[An autopsy case of primary non-Hodgkin lymphoma of the extrahepatic bile duct].
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Bile Duct Neoplasms↗
Biomedical subjects
N Ban
Publications and source records attributed to N Ban.
[What is expected in instructors of clinical internal medicine. 2. History taking and physical examination: latest educational technology].
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Education, Medical↗
A 9 A resolution X-ray crystallographic map of the large ribosomal subunit.
The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of protein synthesis. We have generated X-ray crystallographic electron density maps of the large ribosomal subunit from Haloarcula marismortui at various resolutions up to 9 A using data from crystals that diffract to 3 A. Positioning a 20 A resolution EM image of these particles in the crystal lattice produced phases accurate enough to locate the bound heavy atoms in three derivatives using difference Fourier maps, thus demonstrating the correctness of the EM model and its placement in the unit cell. At 20 A resolution, the X-ray map is similar to the EM map; however, at 9 A it reveals long, continuous, but branched features whose shape, diameter, and right-handed twist are consistent with segments of double-helical RNA that crisscross the subunit.
Crystallography, X-Ray↗
A proof of glutathione S-transferase-pi-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell.
In order to directly prove the involvement of GST-pi in drug resistance, it's antisense gene was transduced into human colorectal cancer cell line which has been shown to express high level of GST-pi and the sensitivity of this cell line to anticancer drugs were assessed. The transfectant showed higher sensitivity to adriamycin (3.3-fold), Cisplatnum (2.3-fold), Melphalan (2.2-fold), Etoposode (2.2-fold) than the parental cell, while the sensitivity to vincristine, mitomicin C, 5-fluorouracil was unchanged by transfection. When the transfectant and parental cells were innoculated in nude mice and treated with adriamycin, a significant suppression of tumor growth was observed with the transfectant as compared to the parental cell. On the basis of this observation, we then transduced sense GST-pi gene into human bone marrow stem cells (CD34+ cells) to protect them from toxicity of anticancer drug. The gene transduced CD34+ cells formed more CFU-GM than nontransduced CD34+ cell in the presence of adriamycin (30 ng/ml). Thus, the autotransplantation of GST-pi gene transduced cell into cancer patients to protect the bone marrow from subsequent highdose chemotherapy is considered to be a new strategy for cancer gene therapy.
Animals↗
Chromosome aberrations in bone marrow cells of C3H/He mice at an early stage after whole-body irradiation.
Murine acute myeloid leukemia is characterized by chromosome 2 aberrations, and genesis of the marker chromosome 2 by radiation is suspected to be an initiating event of radiation leukemogenesis. A detailed analysis of the type and frequency of chromosome 2 aberrations in murine bone marrow cells at an early stage after irradiation is provided here. A total of 40 male C3H/He mice was exposed to 137Cs gamma-ray at a dose of 1, 2 or 3 Gy, and sacrificed 24 hours after irradiation. Metaphase samples prepared from bone marrow cells were Q-banded for karyotyping or painted with DNA probes specific to chromosome 2. In 5 mice analyzed by karyotyping, one mouse showed high frequency of the marker aberrations as well as other chromosome 2 aberrations. Chromosome painting analysis for the rest of the mice also detected 3 animals showing significantly high frequencies of chromosome 2 aberrations. Dose-dependence of the frequencies was observed even among those mice that tended to be sensitive. The results indicated that there was a subgroup of mice carrying hypersensitive chromosome 2. The subgroup could be leukemia-sensitive if radiation-induced chromosome aberrations are responsible for an early change in myeloid leukemogenesis.
Animals↗
Transfection of glutathione S-transferase (GST)-pi antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide.
