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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 361 records · Page 20Linked to original sources

Elevation of immunoreactive serum Mn-superoxide dismutase in patients with acute myocardial infarction.

Serum Mn-superoxide dismutase (Mn-SOD) levels were determined in patients with acute myocardial infarction by an enzyme-linked immunosorbent assay (ELISA). The serial determinations performed on 29 patients with acute myocardial infarction indicated that Mn-SOD appears in serum in a biphasic manner; an early small elevation was observed at approximately 16.2 (+/- 7.3) h and a high elevation at approximately 108 (+/- 20.6) h after the onset of symptoms. A negative correlation was found between the maximum value of the late elevation of Mn-SOD and left ventricular function. Plasma levels of tumor necrosis factor-alpha (TNF-alpha) were also elevated in acute myocardial infarction. These facts suggest that TNF-alpha secretion from the infarcted area resulted in the production of Mn-SOD and that the induced Mn-SOD was released from myocytes into serum through damaged membranes, resulting in the late elevation.

Adult↗

[A report of two cases of cervical necrotizing soft-tissue infection].

Two recent cases of cervical necrotizing soft-tissue infection are herein presented. Case 1. A 52-year-old man with uncontrolled diabetes was hospitalized because of an erythematous swelling of the left side of his neck and high grade fever. Fetid yellowish pus exuded from the left parotid area. The swelling extended from the left temporal area to the left supraclavicular fossa, with necrosis of the parotid gland, sternocleidomastoid, masseter and a portion of the strap muscles. Wound cultures revealed Staphylococcus aureus and alpha-hemolytic streptococcus. No anaerobic bacteria were detected. Treatment consisted of intravenous administration of antibiotics, control of diabetes with insulin, and debridement of the necrotic tissue, which left an epidermal defect in the initially swollen area. Transfer of a forearm free flap was done after the growth of healthy granulation tissue over the affected area. Case 2. A 55-year-old woman with rheumatoid arthritis was transferred to our hospital after tracheotomy performed in another hospital because of dyspnea due to severe crepitant swelling of her cheeks and submandibular areas bilaterally, and her left temporal area. A copious amount of fetid pus exuded from the incisions made in the left temporal area, left cheek, and right submandibular area. There were bilateral diffuse rales. Culturing the pus revealed alpha-hemolytic streptococci, while MRSA and Pseudomonas aeruginosa were detected from cultures of sputum. No anaerobic bacteria were found. After intravenous administration of antibiotics, infected wounds and pneumonia were ameliorated, and necrotic subcutaneous tissue and fascia were debrided. The patient was discharged with a residual depression in her left cheek and a scar on her left temporal area.

Connective Tissue Diseases↗

[Effect of HLA matching in renal transplantation].

Evaluation of HLA-matching is useful in determining graft function and survival in a recipient in cadaveric renal transplantation. The effects of HLA on graft function, which serum creatinine indicative of, and graft survival were examined in both living and cadaveric transplantation in 280 Japanese renal transplants performed at Osaka University and Osaka Prefectural Hospital between October, 1982 and December, 1991 (cadaver 68, living 212). HLA-DR mismatch had a strong effect in living transplants, whereas no disparity was found in cadaver transplants with HLA-DR mismatch. HLA-B, DR mismatch had more effect than HLA-DR in cadaver transplants, and the same effect as HLA-DR in living transplants. HLA-AB affected graft function. It can be used to predict the effect of long-term graft survival. The HLA-haplotype match had the strongest association with graft survival and function in both cases of living and cadaver transplants. HLA-haplotypes of a cadaveric donor and a recipient were presumed by means of the linkage disequilibrium. These findings showed that HLA-matching, especially of haplotype, is an essential factor in relatively low risk renal transplant survival and function. 1-haplotype-matched transplantation, determined by the family study or presumed by the linkage disequilibrium is recommended if not 2-haplotype matched.

Adult↗

[Proton pump inhibitor for maintenance therapy of peptic ulcer].

The strategy for peptic ulcer therapy has been changing with the clinical application of the gastric proton pump inhibitor (PPI). In Japan, Miyoshi et al and Takemoto et al reported an earlier reepithelialization of peptic ulcer with omeprazole (OME) or lansoprazole (LAN) than famotidine (FAM). Miyoshi et al also reported that there was no significant difference between OME and FAM in ulcer relapse rate during a one year follow-up period. Therefore, there were two problems. One is application of PPI for prevention of ulcer relapse, and the other is the more accurate diagnosis of ulcer healing. Application of PPI for maintenance therapy is not yet realized in Japan, but, Lauritsen et al had already reported on the efficacy and safety of OME, 20 mg, three days a week and 10 mg, daily in prevention of duodenal ulcer relapse. Reepithelialization (red scar) is already established as a starting point of maintenance therapy, and from Miyake's report, a white scar is believed a favorable (non relapsing) end point.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha].

Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.

Animals↗

[Kallmann's syndrome in a child--a case report].

The patient was a male child 6 years and 6 months old. He visited our hospital because of bilateral cryptorchism and true phimosis. Since he was found to have fairly small testis, micropenis, and anosmia, endocrinological examination was performed. The plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were at the lower limit of normal values. LH gave a low reaction to the LH-releasing hormone test, while the reaction of FSH was near the lower limit of normal values. In the human chorionic gonadotropin test, there was no rise in the plasma levels of testosterone. Nor was there any reaction to the venous olfactory test with Alinamine (thiamine propyldisulfide). Accordingly, the patient was diagnosed as having Kallmann's syndrome. A search of the literature reveals few reports that deal with Kallmann's syndrome in infancy. Early diagnosis seems to be of significance, however, to institute early appropriate treatment to prompt the development of proper secondary sexual characteristics and ensure normal future fertility.

Child↗

Resolution of acute hepatitis C after therapy with natural beta interferon.

To test whether interferon can prevent acute non-A, non-B hepatitis from becoming chronic, a prospective controlled trial was conducted in 25 patients; 11 were treated for an average of 30 days with a mean of 52 megaunits of interferon and 14 acted as controls. 4 patients in the treatment group who continued to have raised serum aminotransferase concentrations after a year's follow-up were given a second course of interferon. Follow-up at 3 years has revealed that all but 1 of those treated showed normal serum aminotransferase, whereas only 3 controls showed such change (p less than 0.02). Serum hepatitis C virus RNA became undetectable in 10 of 11 treated and in only 1 of 12 control patients, which suggests that interferon prevents the progression of acute non-A, non-B hepatitis to chronicity by eradicating HCV.

Acute Disease↗

Different effects of DNA adducts induced by carcinogenic and noncarcinogenic azo dyes on in vitro DNA synthesis.

M13mp10 phage DNA modified with the carcinogen 3-methoxy-4-aminoazobenzene (3-MeO-AAB) or the noncarcinogen 2-methoxy-4-aminoazobenzene (2-MeO-AAB) was used as a template for E.coli DNA polymerase I. Analysis of the reaction products on DNA sequencing gels showed that with both types of compound the induced lesions blocked DNA synthesis, mainly at one base prior to guanine adducts, but that the inhibition by 3-MeO-AAB-adducts was substantially greater than that by 2-MeO-AAB-adducts. Thus different effects on DNA replication between 3-MeO-AAB- and 2-MeO-AAB-adducts might be a reflection of differences in their carcinogenic potency.

Bacteriophages↗

Spectrophotometrical and immunochemical studies on the conformational changes in poly(dG-dC).poly(dG-dC) after modification by 4-hydroxyaminoquinoline 1-oxide.

Poly(dG-dC).poly(dG-dC) was modified by the reaction with 4-hydroxyaminoquinoline 1-oxide (4HAQO) in the presence of seryl-AMP. The conformations of 4HAQO-modified poly(dG-dC).poly(dG-dC) and of poly(dG-dC).poly(dG-dC) were studied by circular dichroism spectra under various salt concentration conditions. 4HAQO residues to guanine bases are inefficient in inducing the transition of poly(dG-dC).poly(dG-dC) from B-form to Z-form conformation. We have elicited monoclonal antibodies against 4HAQO-poly(dG-dC).poly(dG-dC). They were characterized using enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and binding to supercoiled DNA. These antibodies reacted with 4HAQO-poly(dG-dC).poly(dG-dC) specifically but not with 4HAQO-modified DNA or poly(dG).poly(dC). However, they cross-reacted with N-acetoxy-2-acetylaminofluorene-modified poly(dG-dC).poly(dG-dC) in Z-form conformation. These monoclonal antibodies may recognize a unique conformation in poly(dG-dC).poly(dG-dC) after 4HAQO modification.

4-Hydroxyaminoquinoline-1-oxide↗

32P-postlabeling analysis of DNA adducts in rat livers after treatment with genotoxic and non-genotoxic 4-aminoazobenzene derivatives.

