[Adrenocorticosteroid preparations].
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Adrenal Cortex Hormones↗
Biomedical subjects
H Hashimoto
Publications and source records attributed to H Hashimoto.
Hyperthermostable protein structure maintained by intra and inter-helix ion-pairs in archaeal O6-methylguanine-DNA methyltransferase.
The crystal structure of O6-methylguanine-DNA methyltransferase (EC 2.1.1.63) of hyperthermophilic archaeon Pyrococcuskodakaraensis strain KOD1 (Pk -MGMT) was determined by single isomorphous replacement method with anomalous scattering (SIRAS) at 1.8 A resolution. The archaeal protein is extremely thermostable and repairs alkylated DNA by suicidal alkyl transfer from guanine O6 to its own cysteine residue. Archaea constitute the third primary kingdom of living organisms, sharing characteristics with procaryotic and eucaryotic cells. They live in various extreme environments and are thought to include the most ancient organisms on the earth. Structural studies on hyperthermophilic archaeal proteins reveal the structural features essential for stability under the extreme environments in which these organisms live, and will provide the structural basis required for stabilizing various mesophilic proteins for industrial applications. Here, we report the crystal structure of Pk-MGMT and structural comparison of Pk-MGMT and methyltransferase homologue from Escherichia coli (AdaC, C-terminal fragment of Ada protein). Analyses of solvent-accessible surface area (SASA) reveals a large discrepancy between Pk-MGMT and AdaC with respect to the property of the ASA. In the Pk-MGMT structure, the intra-helix ion-pairs contribute to reinforce stability of alpha-helices. The inter-helix ion-pairs exist in the interior of Pk-MGMT and stabilize internal packing of tertiary structure. Furthermore, structural features of helix cappings, intra and inter-helix ion-pairs are found around the active-site structure in Pk-MGMT.
Amino Acid Sequence↗
Molecular characterization of Vig4/Vrg4 GDP-mannose transporter of the yeast Saccharomyces cerevisiae.
Saccharomyces cerevisiae Vig4/Vrg4 protein is a Golgi membrane protein which has multiple transmembrane domains and is essential for transport of GDP-mannose across the Golgi membrane. By immunoprecipitation of detergent-solubilized tagged protein, we found that this protein exists as oligomer. Two mutants vig4-1 and vig4-2 had amino acid substitutions in the C-terminal region, Ala286Val and Ser278Cys, respectively. In accord with these mutations, trimming of the C-terminal hydrophobic part close to the region impaired the function and traffic of the proteins from the endoplasmic reticulum to the Golgi compartments.
Amino Acid Sequence↗
Sarcomatoid carcinoma of the lung: a clinicopathologic study of 37 cases.
BACKGROUND: Spindle and giant cell carcinomas of the lung are rare subtypes and are regarded as one type of lung carcinoma, termed pleomorphic carcinoma in the Armed Forces Institute of Pathology classification. This classification is different from the World Health Organization classification. METHODS: Thirty-seven cases of sarcomatoid (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy, conventional histochemistry, and immunohistochemistry to establish their clinical and histologic characteristics. RESULTS: The patient population was comprised of 29 men and 8 women ages 33-81 years. Seventeen patients died of their disease and there was no statistically significant difference in patient prognosis between sarcomatoid carcinoma and nonsarcomatoid carcinoma of the lung. Using light microscopy, 5 cases (13.5%) comprised entirely of sarcomatoid components without carcinomatous elements were classified as Group A. In the remaining 32 cases (86. 5%), classified as Group B, carcinomatous components were present (adenocarcinoma [18 cases; 48.7%], squamous cell carcinoma [8 cases; 21.6%], and large cell carcinoma [6 cases; 16.2%]). Sarcomatoid components were divided further into three categories: spindle cell type, giant cell type, and mixed spindle and giant cell type. Immunohistochemically, the sarcomatoid components of all 37 cases were positive for cytokeratins. Statistically, there was no significant prognostic difference between the 37 cases of sarcomatoid carcinoma and 647 cases of nonsarcomatoid, nonsmall cell carcinoma of the lung (P = 0.8537). CONCLUSIONS: The sarcomatoid portions in all sarcomatoid carcinomas in the current study showed an epithelial differentiation, and there was no apparent difference in biologic behavior between sarcomatoid carcinoma and ordinary lung carcinoma.
