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Biomedical subjects

C Ellis

Publications and source records attributed to C Ellis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a clinical syndrome defined by the presence of thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent etiology. Patients may also have multiple other symptoms and signs including neurologic and renal abnormalities and fever. In the era prior to effective therapy with plasma exchange, most patients developed multisystem abnormalities and the syndrome was more easily recognized. Now, since there is urgency to begin treatment, sufficient diagnostic criteria for TTP-HUS are only thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent cause; patients may have no neurologic symptoms, renal abnormalities, or fever. This has lead to an apparent increased incidence because of both the increased importance of early recognition and the decreased specificity of the diagnostic criteria. Effective treatment has also revealed new aspects of the clinical course of TTP-HUS following the initial response to plasma exchange treatment: prompt exacerbations, which are common when plasma exchange is diminished in frequency or discontinued, and later relapses, which may occur many years after the initial episode. This review describes the evolution of the syndrome of TTP-HUS in the current era of effective treatment, and describes the management and clinical outcomes among patients treated by the Oklahoma Blood Institute.

Hemolytic-Uremic Syndrome↗
PubMed1998

Cyclosporine consensus conference: with emphasis on the treatment of psoriasis.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy.

Contraindications↗
PubMed1998

Influence of method of alveolar air collection on results of breath tests.

The influence of the method alveolar air collection on measurements of trace gas concentration has received little attention. We measured the concentrations of H2, CH4, CO, and CO2 in sequential fractions of alveolar air collected with and without breath-holding. Without breath-holding, the concentration of these gases increased appreciably as increasing quantities of alveolar air were expelled. Twenty seconds of breath-holding markedly reduced this nonhomogeneity of alveolar air. Prediction of the excretion rate of trace gases from measurements of their concentration relative to CO2 and literature values for resting CO2 excretion underestimated the true excretion rate. We conclude that breath-holding prior to sample collection enhances the reproducibility of trace gas measurements. When calculating the rate of excretion of trace gases, the use of literature values for resting ventilation or CO2 excretion may result in appreciable underestimations of the true rate.

Adult↗
PubMed1998

Orphan G-protein-coupled receptors: the next generation of drug targets?

The pharmaceutical industry has readily embraced genomics to provide it with new targets for drug discovery. Large scale DNA sequencing has allowed the identification of a plethora of DNA sequences distantly related to known G protein-coupled receptors (GPCRs), a superfamily of receptors that have a proven history of being excellent therapeutic targets. In most cases the extent of sequence homology is insufficient to assign these 'orphan' receptors to a particular receptor subfamily. Consequently, reverse molecular pharmacological and functional genomic strategies are being employed to identify the activating ligands of the cloned receptors. Briefly, the reverse molecular pharmacological methodology includes cloning and expression of orphan GPCRs in mammalian cells and screening these cells for a functional response to cognate or surrogate agonists present in biological extract preparations, peptide libraries, and complex compound collections. The functional genomics approach involves the use of 'humanized yeast cells, where the yeast GPCR transduction system is engineered to permit functional expression and coupling of human GPCRs to the endogenous signalling machinery. Both systems provide an excellent platform for identifying novel receptor ligands. Once activating ligands are identified they can be used as pharmacological tools to explore receptor function and relationship to disease.

Animals↗
PubMed1997

Postprandial hypotension and parkinsonian state in Parkinson's disease.

Abnormal postprandial cardiovascular responses such as postprandial hypotension (PPH) occur in primary autonomic failure and contribute significantly to morbidity. The extent and frequency of PPH and its relationship to the parkinsonian state in idiopathic Parkinson's disease (IPD) is unknown. By studying 20 patients with IPD (without autonomic failure) and 16 age-matched controls after both groups ingested a standard isocaloric balanced liquid meal, we have shown that supine PPH complicates IPD and is related to marked worsening of the parkinsonian state as measured by a cumulative score of tremor, rigidity, bradykinesia, posture, and gait. Furthermore, significant postural hypotension is unmasked that results in postural intolerance due to presyncopal symptoms. Our study indicates that, in patients with IPD, ingestion of a meal may lead to abnormal postprandial cardiovascular responses and aggravation of the parkinsonian stage. The underlying mechanisms are unclear, although vasodilatory gut peptides released in response to food ingestion may be contributory.

Adult↗
PubMed1996

Molecular cloning and characterization of the human anaphylatoxin C3a receptor.

In a human neutrophil cDNA library, an orphan G-protein-coupled receptor, HNFAG09, with 37% nucleotide identity to the C5a receptor (C5a-R, CD88) was identified. A novel feature of this gene, unlike C5a-R and other G-protein-coupled receptors, is the presence of an extraordinarily large predicted extracellular loop comprised of in excess of 160 amino acid residues between transmembrane domains 4 and 5. Northern blot analysis revealed that expression of mRNA for this receptor in human tissues, while similar, was distinct from C5a-R expression. Although there were differences in expression, transcripts for both receptors were detected in tissues throughout the body and the central nervous system. Mammalian cells stably expressing HNFAG09 specifically bound 125I-C3a and responded to a C3a carboxyl-terminal analogue synthetic peptide and to human C3a but not to rC5a with a robust calcium mobilization response. HNFAG09 encodes the human anaphylatoxin C3a receptor.

