Biomedical subjects
Publications and source records attributed to P Todd.
Two patients with lichen sclerosus (et atrophicus) are described in whom there was conspicuous localization of lesions to sites subjected to friction from tight clothing. This was highly suggestive of the Köbner phenomenon. Both patients experienced symptomatic improvement following avoidance of pressure on the skin from tight clothing.
A 52-year-old man with primary Raynaud's disease developed increasingly severe Raynaud's phenomenon with digital ischaemia in all limbs, and gangrene in two digits of the left hand. He was subsequently found to have Hodgkin's disease. Cervical sympathectomy led to initial improvement in acute ischaemia, and chemotherapy was followed by further improvement in the general severity of Raynaud's phenomenon together with remission of the lymphoma.
Studies were conducted to characterize the effect of gene amplification and foreign gene expression on recombinant CHO cell growth. Chinese hamster ovary (CHO) cells were transfected with an expression vector containing the gene for dihydrofolate reductase (dhfr) and the gene for human beta-interferon (beta-IFN) or the lac Z gene which codes for beta-galactosidase (beta-gal). The recombinant genes in these CHO cells were amplified stepwise by growth in 0, 10(-7), and 10(-6) M methotrexate (MTX), and the beta-gal expressing cells were adapted to suspension culture. Flow cytometric methods (FCM) were used to measure the distribution of amplified dhfr gene content and foreign beta-gal gene expression in the cell populations. A biochemical assay for beta-gal was also used. Beta-gal expression was found to increase with increasing gene amplification. The growth rate of recombinant CHO cells at 10(-7) M MTX was found to be 20% lower than that of recombinant CHO cells in MTX-free medium, and the cell growth rate at 10(-6) M MTX was 20% lower than that of recombinant CHO cells at 10(-7) M MTX. There was no effect of 10(-5) M MTX on the growth of CHO-DG44 (dhfr-) cells. The reduction of growth rate in recombinant CHO cells is therefore thought to be mainly due to the effect of dhfr and foreign gene amplification and increased beta-galactosidase expression.
Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 degrees C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another.
Relative Biological Effectiveness (RBE) and Quality Factor (Q) at extreme values of Linear Energy Transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In tissue end-point experiments each heavy particle passes through several cells, and the LET can exceed 200 keV/micrometer in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point of interest to the investigator, such as cell killing, mutation or carcinogenesis. The following question must therefore be addressed: Do RBE's and Q factors derived from single-cell experiments properly account for the increased probability of multiple-cell damage by HZE tracks? A model is offered in which measured radiation effects and known tissue properties are combined to estimate the value of a multiplier of damage effectiveness on the basis of number of cells at risk, p3n, per track containing a hit cell, where n is the number of cells per track, based on tissue and organ geometry, and P3 is the probability that a cell in the track is capable of expressing the experimental end-point.
Several modifications of differentiated functions of animal cells cultivated in vitro have been reported when cultures have been exposed to increased or decreased inertial acceleration fields by centrifugation, clinorotation, and orbital space flight. Variables modified by clinorotation conditions include inertial acceleration, convection, hydrostatic pressure, sedimentation, and shear stress, which also affect transport processes in the extracellular chemical environment. Autocrine, paracrine and endocrine substances, to which cells are responsive via specific receptors, are usually transported in vitro (and possibly in certain embryos) by convection and in vivo by a circulatory system or ciliary action. Increased inertial acceleration increases convective flow, while microgravity nearly abolishes it. In the latter case the extracellular transport of macromolecules is governed by diffusion. By making certain assumptions it is possible to calculate the Peclet number, the ratio of convective transport to diffusive transport. Some, but not all, responses of cells in vitro to modified inertial environments could be manifestations of modified extracellular convective flow.
Relative biological effectiveness (RBE) and quality factor (Q) at extreme values of linear energy transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single-cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In experiments on animal tissues, however, each heavy particle passes through several cells, and the LET can exceed 200 keV micrometers-1 in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point being measured, such as cell killing, mutation or carcinogenesis. The following question was therefore addressed: do RBEs and Q factors derived from single-cell experiments properly account for the damage at high LET when multiple cells are hit by HZE tracks? A review is offered in which measured radiation effects and known tissue properties are combined to estimate on the one hand, the number of cells at risk, p3n, per track, where n is the number of cells per track based on tissue and organ geometry, and p3 is the probability that a cell in the track is capable of expressing the experimental end-point. On the other hand, the tissue and single-cell responses are compared by determining the ratio RBE in tissue/RBE in corresponding single cells. Experimental data from the literature indicate that tissue RBEs at very high LET (Fe and Ar ions) are higher than corresponding single-cell RBEs, especially in tissues in which p3n is high.
