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Biomedical subjects

S C Thompson

Publications and source records attributed to S C Thompson.

At least 73 records · Page 4Linked to original sources

Characterization of a cell surface adhesion molecule expressed by a subset of developing chick neurons.

We have isolated a 105-kDa membrane glycoprotein expressed by subsets of developing chick neurons. This glycoprotein, identified by the JC7 monoclonal antibody, is present on the surface of axons and cell bodies of developing spinal motor neurons, dorsal root ganglion sensory neurons, sympathetic and parasympathetic neurons, and a small subset of brain neurons. Late in development the JC7 antigen is expressed at high levels on CNS nonneuronal glial-like cells. When attached to latex beads this glycoprotein can mediate homophilic adhesion and when used as a culture substrate stimulates a highly branched pattern of neurite outgrowth from dorsal root ganglion explants. The JC7 antigen appears to be identical to the SC1, BEN, and DM antigens. Its limited distribution, adhesive qualities, and ability to stimulate neurite outgrowth suggest it may play a role in the selective growth of neural processes during development.

Animals↗

A demonstration of the intrinsic importance of stabilizing hydrophobic binding and non-covalent van der Waals contacts dominant in the non-covalent CC-1065/B-DNA binding.

The comparative DNA binding properties and cytotoxic activity of CDPIn methyl esters (n = 1-5) vs. PDE-In methyl esters (n = 1-3) are detailed in studies which provide experimental evidence for the intrinsic importance of stabilizing hydrophobic binding and non-covalent van der Waals contacts dominant in the CC-1065/B-DNA minor groove binding. High affinity minor groove binding to DNA was established through: (1) the observation of CDPI3 binding (UV) but not unwinding of supercoiled DNA (phi 174 RFI DNA) thus excluding intercalative binding; (2) the observation of CDPI3 binding to T4 phage DNA (UV, delta Tm) in which the major groove is occluded by glycosylation thus excluding major groove binding; (3) the observation of salt (Na+) concentration independent high affinity CDPI3 binding to poly(dA . poly(dT) thus excluding simple electrostatic binding to the DNA phosphate backbone; and further inferred through (4) the observation of an intense induced dichroism (ICD, poly(dA) . poly(dT) and poly(dG) . poly(dC) [phi]23(358) = 24,000 and 23,500). This high affinity minor groove binding is sufficient to produce a potent cytotoxic effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Patient-oriented interventions to improve communication in a medical office visit.

Examined a simple intervention to improve the patient's contribution to communication in a medical office visit. In the first study, women awaiting a medical appointment were randomly assigned either to a group that was asked to list three questions to ask their physician or to a control group. Women who listed questions asked more questions in the visit and reported being less anxious. In the second study, a third group that received a message from their physician encouraging question asking was added. Both experimental groups asked more of the questions they had wished to, had greater feelings of control, and were more satisfied with the visit in general and with the information they received. The two experimental groups did not differ significantly, suggesting that the effect may be attributed either to thinking one's questions out ahead of time or to the perception that one's physician is open to questions.

Anxiety↗

Fetal pig pancreas. Preparation and assessment of tissue for transplantation, and its in vivo development and function in athymic (nude) mice.

The possibility of using xenogeneic islets for transplantation in insulin-dependent diabetes mellitus (IDDM) necessitates characterization of their potential for growth and functional differentiation. Fetal pig pancreas (FPP) of various gestational ages was examined with respect to morphology, ability to produce insulin before and during culture, and development and function in nude mice. Insulin-containing beta cells were present, but distinct islets were not apparent in FPP even in late gestation, and did not develop during culture. FPP remained viable and produced insulin for up to 30 days in vitro. Mitotic figures were seen in cultured tissue. Culture on a gelfoam raft resulted in more viable tissue than free-floating culture. Culture in a high concentration of O2 (90% O2/10% CO2) was detrimental compared with culture in 10% CO2 in air. Responses to static incubation in secretagogues showed that IMBX, theophylline, and tolbutamide all stimulated insulin secretion, but high glucose concentration (5 g/L), arginine, and leucine did not. The potential of this tissue for growth and its ability to regulate blood glucose levels appropriately were tested in athymic (nu/nu) mice. Pancreatic tissue from fetuses as young as 4 weeks gestation showed growth after transplantation into athymic mice, with representation of the major pancreatic endocrine cells demonstrated by selective immunochemical staining. The increase in the size of the grafts showed an impressive proliferative capacity, and histology confirmed mitotic activity and islet structure in the graft. The amount of endocrine tissue in grafts reflected the condition of the explants at the time of grafting, and prolonged culture times were detrimental to eventual graft size. Functional capability of the grafted FPP to release insulin in response to hyperglycemia was tested by transplantation into mice made diabetic with streptozotocin. Blood glucose levels, animal weights and survival, and the histological appearance of the tissue after graft nephrectomy indicated that either fresh tissue or tissue cultured for up to 8 days (Gelfoam; 10% CO2 in air) had better eventual graft function then FPP grown in 90% O2 or transplanted as a secondary graft following an interim period to allow gestational maturation in a nondiabetic nu/nu host. Return to euglycemia took 3-4 months after transplantation of FPP. The in vitro characteristics of FPP are similar to those reported for human fetal tissue, and since FPP is capable of growth and proliferation in vivo and has the ability to normalize hyperglycemia, further investigation of FPP to establish its suitability as a source of xenogeneic insulin-secreting tissue for human transplantation is warranted.

