Arrhythmogenic potential and histopathologic effects of transluminal endomyocardial laser ablation.
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Biomedical subjects
Publications and source records attributed to G Lee.
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This is the first report characterizing HLA antigen distribution in North American Indians of the Chippewa tribe. One hundred seventy-four Chippewa from Minnesota underwent HLA-A,B,C,DR, and DQ typing in a search for a single unrelated bone marrow donor. The high matching rate of this successful search is attributed to homozygosity and the extreme frequency of certain antigens in this small ethnic community. It is emphasized that smaller donor pools are required in searches within a minority population. GM and KM allotype typing as well as blood group Diego typing show patterns similar to those reported in other North American Indian groups.
We have utilized subtractive hybridization to isolate 16 distinct cDNA sequences representing genes expressed in pre-B-cell lines but not myeloma cell or fibroblast lines. These sequences represent RNA transcripts that vary in abundance in pre-B-cell lines from 0.001% to 0.05%. Five of these sequences were not related to any known genes. One was related to but distinct from known myosin regulatory light chain genes and another encoded a protein with lectin domains. Three represented previously identified genes encoding carbonic anhydrase type II, thymosin, and CD2; these genes were not previously known to be specifically expressed in early stages of B-cell development. Other isolated genes corresponded to pre-B-cell-specific or pre-B-cell/B cell-specific genes recently described by others. The isolated cDNA sequences may be divided into two general categories--those representing genes expressed only in the pre-B-cell stage of B-cell development and those expressed in both the pre-B-cell and B-cell stages. The in vivo expression patterns of the identified genes suggest that some function specifically in lymphocytes while others may have roles in additional lineages.
Two new microscopic techniques make it possible to obtain images of biologically interesting molecules directly in air, vacuum, or under water. Scanning tunneling microscopy and atomic force microscopy both have the capacity to visualize atoms on the surface of rigid structures and provide details of molecular structure for lipids, proteins, carbohydrates, and nucleic acids. In addition to providing visualizations of individual molecules, these scanning probe techniques allow direct imaging of complexes between molecules or between molecules and higher-order subcellular structures such as membranes and cytoskeletal components. Both microscopes can be operated under a variety of ambient conditions ranging from high vacuum to above atmospheric pressure. Specimens need not be dry; both techniques have been used to image molecules in aqueous media under nearly physiological conditions. It is proposed that as these techniques mature they will allow direct observation of many molecular interactions under physiological conditions or even in vivo while they are occurring within the cell.
HLA-DR, DQ specificities are determined by serological methods in 2,586 North American Caucasians. Antigen frequency, gene frequency and haplotype frequency are computed for each phenotype observed. The DR and DQ loci antigen distributions are well-fitted to a Hardy-Weinberg equilibrium (p greater than 0.25 for DR locus, p greater than 0.10 for DQ locus). All World Health Organization (WHO) recognized HLA-DR,DQ specificities were found except HLA-DRw18, which has been identified only in the black population. DR and DQ linkage disequilibria among recently defined splits is observed. The following DR and DQ associations are found: DR1 and DQw5; DR4 and DQw7, DQw8; DR7 and DQw2, DQw9; DR8 and DQw4, DQw6, DQw7; DR9 and DQw2, DQw9; DRw10 and DQw5; DRw11 and DQw6, DQw7; DRw12 and DQw5, DQw7; DRw13 and DQw6, DQw7; DRw14 and DQw5, DQW7; DRw15 and DQw6, DQw7; DRw16 and DQw5; DRw17 and DQw2. In this large study population, the following unusual DR and DQ associations are found: DR4, DQw2; DR4, DQw1; DR1, DQw7; DR7, DQw5; DRw17, DQw6; and other unusual haplotype phenotypes containing DRX, DQX.
The three-dimensional structure of a chemotactic protein CheY from Salmonella typhimurium has recently been determined by X-ray crystallography. The structure of this small protein, containing 129 amino acid residues, shows a domain consisting of a central beta-pleated sheet surrounded on both sides by alpha-helices. We have examined the sequence and the arrangement of the structural domains of the CheY protein and have compared them with other nucleotide binding protein sequences and structures. We find that the CheY protein has significant sequence homology to the ras-gene encoded p21 protein. In addition, the structural domains of the two proteins are arranged in a fundamentally similar manner, including the phosphate-binding site (both proteins bind phosphate-containing ligands). The striking similarity in the arrangement of the structural domains of the two proteins suggests that both may serve similar functions as signal transducers.
