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Biomedical subjects

S Sell

Publications and source records attributed to S Sell.

At least 109 records · Page 6Linked to original sources

[NMR tomography of the shoulder joint: clinical experiences with the saturation pulse technic].

High zoom factors for MRT of the shoulder joint can lead to disturbing artifacts. The use of special saturation coils can improve longitudinal magnetisation of the central image, making it possible to produce artifact-free images of the shoulder with high resolution. Two normals and 20 patients with the rotator cuff syndrome, as well as other inflammatory and neoplastic processes, have been examined. The findings have been correlated with those of arthrography, arthro-sonography, bone scintigraphy, CT and simple radiographic examination. The MRT findings were compared with the other imaging techniques and the results are discussed. MRT proved superior to other techniques, particularly in the elucidation of soft tissue abnormalities in the rotator cuff syndrome.

Adolescent↗

Sequence analysis of the 47-kilodalton major integral membrane immunogen of Treponema pallidum.

The complete primary amino acid sequence for the 47-kilodalton (kDa) major integral membrane immunogen of Treponema pallidum subsp. pallidum was obtained by using a combined strategy of DNA sequencing (of the cloned gene in Escherichia coli) and N-terminal amino acid sequencing of the native (T. pallidum subsp. pallidum-derived) antigen. An open reading frame believed to encode the 47-kDa antigen comprised 367 amino acid codons, which gave rise to a calculated molecular weight for the corresponding antigen of 40,701. Of the 367 amino acids, 113 (31%) were sequenced by N-terminal amino acid sequencing of trypsin and hydroxylamine cleavage fragments of the native molecule isolated from T. pallidum subsp. pallidum; amino acid sequence data had a 100% correlation with that of the amino acid sequence predicted from DNA sequencing of the cloned gene in E. coli. Although no consensus sequences for the initiation of transcription or translation were readily identifiable immediately 5' to the putative methionine start codon, a 63-base-pair PstI fragment located 159 nucleotides upstream was required for expression of the 47-kDa antigen in E. coli. The 47-kDa antigen sequence did not reveal a typical leader sequence. The overall G+C content for the DNA corresponding to the structural gene was 53%. Hydrophilicity analysis identified at least one major hydrophilic domain of the protein near the N terminus of the molecule which potentially represents an immunodominant epitope. No repetitive primary sequence epitopes were found. The combined data provide the molecular basis for further structural and functional studies regarding the role of the antigen in the immunopathogenesis of treponemal disease.

Amino Acid Sequence↗

Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma.

A review of the morphologic, autoradiographic, and phenotypic analysis of the cellular changes seen during induction of cancer of the liver in rats by chemical carcinogens is used to develop an alternative to the established hypothesis that chemically induced hepatocellular carcinoma arises from premalignant nodules. The authors propose that hepatocellular and ductular carcinomas arise from a pluripotent liver stem cell and that enzyme-altered foci and nodular changes are adaptive non-oncogenic responses to the toxic effects of carcinogens. It is further postulated that persistent nodules may provide an environment that nurtures development of neoplastic cells other than the altered hepatocytes that originally form the nodule. It is possible, however, that there may be more than one cellular lineage to hepatocellular cancer and that persistent nodules contain these different lineages.

Adenoma, Bile Duct↗

Humoral immunopathological mechanisms in the skin.

Thus the skin is a unique organ in terms of location. Our skin directly interfaces with our environment and thus, unlike any other organ, is constantly subjected to foreign substances and microorganisms. Many of its structures are unique, and many of the proteins expressed by epidermal cells are also unique. Exposure to ultraviolet light affects the expression of some of these proteins as well as other biochemical substances. Although the skin also functions as an immunologic organ, it is not surprising that it can be the subject of immunologic attack. Thus, all of the major humoral immune mechanisms, cytotoxic or cytolytic, immune complex and atopic or anaphylactic, are manifested in terms of skin diseases.

Anaphylaxis↗

[Bristow surgical treatment of shoulder dislocation].

