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Biomedical subjects

L Campbell

Publications and source records attributed to L Campbell.

At least 37 records · Page 2Linked to original sources
PubMed2001

From first base: the sequence of the tip of the X chromosome of Drosophila melanogaster, a comparison of two sequencing strategies.

We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different transposable elements. We show that an interval between bands 3A2 and 3C2, believed in the 1970s to show a correlation between the number of bands on the polytene chromosomes and the 20 genes identified by conventional genetics, is predicted to contain 45 genes from its DNA sequence. We have determined the insertion sites of P-elements from 111 mutant lines, about half of which are in a position likely to affect the expression of novel predicted genes, thus representing a resource for subsequent functional genomic analysis. We compare the European Drosophila Genome Project sequence with the corresponding part of the independently assembled and annotated Joint Sequence determined through "shotgun" sequencing. Discounting differences in the distribution of known transposable elements between the strains sequenced in the two projects, we detected three major sequence differences, two of which are probably explained by errors in assembly; the origin of the third major difference is unclear. In addition there are eight sequence gaps within the Joint Sequence. At least six of these eight gaps are likely to be sites of transposable elements; the other two are complex. Of the 275 genes in common to both projects, 60% are identical within 1% of their predicted amino-acid sequence and 31% show minor differences such as in choice of translation initiation or termination codons; the remaining 9% show major differences in interpretation.

Animals↗
PubMed2001

Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10.

We describe the cloning and expression of HSPDE4A10, a novel long form splice variant of the human cAMP phosphodiesterase PDE4A gene. The 825 amino acid HSPDE4A10 contains a unique N terminus of 46 amino acids encoded by a unique 5' exon. Exon-1(4A10) lies approximately 11 kilobase pairs (kb) downstream of exon-1(4A4) and approximately 13.5 kb upstream of the PDE4A common exon 2. We identify a rat PDE4A10 ortholog and reveal a murine ortholog by nucleotide sequence database searching. PDE4A10 transcripts were detected in various human cell lines and tissues. The 5' sequence flanking exon-1(4A10) exhibited promoter activity with the minimal functional promoter region being highly conserved in the corresponding mouse genomic sequence. Transient expression of the engineered human PDE4A10 open reading frame in COS7 cells allowed detection of a 121-kDa protein in both soluble and particulate fractions. PDE4A10 was localized primarily to the perinuclear region of COS7 cells. Soluble and particulate forms exhibited similar K(m) values for cAMP hydrolysis (3-4 microM) and IC(50) values for inhibition by rolipram (50 nM) but the V(max) value of the soluble form was approximately 3-fold greater than that of the particulate form. At 55 degrees C, soluble HSPDE4A10 was more thermostable (T(0.5) = 11 min) than the particulate enzyme (T(0.5) = 5 min). HSPDE4A10 and HSPDE4A4B are shown here to be similar in size and exhibit similar maximal activities but differ with respect to sensitivity to inhibition by rolipram, thermostability, interaction with the SRC homology 3 domain of LYN, an SRC family tyrosyl kinase, and subcellular localization. We suggest that the unique N-terminal regions of PDE4A isoforms confer distinct properties upon them.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Lies, damned lies and statistics.

Readers may remember Jim Miller's introductory article in this series (Miller 2001), where lessons learnt from the Titanic disaster were related to lessons to be learnt in the NHS today. Unfortunately many of those lessons are yet to be learnt by some of our organisations or, certainly, lessons which need to be applied consistently. One of those lessons related to the need for accurate data and using it to inform action and priorities. This article identifies some of the data requirements. where they might be obtained and the need for a systematic process to inform strategy.

Data Collection↗
PubMed2001

The development of clinical practice guidelines for the use of aromatherapy in a cancer setting.

The need to develop guidelines for the use of aromatherapy was identified to ensure safe and appropriate use in clinical practice. Therapeutic actions and safety data were reviewed along with literature relating to nurses' use of aromatherapy. A policy was developed with the needs of the oncology patient being the foremost consideration. Methods of administration and dosage of essential oils were stipulated to address safety issues.

Aromatherapy↗
PubMed2000

Direct interaction of Smn with dp103, a putative RNA helicase: a role for Smn in transcription regulation?

Spinal muscular atrophy is an autosomal recessive neurodegenerative disease of childhood, resulting from deletion or mutation of the survival motor neuron ( SMN ) gene on chromosome 5q13. SMN exists as part of a 300 kDa multi-protein complex, incorporating several proteins critically required in pre-mRNA splicing. Although SMN mutations render SMN defective in this role, the specific alpha-motor neuron degenerative phenotype seen in the disease remains unexplained. Here we demonstrate the isolation from mouse brain of the murine homologue of a recently identified novel RNA helicase of the DEAD box family, DP103, and its direct and specific binding of SMN. Previous work has shown that DP103 binds viral proteins known to interact with a cellular transcription factor to modulate gene expression. We suggest that the interaction between SMN and DP103 is further evidence for a role for SMN in transcriptional regulation and that SMN may be involved in the regulation of neuron-specific genes essential in neuronal development.

