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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 775 records · Page 43Linked to original sources

Two cases of retained foreign bodies after cholecystectomy: diagnosis by sonography, CT, angiography, and MRI.

We encountered two cases of subphrenic abscesses around surgical sponges that had been left at cholecystectomy. These cases had been operated on either eight years or seven years earlier, respectively. These lesions resembled another diseases, especially, liver tumors. In order to make a differential diagnosis, various diagnostic procedures were carried out. Sonography showed a cystic mass with spongiform structures in one case. But in another case, no information of internal structures could be obtained because of the presence of a calcified wall. On CT, the lesions appeared as either round or elliptic masses that contained calcified foci in both cases. Angiography showed the extended and compressed branches of the hepatic artery. Spotty stains were also observed in one case. This appearance resembled a hepatic tumor. MR demonstrated both T1 and T2 elongated masses. The internal structures of the mass were clearly revealed by the improved version of the MR machine. MR proved to be extremely useful in making a differential diagnosis. It is, however, important to evaluate the findings of these imaging procedures synthetically and in association with a careful review of a patient's prior surgical history.

Aged↗

An application of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a case of hepatocellular carcinoma combined with liver cirrhosis in which leukopenia developed after chemoembolization.

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.

Antineoplastic Combined Chemotherapy Protocols↗

Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin's lymphoma.

We have assessed levels of surface-expressed complement regulatory proteins, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) on cells from patients with hematological malignancies. Neither malignant cells nor unaffected nucleated blood cells from the patients lacked MCP. On the other hand, complete deficiency of DAF was found in 2/10 of non-Hodgkin's lymphoma (NHL), while none of the 38 patients with acute nonlymphocytic leukemia (ANLL) (14 cases), chronic myelogenous leukemia (CML) (6 cases), acute lymphocytic leukemia (ALL) (12 cases) and chronic lymphocytic leukemia (CLL) (6 cases) lacked DAF. The two patients with DAF-negative NHL had no history of paroxysmal nocturnal hemoglobinuria (PNH), and their peripheral blood cells were DAF-positive. One DAF-negative NHL exhibited T cell markers and the other those of B cell. In both cases, treatment of the DAF-negative lymphoma cells with antibody against MCP (M177) followed by Mg(2+)-EGTA-serum resulted in efficient deposition of homologous C3. These results infer that some NHL specifically lack DAF and, through treatment with M177, are targeted by homologous C3.

Antibodies, Monoclonal↗

DHT formation and degradation in cultured human skin fibroblasts: DHT accumulation in the genital skin.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) by 3 alpha-hydroxy-steroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 22 males and 6 females, and from the nongenital skin of 19 males and 9 females with normal gonadal function. The formation of DHT from testosterone (5 alpha-reduction) was significantly greater in fibroblasts from genital skin than in those from nongenital skin in both males (2.15 +/- 1.43 vs 0.81 +/- 0.46 pmol/mg protein/h, mean +/- SD, P less than 0.001) and females (2.52 +/- 1.99 vs 0.69 +/- 0.18, P less than 0.01). Furthermore, DHT formation from 3 alpha-diol (3 alpha-HSOR oxidation) was also significantly greater in genital skin fibroblasts than in nongenital skin fibroblasts of males (5.47 +/- 3.37 vs 2.52 +/- 1.74 pmol/mg protein/h, P less than 0.01). However, the degradation of DHT to 3 alpha- and/or 3 beta-diol (3 alpha- and/or 3 beta-HSOR reductions) was not different between genital and nongenital skin fibroblasts of either males or females. Respective ratios of DHT formation to DHT degradation (5 alpha-reduction/3 alpha-HSOR reduction, 3 alpha-HSOR oxidation/3 alpha-HSOR reduction) were also significantly greater (P less than 0.002) in genital skin fibroblasts than in nongenital skin fibroblasts of males. On the other hand, both DHT formation and degradation were not different between male and female genital skin fibroblasts. These results suggest that the increased production of DHT in genital compared to nongenital skin results from increased 5 alpha-reduction and 3 alpha-HSOR oxidation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Enhancement of lymphocyte-mediated K562 cytotoxicity by antibodies against complement membrane cofactor protein (CD46) and decay-accelerating factor (CD55).