14 shoulders with recurrent anterior dislocation were treated with a modified Bristow procedure and had a 38 to 66 months follow up after surgery. Postoperatively no patient had recurrent anterior dislocation. 4 patients had an average loss of external rotation of 10-15 degrees, one patient had a non-union of the transplanted coracoid. None of the patients was disappointed by the results.

Adolescent↗

[Magnetic resonance tomography--a possibility for non-invasive meniscus diagnosis. 1. Experimentally produced lesions].

Meniscus tears were experimentally produced by surgery in 5 pigs. They were identified via MR tomography with the selected routine sequence (SE: TR 1600, TE 22/80 msec, SD 3 mm) independent of position, orientation and severity. The best imaging was obtained between the 2nd and 8th weeks after the operation in the sagittal plane. Subsequently the contrast and with it simultaneously the delineation between intact fibrous cartilage and rupture cleft decreased; this could be observed in sequences weighted according to proton density and T2 in different degrees of intensity. Parallel to this a trial to induce degeneration in the meniscus tissue resulted 8 weeks after the operation in central, signal-intensive zones in the menisci. No success was achieved in trying to improve imaging of the pathological changes by means of intraarticular injections of Gd-DTPA; this was tried out at various points of time. Besides enabling the imaging of lesions of the fibrous cartilage as a matter of principle, MR tomography can also give limited information on the age of a meniscus tear.

Animals↗

Two episodes of calcium uptake associated with T-lymphocyte activation.

The hypothesis that prolonged mitogenic exposure, such as that required for maximal proliferative stimulation of lymphocytes, induces a similarly prolonged uptake of extracellular calcium was tested on rabbit peripheral T cells by examining the effects of varied lectin dose and duration on calcium accumulation. Concanavalin A stimulation of peripheral T cells was accompanied by two lengthy episodes of calcium accumulation. The first episode was dependent on the presence and concentration of lectin. Sub- and supraoptimal dosages of lectin which are nonmitogenic produced sub- and supraoptimal calcium accumulation profiles suggesting that for optimal cellular stimulation the cellular calcium levels must fall within certain thresholds. The second episode of calcium accumulation occurred at a time when the continued presence of lectin is no longer required for stimulation but the uptake of growth factors is essential. The second episode of calcium uptake was unaffected by lectin dosage and only moderately affected by the duration of lectin exposure. Both episodes of calcium uptake as well as cellular proliferation indices were inhibitable by the calcium channel antagonists verapamil and nifedipine.

Animals↗

[Triathlon--continuous stress on muscles, tendons and bones?].

Injuries in triathletes are in the majority of the cases exertion injuries; trauma is rare. An athlete developed in triathlon races, after two metatarsal stress fractures and one in the distal tibia, a fourth stress fracture in the proximal tibia. The injury-provoking factors were a steep increase of the weekly mileage in combination with a pronated flat foot.

Adult↗

Genetic and physicochemical characterization of the recombinant DNA-derived 47-kilodalton surface immunogen of Treponema pallidum subsp. pallidum.

Previous work has established the importance of the 47-kilodalton (kDa) surface immunogen of Treponema pallidum subsp. pallidum (T. pallidum) in the immunopathogenesis of syphilis; the 47-kDa immunogen gene was cloned and expressed in Escherichia coli (M. V. Norgard, N. R. Chamberlain, M. A. Swancutt, and M. S. Goldberg, Infect. Immun. 54:500-506, 1986). To facilitate additional structural-functional analysis of this protein for immunopathogenesis studies, the recombinant DNA-derived molecule was examined with respect to its genetic expression and physicochemical properties. Subcloning of partial PstI digests of the original 47-kDa antigen-encoding DNA segment localized the 47-kDa antigen gene to a 1.3-kilobase (kb) T. pallidum DNA fragment. A 20- to 100-fold enhanced expression of the 47-kDa antigen was obtained when a 2.85-kb DNA insert containing the entire 1.3-kb structural gene was subcloned into a T7 RNA polymerase-dependent expression vector system. Under these conditions, several derivatives of the recombinant 47-kDa protein possessing different molecular masses were observed that were identical to those previously detected on Western blots of native T. pallidum antigens with monoclonal antibodies. Sarkosyl extraction of E. coli recombinant cell envelopes localized the 47-kDa protein to both the inner and outer membranes of E. coli. The absolute requirement of detergents (N-lauroylsarcosine, 3-[(3-chloramidopropyl)dimethylammonio]-1-propane sulfonate, N-octyl-beta-D-glucopyranoside, or Nonidet P-40) for solubilization of the antigen from E. coli cell envelopes and the observation that the recombinant protein partitioned into the detergent phase on Triton X-114 solubilization were consistent with the fact that it is a hydrophobic, integral membrane protein. Western blots of the 47-kDa antigen purified by immunoaffinity chromatography supported results of previous reports that the 47-kDa protein is specific to pathogenic treponemes.