Formation of hepatic DNA adducts was studied in rats following intraperitoneal administration of a hepatocarcinogen, 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and a non-hepatocarcinogen, 2-methoxy-4-aminoazobenzene (2-MeO-AAB). The 32P-post-labeling assay revealed 3-MeO-AAB to give more than 20-fold higher amounts of DNA adducts than did 2-MeO-AAB. Furthermore, five adducts, one of which accounted for over 70% of the total modified bases, were found in DNA from 3-MeO-AAB-treated rats, whereas only one adduct was apparent in 2-MeO-AAB-treated DNA. Our data thus suggested that the difference in hepatocarcinogenic activity between 3-MeO-AAB and 2-MeO-AAB might be, at least in part, dependent on quantitative and qualitative differences in their azo dye-DNA adduct formation in the rat liver.

Animals↗

Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.

We have isolated and characterized genomic DNA clones encoding rabbit phospholamban. Only a single gene for phospholamban was detected in the rabbit genome. The phospholamban gene of 13.2 kilobases contains only one 10.5-kilobase intron, which separates exonic sequences located in the 5'-untranslated region. Two potential transcription initiation sites were mapped to 335 and 185 nucleotides upstream from the translation initiation site in the mRNA or 239 and 89 nucleotides upstream from the exon/intron boundary. Phospholamban gene expression in various smooth muscle tissues, as well as in cardiac and slow twitch skeletal muscle, was detected by Northern blotting. The phospholamban gene was mapped to human chromosome 6, using a human phospholamban cDNA.

Adenosine Triphosphatases↗

Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases.

Five intraductal papillary neoplasms of the pancreas were analyzed for the presence of the Ras gene mutations. Three (60%) of the five neoplasms showed point mutations at K-ras codon 12. This incidence of the mutations was rather low compared with that found with ordinary pancreatic adenocarcinoma. The presence of the mutations did not correlate with the severity of cellular atypia, but was apparently related to the size of the tumor. The two neoplasms that had no mutations were smaller than the others that had mutations. The analysis suggested that Ras gene mutation is not the first genetic alteration of tumor progression, but that it occurs during the development of neoplasms of the pancreas.

Adenocarcinoma, Papillary↗

Randomized, double-blind, placebo-controlled trial of eight-week course of recombinant alpha-interferon for chronic non-A, non-B hepatitis.

Forty-nine Japanese patients were enrolled in a randomized, placebo-controlled, double-blind trial of alpha-interferon for chronic non-A, non-B hepatitis: 24 patients received 3 million units of recombinant human alpha alpha-interferon (alpha-2a) thrice weekly for eight weeks, and 25 patients received placebo in a similar schedule. The mean serum alanine aminotransferase (ALT) dropped from 155 +/- 91 (SD) to 69 +/- 72 during interferon treatment, but remained unchanged (158 +/- 140 to 147 +/- 130) during placebo treatment (P less than 0.001). Serum ALT level fell to the normal range in 29% of interferon-treated patients, but in only 4% of placebo-treated patients. Pre- and posttreatment liver biopsies were obtained in all but one case. Average histological activity indices (HAI) were markedly improved in the interferon-treated group (9.5 +/- 3.7 to 7.0 +/- 4.3), but were unchanged in the placebo group (8.5 +/- 4.3 to 8.5 +/- 4.9). In addition, we compared the efficacy of interferon treatment between anti-hepatitis C virus (HCV) antibody positive and negative groups. Biochemical and histological improvements were similar and statistically significant in patients with and without antibody to hepatitis C virus. These data indicate that a eight-week course of alpha-interferon induces biochemical and histological improvement in more than half the patients with chronic non-A, non-B hepatitis.

Alanine Transaminase↗

Emergency colonoscopy for the diagnosis of lower intestinal bleeding.

During the past 8 years, we performed emergency colonoscopy in 206 patients in whom severe bloody stools suggested bleeding of the lower digestive tract. The site of hemorrhage could be determined in 184 patients (89.3%). In cases with severe hemorrhage, the causes were stercoral rectal ulcer and bleeding from the small intestine or the upper GI tract. The bleeding tended to be mild in patients with other colon diseases. Determination of the bleeding site was impossible or difficult when a large amount of blood was present in the intestinal lumen or the blood was completely discharged. These observations suggest that emergency colonoscopy is effective for determination of the site of GI bleeding, but improvements are considered to be needed especially in the preparation for the examination in patients in critical condition.

Adult↗

Detection and direct sequencing of hepatitis B virus genome by DNA amplification method.

