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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 253 records · Page 14Linked to original sources

Hepatocellular carcinoma in children with hepatitis B surface antigen.

This study discusses four children of hepatocellular carcinoma (HCC) who were asymptomatic HBsAg carriers or had HBsAg-positive chronic hepatitis for 3 to 11 years before the occurrence of the carcinoma. Three of these four patients were positive for anti-HBe at 3 to 5 years before the diagnosis of hepatocellular carcinoma. Autopsy findings disclosed liver cirrhosis in all the four patients. To the best of our knowledge few reports have documented children in HBsAg carrier status or with HBsAg-positive hepatitis prior to the development of hepatocellular carcinoma. It is emphasized that HBsAg-positive children, with or without detectable hepatic lesions in routine examinations, have a possibility of developing HCC, and should be carefully monitored for long periods.

Adolescent↗

Two fatal cases of hepatitis B virus carriers after corticosteroid therapy for bronchial asthma.

We report two hepatitis B virus (HBV) carriers who had liver failure after withdrawal of corticosteroids (steroids) administered for treatment of serious asthmatic attacks. Liver functions deteriorated 1 to 2 wk after withdrawal of the steroid therapy and liver failure occurred. Steroid readministration and intensive therapy for liver failure did not prevent death. An excessive immune response provoked by steroid withdrawal and decreased reserve capacity due to underlying chronic liver disease were thought to be factors in the liver failure. Caution must be exercised in the administration of steroids to patients with underlying chronic HBV infection to prevent exacerbation of hepatitis. Prompt readministration of steroids is indicated if evidence of liver failure develops.

Aged↗

[Intra-arterial infusion chemotherapy for hepatocellular carcinoma using an implantable drug delivery system].

Intra-arterial chemotherapy and chemoembolization using implantable drug delivery system were performed in sixty-one cases of unresectable hepatocellular carcinoma (HCC). The following results were obtained. (1) The follow-up period was 253 days, and the administrations numbered 13.9 times on average. (2) Response rate was 31.1%. (3) AFP decreased in 80% cases, and PIVKA-II in 83.3% cases. (4) Tumor thrombus in the portal vein disappeared in 4 of 40 cases(10%). (5) Free-CDDP continued for 60 minutes after injection of cisplatin-phosphatidyl-choline-Lipiodol (CPL), and the response rate was 47%. (6) The survival rates were 56% in one year, 25% in two years, and 20% for three years. These results were significantly higher than those of one shot therapy. It is suggested that good therapeutic effects can be obtained by the implantable drug delivery system, and CPL was a useful anticancer agent for the therapy.

Biomarkers↗

Variation of pharmacokinetics after oral administration of slow-release metoprolol tablets and pharmacogenetic considerations.

The maximum plasma concentrations (Cmax) after oral administration of 120 mg tablets of slow-release metoprolol (CAS 37350-58-6) to 75 Japanese healthy male volunteers and 15 arrhythmic patients were measured. Extensive and poor metabolizers after oral administrations of slow-release metoprolol tablets were classified by means of the frequency distribution of Cmax values. In addition, the frequency distribution of Cmax values after oral administration of slow-release metoprolol 120 mg tablets was compared with that of conventional metoprolol 40 mg tablets. 1. Mean +/- S.E. values of Cmax, tmax and AUC0-24 after oral administration of slow-release metoprolol tablets to 75 healthy male volunteers and 15 arrhythmic patients were 95.3 +/- 6.6 ng/ml, 4.4 +/- 0.2 h and 1000.4 +/- 70.9 ng.h/ml, respectively. 2. The number of poor metoprolol metabolizers after the oral administration of slow-release tablets in 75 healthy volunteers and 15 patients was estimated to be 2 subjects (2.2%). 3. The frequency distribution of Cmax values after oral administration of conventional metoprolol tablets was similar to that of slow-release metoprolol tablets. In addition, from the result of this study and that obtained in another study, in which the frequency of poor metoprolol metabolizers in British people has been examined, it is concluded that the frequency of poor metoprolol metabolizers varies between ethnic groups (2.2% in Japanese population and 11.3% in British population.

Administration, Oral↗

Tissue eosinophilia and eosinophil degranulation in syndromes associated with fibrosis.