One hundred consecutive histologically benign lesions seen at a pigmented lesion clinic were studied prospectively to assess the diagnostic accuracy of the seven-point check-list. Lesions were scored by both patient and physician. Thirty per cent of lesions attained a suspicious score. While there was a high level of agreement between patient and clinician regarding the individual characteristics of a lesion as defined in the check-list, final assessments differed. Most patients considered their lesions suspicious, whereas the clinicians correctly recognized that in 94% cases they were benign. The seven-point check-list often fails to exclude common benign pigmented lesions. The revised (1989) check-list is even less specific (70% of lesions achieving a suspicious score). Such check-lists are difficult for the inexperienced to interpret. Clinical familiarity is required in order to provide a confident diagnosis. Future emphasis should be directed towards improving screening in primary care.
Collagen IV contains an amino-terminal tetramerization domain (7 S) that is involved in aggregation and cross-linking as part of the process of self-assembly of the collagen IV matrix of basement membranes. We determined the structure and location of the Asn-linked oligosaccharides of the 7 S tetramer. Two glycopeptides, GP-1 and GP-2, were isolated from tryptic digests of the 7 S tetramer and were characterized. GP-1 and GP-2 are derived from the alpha 1(IV) chain and the alpha 2(IV) chain, respectively. Each glycopeptide contained one sequence, -Asn-Xaa-Thr-, which was shown to be N-glycosylated at Asn, corresponding to position 126 of the alpha 1 chains and 138 of the alpha 2 chain. 1H NMR spectroscopic analysis of the oligosaccharide is a biantennary N-acetyllactosamine type of N-linked oligosaccharide with a broad heterogeneity in the presence of the sugar residues at their nonreducing termini as indicated. [formula: see text] The location of the Asn-linked oligosaccharide units and Hyl-linked disaccharide units and their orientation with respect to the surface of the triple helix were calculated using two models. We conclude that both units are important determinants in the assembly of the 7 S tetramer.
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Lymphoproliferative and myeloproliferative malignancies have been noted in patients with systemic mastocytosis and urticaria pigmentosa. However, to our knowledge an association between mastocytosis and malignant melanoma has not been reported previously.
Most organelles large enough to sediment or to undergo isothermal settling within eukaryotic cells are held in position by one or more components of the cytoskeleton. The interior of eukaryotic cells is considered to be very crowded, and the evaluation of natural-convective processes is very difficult. In a most simple view, the cell may be considered as consisting of four immiscible phases among which solutes are exchanged causing steep concentration gradients and thermodynamic conditions far from equilibrium. Extracellular gravity-related forces may include natural convection due to solute gradients external to single cells or the work performed by swimming, ciliated, or elongating cells.
This paper presents the design, operation and experiment protocol of the Bioserve sponsored flights of the ITA Materials Dispersion Apparatus Payload (BIMDA) flown on the Space Shuttle on STS-37. The BIMDA payload represents a joint effort between ITA (Instrumentation Technology Associates, Inc.) and Bioserve Space Technologies, a NASA Center for the Commercial Development of Space, to investigate the methods and commercial potential of biomedical and fluid science applications in the microgravity environment of space. The BIMDA payload, flown in a Refrigerator/Incubator Module (R/IM) in the Orbiter middeck, consists of three different devices designed to mix fluids in space; four Materials Dispersion Apparatus (MDA) Minilabs developed by ITA, six Cell Syringes, and six Bioprocessing Modules both developed by NASA JSC and Bioserve. The BIMDA design and operation reflect user needs for late access prior to launch (<24 h) and early access after landing (<2 h). The environment for the payload is temperature controlled by the R/IM. The astronaut crew operates the payload and documents its operation. The temperature of the payload is recorded automatically during flight. The flight of the BIMDA payload is the first of two development flights of the MDA on the Space Shuttle. Future commercial flights of ITA's Materials Dispersion Apparatus on the Shuttle will be sponsored by NASA's Office of Commercial Programs and will take place over the next three years. Experiments for the BIMDA payload include research into the following areas: protein crystal growth, thin film membrane casting, collagen formation, fibrin clot formation, seed germination, enzymatic catalysis, zeolite crystallization, studies of mixing effects of lymphocyte functions, and solute diffusion and transport.
By complexing polyols with borate in recycling isoelectric focusing and by varying the ratio of polyol to borate over the useful pH range of 4.0-6.0, it is possible to control pH. Twelve solutions of 0.1 M boric acid and varying glycerol concentration were used to vary pH in a twelve-compartment commercial recycling isoelectric focusing (RIEF) system. Various concentrations of boric acid were tested as anolyte, and various Tris(hydroxymethylamino)methane-borate buffer systems were tested as catholyte. Electroosmosis, hydrogen ion flow, and fluid balancing were characterized in two glycerol gradients; one was maintained at 0.06 pH/fraction and the other at 0.12 pH/fraction. In the latter case, ovalbumin (pI4.70) migrated to the pH 4.61 and 4.72 compartments. It is concluded that the borate-glycerol system can be adequately stabilized in RIEF for isoelectric purification of certain proteins.
A family is described in which five of the six members with the Jackson-Lawler type of pachyonychia congenita also had varying degrees of hidradenitis suppurativa. We suggest an association between this type of pachyonychia congenita and hidradenitis suppurativa.
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