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Biomedical subjects

J West

Publications and source records attributed to J West.

At least 55 records · Page 3Linked to original sources
PubMed2001

Nurse-led direct access endoscopy clinics: the future?

BACKGROUND: Many studies have shown that rectal bleeding is a good indicator of underlying colorectal pathology, and that ost of the lesions in patients presenting with rectal bleeding lie in the left side of the colon [1, 5, 9, 12, 23, 26]. The recent acceptance of the nurse-practitioner by the National Health Service may allow the use of nurse-endoscopists to develop throughout the United Kingdom. This study aimed to audit a unique nurse-led direct-access nurse-endoscopy service with regard to its efficacy and cost effectiveness, and to monitor patient satisfaction and direct referrals from the primary health sector. METHODS: A nurse-led open-access flexible sigmoidoscopy (OAFS) service for patients reporting fresh rectal bleeding was established at our center in February 1996. A prospective audit of sigmoidoscopic findings and a retrospective analysis of referral patterns from local general practitioners were conducted. A questionnaire survey of both patient and general practitioner satisfaction also was conducted at the same time. RESULTS: Since February 1996, 706 patients have been referred to our service. Rectal bleeding was by far the most common cause for referral, representing the dominant symptom in 92% of the referrals received. Although 99% of the patients underwent a complete sigmoidoscopic examination, 16% of these examinations were limited because of several factors combined. A cause for bleeding was identified in 91% of the patients, with 24% of them experiencing subsequent significant pathology. Of the patients surveyed, 99% were satisfied with the service provided. The results also show nurse-led OAFS to be a more effective use of financial resources, costing $90 less per patient than general practitioner referrals sent to a consultant for further action. CONCLUSIONS: Rectal bleeding is a good indicator of underlying colorectal disease. Most of the significant lesions presenting with this symptom are found in the left side of the colon. A nurse-led OAFS is safe, effective, and acceptable to patients. It also is more cost effective than a consultant-led service.

Abdominal Pain↗
PubMed2001

Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affinis.

Several members of the Rubiaceae and Violaceae families produce a series of cyclotides or macrocyclic peptides of 29-31 amino acids with an embedded cystine knot. We aim to understand the mechanism of synthesis of cyclic peptides in plants and have isolated a cDNA clone that encodes the cyclotide kalata B1 as well as three other clones for related cyclotides from the African plant Oldenlandia affinis. The cDNA clones encode prepropeptides with a 20-aa signal sequence, an N-terminal prosequence of 46-68 amino acids and one, two, or three cyclotide domains separated by regions of about 25 aa. The corresponding cyclotides have been isolated from plant material, indicating that the cyclotide domains are excised and cyclized from all four predicted precursor proteins. The exact processing site is likely to lie on the N-terminal side of the strongly conserved GlyLeuPro or SerLeuPro sequence that flanks both sides of the cyclotide domain. Cyclotides have previously been assigned an antimicrobial function; here we describe a potent inhibitory effect on the growth and development of larvae from the Lepidopteran species Helicoverpa punctigera.

Amino Acid Sequence↗
PubMed2001

Solution structures by 1H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant.

SFTI-1 is a recently discovered cyclic peptide trypsin inhibitor from sunflower seeds comprising 14 amino acid residues. It is the most potent known Bowman-Birk inhibitor and the only naturally occurring cyclic one. The solution structure of SFTI-1 has been determined by 1H-NMR spectroscopy and compared with a synthetic acyclic permutant. The solution structures of both are remarkably similar. The lowest energy structures from each family of 20 structures of cyclic and acyclic SFTI-1 have an rmsd over the backbone and heavy atoms of 0.29 A and 0.66 A, respectively. The structures consist of two short antiparallel beta-strands joined by an extended loop containing the active site at one end. Cyclic SFTI-1 also has a hairpin turn completing the cycle. Both molecules contain particularly stable arrangements of cross-linking hydrogen bonds between the beta-strands and a single disulfide bridge, making them rigid and well defined in solution. These stable arrangements allow both the cyclic and acyclic variants of SFTI-1 to inhibit trypsin with very high potencies (0.5 nM and 12.1 nM, respectively). The cyclic nature of SFTI-1 appears to have evolved to provide higher trypsin inhibition as well as higher stability. The solution structures are similar to the crystal structure of the cyclic inhibitor in complex with trypsin. The lack of a major conformational change upon binding suggests that the structure of SFTI-1 is rigid and already pre-organized for maximal binding due to minimization of entropic losses compared to a more flexible ligand. These properties make SFTI-1 an ideal platform for the design of small peptidic pharmaceuticals or pesticides.