Antigens, Surface↗

Isolation and characterization of recombinant Escherichia coli clones secreting a 24-kilodalton antigen of Treponema pallidum.

Escherichia coli clones containing Treponema pallidum DNA in the pUC8 vector and secreting a 24-kilodalton antigen of T. pallidum have been isolated. Both syphilitic human and syphilis-immune rabbit sera reacted with the recombinant p24 antigen, indicating that an equivalent protein in T. pallidum is capable of eliciting antibody responses during natural infections. The p24 antigen of T. pallidum was identified by using two-dimensional gel electrophoresis and immunoblotting with monospecific anti-p24 serum. We tentatively concluded that this cloned antigen is a secreted protein or a labile or minor component of T. pallidum because (i) p24 was secreted by the recombinant E. coli cells; (ii) recombinant p24 in E. coli cells was processed into several smaller species with molecular masses ranging from 12 to 20 kilodaltons, which correlate well with the masses of secreted antigens described by others; and (iii) p24 protein appeared to be highly antigenic during natural infections, but only a very small amount of this antigen was associated with or retained by the purified organisms. The possible role of the p24 protein in determining the growth characteristics of T. pallidum is suggested by the ability of recombinant p24 to induce growth changes in E. coli cells. All E. coli colonies expressing the p24 polypeptide exhibited a flat and rough colony morphology and a filamentous growth pattern that were different from those of other E. coli cells. The DNA sequence coding for the p24 polypeptide is located on a 1.7-kilobase-pair BamHI fragment of the T. pallidum genomic DNA and is absent in the nonpathogenic Treponema phagedenis DNA. However, any possible relationship between the p24 antigen and the virulence of T. pallidum remains to be determined. In preliminary studies, rabbits immunized with the purified p24 were not protected from the infection with live T. pallidum organisms.

Antibodies, Bacterial↗

Resting lymphocytes are the target of cyclosporin action.

Immunomodulation with Cyclosporin may allow better management of the patient with insulin dependent diabetes mellitus. The cellular effects of CsA were determined on rabbit lymphocytes which are a resting (Go) population for which the kinetics of activation have been defined. Cyclosporin inhibited polyclonal T-cell activation as well as B-cell activation by T-dependent and T-independent antigens. Resting lymphocytes were the exclusive target of CsA. Primed or activated cells, as well as cells in G1, were resistant to the drug. Cyclosporin inhibited the generation of T-helper cells and spared suppressor cell generation. The inhibitory effects of cyclosporin were not reversible.

Animals↗

DNA and immunoglobulin synthesis by rabbit peripheral blood lymphocytes in vitro: complete and incomplete stimulation.