Adult↗
Genomic organization and chromosomal location of the mouse vasoactive intestinal polypeptide 1 (VPAC1) receptor.
The gene encoding the mouse vasoactive intestinal polypeptide type 1 (VPAC1) receptor was cloned, and its structural organization was determined. The gene (Vipr1) is more than 16 kb in length and is divided into 13 exons. The 5'-flanking region is highly GC-rich and lacks an apparent TATA box, but contains a CCAAT box, three potential Sp1-binding sites, and two potential AP-2-binding sites. Promoter analysis of the 5'-flanking region of Vipr1 using a luciferase gene reporter system revealed that the isolated 5'-flanking region has functional promoter activity. The mouse Vipr1 gene is encoded by a single gene, which was mapped to the distal region of mouse chromosome 9. This region is syntenic with human chromosome 3p, where the human VPAC1 receptor gene has been mapped.
Animals↗
HIV type 2 can bind to CD8 molecules but does not infect CD8+ T cells.
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CD4-Positive T-Lymphocytes↗
Rapid and sensitive XAFS using a tunable X-ray undulator.
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Journal Article↗
A low rate of nucleotide changes in Escherichia coli K-12 estimated from a comparison of the genome sequences between two different substrains.
Two genome sequences of Escherichia coli K-12 substrains, one partial W3110 and one complete MG1655, have been determined by Japanese and American genome projects, respectively. In order to estimate the rate of nucleotide changes, we directly compared 2 Mb of the nucleotide sequences from these closely-related E. coli substrains. Given that the two substrains separated about 40 years ago, the rate of nucleotide changes was estimated to be less than 10(-7) per site per year. This rate was supported by a further comparison between partial genome sequences of E. coli and Shigella flexneri.
Escherichia coli↗
Affinity of 5-thio-L-fucose-containing Lewis X (LeX) trisaccharide analogs to anti-LeX monoclonal antibody.
5-Thiofucose-containing LeX trisaccharide analogs Gal beta(1,4)[5SFuc alpha(1,3)]GlcNAc-OMe (2) and Gal beta(1,4)[5SFuc beta(1,3)]GlcNAc-OMe (4) were synthesized via 5-thiofucosylation of methyl 2-azido-lactoside derivative 6 by the trichloroacetimidate method. Inhibitory activity of these analogs for the binding of LeX to anti-Lex antibody was evaluated by enzyme immunoassay, indicating that anti-LeX strictly recognizes alpha-configuration of the fucose moiety and its binding pocket includes no advantageous region, such as hydrophobic area, for recognizing the ring sulfur atom of 5-thiofucosyl LeX analog 2.
Antibodies, Monoclonal↗
Syntheses of two trimannose analogs each containing C-mannosyl or 5-thio-C-mannosyl residue: their affinities to concanavalin A.
C-Mannosyl residue-containing trimannose ManC alpha(1,6)[Man alpha(1,3)Man] (2) and 5-thio-C mannosyl residue-containing trimannose 5SManC alpha(1,6)[Man alpha(1,3)Man] (3) were synthesized via a glycosyl radical addition to enone derivative of mannose (6). Dissociation constants for the binding of these trisaccharides to concanavalin A (ConA) were determined by a fluorescence anisotropy inhibition assay: Kd = 198 and 31 microM, respectively. The unexpectedly large Kd value for the compound 2 compared with the compound 3 and the natural trimannose 1 demonstrates a characteristic of C-glycoside.
Concanavalin A↗
Establishment and characterization of nurse cell-like stromal cell lines from synovial tissues of patients with rheumatoid arthritis.
