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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

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↗

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↗

Human AT1 receptor is a single copy gene: characterization in a stable cell line.

To address conflicting reports concerning the number of angiotensin II (AII) receptor type 1 (AT1) coding loci in vertebrates, Southern blot analysis was used to determine the genomic representation of AT1 receptor genes in animals comprising a divergent evolutionary spectrum. The data demonstrate that the AT1 receptor gene is present as a single genomic copy in a broad spectrum of animals including human, monkey, dog, cow, rabbit, and chicken. In contrast, members of the rodent taxonomic order contain two genes in their genomes. These two genes may have arisen in rodents as a consequence of a gene duplication event that occurred during evolution following the branching of rodents from the mammalian phylogenetic tree. In order to investigate the properties of the human AT1 receptor in a pure cell system, the recombinant human AT1 receptor was stably expressed in mouse L cells. An isolated cell line, designated LhAT1-D6, was found to express abundant levels of recombinant receptor [430 +/- 15 fmol/mg] exhibiting high affinity [KD = 0.15 +/- 0.02 nM] for [125I][SAR1, Ile8] angiotensin II (SIA). The pharmacological profile of ligands competing for [125I] SIA binding to the expressed receptor was in accordance with that of the natural receptor. Radioligand binding of the expressed receptor was decreased in the presence of the non-hydrolyzable analog of GTP, guanosine 5'-(gamma-thio) triphosphate [GTP gamma S]. Angiotensin II evoked a rapid efflux of 45Ca2+ from LhAT1-D6 cells that was blocked by AT1 receptor specific antagonists. In addition, AII inhibited forskolin-stimulated cAMP accumulation in these cells which was blocked by the AT-1 antagonist. Thus, the LhAT1-D6 cell line provides a powerful tool to explore the human AT1 receptor regulation.

Animals↗

Use of alveolar carbon monoxide measurements to assess red blood cell survival in hemodialysis patients.

We recently described a simple technique for measuring RBC survival based on measurements of the concentration of carbon monoxide (CO) in alveolar air, corrected for environmental CO using a device that equilibrates with atmospheric CO at the same rate as does the patient. The purpose of the present report is to demonstrate the clinical utility of this method via measurements of RBC turnover in hemodialysis patients. Prior to dialysis, the mean RBC survival of 9 chronic dialysis patients was 70 +/- 9 days, about 50% shorter than that of 32 healthy subjects. During the dialysis, the endogenous PCO increased by 14% (P < 0.05) while subjects not undergoing dialysis had a 6% fall in endogenous PCO over this same time period. Thus, this technique demonstrated that the hemodialysis procedure resulted in about a 20% increase in RBC destruction. This increased RBC destruction has not been detectable with previous methodologies (including conventional measurements of CO production) due to the insensitivity and lack of reproducibility of conventional techniques. We conclude that the simple, non-invasive measurement of endogenous PCO provides the most accurate available means of assessing the influence of a variety of acute manipulations on RBC survival.

Breath Tests↗

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↗

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↗

Diurnal rhythm of heme turnover assessed by breath carbon monoxide concentration measurements.

Measurements of pulmonary carbon monoxide (CO) excretion can be used as a quantitative indicator of heme turnover. We determined whether a diurnal variation of heme turnover occurs by using a recently described technique that estimates breath CO excretion from measurements of alveolar CO concentration corrected for environmental CO to yield an endogenous PCO. This simple technique, unlike the previously employed rebreathing method, makes it possible to repeatedly measure CO excretion throughout a 24-hour period. Nine studies in seven healthy adult subjects demonstrated a diurnal rhythm of CO excretion with a peak excretion rate at about noon that was 26% greater than the nadir, which occurred at about midnight. The rhythm of CO production underlying the observed breath CO excretion was calculated to have an amplitude of about twice that of CO excretion and a phase shift relative to excretion of about 4 hours. We conclude that a diurnal variation in the rate of heme turnover occurs, and when CO determinations are used to assess minor alterations in heme turnover, consideration must be given to the time of day at which the measurements are obtained.

