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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 235 records · Page 13Linked to original sources

[Postoperative complications of anterior and middle skull base surgery].

The authors present the postoperative complications of skull base surgery based on a 10-year experience with 26 patients operated on via the supraorbital trans-basal or orbitozygomatic approach. The lesions included 19 malignant tumors and seven benign tumors. Postoperative cerebrospinal (CSF) leak occurred in one of the two patients in whom the dural defects were repaired with a fascia lata graft. None of the remaining 24 patients who were repaired with a musculopericranial flap suffered postoperative CSF leak. Three patients developed epidural abscess, but no infection was seen in the patients who had been reconstructed with a vascularized musculo-cutaneous flap to occlude the dead space. Preoperative radiation therapy correlated with a high incidence of postoperative infection. Cranial nerve deterioration or palsy occurred in four patients. Intraoperative injury of the internal carotid artery occurred in one patient who developed severe neurological deterioration. After an average follow-up period of 40 months (range 12 to 109 months), 68% of patients with malignant tumors and 100% of patients with benign tumors were alive with no evidence of recurrence.

Abscess↗

[Hereditary progressive dystonia with marked diurnal fluctuation--clinical features and GTP cyclohydrolase I gene mutations].

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a disorder characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of levodopa. Recently the GTP cyclohydrolase I(GCH-I) gene was isolated as the first causative gene for HPD. We analyzed the GCH-I gene in 8 clinically diagnosed HPD patients and found different point mutations in GCH-I gene in 3 subjects. The clinical features of these patients considerably resembled each other. Our results imply that although clinically diagnosed HPD subjects could present diverse symptoms, patients with a mutant GCH-I gene might share homogeneous clinical manifestations.

Adolescent↗

[Short-term intensive treatment for acute myelogenous leukemia (excluding M3 subtype) in adults].

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

Aclarubicin↗

[Myelodysplastic syndrome with monosomy 7 following combination therapy with granulocyte colony-stimulating factor, cyclosporin A and danazole in an adult patient with severe aplastic anemia].

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75 mg (1.25 mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

Adult↗

A cell surface antigen that cross-reacts with My4, a monoclonal antibody to CD14, is expressed on human monoblastic cell line U937, B-lymphoma cells, and polymorphonuclear leukocytes.

The CD14 antigen was originally identified on monocytes as a differentiation marker and usually detected by a panel of monoclonal antibodies, including My4 and LeuM3. Recent studies have shown that CD14 antigen is expressed on Langerhans cells, a subject of normal B-lymphocytes, neutrophils, and subtypes of B-cell non-Hodgkin's lymphomas. These antigens, however, react with My4, but not with LeuM3, and the reason for this has not been elucidated. In this study, we found that similar My4+/LeuM3- epitopes are expressed on the human monoblastic cell line, U937. Northern blotting demonstrated that the U937 cells express neither 1.4 kb CD14 transcripts nor possible alternative spliced forms of CD14 transcripts. The molecule was resistant to phosphatidylinositol specific phospholipase C, which effectively hydrolyzes glycosyl-phosphatidylinositol anchored protein, decay accelerating factor, on the same cells. Lipopolysaccharide, which down-regulates the expression of CD14 on monocytes, did not alter the expression of the molecule. We concluded that the My4+/LeuM3- molecule on U937 cells is not CD14 antigen but another surface protein. A similar molecule was also detected on B-lymphoma cells from a patient with non-Hodgkin's lymphoma and on polymorphonuclear leukocytes from healthy donors.

Antibodies, Monoclonal↗

[Efficacy and safety of sulbactam/cefoperazone for hepato-biliary infections].

We studied efficacy and safety of sulbactam/cefoperazone (SBT/CPT) in the treatment of biliary tract infections in hospitalized patients at 26 hospitals from February 1993 to March 1995. Secondary to dropout, 273 out of 338 patients entered in the study were evaluated, 127 patients with cholecystitis, 132 patients with cholangitis, and 14 patients with liver abscesses. Of these, 93 patients (34.1% had malignancy as an underlying disease. SBT/CPZ had an efficacy of 79.9% (218 patients; excellent: 52, good: 166), with the efficacy in patients with cholecystitis, cholangitis and liver abscess at 89.0% (113 patients), 77.3% (102 patients and 21.4% (3 patients), respectively. A significant difference (p < 0.05) was observed in the efficacy rates of patients with (59 patients [63.4%]) and without malignancy (159 patients [88.3%]). A total of 84 strains were isolated from bile specimens of 53 patients, and the major isolates were Escherichia coli, Pseudomonas aeruginosa and Enterococcus spp. Two or more bacterial strains were isolated simultaneously in 20 patients. Mild or moderate side effect (allergic reaction including rash etc.) were noted in 4 patients (1.18%), and laboratory abnormalities (increased GOT, etc.) were in 16 patients (4.71%) out of the total 338 patients. This study clearly demonstrated that SBT/CPZ retains its excellent clinical efficacy and safety profile, throughout its use over the past decade.