The goal of this study was to demonstrate that glutathione S-transferase (GST)-pi is directly involved in the intrinsic and acquired resistance of cancer cells to anticancer drugs. To this end, GST-pi antisense cDNA was transfected into the cultured human colon cancer cell line M7609, which expresses an innately high level of GST-pi and shows intrinsic drug resistance, and into an M7609 strain with acquired resistance to Adriamycin (ADR;i.e., M7609/ADR cells). The changes in the sensitivity of these transfectants to various anticancer drugs were investigated. The intracellular concentrations of GST-pi in M7609/anti-1 cells and M7609/anti-2 cells, two clones that were established by transfection of GST-pi antisense cDNA into M7609 cells, were decreased to approximately half of those detected in the parent cells (M7609) and in the control cells transfected with vector alone (M7609/pLJ). The sensitivities of the antisense transfectants in relation to ADR, cisplatin, melphalan, and etoposide were increased -3.3-fold, 2.3-fold, 2.2-fold, and 2.1-fold, respectively, compared with those of M7609 and M7609/pLJ. On the other hand, the sensitivities of the antisense transfectants to Taxol, vincristine, 5-fluorouracil, and mitomycin C were not significantly changed. Similarly, the transfection of antisense cDNA into M7609/ADR cells resulted in the reduction of intracellular GST-pi concentration (by about half) and an increased sensitivity to ADR (4.4-fold), but no increase in 5-fluorouracil sensitivity. Thus, GST-pi is considered to be a multidrug resistance factor that is responsible for both the intrinsic and acquired resistance of cancer cells to anticancer drugs such as ADR, cisplatin, melphalan, and etoposide.
Antineoplastic Agents↗
The crystal structure of peanut peroxidase.
BACKGROUND: Peroxidases catalyze a wide variety of peroxide-dependent oxidations. Based on sequence alignments, heme peroxidases have been divided into three classes. Crystal structures are available for peroxidases of classes I and II, but until now no structure has been determined for class III, the classical extracellular plant peroxidases. RESULTS: The crystal structure of peanut peroxidase has been solved to 2.7 A resolution. The helical fold is similar to that of known peroxidase structures. The 294-residue polypeptide chain is accompanied by a heme and two calcium ions, and there is some evidence of glycosylation. CONCLUSIONS: This is the first complete structure of a class III peroxidase and as such should serve as a model for other class III enzymes including the much-studied horseradish peroxidase. It may also aid in the interpretation of functional differences between the peroxidase classes. Ten helices conserved in class I and II peroxidases are also found in peanut peroxidase. Key residues of the heme environment and the location of two calcium ions are shared with class II peroxidases. Peanut peroxidase contains three unique helices, two of which contribute to the substrate access channel leading to the heme edge.
Amino Acid Sequence↗
Glutathione S-transferase-pi is secreted as a monomer into human plasma by platelets and tumor cells.
By employing an ELISA for detection of glutathione S-transferase-pi (GST-pi) established in our laboratory, gel filtration profiles of GST-pi in the plasma of normal subjects and patients with malignant tumors were investigated. The results showed that the plasma GST-pi for both of these groups was approximately half the molecular size of placental GST-pi used as a standard control. Similar analyses were performed on GST-pi of platelets and cultured cancer cells, which are considered to be the main sources of the GST-pi in the plasma of normal subjects and cancer patients, respectively. The results indicated that the GST-pi in both the centrifuged supernatants of aggregated platelets and in the culture medium of cancer cells was about half of the molecular size on intact GST-pi. Moreover, the GST-pi in the culture medium was shown to have an N-terminus and a C-terminus, by analysis with specific ELISA. Western blot analysis of the GST-pi in the culture medium detected a single band migrating at 23 kDa, confirming that the extracellular GST-pi was the monomer, not a cleaved form of intact GST-pi. The release of GST-pi from cancer cells was suppressed at 4 degrees C, or by sodium azide, but not suppressed by colchicine or cytochalasin B. These findings suggest that GST-pi may be released by an energy-dependent, active process, and not by a secretion mechanism.
Blood Platelets↗
Crystal structure of an anti-anti-idiotype shows it to be self-complementary.