Amino Acid Sequence↗
PubMed2001

Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas.

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the adenomatous polyposis coli (APC)/ beta-catenin/Tcf pathway in human tumorigenesis, there have been very few reports on mutations of the beta-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma cell lines for mutations in exon 3 of the beta-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the gamma-catenin gene. Mutational analysis for the entire coding region of beta-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical carcinoma cell lines. Deletion of most beta-catenin coding exons was confirmed in line NCI-H28 (lung mesothelioma) and a silent mutation at codon 214 in exon 5 was found in HeLa (cervical adenocarcinoma). A missense mutation at codon 19 and a silent mutation at codon 28 in the NH2-terminal regulatory region of the gamma-catenin gene were found in H1726 (squamous cell lung carcinoma) and H1048 (small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that beta- and gamma-catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian carcinomas.

Cytoskeletal Proteins↗
PubMed2001

Factors modulating the epithelial response to toxicants in tracheobronchial airways.

As one of the principal interfaces between the organism and the environment, the respiratory system is a target for a wide variety of toxicants and carcinogens. The cellular and architectural complexity of the respiratory system appears to play a major role in defining the focal nature of the pulmonary response to environmental stressors. This review will address the biological factors that modulate the response of one of the major target compartments within the respiratory system, the tracheobronchial airway tree. Individual airway segments respond uniquely to toxic stress and this response involves not only the target cell population, e.g. epithelium, but also other components of the airway wall suggesting a trophic interaction within all components of the airway wall in maintaining steady state and responding to injury. A number of biological factors modulate the nature of the response, including: (1) metabolic potential at specific sites for activation and detoxification; (2) the nature of the local inflammatory response; (3) age of the organism at the time of exposure; (4) gender of the exposed organism; (5) history of previous exposure; and (6) species and strain of the organism exposed.

Aging↗
PubMed2001

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

Animals↗
PubMed2001

Axillary nerve temperatures during radiofrequency capsulorrhaphy of the shoulder.

PURPOSE: The purpose of this study was to determine the temperatures along the course of the axillary nerve during radiofrequency (RF) capsulorrhaphy of the shoulder in a cadaver model. The hypothesis of this project was that temperatures capable of damaging neural tissue would be recorded during simulated RF capsulorrhaphy. TYPE OF STUDY: Basic science evaluation. METHODS: This study used 9 fresh-frozen cadaver shoulder capsules removed en bloc along with the underlying axillary nerve and soft tissue. The axillary nerve was instrumented with 4 thermocouples placed along the course of the nerve (2 thermocouples anterior and 2 posterior to the 6 o'clock position, spaced 7 mm apart). Each of the specimens underwent RF thermal capsulorrhaphy during which the temperature at each of the thermocouple positions was continuously recorded. RESULTS: The average of the maximum temperature at each of the 4 positions measured along the course of the axillary nerve were 52.2 +/- 18.0 degrees C at the most anterior place probed, 45.8 +/- 5.44 degrees C (mid anterior), 44.5 +/- 8.7 degrees C (mid posterior), and 42.8 +/- 10.1 degrees C at the most posteriorly positioned probe. Two specimens had a maximum temperature greater than the 67 degrees C set point of the device, and 7 specimens had a maximum temperature greater than 45 degrees C in at least 1 thermocouple position. CONCLUSIONS: This study shows that heating of the axillary nerve can occur during RF capsular shrinkage of the shoulder and may potentially reach levels that can damage neural tissue.

Body Temperature↗
PubMed2001

Macular hole surgery using silicone oil tamponade.