The GTP-binding p21 protein, encoded by the ras-oncogene, becomes transforming if amino acid substitutions are made at critical positions in the polypeptide chain, e.g., at Gly 12, Gly 13, Ala 59, Gln 61 and Glu 63. Most of these substitutions occur in two phosphate-binding loop regions, Tyr 4-Thr 20, herein designated as segment 1, and Ile 55-Met 67, herein designated, as segment 2. These two segments are homologous to two corresponding regions in the two purine nucleotide binding proteins, bacterial elongation factor (EF-tu) (Val 12-Thr 28 corresponds to segment 1; His 78-Ile 92 corresponds to segment 2) and adenylate kinase (ADK) (Lys 9-Cys 25 corresponds to segment 1 and Tyr 95-Arg 107 corresponds to segment 2). We find that the conformations of the segment 1 region in the p21 protein, EF-tu and ADK are similar to one another and that the conformation of the segment 2 region of EF-tu is superimposable on that of segment 2 of ADK. Furthermore, the relative position of the two segments in EF-tu is strikingly similar to that of the two segments in ADK. In the originally proposed X-ray structure for the p21 protein, the conformation of segment 2 in the p21 protein is not similar to that found for the other two proteins, and its disposition relative to segment 1 and the remainder of the protein is also different from that observed for the other two proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
NF-kappa B activation is a crucial late step in the induction of immunoglobulin kappa light-chain gene expression in pre-B cells by lipopolysaccharide (LPS). We have analyzed NF-kappa B activation in three independent mutant lines of 70Z/3 pre-B cells which are unresponsive to LPS. All three variant cell lines failed to activate NF-kappa B when induced with LPS or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. However, all three cell lines contained functional NF-kappa B, as revealed by detergent treatment of cytoplasmic extracts. Moreover, cycloheximide induced limited activation of NF-kappa B comparable to that in wild-type 70Z/3 pre-B cells in two of the three variant lines. These results indicate that the mutations blocking kappa gene induction in these variant 70Z/3 pre-B-cell lines affect NF-kappa B activation.
Stereotactically implanted depth electrodes are one means of localization of seizure foci. Unilateral seizure focus localization was obtained in 72.7% mesial temporal (MT) implants and 50% of focus/extramesial temporal (MT-XMT) implants. Recent increase in localization to over 80% in MT implants was possible because a larger percentage of patients had MT-XMT implants. Increased localization to 60% in MT-XMT implants was related to using more XMT electrodes per patient and to orienting electrodes to monitor larger limbic XMT and neocortical areas. Since MT foci were localized in 25% of MT-XMT cases, MT electrodes should be included with all MT-XMT implants. Depth electrography can also be used to rule out certain patients as surgical candidates. Therefore, a surgical decision can be reached in a very high percentage of patients undergoing depth implantation. Surgical results are comparable to those in our overall series.
Adenoid cystic carcinoma of the nasopharynx is an occurrence with only 44 previously reported cases in the English literature. We report herein one additional case. This 62-year-old female patient suffered from right facial numbness for 1 year. A CT scan of the brain showed tumor shadow in right C-P angle. Subsequently, the patient underwent a temporal craniotomy. A mass was noted in medial temporal fossa, encasing the trigeminal nerve. The tumor was totally removed and pathologic examination showed a picture of metastatic adenoid cystic carcinoma. High resolution CT scan of nasopharynx after surgery revealed bulging of fossa of Rosenmüller, although no gross abnormality was found in the mirror examination of nasopharynx. Thus, nasopharyngeal biopsy was done resulting in a diagnosis of adenoid cystic carcinoma which was considered to be the primary site of origin. The patient received radiotherapy and she was followed up in our clinic.
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The human B cell restricted activation antigen B7 identifies an in vivo primed subpopulation of B cells that demonstrate an accelerated response to triggers of B cell activation and proliferation. The cDNA encoding B7 was molecularly cloned by cDNA expression. The identity of the B7 cDNA was confirmed by indirect immunofluorescence and immunoprecipitation of a 44/54-kDa protein from B7 transfected COS cells. The sequence of the B7 polypeptide predicts a type I membrane protein of 262 amino acids with eight potential N-linked glycosylation sites in the extracellular region and a short, highly positively charged cytoplasmic tail. The extracellular region is homologous to the Ig gene superfamily and consists of two contiguous Ig-like domains. The first Ig domain has the characteristics of a variable domain and the second that of a constant region domain. B7 mRNA was detected only on anti-Ig activated B lymphocytes and not in other hematopoietic cells. After in vitro activation of B cells with anti-Ig, B7 mRNA was maximally expressed between 4 and 12 h with four RNA transcripts of 1.7, 2.9, 4.2, and 10 kb. The 2.9-kb mRNA predominated in in vitro-activated B cells whereas the 1.7-kb mRNA was most abundant in tumor cells of B cell origin. B7 expression was confined to several histologically defined subgroups of B cell malignancies. The majority of non-Hodgkin's lymphomas were B7+ whereas the B cell leukemias and circulating non-Hodgkin's lymphomas were generally negative. These results demonstrate that the B7 gene encodes a unique molecule belonging to the Ig superfamily and that B7 expression is limited to normal activated B cells and noncirculating B cell malignancies.
