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Biomedical subjects

C Ellis

Publications and source records attributed to C Ellis.

At least 19 recordsLinked to original sources
PubMed1995

Carbon monoxide generation from hydrocarbons at ambient and physiological temperature: a sensitive indicator of oxidant damage?

This paper shows that a variety of carbon-containing materials (wool, cotton, wood, paper, latex, Tygon) release CO during incubation at ambient temperature. This CO production was enhanced by aerobic versus anaerobic incubation, increasing temperature, and exposure to fluorescent light. CO production from glucose solutions was enhanced by alkaline pH or prior boiling or autoclaving and reduced by the presence of superoxide dismutase or catalase. We conclude that a variety of materials are constantly undergoing oxidation at ambient or physiological temperature as evidenced by the release of CO. Measurements of this CO production could provide a simple, rapid and sensitive means of assessing oxidative damage.

Carbon Monoxide↗
PubMed1994

Calcineurin immunoreactivity in Alzheimer's disease.

Aberrant phosphorylation of tau is linked to formation of the paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases such as mitogen-activated protein kinase, and calcium-regulated protein kinases may, in part, be responsible for addition of phosphate groups to serine residues of PHFtau; however, less is known concerning the phosphatases which regulate tau. In this report, we used several well-characterized antibodies to document calcineurin immunoreactivity in brain tissue from patients with Alzheimer's disease. We now report that levels of immunoreactive calcineurin are not significantly altered in neocortex and cerebellum of Alzheimer's patients relative to similar regions of age-matched controls. Immunocytochemical studies indicated that calcineurin immunoreactivity was present in dendrites and perikarya of many different neuronal populations in both control and Alzheimer brain. When specific antibodies against PHFtau were used in double-labeling experiments with anti-calcineurin antibodies, calcineurin immunoreactivity was seen in association with neurofibrillary tangles. However, calcineurin was not seen in all tangle bearing neurons. These data suggest that calcineurin levels per se are not significantly altered in Alzheimer's disease, but that calcineurin is distributed around some neurofibrillary tangles and may play a role in regulation of tau phosphorylation.

Aged↗
PubMed1994

Methanogens outcompete sulphate reducing bacteria for H2 in the human colon.

Methanogens and sulphate reducing bacteria compete for H2 in the human colon, and, as a result, faeces usually contain high concentrations of just one of these two organisms. There is controversy over which of these organisms wins the competition for H2, although theoretical data suggest that sulphate reducing bacteria should predominate. To elucidate this question experiments were undertaken in which sulphate enriched homogenates of human sulphate reducing faeces and methane producing faeces were incubated separately or mixed together. Co-incubation of sulphate reducing faeces with methanogenic faeces resulted in a sixfold reduction in the activity of the sulphate reducing bacteria (measured as sulphide production), whereas methane production was not inhibited by co-incubation with sulphate reducing bacteria. Methanogenic faeces also consumed H2 more rapidly and reduced the H2 tension of the homogenate to a lower value than did sulphate reducing faecal samples. In these experiments, methanogens seem to outcompete sulphate reducing bacteria for H2.

Adult↗
PubMed1993

Atypical pneumonias.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1992

Heat shock protein Hsp60-reactive gamma delta cells: a large, diversified T-lymphocyte subset with highly focused specificity.

Previously, we detected a subset of gamma delta T cells in the newborn mouse thymus that responded to the mycobacterial heat shock protein Hsp60, as well as with what seemed to be a self-antigen. All of these cells expressed V gamma 1, most often in association with V delta 6+. It was not clear, however, whether similar, mature gamma delta cells with Hsp60 reactivity are common outside of the thymus, or rather, whether they are largely eliminated during development. From the data presented here, we estimate that gamma delta cells responding to Hsp60 comprise 10-20% of normal splenic and lymph node gamma delta T cells. Such cells, derived from adult spleen, always express a V gamma 1-J gamma 4-C gamma 4 gamma chain, although not all cells with this gamma chain show Hsp60 reactivity. Many of these V gamma 1+ cells also express V delta 6-J delta 1-C delta, though fewer than in V gamma 1+ cells from the newborn thymus. Extensive diversity is evident in both the gamma and delta chain junctional amino acids of the receptors of these cells, indicating that they may largely develop in the thymus of older animals or undergo peripheral expansion. Finally, we found that all such cells responding to both a putative self-antigen and to mycobacterial Hsp60 respond to a 17-amino acid synthetic peptide representing amino acids 180-196 of the Mycobacterium leprae Hsp60 sequence. This report demonstrates that a large subset of Hsp60-reactive peripheral lymphoid gamma delta T cells preexists in normal adult mice, all members of which respond to a single segment of this common heat shock protein.