Eosinophilia has long been associated with endomyocardial fibrosis, but the involvement of the eosinophilia in fibrosis of other organs is unclear. To investigate this question, the authors tested whether tissue eosinophilia and eosinophil degranulation are present in syndromes associated with fibrosis. The authors used an indirect immunofluorescent technique to localize eosinophil granule major basic protein (MBP) in formalin-fixed, paraffin-embedded tissue specimens from 50 patients. Thirty-four specimens were obtained from patients with inflammatory fibrosis: 12 with idiopathic retroperitoneal fibrosis, seven with sclerosing mediastinitis, four with sclerosing cholangitis, and 11 with pulmonary fibrosis. The remaining 16 specimens were obtained from patients with noninflammatory fibrous proliferations: four with keloids, six with scars, three with Dupuytren's contracture and three with dense stromal fibrosis of the breast. Eosinophil infiltration and/or extracellular MBP deposition were observed in 28 of the 34 specimens (82%) from patients with inflammatory fibrosis, including 11 of the 12 cases of retroperitoneal fibrosis, five of the seven cases of sclerosing mediastinitis, all four cases of sclerosing cholangitis, and 8 of the 11 cases of pulmonary fibrosis. In contrast, eosinophil infiltration and MBP deposition were not observed in specimens from the 16 patients with noninflammatory fibrous proliferation (P less than 0.001). These results indicate that eosinophil infiltration and release of a granule protein, namely MBP, commonly occur in inflammatory fibrotic lesions.

Adult↗

The carboxyl terminal amino acid residues of Pseudomonas aeruginosa exotoxin A involved in cell toxicity and pathogenesis, characterized by a neutralizing human monoclonal antibody.

Human monoclonal antibody HI-1A4 (IgG3, lambda) neutralized a toxicity caused by pseudomonal exotoxin A (Ex-A) in cell culture and in vivo, and was effective in experimental Pseudomonas aeruginosa infections in mice. HI-1A4 inhibited an Ex-A catalyzed ADP-ribosylation of elongation factor 2 but did not inhibit an incorporation of toxin into a target cell at all. One molecule of HI-1A4 neutralized at least 2 molecules of Ex-A. HI-1A4 retained its binding activity at pH 4.0. The epitope region for HI-1A4 was demonstrated to be a carboxyl terminal end of amino acid residues 591-613 of Ex-A. HI-1A4 might bind to Ex-A carboxyl terminal region outside a target cell, be incorporated into cells as a complex with Ex-A, and inhibit the intracellular function in which the carboxyl terminal part of Ex-A was involved, resulting in the interruption of intoxication of Ex-A.

3T3 Cells↗

Effects of pH on the cold preservation of the isolated rat heart.

Storage solutions of varying pH have been used for the simple cold preservation of the heart for transplantation. However, few studies have focused on the optimal pH for a storage solution. In the present study, we investigated the effects of storage solutions with 5 different pHs (6.60, 7.00, 7.40, 7.80, and 8.20 at 4 degrees C) on cardiac function, the leakage of cytosolic enzymes, and the myocardial metabolites content. We used the isolated perfused working rat heart model and a 6-hour preservation period in the different storage solutions. We found that cardiac function was best preserved at a pH of 7.00 or 7.80. In the hearts preserved at a pH of 7.00 or 7.80, the leakage of creatine kinase and lactate dehydrogenase was significantly less than at a pH of 7.40 (p less than 0.01). ATP was maintained at a significantly higher concentration in the pH 7.00 solution as compared with the other solutions (p less than 0.01). No significant differences were observed in the creatine phosphate and lactate levels among the five different pH groups. The results showed that the cardiac function and other parameters of cold-preserved hearts were relatively well maintained at both a pH of 7.00 and 7.80, suggesting the possible existence of a biphasic optimum pH for cold preservation.

Animals↗

Purification and characterization of three forms of differently glycosylated recombinant human granulocyte-macrophage colony-stimulating factor.

