 of the 18 patients studied (33.3%). Of the 9 patients with preoperative PaO2 of under 70 mmHg, pulmonary complications developed in 6 patients (66.7%). Of the 7 patients with preoperative PaCO2 over 50 mmHg, pulmonary complications developed in 5 patients (71.4%). We found that postoperative pulmonary complications correlate well with preoperative PaO2 and PaCO2, in patients with severely disturbed respiratory functions.

Blood Gas Analysis↗

Rheumatoid factors in patients with minimal change nephrotic syndrome.

Several immunological aberrations, especially T-cell abnormalities, have been shown to be involved in the development of the minimal change nephrotic syndrome (MCNS) although the responsible factors have not been identified. We studied rheumatoid factors (RF), thought to be a consequence of polyclonal B-cell hyperactivation, in sera from patients with MCNS using a sensitive fluorescence immunoassay (FIA). Significant increases of IgG and IgM RFs and marginal increase of IgA RF were observed during the nephrotic stages. Some patients still showed high titers of IgM RF in the early remission phases. The levels of RFs were normalized during complete remission. It was suggested that polyclonal B cell activation might be involved in the development of this disorder along with T cell abnormalities.

Adult↗

Preparation of specific antisera against antigens from pharyngeal cells in patients with IgA nephropathy.

Rabbit antisera were produced against antigens obtained from pharyngeal cells of patients with IgA nephropathy (IgAN). Extracts of pharyngeal cells from patients with IgAN were frozen and thawed, and the supernatants were cocultured with fibroblasts (Vero and Hel cells). Pieces of renal biopsy specimens of the same patients were sectioned and centrifuged. The supernatants which contained IgA were incubated with the fibroblasts, and were stained with FITC-labeled anti human IgA antisera. Two positive (A and B) and one control Vero cell lines were destroyed and centrifuged. The precipitates were injected into rabbits, and rabbit antisera (A, B and control) were produced. Renal tissues from patients with IgAN and proliferative glomerulonephritis without IgA deposition (PGN) were stained with the FITC-labeled antisera. Positive stainings with FITC-labeled antiserum A was observed in 87% and that with FITC-labeled antiserum B in 55% of the patients with IgAN. No positive staining was detected with FITC-labeled control antiserum. There was also no positive staining with these antisera in renal tissues with PGN. The immunological specificity of the antisera was evaluated. It was found that these antisera did not react with complements components or immunoglobulins. The above findings suggested that some antigens from pharyngeal cells were deposited in the glomeruli from IgAN patients.

Animals↗

Responsibility of tRNA(Ile) for spermine stimulation of rat liver Ile-tRNA formation.

To determine whether tRNA or aminoacyl-tRNA synthetase is responsible for spermine stimulation of rat liver Ile-tRNA formation, homologous and heterologous Ile-tRNA formations were carried out with Escherichia coli and rat liver tRNA(Ile) and their respective purified Ile-tRNA synthetases. Spermine stimulation was observed only when tRNA from the rat liver was used. Spermine bound to rat liver tRNA(Ile) but not to the purified aminoacyl-tRNA synthetase complex. Kinetic analysis of Ile-tRNA formation revealed that spermine increased the Vmax and Km values for rat liver tRNA(Ile). The Km value for ATP and isoleucine did not change significantly in the presence of spermine. Furthermore, higher concentrations of rat liver tRNA(Ile) tended to inhibit Ile-tRNA formation if spermine was absent. Spermine restored isoleucine-dependent PPi-ATP exchange in the presence of rat liver tRNA(Ile), an inhibitor of this exchange. The nucleotide sequence of rat liver tRNA(Ile) was determined and compared with that of E. coli tRNA(Ile). Differences in nucleotide sequences of the two tRNAs(Ile) were observed mainly in the acceptor and anticodon stems. Limited ribonuclease V1 digestion of the 3'-32P-labeled rat liver tRNA(Ile) showed that both the anticodon and acceptor stems were structurally changed by spermine, and that the structural change by spermine was different from that by Mg2+. The influence of spermine on the ribonuclease V1 digestion of E. coli tRNA(Ile) was different from that of rat liver tRNA(Ile). The results suggest that the interaction of spermine with the acceptor and anticodon stems may be important for spermine stimulation of rat liver Ile-tRNA formation.