BACKGROUND/AIMS: Most surgeons performing macular hole surgery using long acting gas recommend strict postoperative face down posturing for 10-15 days. Patients with chronic systemic illness such as arthritis may be unable to carry out this postoperative regime. Thus there is a need for alternative techniques that would eliminate such a regime. The authors review a series of patients who underwent macular hole surgery using silicone oil without any postoperative posturing. METHODS: A retrospective case note review was performed of patients who had undergone macular hole surgery with silicone oil tamponade. The patients were unable to posture due to chronic illness and had stage 2, 3, or 4 full thickness macular holes. Removal of silicone oil performed with or without cataract surgery was arranged 3 months or more after surgery. RESULTS: 10 eyes of 10 patients underwent surgery. Duration of oil tamponade ranged from 3-9 months. Following oil removal the hole was closed in eight eyes (80%), of which only three showed any improvement in visual acuity (38%) even after cataract extraction. All eyes developed cataract to varying degrees and one eye developed raised intraocular pressure which settled after oil removal. A serious complication, endophthalmitis, occurred in one eye following removal of sutures after cataract extraction. CONCLUSION: The anatomical results (80%) in this series are in keeping with those reported in other studies using gas tamponade. The visual results are disappointing and less rewarding than those obtained after successful surgery using gas tamponade.

Aged↗
PubMed2001

Endometritis in postparturient cattle associated with bovine herpesvirus-4 infection: 15 cases.

Suppurative, ulcerative endometritis associated with bovine herpesvirus-4 (BHV-4) infection was identified in 15 postparturient dairy cows from 5 separate dairies. Characteristic eosinophilic to amphophilic intranuclear viral inclusion bodies were identified within degenerate endometrial lining epithelium and endothelial cells. Bovine herpesvirus-4 was confirmed as the etiology by a combination of fluorescent antibody assays, viral isolation, heminested PCR, ultrastructural examination of the uterus and inoculated tissue culture cells, and negative-stain electron microscopy of tissue culture supernatant. Viral particles measuring 70-95 nm were demonstrated in uterine epithelial and endothelial cells by electron microscopy. Bacteria including Arcanobacterium pyogenes, Escherichia coli, and an alpha-Streptococcus isolate were isolated from all uteri. Bovine herpesvirus-4-associated endometritis has been previously reported in sporadic cases in Europe but has not been previously reported in the United States. Endometritis associated with BHV-4 appears to be an emerging syndrome in Georgia dairy herds.

Animals↗
PubMed2001

Gene therapy for pulmonary diseases.

Gene therapy for pulmonary disease has attracted a great deal of attention since the first report of successful gene delivery 10 years ago. Potential indications for gene therapy include chronic illnesses such as cystic fibrosis and alpha(1)-antitrypsin deficiency, and acute illnesses such as acute transplant rejection and chemotherapy-induced lung injury. The key technological impediment to successful gene therapy is vector optimization. Viral vectors, including adenovirus and adeno-associated virus, have relatively low efficiency in vivo. In addition, adenovirus has been associated with a brisk inflammatory response and limited duration of expression in the lung. Nonviral vectors, particularly liposomes, have also been tried, with limited expression efficiency and some toxicity. Although work is ongoing to improve adenoviral and adeno-associated viral vectors and test other viral and nonviral vectors, an ideal vector has not yet been identified. Several important barriers to successful gene therapy, including the host inflammatory response, promotor down-regulation, tissue-specific targeting, and physical barriers to gene delivery in the airway, will need to be overcome. Despite these daunting problems, several human gene therapy trials have been completed, using adenovirus, adeno-associated virus, and liposomes. In general, these trials have been focused on safety, and have shown that there is dose-dependent inflammation in response to adenovirus. Adeno-associated virus appears to cause little inflammation. Demonstration of successful gene delivery and transcription has been quite variable in human trials. In general, the level of expression of transgene appears to be quite low. In summary, although there is great promise for gene therapy in the lung, significant challenges remain in translating this technology to successful human therapy.

Adenoviridae↗
PubMed2001

Adjusting interphase FISH results in epithelial tissue sections to whole cell complement.

OBJECTIVE: To derive an equation to compensate for the discrepancies between whole cell preparations and tissue sections for more accurate enumeration of fluorescence in situ hybridization (FISH) signals per cell. STUDY DESIGN: Mean centromere signal counts in touch preparations and corresponding 4-6-micron sections of paraffin-embedded tissue were calculated. Mean widest nuclear diameters were also determined from the tissue sections. The observed data were analyzed to define the volumetric relationships between tissue sections and whole cell preparations. RESULTS: Analysis of results from six lung specimens yielded an equation that approximates whole versus sectioned nuclear volume and permits accurate quantification of mean FISH signal count in histologic sections, as follows: [formula: see text].