Aged↗

rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo.

rho family GTPases link extracellular signals to changes in the organization of cytoskeletal actin. Serum stimulation of quiescent Swiss 3T3 fibroblasts leads to rho-dependent actin stress fibre formation and focal adhesions, whilst several growth factors initiate signalling pathways leading to rac-dependent actin polymerization at the plasma membrane, and membrane ruffling. The product of the breakpoint cluster region gene bcr, rho GTPase accelerating protein (rhoGAP) and rasGAP-associated p190 share structurally related rho GAP domains, and possess GAP activity for rho family members in vitro. We have directly compared the activities of the isolated GAP domains of these three proteins in regulating different rho family GTPases, both by in vitro assays and by microinjection, to address their possible physiologic functions. We show that bcr accelerates the GTPase activity of rac, but not rho in vitro, and inhibits rac-mediated membrane ruffling, but not rho-mediated stress fibre formation, after microinjection into Swiss 3T3 fibroblasts. In vitro, rhoGAP has a striking preference for G25K as a substrate, whilst p190GAP has marked preferential activity for rho. Furthermore, p190 preferentially inhibits rho-mediated stress fibre formation in vivo. Our data suggest that p190, rhoGAP and bcr play distinct roles in signalling pathways mediated through different rho family GTPases.

3T3 Cells↗

Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy.

At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them "very well", 32% "adequately" and none "poorly" for their chemotherapy. Separate interviews with medical and nursing staff were thought a "good idea" by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as "not worthwhile". This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy.

Adult↗

The black American nose.

A study of 201 black American noses has led us to divide the black American nose into three groups, i.e., Groups A, B, and C, which we have called the "African," the "Afro-Caucasian," and the "Afro-Indian." Belonging to the African group (Group A) were 44% of the noses, 37% were Afro-Caucasian (Group B), and 19% were Afro-Indian (Group C). Fifty-three percent of the African noses had a concave dorsum, whereas only 10% of the Afro-Caucasian and 8% of the Afro-Indian group had a concave dorsum. On the other hand, 36% of the Afro-Caucasian group had a hump as did 63% of the Afro-Indian group. Only 18% of the African group had a hump. The most common nostril types were type IV (20%), type V (27%), and type VI (25%), the distribution of which varied with the nasal type. Anthropometric measurements showed variations according to type, with the African noses being the shortest and widest, the AFro-Caucasian the narrowest, and the Afro-Indian being the longest. Cadaver dissection showed that the alar cartilages varied from small and thin in the African group to large and thick in the Afro-Indian. All were covered by a heavy layer of fibrofatty tissue. The value of this grouping in the evaluation and surgery of the black American nose is discussed.

Anthropometry↗

Obstructive sleep apnoea associated with syringomyelia.

We present a case of obstructive sleep apnoea in association with syringomyelia. We describe the successful treatment of the respiratory obstruction by continuous positive airway pressure and then by surgical means. This rare combination of conditions and the management is reviewed.

Adult↗

Atypical pneumonias.

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Diagnosis, Differential↗

Isolation and expression of a novel angiotensin II receptor from Xenopus laevis heart.

A Xenopus laevis heart cDNA library was screened using the human angiotensin type 1 (AT1) receptor cDNA coding sequence as a hybridization probe. A cDNA was isolated that encodes a protein of 363 amino acids that shares 63% sequence identity with the human AT1 receptor. Radioligand binding studies with the cloned receptor expressed in COS cells indicated that it is an angiotensin II receptor that possesses pharmacological properties distinct from those of the two known mammalian receptor subtypes, AT1 and AT2. Electrophysiological studies with the recombinant receptor expressed in X. laevis oocytes revealed that the amphibian receptor, like the mammalian AT1 receptor, can functionally couple to a second messenger system, leading to the mobilization of intracellular stores of calcium. However, nonpeptide antagonists selective for the mammalian AT1 and AT2 receptors do not block angiotensin II-stimulated functional responses in injected oocytes, which confirms that the amphibian receptor is a pharmacologically unique angiotensin II receptor. Nevertheless, based on conservation of structural features and motifs and similarity in coupling mechanisms, we speculate that the cloned Xenopus receptor is the amphibian counterpart of the mammalian AT1 receptor, having acquired its unique pharmacology as a consequence of evolutionary divergence.

Amino Acid Sequence↗