Amino Acid Sequence↗
PubMed2000

Characterization of Ngef, a novel member of the Dbl family of genes expressed predominantly in the caudate nucleus.

We have identified Ngef as a novel member of the family of Dbl genes. Many members of this family have been shown to function as guanine nucleotide exchange factors for the Rho-type GTPases. Ngef is predominantly expressed in brain, with the strongest signal in the caudate nucleus, a region associated with the control of movement. Ngef contains a translated trinucleotide repeat, a polyglutamic acid stretch interrupted by a glycine. We have localized the Ngef gene to mouse chromosome 1 and the human homologue of Ngef to human chromosome 2q37. We have shown in preliminary experiments that Ngef has transforming potential in cell culture and is able to induce tumors in nude mice.

3T3 Cells↗
PubMed2000

Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes.

The skin represents an attractive site for the localised gene therapy of dermatological pathologies and as a potential antigen bioreactor following transdermal delivery. Potential also exists for the gene therapy of skin as a cosmetic intervention. The most exploited non-viral gene delivery system involves the complexation of cationic liposomes with plasmid DNA (pDNA) to form lipid:pDNA vectors that protect the DNA from nuclease-mediated degradation and improve transgene-cell interactions. Despite numerous studies examining the potential for these vectors in delivering genes to a variety of keratinocyte models, investigations into the topical application of such complexes to intact skin tissue is limited. This ex-vivo study, conducted with intact skin tissue derived from hairless mice, provides quantitative confirmation that topical administration of cationic lipid:pDNA complexes can mediate uptake and expression of reporter pDNA (33-fold higher compared with control) in viable epidermal tissue. The ex-vivo study design provides for intact skin tissue that has not been subjected to depilatory procedures of potential detriment to stratum corneum barrier function, and can be utilised for the quantitative and efficient examination of a potentially wide range of non-viral gene vectors designed for epidermal expression.

Administration, Topical↗
PubMed2000

Caveolae: an alternative membrane transport compartment.

Caveolae are omega-shaped invaginations of the plasma membrane with a diameter of 50-100 nm. Caveolae invaginations can detach from the plasma membrane to form discrete functional caveolae vesicles within the cell cytoplasm. Caveolae are most prominent in adipocytes, fibroblasts, muscle cells (skeletal, smooth and cardiac), capillary endothelium and type I pneumocytes, although other cell types also display these structures but at a lower numerical density. The key structural and functional protein for caveolae is caveolin. At the plasma membrane caveolae serve to compartmentalize and integrate a wide range of signal transduction processes. Caveolae also serve transport functions including that of the vesicular internalisation of small molecules by the process of potocytosis, and the endocytic and transcytotic movements of macromolecules. Opportunities exist for basic and applied investigators working within the pharmaceutical sciences to exploit caveolae membrane interactions with the aim to develop novel cellular or transcellular drug delivery strategies.

Animals↗
PubMed2000

Aberrant caveolin-1 expression in psoriasis: a signalling hypothesis.

A preliminary retrospective immunocytochemical study was conducted examining the expression of caveolin-1 in skin biopsies resected from clinically defined psoriatic subjects. These pilot investigations revealed a dramatic down-regulation of caveolin-1 (a protein product of the caveolin supergene family known to regulate signal transduction events and cell cycle dynamics) in the hyperproliferative basal regions of the epidermis in all psoriatic biopsies examined when compared to normal control samples. These results lead us to hypothesise that caveolin-1 negatively regulates key signal transduction pathways in epidermal keratinocytes and through it's reduced expression in psoriasis, pertubations in keratinocyte cell signalling and abnormal cell differentiation ensue, events fundamental to the development of the psoriatic phenotype. Novel therapeutic strategies for the treatment of psoriasis based upon caveolin-1 protein can be envisaged.

Biopsy↗
PubMed2000

Effect of short-term ketorolac infusion on recovery following laparoscopic day surgery.

This study tested the hypothesis that, by the addition of parenteral ketorolac to an oral analgesic regimen for one day following laparoscopic surgery, analgesia would be improved and thus the return of normal function hastened. Seventy-two female patients were randomly assigned to receive ketorolac 10.5 mg subcutaneously at the end of surgery followed by a subcutaneous infusion of 1.75 mg/h for 24 to 36 hours, or an equivalent volume of saline. All patients were provided with codeine tablets (30 mg) for analgesia if required. For the first four postoperative days patients recorded details of pain, side-effects and discomfort on performing everyday activities. Patients who received ketorolac received significantly less fentanyl in the Recovery Ward and significantly less codeine prior to discharge than the saline group. They also took significantly fewer codeine tablets over the four-day postoperative period. Pain scores in the ketorolac group were not significantly lower than in the saline group on the first postoperative day (P = 0.052) and subsequently remained similar. Levels of discomfort on performing six common activities were similar in the two groups over the four-day postoperative period. We conclude that, despite beneficial effects during the period of ketorolac administration, there was no continuing benefit after this time other than reduced analgesic use, and no improvement in the patients' ability to perform common activities.