OBJECTIVE: To investigate the features of synovial stromal cells established from patients with rheumatoid arthritis (RA), and to define these cells as nurse cells. METHODS: Synovial nurse-like stromal cell lines (RA-SNCs) were established from patients with RA. These cell lines were examined for morphology, pseudoemperipolesis activity, cell surface markers, and cytokine production. The interaction between these RA-SNCs and a synovial tissue B cell clone was also examined. RESULTS: RA-SNCs had nurse cell activity. They spontaneously produced interleukin-6 (IL-6), IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Furthermore, they produced IL-1beta and tumor necrosis factor alpha and expressed higher levels of the other cytokines after coculture with the B cell clone. Proliferation and Ig production by the B cell clone were dependent on direct contact with RA-SNCs. CONCLUSION: These results indicate that the RA-SNCs were nurse cells. The findings suggest that RA-SNCs may play an important role in the pathogenesis of RA by producing large amounts of cytokines and maintaining infiltrating lymphocytes.
Antibodies, Monoclonal↗
Suppressive influences of methotrexate on the generation of CD14(+) monocyte-lineage cells from bone marrow of patients with rheumatoid arthritis.
An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of methotrexate (MTX), a potent disease modifying antirheumatic drug (DMARD), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate its mechanism of action. CD14(-) cells purified from bone marrow specimens of 14 patients with active RA were cultured in the presence or the absence of pharmacologically attainable concentrations of MTX (0.2 microM). After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by MTX. However, the expression of HLA-DR on bone marrow-derived CD14(+) cells was not significantly influenced by MTX. There was no significant difference in the effect of MTX on the generation of CD14(+) cells between patients with prednisolone and those without prednisolone. The production of IL-12 in bone marrow cell cultures was not inhibited, but was rather enhanced, by MTX, suggesting that the suppression of the generation of CD14(+) cells might not be due to the inhibition of cytokine production. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data suggest that the generation of CD14(+) cells and the expression of HLA-DR on such marrow-derived CD14(+) cells are regulated by different mechanisms.
Adult↗
The radiological findings in chronic expanding hematoma.
OBJECTIVE: To identify the characteristic MRI findings of chronic expanding hematoma correlated with the pathology. DESIGN AND PATIENTS: Three patients who had a chronic expanding hematoma involving the musculoskeletal system were reviewed retrospectively. RESULTS AND CONCLUSION: Huge soft tissue masses suggestive of malignancy with destruction of the bony structure were revealed on radiography and computed tomography. MRI showed the masses to exhibit heterogeneous signal intensity on both T1 and T2-weighted images with a peripheral rim of low signal intensity, reflecting the central zones of fluid collection due to fresh and altered blood with a wall of collagenous fibrous tissue. These MRI findings were seen in all three patients and are considered to be characteristic; they assist in differentiation from neoplasm in consideration of the history of trauma or surgery.
Aged↗
Changes in guanylate cyclase activity in arteriolar smooth muscle cells and hemodynamics after ischemia-reperfusion in rats.
Participation of nitric oxide (NO) and hydroxyl radicals in the pathogenesis of hemodynamic alterations after postischemic recirculation were examined by measuring cerebral blood flow (CBF) and estimating guanylate cyclase activities in arteriolar smooth muscle cells using a reversible 2-h thread occlusion model in rats and an electron microhistochemical technique. In the reversible 2-h ischemia model, guanylate cyclase activity in the arteriolar smooth muscle cells increased at the peak of hyperemia and decreased during postischemic hypoperfusion. Administration of N(omega)-nitro-l-arginine (L-NNA), a NO synthase inhibitor, in this model decreased infarct volume and completely inhibited both hyperemia and guanylate cyclase activation at hyperemia. Administration of 1,2-bis(nicotinamido)-propane (AVS), a free radical scavenger, affected neither CBF nor guanylate cyclase activity during hyperemia despite a significant reduction in infarct volume. Administration of L-NNA and AVS significantly suppressed the decrease in CBF during postischemic hypoperfusion and the effect of AVS was greater than that of L-NNA. Although continuous infusion of sodium nitroprusside (SNP) following postischemic hypoperfusion in the reversible 2-h ischemia rats without treatment with L-NNA and AVS did not alter either CBF or guanylate cyclase activity, it significantly elevated both CBF and guanylate cyclase activities in rats administered L-NNA and AVS. The responses of CBF and guanylate cyclase to SNP were also greater in AVS- than L-NNA-treated rats. These results suggest that a physiological vasodilative mechanism is involved in the induction of postischemic hyperemia through the NO-guanylate cyclase pathway in arteriolar smooth muscle cells. Both NO-related and non-related radicals are involved in the pathogenesis of postischemic delayed hypoperfusion through the loss of arteriolar smooth muscle relaxation capability.
