Biomedical subjects
S B Smith
Publications and source records attributed to S B Smith.
Mechanisms of isoalloxazine (flavine) hydrolysis.
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Buoyant density separation of cells. I. The buoyant distribution of guinea pig bone marrow cells.
Guinea pig bone marrow cells were separated by buoyant density utilizing linear gradients of bovine serum albumin (BSA). It has finally become possible to characterize the cells present in the density fractions in terms of classical morphology. The development of the Cell Type computer program which calculates the percentages of the individual types of cells present in the fractions and their buoyant density distributions and plots the data has greatly facilitated and improved the accuracy of these studies. Approximately 40 cell types were observed in guinea pig bone marrow. Cells with definitive morphologies such as erythrocytes, the neutrophilic series, the binucleate blast megakaryocyte precursor and cells in mitosis band as virtually single peaks. Cells which are parts of continua or can easily be wrongly classified are found in multiple peaks. The small lymphocytes which are known to be polydisperse are found as five peaks. Because of the very strong benzidine staining by the glutaraldehyde-fixed hemoglobin, some of the erythroblasts were wrongly staged, resulting in a multimodal distribution. The presence of macrocytes further complicated these distributions. The rule that the younger cells are always less dense than the mature cells was adhered to in those cases where the cells could be definitively characterized, such as the neutrophilic series and the blasts. These results indicate that morphology is a good first approximation of reality.
Specific heterologous antimacrophage serum: in vitro effects, and the effect on the efferent arm of cutaneous delayed hypersensitivity.
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Platelets in host resistance: in vitro interaction of platelets, bacteria and polymorphonuclear leukocytes.
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Mapping of concanavalin A binding sites on the surface of several cell types.
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Cryofibrinogenemia: incidence, clinical correlations, and a review of the literature.
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Studies on a crystalline myeloma protein.
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Microdetermination of lead in blood by flameless atomic absorption spectrometry.
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Passive transfer and labelling studies on the cell infiltrate in experimental allergic encephalomyelitis.
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The thymus and the tolerance function.
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Role of the thymus in tolerance. II. Transfer of specific unresponsiveness to BSA with thymus grafting.
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Role of the thymus in tolerance. I. Tolerance to bovine gamma globulin in thymectomized, irradiated rats grafted with thymus from tolerant donors.
Rats thymectomized and irradiated as adults were restored to immunologic reactivity by grafts of normal adult rat thymus and bone marrow. Reactivity of the delayed (cellular) type and formation of mercaptoethanol-sensitive (MES) and mercaptoethanol-resistant (MER) antibody returned within 3 weeks, while Arthus reactivity remained subnormal till 9 weeks after irradiation and grafting. When the thymus donor was tolerant to BGG, the recipient showed specific non-reactivity to this antigen 3 weeks and, to a much lesser extent, 6 weeks after grafting. This non-reactivity affected delayed responses and MER antibody. No effect was noted on Arthus reactivity and a slight effect on MES antibody. Controls showed that the non-reactivity was not due to transfer of free antigen at the time of grafting. It was concluded that different source organs are responsible for different immune functions and that specific immunologic tolerance may be induced within such an organ as the thymus.
Electrophoretic charge density and persistence length of DNA as measured by fluorescence microscopy.
Individual ethidium-stained DNA molecules, embedded in an agarose gel made with electrophoresis buffer (0.05 molar salt), are observed using a fluorescence microscope. In the first experiment, open circular 66 kilobase pair (kbp) plasmids, immobilized by agarose fibers threaded through their centers, display entropic "rubber" elasticity. The charged molecules extend in an electric field of several volts per centimeter and contract to a compact random coil when the field is removed. The extension of the plasmids as a function of field strength is consistent with the freely jointed chain model when the effective electrophoretic charge density is set at 15 e-per persistence length. In a second experiment, stained linear 48.5 kbp DNA molecules are observed as random coils immobilized in agarose. A measure of their size, here named the "maximal-X-extent," is taken for 100 molecules and found to average 1.47 mu. A Monte Carlo computer simulation of random coils (freely jointed chain model) gives the same maximal-X-extent value when the persistence length is set at 0.08 mu.
The rhodopsin cycle is preserved in IRBP "knockout" mice despite abnormalities in retinal structure and function.
In the vertebrate retina, vision is initiated and maintained by the photolysis and regeneration, respectively, of light-sensitive pigments in the disk membranes of the photoreceptor outer segments. This cyclical process depends on an exchange of retinoids between the photoreceptors and the retinal pigment epithelium (RPE). There is a great deal of indirect evidence that the transport of retinoids between these cellular compartments is mediated by the interphotoreceptor retinoid-binding protein (IRBP), a large glycoprotein synthesized in the photoreceptors and extruded into the interphotoreceptor matrix (IPM) that fills the subretinal space. Nevertheless, a number of in vitro experiments have demonstrated that an intermembranous transfer of retinoids can occur through an aqueous medium independent of any retinoid-binding protein. This led to the suggestion that IRBP may play the more passive role of an extracellular buffer, serving to prevent the degradation and potentially cytotoxic effects of free retinoids when large amounts are released into the IPM. We have studied the structural and functional properties of transgenic mice in which homologous recombination was used to delete the IRBP gene. Light- and electron-microscopic examination of the retinas of "knockout" (IRBP-/-) mice revealed a significant loss of photoreceptor nuclei, and profound changes in the structure and organization of the receptor outer segments. Consistent with these observations, electroretinographic recordings showed a marked reduction in response amplitude for both rod- and cone-mediated potentials. However, despite the histological and electrophysiological changes, there was no evidence of gross abnormalities in the visual cycle. After bleaching a significant fraction of the available rhodopsin, electroretinogram amplitude and rhodopsin density gradually increased toward their pre-bleach levels, and the rates of recovery were even more rapid than those seen in wild-type (IRBP+/+) mice.
Lichen striatus: simultaneous occurrence in two nonrelated siblings.
Lichen striatus is an uncommon, self-limited eruption of unknown etiology. What role genetic or environmental influences play in its pathogenesis is unclear. We report two nonrelated, adopted children living in the same household who simultaneously developed lichen striatus.
The use of C0t-1 probe DNA for the detection of low levels of DNA fragmentation.
In many apoptotic systems the final demise of the DNA results in the generation of multinucleosomal-sized DNA fragments, which appear as a DNA ladder after agarose electrophoresis. Extensive DNA fragmentation can be detected by ethidium bromide staining. Visualization of low levels of DNA fragmentation, however, requires both a more sensitive detection system, as well as a method of DNA extraction, that limits the extent of high molecular weight DNA shearing. We have found that the use of C0t-1 repetitive DNA as a probe for Southern analysis of DNA ladders is a sensitive method to detect low levels of DNA fragmentation. We have applied this methodology in the detection of DNA fragmentation in the normal developing C57BL/6 mouse retina at stages in which there is known DNA fragmentation, as well as in human Y-79 retinoblastoma cells grown in culture. We have found that in many instances in which there is no detectable DNA ladder with ethidium bromide staining a very definitive DNA ladder can be visualized via Southern blot analysis with a C0t-1 DNA probe.