Amino Acyl-tRNA Synthetases↗

Rheumatoid factors and glomerulonephritis.

It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid-phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC-conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN, and the increase was significantly lower in patients with MLN, IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN.

Antigen-Antibody Complex↗

Studies on cardiotonic agents. III. Synthesis of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives.

A series of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives was synthesized and examined for cardiotonic activity in anesthetized dogs. Alkylation of the 2-imidazolidinone (1) afforded the N-alkylated products, while alkylation of the 2-imidazolidinethione (12) afforded the S-alkylated derivatives accompanied with a small quantity of the N-alkylated products. The N-alkylated derivatives showed generally potent activity, and the S-alkylated ones exhibited weak activity. Insertion of an alkyl group between the piperidine and the imidazolidinone moiety generally resulted in a fall in activity.

Animals↗

Studies on cardiotonic agents. IV. Synthesis of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying substituted hydantoin and 2-thiohydantoin rings.

A series of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying substituted hydantoin and 2-thiohydantoin rings was synthesized and examined for cardiotonic activity in anesthetized dogs. Introduction of isopropyl and sec-butyl group at the 5-position of the hydantoin and thiohydantoin rings led to potent inotropic activity. Effects of insertion of an alkyl chain between the piperidine and the hydantoin rings were also examined. The structural requirements necessary for optimal cardiotonic activity within the series were investigated.

Animals↗

Influenza antibody titers after vaccination of chronic renal failure patients; before and during hemodialysis, or on continuous ambulatory peritoneal dialysis.

Anti-influenza antibody (Ab) titers were measured in order to elucidate whether there are any disturbances in Ab production in chronic renal failure (CRF) patients. A total of 55 CRF patients plus 15 normal individuals were vaccinated with influenza vaccine twice, 4 weeks apart of the 55 CRF patients, 15 were not on dialysis, 10 were undergoing hemodialysis (HD), and 30 were on continuous ambulatory peritoneal dialysis (CAPD). Of the 30 CAPD patients, 14 had peritonitis. Serum Ab titers were measured by complement fixation (CF) and hemagglutination inhibition (HI) tests, and IgG and IgM class specific antibodies by ELISA. All groups responded to immunization, but CAPD patients with peritonitis and CRF patients not yet on dialysis did not show a significant elevation in IgM class Ab titers. The number of CAPD patients with peritonitis who achieved positive titers was significantly lower in HI (p less than 0.01) and IgG class antibodies (p less than 0.05) compared with normal controls. Two patients with frequent peritonitis did not show any response to vaccination. It was concluded that patients with renal dysfunction have some abnormalities in Ab production against influenza vaccine, the effects of which were more pronounced in the CAPD patients with frequent peritonitis.

Adolescent↗

Functional interpretation of the kidney juxtaglomerular apparatus using renin immunohistochemistry in Bartter's, pseudo-Bartter's and Conn's syndromes.

A comparative study of renin immunoreactivity in the juxtaglomerular apparatus of the human kidney was performed using the indirect immunoperoxidase method on a random microscopic sections. In renal biopsies taken from a case of Bartter's syndrome and a case of pseudo-Bartter's syndrome, the number of renin-positive juxtaglomerular apparatus (JGA) and the number of renin-positive cells in each JGA were significantly greater than in five renal specimens from control autopsy cases. In Conn's syndrome, none of the glomeruli contained renin-immunoreactive JGA. The number of renin-positive cells/mm2 in the renal cortex in cases of Bartter's and pseudo-Bartter's syndromes were 17.5 and 20.3, respectively, while in the control group, the range was 0.78-1.77 (mean 1.08). Together with other histochemical findings routinely examined in renal specimens, renin immunohistochemistry on random sections may be helpful in diagnostic renal pathology.