Amino Acid Sequence↗
PubMed1996

A juxtamembrane autophosphorylation site in the Eph family receptor tyrosine kinase, Sek, mediates high affinity interaction with p59fyn.

The large subfamily of receptor tyrosine kinases (RTKs) for which EPH is the prototype have likely roles in intercellular communication during normal mammalian development, but the biochemical signalling pathways utilised by this family are poorly characterised. We have now identified two in vitro autophosphorylation sites within the juxtamembrane domain of the Eph family member Sek, and a candidate binding protein for the activated Sek kinase. Specific antibodies defined Sek as a 130 kDa glycoprotein with protein kinase activity expressed in keratinocytes, whilst a bacterially expressed gst-Sek kinase domain fusion protein autophosphorylated exclusively on tyrosine residues, confirming that Sek encodes an authentic protein tyrosine kinase. Two dimensional phosphopeptide mapping and site-directed mutagenesis defined juxtamembrane residue Y602 as a major site of in vitro autophosphorylation in Sek, whilst Y596 was phosphorylated to a lower stoichiometry. Complimentary approaches of in vitro binding assays and BIAcore analysis revealed a high affinity association between the Y602 Sek autophosphorylation site and the cytoplasmic tyrosine kinase p59fyn, an interaction mediated through the SH2 domain of this intracellular signalling molecule. Moreover, these data identify the novel phosphotyrosyl motif pYEDP as mediating high affinity association with fyn-SH2, extending the previously defined consensus motif for this interaction. The extensive conservation of this fyn-binding motif within the juxtamembrane domain of Eph family RTKs suggests that signalling through fyn, or fyn-related, tyrosine kinases may be utilised by many members of this large subclass of transmembrane receptors.

Amino Acid Sequence↗
PubMed1996

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome.

Two subjects with narcoleptic syndrome and three healthy volunteers underwent functional magnetic resonance imaging during the simultaneous presentation of periodic auditory and visual stimuli both before and after administration of amphetamine. The effect of amphetamine in control subjects was a small reduction in the extent of sensory-induced activation. In the narcoleptic subjects, amphetamine led to an increase in the extent of induced activation within primary and association sensory cortex.

Acoustic Stimulation↗
PubMed1996

New staging system of the fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure (JNC-V) alters assessment of the severity and treatment of hypertension.

The fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure (JNC-V) introduced a new system of blood pressure classification that incorporated systolic blood pressure (SBP) and established new diastolic blood pressure (DBP) cut points. With the previous JNC classification, subjects were classified according to DBP alone. In this study, our purpose was to assess the effect of the new staging system on the assessment of hypertension severity and to determine whether' the new JNC-V staging system better identifies individuals at risk for hypertensive target-organ damage. We compared the assessment of hypertension severity using JNC-IV with that using JNC-V in 1158 subjects enrolled in the Harlem Hospital Hypertension Clinic database from 1975 to 1992. We used pretreatment DBP to classify subjects according to JNC-IV criteria. These subjects were reclassified into one of the four stages of JNC-V. The assessment of hypertension severity and prevalence of organ damage in subjects who remained in the same category of severity in both systems was compared with damage in subjects who were upstaged. With the JNC-V classification, 321 subjects remained in the same category, and 837 were upstaged. Six hundred and four subjects moved up because of the new cut points of DBP, and 275 were upstaged because of higher SBP. Upstaged subjects had more manifestations of hypertensive target-organ damage. With the new JNC-V classification system, hypertension is assessed as severe or very severe in more individuals than with JNC-IV. Subjects who are upstaged in JNC-V are more likely to have evidence of renal disease and other target-organ damage.

Adult↗
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↗
PubMed1995

Pre-sleep behaviour in normal subjects.

Behaviour in the 2-h period before sleep onset was evaluated in 90 subjects with normal sleep/wake habits using an anonymous self-report questionnaire. This determined the timing of events from the initial preparation for sleep. The nature of the pre-sleep environment, the level of physical activity, and patterns of feeding behaviour were recorded together with self-ratings of tiredness, mood and security. Estimated sleep duration and sleep quality were determined. Ninety of 120 subjects responded. Sleep 'preparatory latency', from the time of initial sleep preparation to sleep onset, was 77 +/- 48 min; bed time to sleep onset time (sleep latency) was 41 +/- 42 min; lights out to sleep onset latency was 26 +/- 45 min. The estimated total sleep time was 7 +/- 1 h. In the pre-sleep period, mean noise and illumination levels were low and environmental temperature rating was at the median point on a very cold-very hot scale (mean scale scores: 23, 28 and 50, respectively). All subjects went to the bathroom before going to bed. Twenty-five percent of normal subjects had a snack or meal in the 2-h period before sleep onset. Sixty percentage recorded setting an alarm, 27% had a bath or shower, 23% checked door locks or windows and 49% read in bed. Nine percent of subjects slept with a cat on the bed. Humans, like other animal species, show a complex behavioural sequence in the 2-h period before falling asleep. A constant environment with limited metabolic activity may predispose to thermoregulatory changes prior to sleep onset.

Journal Article↗