Animals↗

Psychosocial adjustment following a stroke.

A stroke can be a serious and debilitating health problem. The present study examined the effect of the severity of the stroke, patients' cognitive adaptation to their situation, the relationship with the caregiver and caregivers' adaptation on patient depression and motivation in outpatient therapy. Forty poststroke patients and their primary caregivers (usually a spouse) were interviewed an average of 9 months poststroke. Three independent predictors of depression were identified: a lack of meaningfulness in life, overprotection by the caregiver, and a less recent stroke. Motivation was independently related to less overprotection and lower perceptions of control over recovery. It was found that psychosocial factors predicted depression and motivation even when the effects of severity and site of the stroke were controlled for. The implications of cognitive adaptation and social support ideas for coping with a stroke are discussed.

Adaptation, Psychological↗

Perceiving mitosis in eukaryotic cells.

A sensitive method has been developed for visualizing eukaryotic cells in mitosis (M) phase. It employs Zenker's fixative, which makes the plasma membrane but not the nuclear envelope permeable to immunoglobulins. Zenker's-fixed cells are exposed to an antibody which recognizes a major constituent of chromatin. In this case the antibody is a monoclonal (MC 21) which recognizes histone H2b. Because cells in M phase do not have an intact nuclear envelope, the antibody has access to and interacts with their chromatin. The presence of a nuclear envelope in Zenker's-fixed interphase cells precludes access of the antibody to the nuclear chromatin. Consequently, this indirect immunofluorescence procedure selectively labels M-phase cells. At high enough magnification some details of the chromatin figures are revealed. MC 21 recognizes the chromatin of cells of many different species. With appropriate fixation it can be used effectively on cells in culture. With some procedural modifications it can also be used with more complex tissue systems. Detailed mitotic patterns for chick embryos up to Day 3 of development have been obtained by this method.

Animals↗

The effect of immunosuppressive agents on lymphocyte subsets in rat peripheral blood.

A method for monitoring circulating lymphocytes subsets in the rat on an automated flow cytometer with monoclonal antibodies was used to ascertain in vivo effects of various doses of immunosuppressive agents. The agents tested were anti-lymphocyte serum (ALS), azathioprine (AZA), cyclophosphamide (CTX), cyclosporin A (CsA) and methylprednisolone (MP). Each immunosuppressive agent varied in its capacity to induce changes in T cell subsets and B cell numbers. The rapidity of onset of action of the agents varied considerably; with ALS and MP maximal effects were seen within hours whilst the effects with CsA, cyclophosphamide (CTX) and azathioprine (AZA) took several days to develop. ALS had marked anti-T cell activity but did not selectively affect the T cell subsets. AZA and CTX both exerted their major effect upon the B cell (OX4+) subpopulation. CsA administration was associated with the appearance of many circulating lymphocytes which expressed the pan-T marker (W3/13) but neither of the T cell subset markers (W3/25, OX8). With CsA there was no significant alteration in the W3/25:OX8 ratio, although a persistent decrease in the number of all T lymphocytes was observed after administration of this drug at a dose of 45 mg/kg had ceased. MP was the only drug which had a marked selective effect on a T cell subset. The numbers of circulating Class II major histocompatibility complex (MHC) reactive lymphocytes (W3/25+) were significantly more depressed than the Class I MHC reactive subset (OX8+). This effect persisted for up to 31 days after the single injection of a depot preparation of this drug, and was found to be associated with prolonged survival of precultured endocrine xenografts.

Animals↗

Factors affecting psychological adjustment to a fetal death.

