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Biomedical subjects

S C Clark

Publications and source records attributed to S C Clark.

At least 199 records · Page 11Linked to original sources
PubMed1984

Expression of the 3' terminal region of human T-cell leukemia viruses.

Human T-cell leukemia viruses (HTLV) are closely associated with some human T-cell leukemias and lymphomas. A unique 3' region of the HTLV genome is believed to be involved in HTLV-induced cellular transformation, although the function of this region has yet to be determined. A subgenomic messenger RNA transcribed from this region of HTLV has now been characterized. These results provide direct evidence for the expression of a novel gene in HTLV.

Base Sequence↗
PubMed1984

Response of resting human peripheral blood natural killer cells to interleukin 2.

The present study shows that recombinant interleukin 2 (IL-2) purified to homogeneity induces a rapid and potent enhancement of spontaneous cytotoxicity of human peripheral blood lymphocytes. The cells mediating cytotoxicity after 18-h treatment with IL-2 have surface markers of natural killer (NK) cells and are generated from the peripheral blood subset containing spontaneous cytotoxic cells. A parallel production of gamma interferon (IFN-gamma) is induced by recombinant IL-2 (rIL-2), and NK cells appear to be the major producer cells, whereas T cells are unable to produce IFN-gamma under these experimental conditions. However, the kinetics of the enhancement of cytotoxicity are faster than those of IFN-gamma production, and monoclonal anti-IFN-gamma antibodies do not suppress this effect, making it unlikely that the IFN-gamma produced is responsible for the enhancement. The enhancement of NK cell activity induced by rIL-2 precedes any proliferative response of the lymphocytes, which is instead observed in longer-term cultures of both NK and T cells.

Adjuvants, Immunologic↗
PubMed1984

Human T-cell growth factor: partial amino acid sequence, cDNA cloning, and organization and expression in normal and leukemic cells.

The partial amino acid sequences of human T-cell growth factors (TCGFs) isolated from normal peripheral blood lymphocytes and from a leukemia T-cell line (Jurkat) show that the amino-terminal sequences of the two proteins (15 residues) are identical. Oligonucleotides based on the published Jurkat TCGF DNA sequence were used to isolate six cDNA clones of TCGF mRNA from normal lymphocytes. The predicted amino acid sequence of normal lymphocyte TCGF was identical to the sequence of the Jurkat protein, showing that the differences in biochemical properties of the two proteins result from post-translational events. Amino acid and nucleotide sequence data suggest that TCGF is derived from a precursor polypeptide that is cleaved at the amino terminus but not at the carboxyl terminus. Hybridization of the cloned lymphocyte TCGF cDNA to cellular DNA and RNA strongly suggested that the TCGF gene is expressed as a single mRNA species from a single-copy gene. No differences in the organization of the TCGF gene in normal, leukemic, and human T-cell leukemia/lymphoma virus-infected cells was detected regardless of whether they produce TCGF or not.

Amino Acid Sequence↗
PubMed1983

Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells.

Human T-cell leukemia-lymphoma virus (HTLV) has now been isolated from many different patients with cutaneous T-cell lymphoma and leukemia, as judged by detection of media reverse transcriptase and virus particles and of antigenic determinants related to those of viral structural proteins p24 and p19. Molecular hybridization experiments with HTLV cDNA to viral mRNA or proviral DNA to ascertain the relatedness of four of these new isolates to the first HTLV isolate have been used. By these assays, three appear virtually indistinguishable from the original isolate, HTLV-I(CR), the second U.S. isolate (HTLV-I[MB]), and the Japanese ATLV isolates. Proviral sequences indistinguishable from those of HTLV-I(CR) were also detected in uncultured leukemic blood leukocytes from a patient of Japanese origin with adult T-cell leukemia. These viral isolates thus form a closely related virus group, HTLV-I. In contrast, however, RNA and DNA from one cell line derived from a patient with a T-cell variant of hairy cell leukemia, which expresses media reverse transcriptase and antigenic determinants related to but distinguishable from HTLV p24, did not hybridize substantially with HTLV cDNA. This latter virus appears to represent a second type of HTLV (HTLV-II), related to but substantially different from HTLV-I.

Cell Line↗
PubMed1982

Staging laparotomy in Hodgkin's disease: Mayo Clinic experience.

Between 1967 and 1979, 316 patients with Hodgkin's disease underwent staging laparotomy. Histologic examination demonstrated lymphocyte predominance in 40 (12.7%) patients, nodular sclerosis in 178 (56.3%), mixed cellularity in 80 (25.3%), and lymphocyte depletion in seven (2.2%); results in 11 (3.5%) patients were considered unclassifiable. There were no deaths. Major complications occurred in 7.9% and required reoperation in 1.9%. Pathologic stage differed from clinical stage in 111 (35.1%) patients. In 90 (28.5%) patients, the stage advanced; in 21 (6.6%) patients, the stage was reduced; and in five (1.6%) patients, the histologic subtype was changed. Stage changes occurred in 40% of those with lymphocyte predominance, in 27.5% with nodular sclerosis, in 46.3% with mixed cellularity, and in 85.7% with lymphocyte depletion. The reliability of staging laparotomy for the determination of appropriate treatment favors its continued use.

