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Biomedical subjects

J L Scott

Publications and source records attributed to J L Scott.

At least 37 records · Page 2Linked to original sources
PubMed1991

Individual embryonic fibroblasts express multiple beta chains in association with the alpha v integrin subunit. Loss of beta 3 expression with cell confluence.

The alpha chain of the vitronectin receptor, alpha v, has been found in association with the integrin subunits beta 1, beta 3, or beta 5 on different cell types. We show here that cultured embryonic fibroblasts simultaneously display alpha v beta 3, alpha v beta 1, and alpha v in association with two other beta subunits, one of which is probably beta 5. Polymerase chain reaction analysis of single cells isolated by micromanipulation identified mRNA for alpha v, beta 1, beta 3, and beta 5 in six of eight clones. Immunoprecipitation of iodinated cell surface proteins with a monoclonal antibody to alpha v indicated that the relative proportions of the different beta chains in association with alpha v varied, particularly between two different cell lines. The cytokines platelet-derived growth factor, transforming growth factor beta 1, and tumor necrosis factor alpha did not appear to alter this ratio although tumor necrosis factor alpha increased the surface expression of the alpha v-associated integrins; but overnight culture in basic fibroblast growth factor caused a lower expression of alpha v beta 1 and alpha v beta 5 with no reduction in alpha v beta 3 expression. When the cell cultures were grown to complete confluence, surface expression of beta 3 was abolished, and the expression of an unknown beta chain (beta u) became more prominent. This effect was not overcome by culturing confluent cells with basic fibroblast growth factor. Affinity column chromatography showed that alpha v beta 5 bound to vitronectin but alpha v beta 1 did not, whereas alpha v beta 1 but not alpha v beta 5 bound to fibronectin. These results suggest that, on individual cells, the beta subunits found in association with alpha v may vary according to the proliferative capacity of the cell and that the promiscuous beta 3 subunit is progressively replaced by beta subunits of individual ligand specificity.

Base Sequence↗
PubMed1989

Characterization of a novel membrane glycoprotein involved in platelet activation.

When platelets bind certain specific ligands they are induced to secrete the contents of their cytoplasmic granules and to aggregate. Studies of the molecular events accompanying this vital physiological response have led to a greater understanding of cell activation in general since the pathways involved are common to a number of cell types. By contrast most of the information about the cell surface molecules that initiate signal transduction has emerged from work on T lymphocyte activation, a process essential to the initiation of the immune response. We have described an activation antigen on T lymphocytes that is involved in the differentiation of these cells. In the present report it is demonstrated that the antigen is expressed on the platelet membrane with about 1,200 copies/platelet. A monoclonal antibody detecting this antigen stimulates platelet secretion and aggregation with a half-maximal response at approximately 10(-8) M. Characterization of the antigen, termed PTA1, reveals a glycoprotein of Mr 67,000 showing extensive N-linked carbohydrate, much of which appears to be heavily sialated. The amino-terminal sequence of PTA1, EEVLWHTSVPFAEXMSLEXVYPSM, indicates that the protein has not previously been characterized. Preliminary investigation of the mechanism by which PTA1 mediates platelet activation suggests involvement of protein kinase C and the 47-kDa protein of platelets is rapidly phosphorylated upon antibody-mediated activation. During this process PTA1 is also phosphorylated, as it is following platelet activation by the other agonists, collagen, thrombin, and 12-O-tetradecanoylphorbol 13-acetate. These results provide the first example of a cell surface glycoprotein that is directly involved in both platelet and T lymphocyte activation.

Amino Acid Sequence↗
PubMed1989

Relationships between fertility, peak milk yields and lactational persistency in dairy cows.

Peak milk yield, lactational persistency and conception rates were studied using 5928 lactation records of high milk-producing cows at three California dairies. Log-linear analysis was used to study relationships between peak milk yield, lactational persistency, dairy of origin, lactation number and conception rates in 3850 completed lactations. Cows with peak milk yields greater than the median (38.2 kg milk per day) were less likely to have conceived in one or two breedings than cows with peak milk yields lower than or equal to the median. Cows with a higher than median (0.755) lactational persistency were less likely to have conceived in one or two breedings than cows with a lactational persistency lower than or equal to the median. Dairy of origin had a significant effect on the probability of conceiving in one or two breedings. Cows in the first lactation were more likely than those in subsequent lactations to conceive in one or two breedings. This retrospective study demonstrated that subfertility is associated with high peak lactational yields in high milk-producing California cows.