A natural killer (NK) target, K562 (a human erythroblastoid cell line), was found by flow cytometry to express three complement regulatory membrane proteins on its surface: decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and p18 (CD59). We examined the effects of F(ab')2 of polyclonal antibodies raised against DAF and MCP and monoclonal antibody to p18 on the susceptibility of K562 to cytolysis by homologous lymphocytes, granulocytes and complement. C3bi-deposition was induced on K562 when the cells were treated with both anti-DAF and anti-MCP. Lymphocyte-mediated K562 cytolysis was markedly enhanced by these two antibodies whereas anti-p18 barely affected the degree of cytolysis. Complement immunocytolysis, on the other hand, became highest by combination treatment with the three antibodies, although anti-p18 and either anti-DAF or anti-MCP induced little potentiation of cytolysis. Granulocytes showed the least cytolysis and minimal potentiation of lysis by treatment with both anti-DAF and anti-MCP.

Antibodies, Monoclonal↗

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

Animals↗

Protein rotation study of cytochrome P-450 in submitochondrial particles: effect of KCl and intermolecular interactions with redox partners.

The rotational diffusion of cytochrome P-450 in submitochondrial particles (SMP) of bovine adrenocortical mitochondria was measured by detecting the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate the effect of KCl on intermolecular interactions involving cytochrome P-450 and to investigate the interactions of cytochrome P-450 with other redox partners. The rotational diffusion of cytochrome P-450 was significantly dependent on KCl concentration. When the KCl concentration was increased from 0 to 1,000 mM, the mobile population of cytochrome P-450 was increased from 33 to 82%. After removing the KCl, the mobile population of cytochrome P-450 returned to the original 33%. These results suggest that nonspecific protein aggregates are dissociated by the presence of KCl, possibly due to the change in electrostatic interactions, resulting in mobilization of cytochrome P-450. SMP were observed to be nearly free from adrenodoxin and adrenodoxin reductase. The addition of adrenodoxin to SMP increased the mobile population of cytochrome P-450 from 35 to 54%. Further addition of adrenodoxin reductase to SMP containing adrenodoxin immobilized cytochrome P-450 by 6%. The addition of only adrenodoxin reductase to SMP, however, did not immobilize cytochrome P-450. The present results are consistent with our previous observations [Ohta, Y., Mitani, F., Ishimura, Y., Yanagibashi, K., Kawamura, M., & Kawato, S. (1990) J. Biochem. 107, 97-104] that cholesterol-bearing P-450SCC forms a transient ternary association with adrenodoxin and adrenodoxin reductase.

Adrenal Cortex↗

Identification of a cross-linked peptide of a covalent complex between adrenodoxin reductase and adrenodoxin.

A cross-linked complex between bovine NADPH-adrenodoxin reductase (AR) and adrenodoxin (AD) was prepared with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and purified, as described previously [Hara, T. & Kimura, T. (1989) J. Biochem. 105, 594-600]. The covalent complex was S-pyridylethylated and digested with lysylendopeptidase, and the resulting peptides were separated by reversed-phase HPLC to identify the cross-linked peptide. Comparison of the HPLC chromatograms of the peptides showed that (i) two tandem peptides (K-4 and K-5) from AD and a peptide (K-1) from AR were missing in the chromatogram of the peptides of the covalent complex and (ii) a single new peak was observed in the chromatogram of the peptides from the covalent complex. Amino acid composition and sequence analyses showed that the newly observed peptide was a covalently cross-linked peptide formed between a peptide K-4-K-5 (Ile-25-Lys-98) derived from AD and a peptide K-1 (Ser-1-Lys-27) derived from AR, in which an amide bond had been formed between the epsilon-amino group of Lys-66 in AD and the gamma-carboxyl group of Glu-4 in AR. These results indicate that the binding site of AR with AD is localized in the amino-terminal part of AR and that of AD with AR is localized around Lys-66 of AD. The six clustered basic amino acid residues (His-24, Lys-27, His-28, His-29, Arg-31, and His-33) present in the amino-terminal portion of AR and the eight clustered acidic amino acid residues (Glu-65, Glu-68, Asp-72, Glu-73, Glu-74, Asp-76, Asp-79, and Asp-86) present in the middle part of AD may play an important role in the complex formation.

Adrenodoxin↗

Congenital laminar defect of the upper lumbar spine associated with pars defect. A report of eleven cases.