Adolescent↗

The carboxyl-terminal region is essential for Sec-A dimerization.

SecA, comprising 901 amino acid residues, exists as a dimer. By means of size exclusion chromatography and chemical cross-linking analysis, five truncated SecA derivatives were examined to identify the region of SecA essential for dimer formation. Among them, only N95 (delta 832-901) retained SecA activity. N95 existed as a dimer, indicating that the carboxyl-terminal three cysteine residues are dispensable for physiological dimerization. Both N76 (delta 675-901) and N66 (delta 583-901) existed as monomers. Monomeric N76 was able to bind to ATP, indicating that the dimerization of SecA is not a prerequisite for ATP binding. However, the rate of ATP hydrolysis by N76 was 25% of that by SecA. C53 (delta 1-437) and C28 (delta 1-661) formed dimers irrespective of the presence or absence of 2-mercaptoethanol. C28, but not C53, also existed as an oligomer in the absence of 2-mercaptoethanol, suggesting that the 438-661 region present in C53 prevents intermolecular disulfide bond formation at the carboxyl-terminal cysteine residue. From these results, the region essential for the physiological dimer formation was concluded to be located in the 662-831 region of SecA.

Adenosine Triphosphatases↗

Molecular cloning and expression of a novel peptide (LN1) gene: reduced expression in the renal cortex of lupus nephritis in MRL/lpr mouse.

A gene has been identified by mRNA differential display whose expression is reduced in the renal cortex of MRL/lpr mouse. The nucleotide sequence of the cDNA contains an open reading frame that encodes a protein of 338 amino acids (termed LN1). In situ hybridization showed that LN1 mRNA is present in glomeruli, and a 39 kDa protein was detected in the kidney by immunoblot. A human LN1 cDNA was also isolated, the deduced amino acid sequence of which is 78% identical to that of mouse LN1. Although the function of LN1 remains to be elucidated, its reduced expression may contribute to the pathogenesis of lupus nephritis.

Amino Acid Sequence↗

Secondary structure and thermostability of the photosystem II manganese-stabilizing protein of the thermophilic cyanobacterium Synechococcus elongatus.

The secondary structure of the manganese-stabilizing protein of the thermophilic cyanobacterium Synechococcus elongatus in solution was investigated by Fourier-transform infrared (FT-IR) and circular dichroism (CD) spectroscopies. Both methods showed a high proportion of disordered structure (40-43%) and a relatively small amount of beta-sheet (23-24%) and alpha-helix (17-19%). The conformation of the protein remained essentially unchanged at temperatures up to 70 degrees C. Unfolding of the protein occurred at higher temperatures and FT-IR spectroscopy revealed that beta-sheet was more strongly unfolded than alpha-helix at 76 degrees C. The protein largely lost the ordered secondary structures at 90 degrees C, but, when cooled down to 30 degrees C, regained its original conformation. Thus, the cyanobacterial protein is very thermostable and its denaturation at an extremely high temperature is reversible.

Bacterial Proteins↗

In vivo visualization of hippocampal cells and dynamics of Ca2+ concentration during anoxia: feasibility of a fiber-optic plate microscope system for in vivo experiments.

The feasibility of a fiber-optic plate (FOP) microscope system employing a bundle of optical fibers and videomicroscopy for in vivo experiments was investigated. The FOP used here consisted of optical fibers 3 microns in diameter. By inserting the FOP into an animal, optical signals from the deep-lying tissue invisible from the surface could be obtained as two-dimensional images. Using this system, hippocampal cells stained with a fluorescent dye in an anesthetized rat were visualized. Elevation of intracellular free calcium concentration ([Ca2+]i) in the hippocampus of the rat during anoxic exposure was also detected with a fluorescent indicator dye. These results showed that the FOP microscope system was sufficiently applicable to in vivo experiments for studying tissue structure and physiological activity even in the deep regions with fluorometric techniques.

Animals↗

An improved quantitative RT-PCR fluorescent method for analysis of gene transcripts in the STS-65 space shuttle experiment.