Journal Article↗
PubMed1989

TGF beta down-regulates TLiSA1 expression and inhibits the differentiation of precursor lymphocytes into CTL and LAK cells.

This study analysed the regulatory effects of transforming growth factor beta (TGF beta) on the expression of a 70,000 MW cell surface activation antigen, TLiSA1, involved in the differentiation of cytotoxic T lymphocytes (CTL) and lymphokine-activated killer (LAK) cells from their precursor(s), and also examined the role of TGF beta in the generation of these functional cells. TGF beta was shown to suppress the expression of TLiSA1 and to inhibit, in a dose-dependent manner, the generation of both CTL and LAK cells when present from the beginning of mixed lymphocyte culture; the same inhibitory effect upon the development of cytotoxic effector cells was observed with a monoclonal antibody and with monospecific rabbit antibodies against the TLiSA1 protein. Antibody to TGF beta reversed the inhibitory effect of the cytokine on differentiation and on TLiSA1 expression. Exogenous IL-2 or, to a lesser extent, tumour necrosis factor alpha (TNF alpha) added to mixed lymphocyte cultures (MLC) augmented both TLiSA1 antigen expression and cytotoxic function by the resulting blast cells; the co-addition of TGF beta inhibited both of these cytokine-mediated effects. Similarly, it was shown that phytohaemagglutini (PHA)-induced lymphoblasts up-regulate their surface expression of TLiSA1 and exhibit increased LAK activity in response to IL-2, and TGF beta inhibited both of these events; this IL-2-induced increase in LAK cell function was also inhibited by antibodies to TLiSA1. It is suggested that TLiSA1 antigen expression is intimately linked to the differentiation of cytotoxic effector cells and that such differentiation may be a distinct process from IL-2-induced proliferation, although both events can be regulated by TGF-beta.

Antigens, Surface↗
PubMed1985

QT interval prolongation.

The QT interval is a function of ventricular repolarization time and is measured from the onset of the QRS complex to the end of the T wave. The length of this interval is inversely related to heart rate. A prolonged QT interval is most often secondary to the use of Type I antidysrhythmic medications (quinidine, procainamide). It is also associated with phenothiazines, organophosphates, hypocalcemia, liquid protein diets and the congenital long QT syndromes. QT prolongation is associated with a variety of ventricular dysrhythmias, most characteristically Torsades des pointes. Treatment consists of correction of the underlying metabolic disorder or discontinuation of the offending medication.

Adrenergic beta-Antagonists↗
PubMed1985

Centipedal hemocyanin: its structure and its implications for arthropod phylogeny.

The oxygen carrier hemocyanin occurs in the blood of Scutigera coleoptrata, a uniramous arthropod, as well as the crustaceans and chelicerates. The native polymer appears to be composed of substructures having the same size and electron-dense image as those of other arthropod hemocyanins but assembled into a unique multiple and arranged in a unique configuration. The simplest explanation of these findings is that the arthropod hemocyanins have a common origin, exemplifying a derived (as opposed to primitive) character shared by each of the three living groups.

Amino Acids↗
PubMed1984

Actinomyces hordeovulneris, a canine pathogen that produces L-phase variants spontaneously with coincident calcium deposition.

The spontaneous production of cell-wall-deficient filaments and protoplasts by a strain of Actinomyces hordeovulneris (UCD 81-332-9) in 10% sucrose L-form media is reported. Multiple mineral deposits were present within the variants at 48 hours. Electron microscopy revealed that these deposits were amorphous, dense, and at the inner face of the cytoplasmic membrane in wall-less protoplasts and also in filaments which had a thin wall of 10 nm. These cell-wall-deficient variants produced L-form colonies when cultured for an additional 48 hours on 10% sucrose-BYE L-form plates. The colonies were composed of only a few filaments and many vesicles which were negative with Dienes' stain. Silver substitution stains of UCD 81-332-9 cells that had been grown in L-form broth for 5 days revealed heavy calcification of all cells including protoplasts. Gram stains of L-form grown cells revealed the presence of long-beaded, infrequently branched gram-positive filaments similar to those observed in clinical specimens. The formation of cell wall-deficient variants with coincident mineralization is believed to be related to the phenomenon of sulfur granule formation in vivo.