We have purified recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF) produced in human lymphoblastoid Namalwa cells. From the results of tunicamycin treatment and N-glycosidase F digestion, it was demonstrated that Namalwa-derived hGM-CSF was highly glycosylated at two potential N-glycosylation sites and several O-glycosylation sites as previously shown for naturally occurring hGM-CSF. We classified the hGM-CSF molecules into three groups according to the molecular weight corresponding to the degree of N-glycosylation: the molecules with two N-glycosylation sites occupied (designated 2N), the molecules with either site glycosylated (1N), and the molecules lacking N-glycosylation (0N). Despite such varied degrees of N-glycosylation, almost all molecules were O-glycosylated. To investigate the role of carbohydrate moieties of hGM-CSF, we isolated each form of hGM-CSF and examined its biological properties. The 2N-type showed 200-fold less in vitro specific activity compared with unglycosylated Escherichia coli-derived hGM-CSF, although the activity of the 0N-type was equivalent to that of the E. coli-derived material. The 1N-type showed an intermediate level of activity. However, in terms of clearance from blood circulation in the rat, the 2N-type showed a half-life five times longer than that of the 0N-type and E. coli-derived hGM-CSF. From these findings, we concluded that N-linked carbohydrate moieties of hGM-CSF play conflicting physiological roles in the efficacy of the protein in vivo but that O-linked carbohydrate moieties do not have such effects.

Animals↗

Second cancer after radiation therapy for cancer of the uterine cervix.

Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone. The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively. No significant increase was observed in the risk of second primary cancers when all sites were combined. However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group. A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors. Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field.

Adult↗

Peripheral vascular permeability following a thermal injury to the airway.

Effects of thermal injury to the airway on the vascular permeability in the region of head and neck, were studied in the canine models. The thermal airway injury was produced by an inhalation of a gas burner's flame through the metallic tracheostomy cannula. The changes in vascular permeability were evaluated by calculating the reflection coefficient, which was obtained by the protein washdown technique into lymph. The reflection coefficient after the flame inhalation did not show any increases, while it increased significantly after a histamine infusion into the carotic artery. We concluded, that the vascular permeability in the unburned area does not increase at least in the first 3 hr after a thermal injury to the airway.

Journal Article↗

Prior bleeding enhances the sensitivity of the in vivo micronucleus test.

It has been reported that the sensitivity of the in vivo mouse bone marrow micronucleus test can be increased by inducing erythropoiesis with exogenous erythropoietin prior to treatment (Suzuki et al., 1989). In these studies we demonstrate that removing approximately 0.5 ml of blood from an adult male BDF1 mouse, another method for increasing the rate of erythropoiesis, synergistically increased the frequency of bone marrow micronucleated polychromatic erythrocytes induced by mitomycin C, with maximal enhancement occurring when the mutagen was given 24 h after bleeding. This enhancement response was also demonstrated for benzo[a]pyrene and dimethylnitrosamine but not for 2-acetylaminofluorene. These results indicate that bleeding mice prior to chemical treatment is a simple method for increasing the sensitivity of the micronucleus assay.

Animals↗

Mechanism of protein folding. II. Lysozyme and phospholipase.

Refolding of hen egg-white lysozyme assuming the formation of secondary structures (alpha-helices and beta-sheets) is carried out by the method presented in the previous paper (N. Saitô et al., Proteins; Struct. Funct. Genet. 3 (1988) 199-208). To do this, the hydrophobic interactions between the hydrophobic residues which are located at the key positions for folding and can be identified without the knowledge of the native structure, and the nonbonded interactions between every pair of atoms (except hydrogen) or groups are introduced successively from short- to medium-distance pairs. The search for the energy minimum by these interactions can afford a conformation of especially the mutual arrangements between neighboring secondary structures. When these local structures are accomplished, some of the long-distance amino-acid pairs come close together and then the possible interactions (hydrophobic, nonbonded) are introduced. The three-dimensional structure of lysozyme thus obtained is shown to have locally correct arrangements of the secondary structures, but mutual relations between long-distance parts of the chain are not similar to the native structure. The introduction of disulfide bonds between appropriate cysteine residues is necessary to reach the native structure. The choice of cysteine pairs for disulfide bonding is made by the criterion given in the paper to follow (K. Watanabe, A. Nakamura, Y. Fukuda and N. Saitô. Biophys. Chem. 40 (1991) 293). The same treatment is applied to bovine pancreatic phospholipase with 7 disulfide bonds. The formation of the antiparallel beta-structures from neighboring beta-strands and the problem of the folding order are also discussed.

Amino Acid Sequence↗

Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor.

To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis.

Adolescent↗

Association of hiatus hernia with postero-lateral diaphragmatic hernia (Bochdalek's hernia).