Animals↗
PubMed1992

Cloning and characterization of a human angiotensin II type 1 receptor.

A human liver cDNA library was screened using a rat type 1 angiotensin II receptor cDNA coding sequence as a probe. cDNA clones were isolated which encoded a protein of 359 amino acids that shared 94.4% and 95.3% identify to rat and bovine type 1 angiotensin II receptors, respectively. Ligand binding studies of the cloned receptor expressed in COS cells suggested that it is pharmacologically a type 1 angiotensin II receptor subtype. Electrophysiological studies of the receptor expressed in Xenopus laevis oocytes revealed that it could functionally couple to a second messenger system leading to the mobilization of intracellular stores of calcium. Southern and Northern blot analyses indicated that the cloned receptor is represented as a single copy in the human genome and is expressed in many tissues of different histogenic origin with the exception of brain, where mRNA transcripts were barely detectable.

Amino Acid Sequence↗
PubMed1992

Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis. Results of placebo-controlled, double-blind, multicenter trials.

BACKGROUND: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. OBJECTIVE: Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. METHODS: Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. RESULTS: Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. CONCLUSION: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.

Antifungal Agents↗
PubMed1992

Cytolytic T-cell activity against mycobacterial antigens in HIV.

OBJECTIVES: The declining incidence of tuberculosis (TB) in developed countries has recently been reversed with the advent of HIV disease. This study proposes to document in vitro T-cell responses to mycobacterial antigens in HIV-infected individuals. DESIGN: T-cell-mediated immunity is recognized as one of the mechanisms of defence against TB. The cellular immunodeficiency and the importance of TB in the context of HIV disease has prompted use of in vitro assays of lymphocyte proliferation and cytolytic activity. METHODS: Peripheral blood mononuclear cells isolated from 29 HIV-infected patients (four with recent TB) and 11 healthy volunteers were stimulated with purified protein derivative (PPD). The responding blasts were presented to autologous antigen-primed macrophages to measure specific cytolytic T-lymphocyte (CTL) activity in vitro. RESULTS: T-cell proliferative responses were significantly lower in late stages of HIV disease. The degree of specific CTL activity was higher in healthy individuals than in Centers for Disease Control (CDC) stage II-III (P = 0.037), and CDC stage IV patients (P = 0.029). CONCLUSIONS: The clinical presentation of TB tends to be typical in early stages of HIV disease and atypical in late stages. The manifestations reflect the degree of immunodepression. This study documents the declining proliferative and cytolytic T-cell-mediated responses in HIV patients with progression of immunodeficiency.

Adolescent↗
PubMed1992

SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors.

Animals↗
PubMed1992

Feeding the ultraendurance athlete: practical tips and a case study.

With the rising popularity of ultradistance sports events lasting from 6 to 24 hours or multiple days, athletes are consulting registered dietitians for specialized dietary advice. Many dietitians, however, lack experience with these types of events. This article provides basic guidelines ffor fueling the ultradistance athlete. The goals are to maintain normal hydration and blood glucose levels, which can be done by enforcing programmed drinking (approximately 250 to 500 mL/15 minutes, depending on the athlete's sweat rate and environmental temperature) and programmed eating (1 to 1.5 + g of carbohydrate per kilogram of body weight per hour, depending on the athlete's acceptance of and tolerance to solid and/or liquid foods during exercise). Athletes who compete longer than 6 to 8 hours should consume adequate electrolytes, particularly sodium (approximately 1 g/hour) through either sports drinks or foods. These guidelines are applied to a case study of the 1991 women's winner of the Race Across America, a 2,930-mile biking event.

Bicycling↗
PubMed1991

SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.

Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.

Amino Acid Sequence↗
PubMed1991

Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.

Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse development. We have analysed the interactions of normal and mutant W/c-kit gene products with cytoplasmic signalling proteins, using transient c-kit expression assays in COS cells. In addition to the previously identified c-kit gene product (Kit+), a second normal Kit isoform (KitA+) containing an in-frame insertion, Gly-Asn-Asn-Lys, within the extracellular domain, was detected in murine mast cell cultures and mid-gestation placenta. Both Kit+ and KitA+ isoforms showed increased autophosphorylation and enhanced association with phosphatidylinositol (PI) 3' kinase and PLC gamma 1, when stimulated with recombinant soluble Steel factor. No association or increase in phosphorylation of GAP and two GAP-associated proteins, p62 and p190, was observed. The two isoforms had distinct activities in the absence of exogenous soluble Steel factor; Kit+, but not KitA+, showed constitutive tyrosine phosphorylation that was accompanied by a low constitutive level of association with PI-3' kinase and PLC gamma 1. Introduction of the point substitutions associated with W37 (Glu582----Lys) or W41 (Val831----Met) mutant alleles into c-kit expression constructs abolished (W37) or reduced (W41) the Steel factor-induced association of the Kit receptor with signalling proteins in a manner proportional to the overall severity of the corresponding W mutant phenotype. These data suggest a diversity of normal Kit signalling pathways and indicate that W mutant phenotypes result from primary defects in the Kit receptor that affect its interaction with cytoplasmic signalling proteins.