Adolescent↗
PubMed2000

Confidentiality. The Caldicott Report.

You will probably look at the title of this and want to move on to more interesting material, but do hang on for a little bit longer. You may already know about it, but there will be an impact on you and your department as a result of this initiative. Caldicott may just be one of the seminal moments in the development of the NHS; it does have impact and could develop the cause of patients' rights a little bit further. This is a very broad overview, but it does have some helpful hints.

Confidentiality↗
PubMed2000

Radiographic osteoarthritis in the elderly population of Zagreb: distribution, correlates, and the pattern of joint involvement.

AIM: To determine the prevalence of radiographic osteoarthritis on five joint groups in an urban population sample of 306 women and 304 men over the age of 45 and to assess the influence of some risk factors on osteoarthritis. The validity of concept of generalized osteoarthritis was also examined by analyzing the association of osteoarthritis on different joint sites. METHODS: Radiographs of both hands, both knees, and the right hip were taken. Osteoarthritic changes on distal interphalangeal, proximal interphalangeal, first carpometacarpal joints, knees, and hip were graded according to the Kellgren-Lawrence scale. The association among osteoarthritis on different joint sites was analyzed using logistic regression. Subjects were tested for age, duration of postmenopause, anthropometric measures, blood pressure, and smoking as risk factors for osteoarthritis. RESULTS: Hip was the most frequent site of osteoarthritis in men (27.3%), whereas distal interphalangeal joints predominated in women (43.5%). Polyarticular osteoarthritis (+/-3 joints) was present in 10.8% women and 5.9% men. There was a significant influence of age on single joint osteoarthritis, but not on multiple joint involvement. Obesity was significantly correlated with knee osteoarthritis in women and with osteoarthritis on distal interphalangeal joints in men. CONCLUSIONS. In our population sample, the prevalence of knee osteoarthritis was lower and the prevalence of hip osteoarthritis higher than reported for most of other populations. The tendency towards polyarticular osteoarthritis that is more common than would be expected by age, suggests a subset of generalized osteoarthritis.

Aged↗
PubMed1999

Usefulness of an exaggerated systolic blood pressure response to exercise in predicting myocardial perfusion defects in known or suspected coronary artery disease.

The clinical importance of an exaggerated systolic blood pressure (BP) response to exercise, or exercise hypertension, is unclear. We have previously reported that exercise hypertension is associated with less severe angiographic coronary artery disease. This study sought to examine the association between exercise hypertension and ischemic "burden," as assessed by thallium-201 single-photon emission computed tomography. The cohort was comprised of consecutive adults (2,216 men, 1,229 women) referred for symptom-limited exercise thallium testing to evaluate known or suspected coronary artery disease. The main variable measured was exercise hypertension, defined as a peak systolic BP > or =210 mm Hg in men and > or =190 mm Hg in women. Thallium perfusion defects were described as: (1) any perfusion abnormality, (2) reversible abnormalities, and (3) any abnormality in > or =3 of 12 myocardial segments ("extensive abnormalities"). Exercise hypertension was present in 1,319 subjects (39%). Patients with exercise hypertension were less likely to have any thallium perfusion abnormality (16% vs 25%, odds ratio [OR] 0.58, 95% confidence intervals [CI] 0.49 to 0.69, p <0.001), reversible thallium abnormalities (7% vs 12%, OR 0.71, 95% CI 0.57 to 0.90, p <0.001), and extensive abnormalities (8% vs 14%, OR 0.53, 95% CI 0.42 to 0.67, p <0.001). After adjusting for possible confounders, the same trend was seen. During 6 years of follow-up there were 283 deaths with no association between exercise hypertension and mortality risk. Thus, exercise hypertension is associated with a lower likelihood of myocardial perfusion abnormalities and is not associated with an increased mortality rate.

Adult↗
PubMed1999

Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures.

Caveolae are omega-shaped invaginations of the plasmalemma possessing a cytoplasmic membrane protein coat of caveolin. Caveolae are present in the in vivo alveolar epithelial type I (ATI) lung cell, but absent in its progenitor, the alveolar epithelial type II (ATII) cell. In primary culture ATII cells grown on a plastic substratum acquire with time an ATI-"like" phenotype. We demonstrate that freshly isolated rat ATII cells lack caveolae and expression of caveolin-1 (a critical caveolae structural protein). As the ATII cells acquire an ATI-like phenotype in primary culture caveolin-1 expression increases, with caveolin-1 signal at 192 h postseeding up to 50-fold greater than at 60 h; caveolae were morphologically evident only after 132 h. When maintaining the differentiated ATII phenotype with time, i.e., culture upon collagen with an apical interface of air, a temporal increase in caveolin-1 expression was not observed, with only very faint signals evident even at 192 h postseeding; at no time did these cultures display caveolae. In late primary ATII cultures caveolin-1 expression and caveolae biogenesis occur as a function of in vitro transformation from the ATII to the ATI-like phenotype. The results have broad implications for the in vitro study of the role of caveolae and caveolin in alveolar epithelial cell biology.

Animals↗