Actinomyces↗
PubMed1983

Nocardia asteroides recovery from a dog with steroid- and antibiotic-unresponsive idiopathic polyarthritis.

This report describes a fatal case of idiopathic polyarthritis in a dog that was partially responsive to vigorous immunosuppressive treatment. Synovial fluids were cultured for L-forms at the following stages of disease: (i) acute arthritic relapse, (ii) incomplete remission, and (iii) death. Nocardia asteroides UCD 1-581 was recovered from the L-form broth culture of the specimen taken during acute relapse, 5 weeks after inoculation, but not at any other stage of disease. Numerous conventional microbiological cultures were unproductive during all phases. Changes occurring in L-form plates included the formation of large irregular mineral deposits and many transferable bodies resembling pseudocolonies. Microscopic examination revealed the presence of many intracellular golden-brown granules and acid-fast bodies in macrophages of the lung and bronchial lymph node tissues. The granules are believed to be the variants embedded in calcium deposits similar to those which developed in the L-form cultures in vitro. Fluorescence of these acid-fast bodies with antibody specific for superoxide dismutase of N. asteroides GUH-2 and labeled anti-immunoglobulin G established their relationship to the isolate. The unrelenting course of disease and the persistence of N. asteroides as an L-form in this animal despite vigorous immunosuppression suggest that this organism plays a direct role in the etiology of this disease.

Adrenal Cortex Hormones↗
PubMed1981

Natural killer cell activity in a population of leukemia-prone wild mice (Mus musculus).

Natural cell-mediated cytotoxicity against YAC-I targets was measured in splenocytes from leukemia-prone wild mice trapped near Lake Casitas (LC) in southern California. Cytotoxicity was mediated by cells that were non-adherent to nylon wool, non-phagocytic and resistant to thy-1.2 antiserum plus complement. Natural MuLV viremia in LC mice did not impair splenic cytotoxicity against TAC-I target cells, Cells infected with amphotropic and ecotropic MuLV of wild mouse origin were not appreciably lysed by LC splenic effectors. Although variable levels of cytotoxicity were detected against TAC-1 by normal spleen cells, consistently low levels of cytotoxicity against allogenic LC lymphoma, sarcoma and carcinoma targets were found using the same splenocytes. These results indicate that LC mice possess splenocytes with the characteristics of natural killer (NK) cells as defined in inbred mice. The resistance of LC-derived targets to lysis by LC NK cells suggests that NK cells may not be involved in natural tumor immunosurveillance or that the development of spontaneous tumors may involve escape from NK-mediated effector mechanisms.

Animals↗
PubMed1981

Immunopathology of natural and experimental lymphomas induced by wild mouse leukemia virus.

Naturally occurring lymphomas of Lake Casitas (LC) wild mice, and the lymphomas induced by LC murine leukemia virus (MuLV) in Swiss mice from the National Institutes of Health, displayed remarkably similar gross, microscopic, and functional characteristics. They spared the thymus, arose primarily in the splenic red pulp, became leukemic, and were comprised of stem cells lacking classic T- and B-cell markers. Cytoplasmic and surface immunoglobulin were undetectable in 34 of 35 spontaneous LC lymphomas and in any of ten LC MuLV-induced lymphomas in NIH Swiss mice. Assays for immunoglobulin secretion, complement (C'3) and Fc receptors, Thy 1.1,2 antigens, Ly 1,2 antigens, and erythroid and myeloid markers were negative on all of the spontaneous and experimental lymphomas. Cell lines were derived from five spontaneous lymphomas of LC mice. Three lines were characterized as null cells, one line as B cells, and one line as macrophages. All cell lines were diploid. The wild mouse spontaneous lymphomas, and lymphomas experimentally induced by LC MuLV in laboratory mice, provide a useful model for childhood acute lymphoblastic leukemia and for study of the early steps of B-lymphocyte differentiation.

Animals↗
PubMed1979

Acute leukemia following prolonged cytotoxic agent therapy.

1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. Multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.

Adult↗
PubMed1978

Aplastic anemia associated with type B viral hepatitis.

Aplastic anemia is a recognized complication of viral hepatitis, but, to our knowledge, no cases associated with type B hepatitis have been described. We report the case of a patient who developed severe aplastic anemia very early in the course of infection with hepatitis B virus.

Adult↗