1-Phosphatidylinositol 4-Kinase↗
PubMed1991

Reproducibility of measurements of trace gas concentrations in expired air.

Measurement of the pulmonary excretion of trace gases has been used as a simple means of assessing metabolic reactions. End alveolar trace gas concentration, rather than excretory rate, is usually measured. However, the reproducibility of this measurement has received little attention. In 17 healthy subjects, duplicate collections of alveolar air were obtained within 1 minute of each other using a commercially available alveolar air sampler. The concentrations of hydrogen, methane, carbon monoxide, and carbon dioxide were measured. When the subject received no instruction on how to expire into the device, a difference of 28% +/- 19% (1SD) was found between duplicate determinations of hydrogen. Instructing the subjects to avoid hyperventilation or to inspire maximally and exhale immediately resulted in only minor reduction in variability. However, a maximal inspiration held for 15 seconds before exhalation reduced the difference to a mean of 9.6% +/- 8.0%, less than half that observed with the other expiratory techniques. Percentage difference of methane measurements with the four different expiratory techniques yielded results comparable to those obtained for hydrogen. In contrast, percentage differences for carbon monoxide measurements were similar for all expiratory techniques. When normalized to a PCO2 of 5%, the variability of hydrogen measurements with the breath-holding technique was reduced to 6.8% +/- 4.7%, a value significantly lower than that obtained with the other expiratory methods. This study suggests that attention to the expiratory technique could improve the accuracy of tests using breath hydrogen measurements.

Breath Tests↗
PubMed1991

Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.

The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein.

The p21ras GTPase-activating protein (GAP) down-regulates p21ras by stimulating its intrinsic GTPase activity. GAP is found predominantly as a monomer in the cytosol of normal cells. However, in cells expressing an activated cytoplasmic protein-tyrosine kinase, p60v-src, or stimulated with epidermal growth factor, GAP becomes phosphorylated on tyrosine and serine and forms distinct complexes with two phosphoproteins of 62 and 190 kDa (p62 and p190). In v-src-transformed Rat-2 cells, a minor fraction of GAP associates with the highly tyrosine phosphorylated p62 to form a complex that is localized at the plasma membrane and in the cytosol. In contrast, the majority of GAP enters a distinct complex with p190 that is exclusively cytosolic and contains predominantly phosphoserine. Epidermal growth factor stimulation also induces a marked conversion of monomeric GAP to higher-molecular-weight species in rat fibroblasts. The GAP-p190 complex is dependent on phosphorylation and shows reduced GAP activity. These results indicate that protein-tyrosine kinases induce GAP to form multiple heteromeric complexes, which are strong candidates for regulators or targets of p21ras.

Animals↗
PubMed1991

Platelet-derived growth factor increases the in vivo activity of phospholipase C-gamma 1 and phospholipase C-gamma 2.

Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of diacylglycerol and inositol 1,4,5-triphosphate. We showed that following stimulation by PDGF, rat-2 cells overexpressing PLC-gamma 1 display an increase in the levels of both tyrosine-phosphorylated PLC-gamma 1 and inositol phosphates compared with the parental rat-2 cells. This increased responsiveness to PDGF is a direct effect of PLC-gamma 1 overexpression, as a cell line expressing similar levels of an enzymatically inactive point mutant of PLC-gamma 1, PLC-gamma 1 335Q, did not show elevated inositol phosphate production in response to PDGF. Hematopoietic cells express PLC-gamma 2, a PLC isoform that is closely related to PLC-gamma 1. When rat-2 cells overexpressing PLC-gamma 2 were treated with PDGF, an increase in both the tyrosine phosphorylation and the in vivo activity of PLC-gamma 2 was observed. Aluminum fluoride (AIF4-), a universal activator of PLC linked to G-proteins, did not produce an increase in the levels of inositol phosphates in either of the overexpressing cell lines compared with parental rat-2 cells, demonstrating that PLC-gamma isoforms respond specifically to a receptor with tyrosine kinase activity.

Animals↗