The structure of the Fab fragment of the mouse anti-anti-idiotypic monoclonal antibody (mAb) GH1002 was solved by X-ray crystallography. mAb GH1002 was elicited with the syngeneic anti-idiotype mAb MK2-23 which mimics the determinant defined by anti-human high molecular weight-melanoma associated antigen (HMW-MAA) mAb 763.74. The Fab fragments of mAb GH1002 exist in the crystal as dimers related by crystallographic 2-fold axes. The interface between dyad-related Fab fragments is formed primarily by interaction of the hypervariable loops of one with the other. The self-interaction of Fab fragments of anti-anti-idiotypic mAb GH1002 through their combining sites is extremely tight and intricate, closely resembling that observed in structures of id-anti-id complexes, and comparable in terms of total contact area, charge complementarity, and number of hydrogen bonds. The self-complementarity of the antibody observed here could be coincidental and thus reflect some non-specific binding capability. It might, on the other hand, be immunologically relevant and exemplify a certain degree of evolved self complementarity characteristic of antibodies participating in idiotypic cascades.
Amino Acid Sequence↗
Bacterial adhesion on hydrophilic heparinized catheters, with compared with adhesion on silicone catheters, in patients with malignant obstructive jaundice.
To study the inhibitory effects on bacterial adhesion of a newly devised, hydrophilic heparinized catheter to be used in patients with malignant obstructive jaundice, a randomized controlled study of indwelling endoprostheses was performed, using implantable port-connected heparinized catheters (n = 25) and silicone catheters (n = 21). Catheters withdrawn from patients were cultured for bacteria and examined by electron microscopy for the presence of adherent organisms. In vitro examination of the two type of catheters exposed to suspensions of Eschericia coli and Staphylococcus aureus was performed using electron microscopy and a luminometer. The formation of a biofilm coated with glycocalyces was found in silicone catheters, but not in the heparinized catheters. In vitro experiments demonstrated little bacterial adhesion to the heparinized surface, but significant formation of biofilm on the silicone surface. Anionically charged heparinized catheters have inhibitory effects on bacterial adhesion, and the surface charge of the catheter may be a factor in inhibiting this adhesion.
Aged↗
Structural comparison of the plant satellite viruses.
Detailed structures are now available for three plant satellite viruses, satellite tobacco necrosis virus (STNV), satellite tobacco mosaic virus (STMV), and satellite panicum mosaic virus (SPMV). It is, therefore, possible to compare the tertiary structure of viral protein subunits, their quaternary interactions, and the interactions of protein subunits with the RNA genome. This analysis indicates that, in spite of common function and preservation of a "jelly-roll" motif in the protein monomer, the three viruses are remarkably different. The differences include the arrangement of secondary structural elements, interactions of adjacent subunits, and the disposition of subunits relative to icosahedral symmetry axes. In each of the three viruses, however, the narrow end of the jelly roll forms fivefold contacts. The fivefold protein interactions are organized about a Ca2+ ion for STNV, an anion for STMV, and, apparently, neither of these for SPMV. Low-resolution neutron diffraction studies using H2O/D2O solvent contrast variation revealed the general location of the RNA genome within the STNV. In the case of SPMV, regions of electron density on the interior of the capsid could be assigned to RNA, although it was not possible to model the nucleic acid. Only for STMV was nucleic acid visible in election density maps, and this was manifested as double-helical RNA segments associated with each coat protein dimer. The observations presented here provide no support for any common evolutionary relationship.
Amino Acid Sequence↗
Bipolal: anti-microalgal compound isolated as a candidate for marine antifouling produced by Bipolaris sp. F5206.
Bipolal [1], a new compound with marine antifouling potential, was isolated from the culture broth of Bipolaris sp. The structure was determined to be an eremophilane derivative on the basis of 2D nmr spectroscopy and chemical transformations.
