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Biomedical subjects

A Lloyd

Publications and source records attributed to A Lloyd.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise.

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS). Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue. No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients' levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise. These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.

Adult↗
PubMed1994

Molecular cloning of lsk, a carboxyl-terminal src kinase (csk) related gene, expressed in leukocytes.

Regulation of the activity of src-family kinases is thought to occur, in part, through the phosphorylation of conserved carboxyl-terminal tyrosine residues. Although the src-family includes several molecules with tissue or cell-type restricted expression, the only kinase implicated in the regulatory phosphorylation of these enzymes is p50csk. Herein we report the molecular cloning of a tissue specific p50csk-related gene. Like p50csk, the deduced protein sequence of this novel cDNA includes a tyrosine kinase catalytic domain, SH2 and SH3 domains, a short amino terminus, and no autophosphorylation or carboxyl-terminal tyrosine residues. Additionally, neither this novel kinase nor p50csk contain the amino-terminal myristoylation site characteristic of the src-family. However, whereas csk is ubiquitously expressed, mRNA corresponding to this novel gene is expressed in brain, natural killer (NK) cells, and activated T cells but not in a variety of other tissues and cell lines. In agreement with the mRNA expression pattern, antiserum reactive with the predicted carboxyl-terminus of the cDNA recognizes a 57 kDa polypeptide in immunoblots of NK cells and PHA-activated T cells. Because of its limited expression and high homology to p50csk, we named this gene lsk; leukocyte carboxyl-terminal src kinase related gene. Identification of a molecule like lsk suggests the existence of tissue specific src-regulatory pathways that function in activated lymphocytes.

Amino Acid Sequence↗
PubMed1993

Nitric oxide-regulated endogenous ADP-ribosylation of rod outer segment proteins.

Both membrane and cytosolic fractions of retinal rod outer segments contain ADP-ribosylases that modify proteins in the respective fractions. Nitroprusside and endogenously produced NO regulate the activities of these ADP-ribosylases. The ADP-ribosylation of the membrane proteins of molecular weight 116K, 66K and 46K is inhibited by NO and nitroprusside, while that of the 38K cytosolic protein and the 39K membrane-associated protein is activated. The 39K protein is identified as the alpha-subunit of G-protein. The ADP-ribosylation of this protein is activated 6 to 11-fold by NO suggesting that NO may play a significant role in modulating the activity of G-protein in visual transduction.

Adenosine Diphosphate Ribose↗
PubMed1993

Impaired in vivo immune responses in patients with melancholia.

Previous attempts to establish a relationship between impaired cell-mediated immunity (CMI) and major mood disorders have been limited by a failure to explore the relevance of depressive subcategories or to assess CMI by in vivo methods. In this case-control study CMI was assessed in 57 patients with major depression (31 with melancholic, 26 with non-melancholic disorders), and in age- and sex-matched controls by both in vitro and in vivo immunological techniques. Compared with control subjects and patients with non-melancholic depression, patients with melancholia demonstrated reduced in vivo CMI as assessed by delayed-type hypersensitivity (DTH) skin responses. Although increasing age, severity of depression, hospital admission for treatment, and reported weight loss are correlates of melancholia, none of these factors alone, or in combination, accounted for the differences in DTH responses observed between the two depressive subtypes. These data suggest that impaired CMI in vivo may be limited to those with melancholic disorders. At this stage the factors which account for this effect are unclear.

Age Factors↗
PubMed1992

Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C.

A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.

Animals↗
PubMed1992

The role of cytokines in the pathogenesis of inflammatory eye disease.

A coherent view of the role of cytokines in inflammatory eye disease is emerging as a result of studies both in man and experimental animals. Cytokines have been demonstrated in ocular tissue obtained from patients with intraocular inflammation (uveitis) (gamma interferon, IL-2) and have been shown to induce inflammation in experimental animals after intraocular injection [(IL-1, IL-6, IL-8, tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF)]. Several unique features of the immunology of the eye such as the immunosuppression associated with anterior chamber associated immune deviation (ACAID) may be due to the effects of cytokines. Similarly, common complications of ocular inflammation such as glaucoma, keratic precipitates, retinal (macular) oedema and neovascularization may be mediated by cytokines. Understanding of the role of cytokines in inflammatory eye disease has the potential to lead to the development of therapies to abrogate the effects of these important mediators of the inflammatory response.

Animals↗
PubMed1992

Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression.

The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.

Adolescent↗
PubMed1992

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI). This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression.

Adolescent↗
PubMed1991

Transformation suppressor activity of a Jun transcription factor lacking its activation domain.

The oncoprotein c-Jun is thought to be a mediator of ras transformation as both its synthesis and activity as a transcription factor are stimulated by ras expression. But c-Jun co-operates with ras in transformation assays, suggesting that they act along different pathways (reviewed in ref. 4). Here we show by means of a dominant-negative mutated transcription factor that c-Jun potentially in conjunction with other factors that interact with it is necessary for transformation by ras. The mutant Jun lacks an activation domain and blocks stimulation of transcription by several oncoproteins, including Ras, v-Src, polyoma middle T, c-Jun and c-Fos, as well as by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibition is specific for motifs that bind Jun: activation of an NF-kappa B/Rel motif is not affected. This Jun mutant acts as an anti-oncogene in ras-transformed cells, generating non-transformed revertants that have acquired anchorage and density-dependent growth, as well as reduced tumorigenicity in vivo. Mutants of other transcription factors designed to inhibit transformation will enable us to study their role in signal transduction.

Animals↗
PubMed1991

Characterization of two Drosophila POU domain genes, related to oct-1 and oct-2, and the regulation of their expression patterns.

We have characterized two genes from Drosophila melanogaster that encode proteins with POU domains showing a high degree of identity with the human Oct-1 and Oct-2 transcription factors. These POU domain genes, pdm-1 and pdm-2, are expressed at high levels during early embryogenesis and at lower levels throughout the rest of development. Both genes are expressed as two stripes in the presumptive abdominal region during the blastoderm stage, followed by thirteen stripes in the germ band extended stage. This pattern of expression is altered in mutants for a gap gene (hunchback) and a pair-rule gene (fushi tarazu). In later stage embryos, both pdm-1 and pdm-2 are expressed in selected neuroblasts in the ventral nervous system, with higher levels in the three thoracic segments and lower levels in the abdominal segments. The low level of expression in the abdominal segments is maintained by the genes within the bithorax complex (BX-C). We have also identified the cells in the dorsal and lateral clusters of the peripheral nervous system that express pdm-1 and pdm-2, and show that some of these cells derive from lineages that require BX-C functions. Together, these results suggest that previously characterized members of the embryonic regulatory hierarchy specify the patterns of the POU domain gene expression, which, in turn, function during neurogenesis and perhaps in earlier stages.

Amino Acid Sequence↗