The loss of a child in utero can be a tragic experience. The purpose of the present study was to examine some patient characteristics that may predict which women are likely to have problems in adjusting to the loss and to examine the effectiveness of interventions by care providers in facilitating emotional recovery. Twenty-eight women who were no more than 4 weeks post partum from a fetal death were interviewed while waiting to see their physicians at the fetal demise clinic at Los Angeles County Women's Hospital. It was found that women were less depressed after the loss if they already had children, if they did not blame themselves for the death, and if they received a picture of the infant or were allowed to see the infant. Women benefited from sympathy from the medical personnel and being kept informed of problems as they developed.

Adaptation, Psychological↗

Streptonigrin and lavendamycin partial structures. Probes for the minimum, potent pharmacophore of streptonigrin, lavendamycin, and synthetic quinoline-5,8-diones.

The preparation and evaluation of 7-amino-5,8-dioxo-2-(2'-pyridyl)quinoline-6'-carboxylic acid (5a) and 7-amino-2-(2'-aminophenyl)-5,8-dioxoquinoline-5'-carboxylic acid (6a) constituting potential minimum, potent pharmacophores of streptonigrin (1a) and lavendamycin (2a), two structurally related naturally occurring antitumor antibiotics, are detailed. In contrast to observations associated with streptonigrin and lavendamycin in which the C-ring C-6' carboxylic acid potentiates the antitumor, antimicrobial, and cytotoxic properties of the naturally occurring, substituted 7-aminoquinoline-5,8-dione AB ring systems, the C-6'/C-5' carboxylic acid of 5a/6a diminishes the observed antimicrobial and cytotoxic properties of the 2-(2'-pyridyl)- and 2-(2'-aminophenyl)-7-aminoquinoline-5,8-diones. A direct comparison of the antimicrobial and cytotoxic properties of a complete set of streptonigrin and lavendamycin partial structures is detailed in efforts to define the role peripheral substituents play in potentiating the biological properties of the naturally occurring and synthetic agents bearing the 7-aminoquinoline-5,8-dione AB ring system and in efforts to define the minimum, potent pharmacophore of the naturally occurring antitumor antibiotics. The relationship of these observations to a chemical mechanism of cellular toxicity is discussed.

Animals↗

Sequential monitoring of peripheral blood lymphocyte subsets in rats.

The methodology of enumeration of T cell subsets in humans is well established and has widespread clinical application. Sequential monitoring of lymphocyte subsets in small animals requires a consistent and reliable methodology for staining and enumerating lymphocyte populations. The optimal conditions for enumerating subclasses of rat peripheral blood lymphocytes with the Spectrum III flow cytometer are described. The sources of biological variation and technical error that were considered in optimizing the techniques and the limitations in applying them are discussed.

Animals↗

The effects of the organophosphate insecticide malathion on very young chick embryos: malformations detected by histological examination.

This histological study sought to determine the nature and incidence of developmental abnormalities induced by one of the reportedly least teratogenic of insecticides injected into very young chick embryos. Using techniques to assure rapid contact between injectant and embryo, eggs incubated for 24, 48, or 72 hr were injected with corn oil or 125 micrograms-4.0 mg malathion. The embryos were recovered 48 hr later, paraffin-embedded, serially cross-sectioned, and examined in detail. Structures affected (and the nature of the defects) were as follows: wing level notochord and spinal cord (folded or undulated); trunk/leg level spinal cord (variously, neural folds unfused, roof infolded, canal partitioned, etc.); eye (lens misshapen or severely thinned, optic cup incompletely invaginated); diencephalon (epiphysis bifurcated or off-center, supernumerary outgrowths); cardiovascular structures (atrium and major blood vessels enlarged); and tailbud (curled into hindgut: ourentery). Overall incidence was both dose- and age-related, doubling for each doubling of dose and tripling for each 24 hr less age at exposure. For most (not all) individual structures, incidence was greatest when exposed at 24 hr and nil at 72 hr. Severity of effect was not consistently dose- or age-dependent. We conclude that contrary to previous reports, 24- to 72-hr embryos are highly vulnerable to insecticide exposure, with the youngest the most vulnerable, and many of the defects detected may be attributed to either of two mechanisms: failure in formation of the supportive sheath, or factors that cause epithelial morphogenesis (e.g., microtubules, microfilaments, extracellular material, cell-to-cell adhesion mechanisms). Previous observations that 1- to 3-day embryos are relatively unresponsive to insecticides are probably artifactual owing to imprecise techniques.

Abnormalities, Drug-Induced↗