Animals↗
Low-dose cyclosporin for multiple colonic ulcers associated with mixed connective tissue disease.
This report describes a patient with multiple colonic ulcers and mixed connective tissue disease. The histological findings of the colonic lesions showed vasculitis with T-cell infiltration, and the peripheral T cells were frequently in the activated phase of the cell cycle. In this patient, low-dose cyclosporin treatment (2.5 mg/kg/day) inhibited the T-cell activation in the peripheral lymphocytes and was very effective in the gastrointestinal disorder, which might be related to T-cell activation. This case suggests the possibility that even low-dose cyclosporin can exert a great influence on peripheral T cells and directly inhibit T-cell activation, thereby improving symptoms related to T-cell activation.
Adult↗
Pharmacokinetic advantages of a newly developed tacrolimus oil-in-water-type emulsion via the enteral route.
We developed an oleic acid oil-in-water (o/w)-type emulsion of a new tacrolimus formulation that presented an improvement in the delivery of the drug for oral absorption. This investigation was undertaken to assess a sustained release drug delivery system and selective drug transfer into the lymphatic system. The whole blood concentration profiles after oral administration at a dose of 2 mg/kg and bone marrow, spleen, liver, lung, small intestine, kidney, brain, and whole blood distribution after oral administration at a dose of 1 mg/kg of o/w emulsion formulation of tacrolimus (O/W group) were compared with those of commercially available formulation (T group) in the rat. The mean diameter of the o/w emulsion droplets was 0.47 microm immediately after preparation. The tacrolimus entrapping efficiency of o/w emulsion was 71.3+/-5.0% in 12 h and did not change for 2 d. The area under the whole blood concentration-time curve (AUC) in the O/W group was significantly higher (P<0.01) than that in the T group. In contrast, the values of constant elimination rate and total clearance in the O/W group were significantly lower (P<0.01) than those in the T group, with a comparative bioavailability of 115.9%. The tissue concentration of tacrolimus in the O/W group was significantly higher levels in the bone marrow, spleen, liver, lung, and small intestine, and significantly lower in the brain and kidney, relative to the T group. The o/w emulsion of tacrolimus may be an improved dosage form via the enteral route.
Administration, Oral↗
Preparation of whole mounts and thick sections for confocal microscopy.
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Animals↗
Effects of dothiepin on delayed conduction produced by ventricular arrhythmia in the canine heart after myocardial infarction.
1. In order to clarify the arrhythmogenic effects of antidepressants, the authors examined the effects of dothiepin and amitriptyline on the ventricular activation time (VAT), effective refractory periods(ERP) and incidence of arrhythmias induced by programmed electrical stimulation(PES) in the dog heart in situ after myocardial infarction. 2. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal zones to apply an electrical stimulation or record ventricular activation. An electrical stimulation with coupling interval 250 or 180 ms was applied on the ventricular surface, and AT was measured. 3. Dothiepin at doses of 1-3 mg/kg increased the heart rate. The VAT of coupling interval 180 ms in the infarcted zone was increased by the administration of 3 mg/kg dosulepin. Dothiepin at 3 mg/kg increased the incidence of ventricular arrhythmias induced by PES. 4. Amitriptyline, at doses of 1-3 mg/kg, significantly increased the heart rate. Amitriptyline increased the VAT dose- and frequency-dependently(2,3 mg/kg zone), and prolonged the ERP and QT c interval. Amitriptyline at doses of 1-3 mg/kg increased the incidence of ventricular arrhythmias by PES. 5. These results indicate that dothiepin, 1-3 mg/kg, has lesser effects on cardiac delayed conduction produced by ventricular arrhythmia than amitriptyline.
Animals↗