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Scanning tunnelling microscopy (STM) has been used to map the surface topography of inorganic materials at the atomic level, and is potentially one of the most powerful techniques for probing biomolecular structure. Recent STM studies of calf thymus DNA and poly(rA).poly(rU) have shown that the helical pitch and periodic alternation of major and minor grooves can be visualized and reliably measured. Here we present the first STM images of poly(dG-me5dC).poly(dG-me5dC) in the Z-form. Both the general appearance of the fibres and measurements of helical parameters are in good agreement with models derived from X-ray diffraction.
In the present study, follicular dendritic cells (FDCs) were purified to homogeneity in order to define the lineage and function of these cells. FDCs were identified by their characteristic morphology and by their expression of receptors for the third complement component, the myeloid-restricted antigen CD14, and the FDC antigen DRC-1. Unclustered FDCs displayed a unique antigenic phenotype since they expressed several B- and myeloid lineage-restricted antigens, but lacked T and NK cell antigens as well as the leukocyte common antigen. FDCs expressed adhesion molecules, including most of the VLA proteins, intercellular adhesion molecule 1 (ICAM-1), and CD11b. FDCs could be isolated to homogeneity by their intense staining with anti-CD14 using flow cytometric cell sorting. These highly purified FDCs expressed CD14 and CD21 but lacked CD20. This antigen pattern and characteristic morphology confirmed that these cells were, in fact, homogeneous FDC preparations. Analysis of polymerase chain reaction-amplified cDNA from highly purified FDCs showed no transcripts for IL-6. The isolation of homogeneous FDC populations will be important for the analysis of the functional role of FDCs within the lymphoid follicle.
The ability of stromal cells in bone marrow to support B lymphopoiesis may be partially mediated by secretion of biologically active factors. The first cytokine with lymphopoietic activity to be molecularly cloned from stromal cells, IL-7, was originally identified by its growth-promoting activity on long term cultured lymphocytes. We now report that murine rIL-7 is a potent proliferative stimulus for B cell progenitors isolated from fresh bone marrow. Proliferation was initially most obvious among large precursor cells which bear the B lineage associated Ag, Ly5/220 and BP1. A majority of these also contained cytoplasmic Ig mu H chains. Extended culture with IL-7 resulted in a predominance of immature c mu- lymphocytes. No effect by IL-7 was observed on the proliferation of mature lymphocytes. It also did not induce maturation in a number of early B lineage cell lines, or promote the formation of LPS-responsive, clonable B cells from precursors. When incorporated into semisolid agar medium, IL-7 specifically and rapidly induced the formation of pre-B cell colonies in a linear fashion with respect to numbers of cells cultured from either purified B cell progenitor preparations or unfractionated bone marrow. In both liquid and agar culture conditions, the IL-7 proliferative activity was inhibitable by two related forms of transforming growth factor (TGF) beta, TGF-beta 1 and TGF-beta 2. Taken together, these results indicate that IL-7 is a stimulus for replication of normal B lineage cells at an early stage of differentiation, and its activity can be modulated by other cytokines. IL-7 also provides a means of studying the progeny of a single B cell progenitor, and of enumerating clonable pre-B cells in the absence of colony formation by other cell types in bone marrow.
The scanning tunneling microscope (STM) has been used to measure properties of poly(rA).poly(rU) and DNA, such as helical pitch, half-period oscillations that were interpreted as the alternation between the major and minor grooves, and interhelical spacing. Average pitches were measured by two-dimensional Fourier transforms and by topographic profiles along the fiber axes. Values were typically 7 percent less than standard dimensions of A-form RNA and B-form DNA fibers. This result is compatible with the mild dehydration that occurred under air-drying conditions. More extensive dehydration typically led to 19 percent shrinkage. Analysis of specific regions allowed local variations in helical pitch as small as 1 angstrom to be detected, thus demonstrating that the STM can visualize functionally significant modulations of nucleic acid structure.