Adolescent↗
PubMed1981

Contacts with a Canadian "street-level" Drug and Crisis Centre, 1975-1978.

This paper presents the work and functioning of the distress Centre/Drug Centre, an agency in Calgary, Alberta, Canada, which has evolved from a youth-oriented drug centre to a general crisis centre. It is staffed by volunteers who are supported by professional staff, and offers a 24-hour telephone service throughout the week. The paper reviews the continuing evolution of this service, the drugs most frequently noted in contacts involving crisis and suicide attempts, and the role of crisis centres that use volunteers as front-line workers. The years 1975-1978 were a period in which alcohol was the drug most frequently reported to be associated with crisis and attempted suicide.

Adolescent↗
PubMed1977

Therapeutic usefulness of propoxyphene napsylate in narcotic addiction.

The maximum doses of propoxyphene napsylate used to treat heroin addicts produce a degree of morphine-like activity equal to that produced by 20 to 25 mg/day of subcutaneously given morphine or 10 mg/day orally given methadone. This degree of activity wound be sufficient to ameliorate abstinence even in patients dependent on large doses of narcotics--an observation that supports the utility of propoxyphene napsylate in detoxification. On the other hand, only patients taking 10 mg/day or less of parenterally administered heroin could be maintained on maximum subtoxic levels of propoxyphene napsylate without abstinence signs or symptoms suggesting that propoxyphene napsylate would be less useful in maintenance therapy.

Administration, Oral↗
PubMed1976

Azidomorphine: subjective effects and suppression of morphine abstinence.

In man, azidomorphine, a new morphine congener, constricted pupils, produced morphine-like subjective effects and euphoria, and suppressed the morphine abstinence syndrome. Azidomorphine was 10 to 50 times as potent as morphine. It is concluded that in man azidomorphine is a typical morphine-like drug.

Azides↗
PubMed1975

Vascular responses to anaesthetic agents.

Data have been presented showing that certain general anaesthetic agents such as halothane decrease the spontaneous activity of the rabbit anterior mesenteric portal vein and decrease the response of venous and aortic strips to exogenous noradrenaline. If these observations can be extrapolated to the intact animal they may indicate that the hypotension occurring with use of such agents may be due not only to cardiac effects but also to peripheral vasodilatation and muting of reflex sympathetic vasoconstriction. Although the response to noradrenaline is antagonized, this appears to be nonspecific effect and no evidence was found for interference with noradrenaline release nor for direct actions on beta-adrenegic receptors. While the thiobarbiturates increased spontaneous activity and tone of the rabbit anterior portal vein no evidence was obtained that this occurred through release of noradrenaline from tissue stores.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Marihuana and the cardiovascular system.

The actions of marihuana on the cardiovascular system in man are the most consistent physiological effects produced by acue administration. Significant tachycardia and conjunctival injection are well established effects. When the subject is upright, marihuana produces a fall in blood pressure; however, either no significant effect or a slight increase in blood pressure occurs when the subject is supine. Marihuana has been reported to increase limb blood flow and produce no significant effect on electrocardiogram of normal subjects. It, however, interferes with the integrity of peripheral vascular reflex responses. Although the detailed mechanism of action has not been elucidated, there is evidence that marihuana produces both sympathetci nervous system stimulation and parasympathetic nervous system blockade. No data are available that indicate the acute administration of marihuana presents a significant hazard to the cardiovascular system of normal subjects.

Animals↗
PubMedDate not supplied

Molecular characterization of genome of a novel human T-cell leukaemia virus.

A novel human retrovirus (HTLV-II) was previously found associated with a T-cell variant of hairy-cell leukaemia. Molecular cloning demonstrates that the complete provirus genome is 8.8 kilobase pairs in size and is transmissible to uninfected cells. Two types of infectious deleted provirus were also characterized. The sequences of HTLV-II are distinct from those of HTLV-I.

Base Sequence↗
PubMedDate not supplied

Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator.

The polymorphonuclear leukocyte (PMN), or neutrophil, is the major host defence cell protecting the body against invasion by bacteria and fungi. Products of oxidative metabolism mediate PMN microbicidal and tumoricidal activity but the mechanisms by which these pathways become activated are not well understood. We have previously described a human granulocyte-macrophage colony-stimulating factor (GM-CSF) of relative molecular mass (Mr) 22,000 that also inhibits neutrophil motility (NIF-T activity). Because of its direct action on granulocytes, this lymphokine is a candidate for a neutrophil-activating factor. We have studied the effect of GM-CSF/NIF-T on superoxide anion generation in response to the bacterial chemo-attractant N-formylmethionyl-leucylphenylalanine (f-MLP), and report here that PMNs preincubated with either purified natural GM-CSF or biosynthetic (recombinant) GM-CSF showed increased (as much as fourfold) superoxide anion production in response to f-MLP. These results indicate that human GM-CSF is a neutrophil-activating factor.

Colony-Stimulating Factors↗
PubMedDate not supplied

Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF.

Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte-macrophage colony-stimulating factor (GM-CSF). Recently, both murine and human GM-CSF have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively, little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice, as can human urinary extracts. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.

Animals↗
PubMedDate not supplied

Suppression of in vitro haematopoiesis following human immunodeficiency virus infection.

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.

AIDS-Related Complex↗