Hepatitis B virus (HBV) DNA was detected with amplification by the polymerase chain reaction method. Cloned HBV DNA equivalent to one virus genome (3 x 10(-6) pg) was detectable by ethidium bromide staining after 50 cycles of polymerase chain reaction. By applying this method, presence of HBV DNA was studied in 23 hepatitis B surface antigen (HBsAg)-positive and 11 HBsAg-negative sera from patients with chronic liver disease. Hepatitis B virus DNA was positive in 8 of 8 hepatitis B e antigen (HBeAg)-positive, in 2 of 2 HBeAg- and anti-HBe-negative, and in 12 of 13 anti-HBe-positive sera. Hepatitis B virus DNA was undetectable in all HBsAg-negative sera even with amplification. To confirm specificity, the amplified product was directly sequenced. Sequences around 122nd and 160th codon of HBs gene, which determines subtypes d/y and w/r, respectively, were analyzed. The results were compatible with recent reports regarding the relation between HBV subtypes and HBV DNA sequence at those codons. Hepatitis B virus DNA could be detected at the level of one virion by gene amplification method, and its sequence could be determined by direct sequencing in a few days.

Base Sequence↗

Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma.

Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations. The site of the mutations is localized in codon 12 of K-ras gene. Such high incidence and localization of the ras gene mutations have not been observed in any other human malignancies. Polymerase chain reaction and direct sequencing method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small quantities of specimens obtained from needle biopsies and aspirate samples for pathological diagnosis. All the materials obtained from 12 patients with pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6 patients with chronic pancreatitis showed no mutations. In several cases using the mutations of K-ras gene as a marker, this analysis supplemented conventional pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The analysis of ras-gene mutations was useful for the clinical diagnosis of pancreatic adenocarcinoma.

Adenocarcinoma↗

Effects of monoclonal antibody against phospholamban on calcium pump ATPase of cardiac sarcoplasmic reticulum.

A monoclonal antibody against phospholamban has been reported to increase Ca2+ uptake by cardiac sarcoplasmic reticulum. We compared the effect of this antibody on Ca2+ pump ATPase activity of cardiac sarcoplasmic reticulum vesicles to the effect of cAMP-dependent phosphorylation of phospholamban. The antibody markedly stimulated the Ca(2+)-dependent ATPase activity in parallel to the increase in Ca2+ uptake by cardiac sarcoplasmic reticulum. When the Ca(2+)-dependent profile of the ATPase activity was compared, the KCa was shifted from 1.24 to 0.62 microM by the antibody, whereas cAMP-dependent phosphorylation of phospholamban shifted the KCa to 0.84 microM. When cardiac sarcoplasmic reticulum vesicles were treated with both cAMP-dependent protein kinase and the antibody, the stimulation was the same as that with the antibody alone. Thus, the Ca2+ pump ATPase seems to be fully activated by the antibody. The stoichiometry between Ca2+ uptake and ATPase rate was around 1 and no significant change was observed by the treatment with the antibody. Therefore, the stimulation of Ca2+ uptake of cardiac sarcoplasmic reticulum by the antibody occurred by the stimulation of Ca2+ pump ATPase, not by other mechanisms such as channel activity of phospholamban. These results indicate that the binding of the antibody to phospholamban produces essentially the same mode of action on Ca2+ pump ATPase as that of phospholamban phosphorylation. The antibody and phospholamban phosphorylation appear to release the inhibitory action of phospholamban on Ca2+ pump ATPase, resulting in the stimulation of Ca2+ pump.

Animals↗

Transcardiac alteration of neutrophil function before and after coronary thrombolysis in human myocardial infarction.

We examined function of isolated neutrophils taken from aorta and coronary sinus before and after thrombolytic reperfusion in 17 patients whose infarct-related coronary arteries were totally occluded. Before reperfusion in left coronary artery disease, free radical generation by activated neutrophils in coronary sinus, assessed by ferricytochrome c reduction (phorbol myristate acetate, 10 ng/ml) and luminol-enhanced chemiluminescence (A23187, 2 microM), was reduced by 20% (P less than 0.05) and 30% (P less than 0.05), respectively, compared with those in aorta. Neutrophil aggregation (A23187, 10 microM) and chemotactic activity (formyl-methionyl-leucyl-phenylalanine, 5 microM) were also reduced in coronary sinus by 21% and 20%. After reperfusion the extent of such neutrophil function in coronary sinus recovered and was similar to that in aorta. There were no significant differences between neutrophil counts in aorta and coronary sinus before and after reperfusion. In right coronary artery disease, no significant changes were seen in these functions of neutrophils of aorta and coronary sinus before and after reperfusion. These results indicate that function of neutrophils passing through coronary circulation fluctuated significantly in association with reperfusion, suggesting (1) factor(s) that depress neutrophil function are produced in coronary circulation during myocardial ischemia and their effects are overcome after reperfusion or (2) activated neutrophils, trapped in the ischemic coronary bed, are washed out to coronary sinus after reperfusion.

Chemotaxis, Leukocyte↗