Lumbar spondylolysis generally is considered to be a fatigue fracture of the pars interarticularis, and no unequivocal case of congenital spondylolysis has been reported. The authors describe 11 cases of unilateral spondylolysis (possibly congenital laminar defect associated with pars defect) of the upper lumbar spine. They have roentgenographic characteristics distinct from conventional spondylolysis of the lumbar spine, including hypoplasia of the spinal accessory process, rotation of the spinous process contralaterally to the spondylolysis, and prominent ipsilateral lamina. The anomaly found in these 11 patients probably is congenital, and its clinical significance is not known.

Adolescent↗

High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility.

Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGG) at a dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune haemolytic disease resistant to phototherapy.

Drug Combinations↗

Molecular structure of the replication origin of a Bacillus subtilis (natto) plasmid, pUH1.

The structure of a 2.0-kb BstEII DNA sequence necessary and sufficient for the replication of a 5.7-kb Natto plasmid, pUH1, which is responsible for gamma-polyglutamate production by Bacillus subtilis (natto), has been characterized by using a trimethoprim resistance gene derived from B. subtilis chromosomal DNA as a selective marker. The 2.0-kb DNA sequence contains an open reading frame, rep, stretching for 999 bp; a promoter region for rep expression; and a possible replication origin for the plasmid upstream of the promotor. The predicted Rep protein has highly homologous amino acid sequences with rep14 of pFTB14 in B. amyloliquefaciens, RepB of pUB110, and protein A, which is necessary for pC194 replication in staphylococci throughout the protein molecule, but is not homologous with RepC of staphylococcal plasmid pT181.

Amino Acid Sequence↗

Detection of granulocyte-macrophage colony-stimulating factor in cerebrospinal fluid of patients with aseptic meningitis.

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid from 14 infants and children with meningitis and 6 patients who suffered other diseases besides meningitis was measured by our sensitive enzyme linked immunosorbent assay for GM-CSF. The minimal detection level of GM-CSF was 40 pg/ml. Six of 9 patients (67%) with aseptic meningitis had detectable GM-CSF in cerebrospinal fluid and the concentrations of GM-CSF ranged from 49 to 114 pg/ml (mean 72 pg/ml), whereas none of 5 patients with bacterial meningitis or 6 patients with other diseases besides meningitis had detectable GM-CSF levels. There was no clear correlation between the GM-CSF levels in cerebrospinal fluid and the leukocyte count in either peripheral blood or cerebrospinal fluid, or the concentration of protein or glucose in cerebrospinal fluid.

Child↗

In vivo effect of human granulocyte colony-stimulating factor derivatives on hematopoiesis in primates.

Using cynomolgus monkeys, we studied the hematopoietic effect and antigenicity of the human granulocyte colony-stimulating factor (hG-CSF) derivatives mutated at N-terminal amino acids (NC-59 and KW-2228) and that lacking N-terminal amino acids (M-7) in comparison with intact hG-CSF. These compounds were subcutaneously administered daily into the back of cynomolgus monkeys at the doses of 1 and 100 micrograms/kg for 2 weeks, and withdrawn for 2 weeks (1st course). After that, the same schedule was repeated (2nd course), and intact hG-CSF and KW-2228 were further administered for 2 weeks (3rd course). In the first course, all of the G-CSF derivatives showed excellent dose-dependent granulopoietic activities. In the 2nd course, however, the activities of NC-59 and M-7 were decreased and the elevations of binding and neutralizing antibody titers were observed. On the other hand, KW-2228 showed granulopoietic activities equal to or better than that of intact hG-CSF and had low antibody titer throughout all the courses.

Amino Acid Sequence↗

Interaction of recombinant human interferon-gamma with liposomes.

The interaction of recombinant human interferon-gamma (IFN) with egg phosphatidylcholine liposomes was studied. IFN which binds to liposomes was dependent on the liposomal charge and pH, and a preferential binding was observed in negatively charged liposomes at pH 7.4-10. Electron-microscopic observation showed that the increased liposomal turbidity induced by IFN was due to liposomal aggregation, and the increased turbidity could be decreased by the addition of NaCl. Thus, ionic binding may participate in this interaction. But, when the incubation time was longer, the liposomal aggregation was not decreased by the addition of NaCl, and the leakage of the entrapped marker, calcein, was observed. Electron-microscopic analysis showed that this leakage resulted from the morphological change of liposomes. From these findings, ionic binding may participate in the interaction between IFN and liposomes and then develop a morphological change in negatively charged liposomes under the neutral pH condition.

Fluoresceins↗