Aldehydes↗
The structure of satellite panicum mosaic virus at 1.9 A resolution.
The crystal structure of satellite panicum mosaic virus (SPMV) has been solved by multiple isomorphous replacement and molecular replacement and refined at 1.9 A resolution. SPMV, a T = 1 icosahedral virus, is the smallest virus structure determined. The coat protein is an eight-stranded 'jelly roll' beta-barrel with an amino-terminal strand that extends into the interior of the virus, presumably interacting with the RNA. Regions of electron density on the interior of the protein capsid may be RNA, although it is not possible to construct any detailed model of the nucleic acid. Basic amino acid residues in contact with the nucleic acid show a considerable degree of disorder. The carboxy-terminal strand of the virus coat protein interacts with adjacent subunits, forming an additional beta-strand.
Amino Acid Sequence↗
Structure of an anti-idiotypic Fab against feline peritonitis virus-neutralizing antibody and a comparison with the complexed Fab.
The crystal structure of anti-idiotopic Fab 409.5.3, made against an E2 specific feline infectious peritonitis virus-neutralizing antibody 730.1.4, has been determined in its free from, at 2.9 A resolution by molecular replacement. This antibody, used as an immmunogen, elicits the production of anti-anti-idiotypic antibodies that in turn neutralize the virus. The structure of the uncomplexed Fab was refined using constrained-restrained least squares minimization and simulated annealing in combination with conjugate gradient techniques to a crystallographic R of 0.22 based on 16,482 unique reflections between 20.0 and 2.9 A. The free antiidiotypic Fab shows, when compared to its complexed form, a 5 degrees rotation of its variable light with respect to its variable heavy domain and rearrangement of complementarity determining region loops, which permits optimization of the stereocomplementarity between interacting molecules. This finding supports the induced fit hypothesis for antibody antigen interaction.
Amino Acid Sequence↗
Case report: intraglomerular metastasis with neoplastic cell interposition.
A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well-recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis.
Adenocarcinoma↗
[Case of Ehlers-Danlos syndrome with giant cavernous hemangioma and Klippel-Weber syndrome].
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Abdominal Neoplasms↗
Characterization of crystals of satellite panicum mosaic virus.
Satellite panicum mosaic virus (SPMV) has been purified from pearl millet and obtained in a variety of different crystal forms, at least two of which appear suitable for high resolution X-ray diffraction analysis. The first is of cubic space group P4(2)32 with a = b = c = 183.1 A and two virus particles in the unit cell. The second is of a primitive orthorhombic space group with a = 166.1 A, b = 266.7 A and c = 269.1 A, with four virus particles in the unit cell. While the cubic crystal has as its asymmetric unit one twelfth of the icosahedron, or five capsid protein subunits, the asymmetric unit of the orthorhombic crystals is an entire particle. The cubic crystals diffract to at least 2.8 A resolution. We have also succeeded in crystallizing, but not yet characterizing the master virus, PMV.
Crystallization↗
Crystal structure of an idiotype-anti-idiotype Fab complex.
Anti-idiotypic monoclonal antibody 409.5.3 is raised against an antibody that neutralizes feline infectious peritonitis virus. This antibody, used as an immunogen, elicits the production of anti-anti-idiotypic antibodies that in turn neutralize the virus. The crystal structure of the complex between anti-idiotypic Fab 409.5.3 and idiotypic Fab fragment of virus-neutralizing antibody has been solved by molecular replacement using real-space Patterson search and filtering by Patterson correlation-coefficient refinement. The structure has been refined to an R value of 0.21 based on 21,310 unique reflections between 40.0 and 2.9 A. The three-dimensional structure reveals extensive, specific interactions that involve 118 van der Waals contacts and at least 9 probable hydrogen bonds. The two Fabs are rotated 61 degrees with respect to each other around the approximate long axis of the complex and are within 26 degrees being aligned along their major axes.
Amino Acid Sequence↗