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Biomedical subjects

C Ellis

Publications and source records attributed to C Ellis.

At least 37 records · Page 2Linked to original sources

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

Complex formation between the p21ras GTPase-activating protein and phosphoproteins p62 and p190 is independent of p21ras signalling.

We have investigated whether complex formation between the p21ras GTPase-activating protein (GAP) and the phosphotyrosine-containing proteins p62 and p190 is dependent on functional p21ras, to test the hypothesis that binding of p21rasGTP to GAP enables GAP to associate with these phosphoproteins. The formation of p21rasGTP was inhibited by a dominant interfering mutant of p21ras, p21ras(Asn-17), which was introduced with a vaccinia virus expression system. We used NIH3T3 cells in which complex formation between GAP and tyrosine-phosphorylated p62 and p190 can be induced either by v-src transformation, by incubating the cells with the phosphotyrosine phosphatase inhibitor pervanadate or by activation of a growth factor receptor tyrosine kinase. In all cases, expression of p21ras(Asn-17) did not affect the presence or the formation of the GAP-phosphoprotein complexes. To monitor the effectiveness of p21ras inhibition, we measured p21ras-mediated phosphorylation of extracellular signal-regulated kinase 2 (ERK2). In all cases, expression of p21ras(Asn-17) completely blocked signalling to ERK2. From these data we conclude that p21rasGTP formation is not essential for complex formation between GAP and tyrosine-phosphorylated p62 and p190, and thus complex formation does not depend on interaction of GAP with p21rasGTP.

3T3 Cells

'W' mutant forms of the Fms receptor tyrosine kinase act in a dominant manner to suppress CSF-1 dependent cellular transformation.

Point mutations in highly conserved amino acid residues in the catalytic domain of the Kit receptor tyrosine kinase (RTK) are responsible for the coat color, fertility and hematopoietic defects of mice bearing mutant alleles at the dominant white-spotting (W) locus. The dominant nature of structural Kit mutations suggests that expression of other kinase-defective RTKs might also specifically interfere with signal transduction by normal receptors. To test this possibility, we have investigated the functional consequences of introducing analogous mutations into the RTK encoded by the c-fms proto-oncogene. Both Fms37 (glu582-->lys) and Fms42 (asp776-->asn) mutant proteins, corresponding to the strongly dominant-negative W37 and W42 mutant c-kit alleles, had undetectable in vitro kinase activity and were unable to transform Rat-2 fibroblasts in the presence of exogenous CSF-1. Moreover, expression of Fms37 or Fms42 proteins in Rat-2 cells specifically inhibited anchorage-independent growth mediated by the normal Fms receptor in the presence of exogenous CSF-1 and conferred a dominant loss of Fms-associated PI3-kinase activity on CSF-1 stimulation. Mutant RTKs, bearing point substitutions identical to those present in mild or severe W mutants, may provide a generally applicable strategy for inducing dominant loss of function defects in RTK-mediated signalling pathways.

Animals

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

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

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

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

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

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

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

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

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