Activation of resting (G0) rabbit peripheral blood lymphocytes (PBLs) into DNA synthesis and IgG synthesis was studied using sheep anti-rabbit IgG (SARIgG), protein A, pokeweed mitogen (PWM), and lipopolysaccharide (LPS). DNA synthesis was assayed by [125I]iododeoxyuridine incorporation. IgG synthesis was measured by determination of Ig in culture supernatants by an ELISA assay. Rabbit PBLs cultured with SARIgG or protein A for 48 hr and then without these reagents for 72 hr showed both DNA synthesis and Ig synthesis, whereas PWM and LPS had very little, if any, effect. PBLs stimulated with SARIgG for 6 hr and then without SARIgG for subsequent 114 hr did not become activated into DNA synthesis or IgG synthesis. However, PBLs prestimulated with SARIgG for 6 hr and then with PWM for 114 hr showed prominent DNA and IgG synthesis. LPS also maintained activation of PBLs after prestimulation of these cells with SARIgG, but the effect was much smaller than that of PWM. No evidence was found for production of factors by SARIgG-stimulated PBLs that could, by themselves, either stimulate resting cells or maintain activation of SARIgG-prestimulated cells. These results suggest that anti-IgG and protein A are complete activating mitogens for resting rabbit B cells to proliferate and differentiate into IgG-producing cells, whereas PWM and LPS are not able to activate G0 cells directly, but have a sustaining effect after activation of resting B cells with anti-IgG, either directly or via production of factors by accessory cells.

Animals↗

Cellular events during hepatocarcinogenesis in rats and the question of premalignancy.

The cellular, biochemical, and genetic changes that occur in the liver of rats exposed to chemical hepatocarcinogens are reviewed. Multiple new cell types appear in the liver of carcinogen-treated rats including foci, nodules, ducts, oval cells, and atypical hyperplastic areas. The application of phenotypic markers for these cell types suggests that hepatocellular carcinomas may arise from more than one cell type, including a putative liver stem cell that proliferates following carcinogen exposure. Study of DNA, RNA, and proteins produced by hepatocellular carcinomas and putative premalignant cells has so far failed to identify a gene or gene product clearly associated with the malignant or premalignant phenotype. Understanding the cellular lineage from normal cell through putative premalignant cell to cancer is critical to understanding the process of carcinogenesis. Application of new immunological (monoclonal antibody, transplantation) and molecular biological (gene cloning, oncogene identification) approaches to this problem holds promise that the process of hepatocarcinogenesis will be better known in the near future.

Animals↗

Treponema pallidum attachment to surface and matrix proteins of cultured rabbit epithelial cells.

Treponema pallidum strain Nichols adheres readily to rabbit epithelial cells (SF1Ep) in tissue culture. We examined a variety of sugars for their ability to inhibit attachment. Mannose, galactose, and N-acetylgalactosamine showed minor but reproducible inhibition of attachment at high concentrations, whereas sialic acid was highly inhibitory even at low concentrations. Whole-cell lysates of SF1Ep cells contained a large number of glycoproteins, which might be related to the sialic acid-inhibitable attachment. When the cells and extracellular matrix were fractionated, only a few proteins were found in the matrix fraction. They included a 220-kilodalton (kDa) protein, shown by immunoblotting to be fibronectin, and an approximately 90-kDa protein (both were isolated on SDS-PAGE gels). When nitrocellulose replicas of these SDS-PAGE gels were exposed to 125I-labeled T. pallidum, adherence was mainly to the 90-kDa protein.

Animals↗

Production and characterization of monoclonal antibodies to rabbit lymphocyte subpopulations. I. Tissue immunofluorescence and flow cytometric analysis.

Nine monoclonal antibodies to rabbit T cells and B subpopulations have been generated from three separate fusions of spleen cells from mice immunized with fractionated populations of rabbit lymphocytes. These monoclonal antibodies, as well as a previously described rabbit T cell monoclonal antibody, 9AE10, have been analyzed by immunofluorescence staining on frozen tissue sections of rabbit thymus, spleen, and appendix. This screening method permits rapid identification of the lymphocyte subdomains in each tissue which is not possible by other screening methods. Each monoclonal antibody selected has a unique tissue staining pattern. Flow cytometric analysis of these monoclonal antibodies, using indirect immunofluorescence techniques on thymocytes, splenocytes, and PBL, revealed varying percentages of positive cells and individual mean fluorescence intensities indicating different epitope densities for each antigen. These monoclonal antibodies are now being used to characterize normal lymphocyte function and the role of specific lymphocyte subpopulations in experimental disease models in the rabbit.