A boy with hiatus hernia following the repair of the left postero-lateral diaphragmatic hernia (Bochdalek's hernia) was reported. At the age of one month, the repair of Bochdalek hernia was performed with transabdominal approach. At that time the stomach was located in the normal position. Eight days after the repair he developed vomiting and hiatus hernia was revealed by barium esophagram. Antireflux surgery was required because there was no response to the conservative management for two months. Esophageal pH study and manometric study were very useful for the diagnosis of hiatus hernia or GER and the evaluation of antireflux surgery.

Abnormalities, Multiple↗

Production and characterization of human monoclonal antibody recognizing the N-terminal residues of Pseudomonas aeruginosa exotoxin A.

Human cell lines producing monoclonal antibodies (MAbs) against Pseudomonas aeruginosa exotoxin A were established by EBV transformation followed by cell fusion. Monoclonal antibody FK-001, IgM (mu, kappa), was demonstrated to be specifically reactive with exotoxin A in ELISA and immunoblotting, by recognizing N-terminal 16 amino acid residues of exotoxin A as an epitope. This epitope region belongs to domain I which is required for the binding of exotoxin A to the receptor on target cells. FK-001 showed a partial neutralizing activity for cell toxicity caused by exotoxin A and appeared to be effective against exotoxin A-producing P. aeruginosa infection in mice. A line of evidence suggests that monoclonal antibody FK-001 neutralizes exotoxin A-induced cell toxicity by the interference of accessibility and/or binding of exotoxin A to animal cell receptors.

ADP Ribose Transferases↗

A protective human monoclonal antibody directed to the outer core region of Pseudomonas aeruginosa lipopolysaccharide.

The protective activity against experimental Pseudomonas aeruginosa infection of a human monoclonal antibody, MH-4H7, which is thought to recognize L-rhamnose and its neighboring residues in the outer core region of P. aeruginosa lipopolysaccharide and which binds to strains of Homma serotypes A, F, G, H, K, and M, was studied in normal, burned, and leukopenic mice. MH-4H7 at doses of 0.1 to 1.0 micrograms per mouse (5 to 50 micrograms/kg) was effective against serotype A, F, G, H, and K clinical isolates of P. aeruginosa tested in normal mice but not against strains of serotype M, B, E, or I. The 50% protective doses were calculated to be 0.01 and 0.1 micrograms per mouse against challenge with serotype G strains and 3 to 8 micrograms per mouse against challenge with serotype A strains. MH-4H7 promoted macrophage-mediated opsonophagocytosis of serotype A, F, G, H, and K strains but not of serotype M strains. The opsonophagocytic activity, expressed as the reduction rate of viable bacteria in the presence of MH-4H7, macrophages, and complement, was higher against serotype G strains (more than 90%) than against serotype A strains (60 to 80%) and serotype F, H, and K strains (50 to 86%). It was correlated with the protective activity but not with the binding intensity of MH-4H7 to the organisms. In addition, burned and leukopenic mice as well as normal mice infected with serotype G strains recovered from a very low dosage of MH-4H7. Thus, a monoclonal antibody directed to the outer core region of P. aeruginosa lipopolysaccharide was effective against infection with a wide range of O-serotype strains of P. aeruginosa.

Animals↗

Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa.

Three stable hybridoma cell lines, IN-2A8, IN-5D6, and ZI-3A8, that secrete human monoclonal antibodies (MAbs) specific for b-type flagella of Pseudomonas aeruginosa were established by fusing peripheral blood lymphocytes from healthy volunteers with murine myeloma P3X63-Ag8.653 cells. The immunoglobulin M MAbs reacted specifically with flagellin (Mr, 52,000) by Western blotting (immunoblotting) analysis and bound specifically to clinical isolates belonging to Homma serotypes A, B, H, I, and M at frequencies of 58, 50, 46, 30, and 35%, respectively, but did not bind to any serotype E or G isolates. Overall, the MAbs bound to 31% of the clinical isolates. MAb IN-2A8 strongly protected burned mice challenged with P. aeruginosa bearing b-type flagella from death following parenteral administration of 0.1 microgram per mouse. This MAb also inhibited P. aeruginosa colony spreading in soft agar at a concentration of more than 1 microgram/ml but only slightly enhanced opsonophagocytosis by human polymorphonuclear leukocytes. A line of evidence suggests that the potent in vivo activity of MAb IN-2A8 in the burned-mouse model is likely to be caused by its inhibition of bacterial motility after binding to flagella.

Animals↗