We describe a reverse transcription polymerase chain reaction (RT-PCR) technique using fluorescent dUTP to examine changes in mRNA level in samples. In this procedure, the amplified product is identified by the fluorescent detection system in an automated DNA sequencer, and if the MW of the DNA/RNA or the fluorescent dye is different, several samples can be analyzed in a single lane. The basis for this technique is similar to that of radiolabeled methods, and we applied this technique for the comparison of the expression level of the rat c-myc gene in osteoblasts exposed to microgravity and unit gravity conditions. Using the fluorescent- and radiolabeled methods, the level of rat c-myc mRNA were compared quantitatively and the results demonstrated that the c-myc expression level was not altered by microgravity. Therefore, this fluorescent RT-PCR technique is useful for gene expression analysis particularly when the samples are limited, such as in space flight experiments. The method also allows for rapid assessment of mRNA changes in many samples simultaneously.

Animals↗

Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat osteoblasts: role in bone demineralization.

It has been suggested that microgravity alters bone metabolism. Evidence for this phenomenon includes the negative calcium balance and decreased bone density in astronauts, as well as, inhibition of bone formation in rats flown for 2 to 3 weeks. However, the specific mechanisms that modulate these changes in microgravity are unknown. The purpose of this study was to clarify the mechanism of microgravity-induced bone demineralization using normal rat osteoblasts obtained from femur marrow cultures. The osteoblasts were cultured for 5 days during a Shuttle-Spacelab flight (STS-65). After collection of the culture medium, the cellular DNA and RNA were fixed on board. Enzyme-immunoassay of the culture medium for prostaglandin E2 (PGE2) indicated that microgravity induced a 4.5- to 136-fold increase in flight samples as compared to the ground control cultures. This increase of PGE2 production was consistent with a 3.3- to 9.5-fold elevation of inducible prostaglandin G/H synthase-2 (PGHS-2) mRNA, quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA induction for the constitutive isozyme PGHS-1 was less than that for PGHS-2. The interleukin-6 (IL-6) mRNA was also increased (6.4- to 9.3-fold) in microgravity as compared to the ground controls. Since PGE2 and IL-6 are both known to play a role in osteoclast formation and bone resorption, these data provide molecular mechanisms that contribute to our understanding of microgravity-induced alterations in the bone resorption process.

Animals↗

Cpk is a novel class of Drosophila PtdIns 3-kinase containing a C2 domain.

We report the identification of a novel class of phosphatidylinositol (PtdIns) 3-kinases whose members contain C-terminal C2 domains. We have isolated Drosophila and murine genes (termed cpk and cpk-m respectively) by polymerase chain reaction amplification of cDNA libraries with degenerate primers corresponding to conserved regions of PtdIns kinases. The amino acid sequences of Cpk and Cpk-m are most similar to that of p110, a family of PtdIns 3-kinases that mediates the responses of cells to mitogenic stimuli. The Cpk and Cpk-m sequences are similar to a large, central region of p110, but differ from p110 at their N and C termini. The N termini of the Cpk proteins do not contain any recognizable protein motif, while the C termini contain "C2 domains," a feature unique among PtdIns kinases. Cpk has an intrinsic PtdIns kinase activity and can phosphorylate PtdIns and PtdIns-4-P, but not PtdIns(4,5)P2, at the D3 position of the inositol ring. Cpk is the first PtdIns 3-kinase identified with this particular substrate specificity. We have identified two potential Cpk-binding proteins, p90 and p190, and have determined that both Cpk and p190 may be tyrosine phosphorylated. This finding suggests that Cpk function may be regulated by tyrosine kinases.

Amino Acid Sequence↗

MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha.

Signal-dependent activation of the transcription factor NF-kappaB is dominantly regulated by degradation of IkappaB-alpha protein. However, the signaling pathways that lead to the degradation are not clear. Here we report that mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) kinase, an activator of stress-activated protein kinases/jun kinase-1 (SAPKs/JNK1), is involved in such signaling pathways. The transient overexpression of MEK kinase in NIH3T3 fibroblasts activates kappaB-CAT reporter expression in a synergistic manner with TNFalpha stimulation. In contrast, overexpression of kinase-negative MEK kinase suppresses TNFalpha-induced reporter expression. The overexpression of MEK kinase suppresses the inhibitory activity of co-transfected IkappaB-alpha on the kappaB-CAT or human immunodeficiency virus-long terminal repeat-luciferase reporter expression and causes the simultaneous disappearance of the overexpressed IkappaB-alpha. The disappearance of exogenous IkappaB-alpha by the overexpression of MEK kinase is prevented by calpain inhibitor-I, an inhibitor of IkappaB-alpha degradation. These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha.

3T3 Cells↗