Animals↗

Transcriptional mapping of early RNA from regions of the Shope fibroma and malignant rabbit fibroma virus genomes.

Malignant rabbit fibroma virus (MV) is a recombinant poxvirus derived from Shope fibroma virus (SFV) and rabbit myxoma virus (D. S. Strayer, E. Skaletsky, G. F. Cabirac, P. A. Sharp, L. B. Corbeil, S. Sell, and J. L. Leibowitz, 1983a, J. Immunol. 130, 399-404; W. Block, C. Upton, and G. McFadden, 1984, Virology 140, 113-124). We report here the transcriptional mapping of early RNAs transcribed from the SFV sequences within MV and from the corresponding regions in SFV. Hybridization analysis and S1 nuclease mapping of RNA using viral DNA probes were used to define 5' and 3' ends of the various transcripts. The RNAs described here are transcribed in one direction in a densely arranged head to tail fashion similar to that described for some vaccinia virus early transcriptional units. At late times of infection the early SFV RNAs are not detected whereas the early MV RNAs are present in minor amounts. The early SFV and MV transcripts range in size from 3170 to 425 nucleotides (nt) long. All of the longer transcripts are produced as a result of read through transcription. Three MV transcripts contain fused SFV and rabbit myxoma virus sequences due to transcription through the recombination junction region in the MV genome. Two other MV transcripts are transcribed from a unique initiation site near another recombination junction region resulting in RNAs that are composed of SFV sequences having unique 5' ends.

Animals↗

Leporine acquired immune deficiency disease.

We have identified a recombinant leporipoxvirus that produces disseminated fibromas and a severe combined immune deficiency disease of sudden onset. The virus is recombinant between the SFV and the MV. MV was identified as a trace contaminant in stocks of SFV (Patuxent strain). Rabbits inoculated with the original uncloned stock of SFV prepared in vitro develop local tumors that subsequently regress. However, tumor extracts prepared from these animals, when injected into a second group of rabbits, produced MV syndrome. Rabbits with MV syndrome develop severe, usually lethal, Pasteurella or Bordetella infections and have disseminated fibroxanthosarcomas more similar to those produced by myxoma virus. The virus that induces this syndrome has been isolated by two cycles of plaque purification. This virus is indistinguishable from SFV using cross-neutralization and electron microscopy. Analyses of restriction enzyme digests of MV and plaque-purified SFV show them to be quite dissimilar and indicate that MV is recombinant between SFV and myxoma virus. This recombinational event resulted in approximately 5.5 kb of myxoma virus DNA within each of the inverted terminal repeats being replaced by a similar amount of DNA derived from the corresponding region of the SFV genome. Thus, MV contains approximately 149 kb of myxoma sequences and 11 kb of SFV sequences. Immunofluorescent studies of spleen and lymph nodes from MV-infected rabbits demonstrate that viral antigens are present predominantly in the sinusoidal lining cells in lymph nodes and in phagocytes in the splenic cords. This contrasts with the distribution of antigen observed in myxoma virus-infected rabbits where myxoma-specific antigens are present in large amounts in hyperplastic epithelium overlying tumors, particularly in the nasal mucosa and in spleen and lymph node cells. MV-infected rabbits essentially lose their lymphocyte proliferative response to T and B cell mitogens and are unable to initiate an antibody response to SRBC, as determined by a modified Jerne plaque assay. In vitro MV severely depresses the mitogen responses of normal B and T lymphocytes after two days of culture. Lymphoid cells and lysates of lymphoid cells from MV-infected rabbits will suppress mitogen- and antigen-induced responses in vitro. MV can grow in lymphocytes, but replication of MV is less efficient in lymphocytes than in RK-13 cells. Thus, MV produces a disseminated viral infection, systemic myxofibromas, and a severe combined immune deficiency in rabbits. The molecular and immunologic basis for these effects is now under study.

Acquired Immunodeficiency Syndrome↗