Adult↗

[Studies on coagulation-fibrinolytic system in diabetic nephropathy--with reference to plasma TAT and alpha 2PIC].

Coagulation-fibrinolytic system is known to be one of the exacerbating factors in patients with diabetic nephropathy. The aim of the present study was to evaluate whether coagulation-fibrinolytic system in patients with diabetic nephropathy were significantly correlated with the development of this disease using new parameters of plasma thrombin antithrombin III complex (TAT) and plasmin alpha 2 plasmin inhibitor complex (alpha 2PIC). Fifty-six patients with NIDDM were examined. None of these patients showed more than 1.3 mg/dl of serum creatinine levels. These patients were divided into three groups according to the levels of albumin creatinine ratio (ACR) in urine as follows: 1) group I had ACR of less than 30 mg/g.Cr; 2) group II had ACR of greater than 30 mg/g.Cr and less than 100 mg/g.Cr; 3) group III had ACR of greater than 100 mg/g.Cr. Correlations of levels of plasma TAT and alpha 2PIC, levels of HbAlc, duration of diabetes, and presence of retinopathy were determined in these groups. The levels of plasma TAT and alpha 2PIC increased as the levels of urinary ACR increased regardless of presence of retinopathy. The levels of TAT and alpha 2PIC with retinopathy increased compared with those without retinopathy. There was a significantly positive correlation between plasma TAT and alpha 2PIC (r = 0.52, p less than 0.01). The levels of HbAlc and duration of diabetes did not significantly correlate to plasma TAT and alpha 2PIC. These data suggest that the existence of increase in coagulation-fibrinolytic system seem to be one of the exacerbating factors in patients with diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Present status and problems of surgical treatment of non-small cell lung cancer].

Surgical treatment and combined chemotherapy of non-small cell lung cancers during the last 10 years were analyzed. Overall 5 year survival rate of non-small cell lung cancer was 37% and those in stages I, II, IIIA and IIIB were 59%, 33%, 21% and 12%, respectively. Poor outcome in IIIA cases depended strongly on surgical respectability, however, adenocarcinoma cases depended more on the T factor and squamous cell carcinoma depended more on the N factor. IIIA cases, even though resected curatively, showed 10-20% local recurrence, indicating the importance of further improvement of the surgical procedure. In the cases with absolutely non-curative resection tumor remained in mediastinal lymph nodes or organs adjacent to the mediastinum, indicating the necessity of extended combined resection including contralateral mediastinal lymph nodes or organs adjacent to the mediastinum for better results of surgical treatment. Preoperative chemotherapy for the suppression of local recurrence and distant metastasis was significant only in very limited circumstances.

Adenocarcinoma↗

Evidence of enhanced uric acid clearance in macrohematuric patients with IgA nephropathy: prognostic significance of macrohematuria.

Renal handling of uric acid and clinical prognosis following episodes of macroscopic hematuria (EMH) were examined in 113 patients with IgA nephropathy (IgAN). EMH was observed in 34 out of 113 patients (30.1%). The levels of blood urea nitrogen, proteinuria, serum uric acid, beta 2-microglobulin in sera and the degrees of glomerular sclerosis in renal tissues in macrohematuric patients were significantly decreased than those in patients without EMH. The levels of uric acid clearance (Cua) and fractional excretion of uric acid (FEua) was significantly enhanced in macrohematuric patients (p less than 0.01, p less than 0.05, respectively). There was a significant correlation between the tubular atrophy and the levels of Cua in macrohematuric patients (p less than 0.005). The levels of serum creatinine in macrohematuric patients before and after three years were significantly decreased when compared with microhematuric patients (p less than 0.005). It is concluded that enhanced Cua was related to renal tubular atrophy, and EMH did not clinically influence the glomerular deterioration in patients with IgAN.

Adult↗