Carcinoma↗
PubMed2001

Plasma sodium-osmotic dissociation and hormonal interaction with drinking-induced hypervolemia at 2800 m altitude.

PURPOSE: To study hormonal factors that may account for the dissociation between beverage-induced plasma sodium p[Na+] and osmotic p[Osm] concentrations that appear to refute the high theoretical correlation between p[Na+] and p[Osm]. METHODS: Ten men (24 +/- SD 3 yr of age) sat reclining (head up) for 12 h in a chamber (21-23 degrees C dry bulb, 25-33% relative humidity) at 2800 m (9184 ft, 539 mm Hg) altitude (ALT), and at 321 m (1053 ft, 732 mm Hg) on the ground (GND). During 1000-1030 hours they consumed 3 fluids (12 ml x kg(-1),X = 948 ml x d(-1)) with large differences in sodium and osmotic contents: AstroAde (AA) with 185 mEq x L(-1) Na+ and 283 mOsm x kg(-1), Performance 1 (Shaklee) (P1) with 22 mEq x L(-1) Na+ and 365 mOsm kg(-1), or H2O at ALT; and only H2O on the GND. RESULTS: After drinking: plasma volume (PV) increased at 1200 hours by 8.3% (p < 0.05) with AA but was not significantly (NS) changed in the other sessions (Xdelta = +0.9%, range -0.9 to 2.8%); p[Na+] and p[Osm] were unchanged. Urinary rates and free-water clearances were attenuated with AA and P1 vs. those with H2O. Correlations between and among p[Na+] and p[Osm] suggest that the pNa+ ion is more tightly controlled than pOsm; and that there was no clear hormonal response that could account for this dissociation from theoretical considerations. CONCLUSIONS: There is significant dissociation between plasma sodium and osmotic concentrations after fluid intake. Induction and maintenance of hypervolemia requires increased (near isotonic) drink Na+ osmols rather than increased non-ionic osmols.

Adult↗
PubMed2001

School milk as a vehicle for fluoride in the United Kingdom. An interim report.

OBJECTIVE: To consider the feasibility of using school milk as a vehicle to deliver fluoride to children, suffering from high rates of dental disease, in socially deprived districts. METHOD: The legal aspects of adding fluoride to milk and availability of milk subsidies were updated. The organisational requirements of using school milk as a vehicle for fluoride were investigated and the consultation process established. The uptake of fluoridated milk was monitored and the fluoridated milk was subjected to rigorous quality control. The costs involved in running a scheme were calculated. OUTCOME: Fluoridated milk can now be called milk with added fluoride and to date the product has attracted subsidies from the European Economic Community and from the Welfare Foods Section in the Department of Health. The demonstration scheme in St. Helens, Merseyside, generated interest from neighbouring health authorities leading to the subsequent expansion of the programme. By working with the dairy, recommendations to improve the quality of school milk have been developed. The main organisations involved in running school based milk fluoridation schemes have been encouraged by the low costs involved. CONCLUSION: The UK programme has demonstrated that it is feasible to use school milk as a vehicle to deliver fluoride on a community basis. Attention must be given to improving the quality and particularly the temperature control of school milk.

Animals↗
PubMed2001

A 10 year prospective followup of patients with rheumatoid arthritis 1986-96.

OBJECTIVE: To determine the 10 year outcome of hospital patients with established rheumatoid arthritis (RA) treated with disease modifying drugs (DMARD). METHODS: All patients with RA of at least a year duration and attending a single clinician were followed prospectively for 10 years. DMARD treatments changed with time but were continued throughout. Measurements of joint tenderness (Ritchie Index), morning stiffness, grip, and disability (Health Assessment Questionnaire, HAQ) and radiographs of hands and feet were documented. A record of joint surgery was maintained. Patients who stopped attending the clinic were traced and an accurate record of deaths was obtained from the National Registry of Deaths. Paired clinical indices were compared where available between 0, 5, and 10 years. RESULTS: At entry there were 289 patients of variable disease duration. Within 10 years, 71 had died (standardized mortality ratio 1.3) and 92 were alive but unavailable. Median joint tenderness, morning stiffness, grip strength, and hemoglobin were not significantly different at 0, 5, and 10 years. Erythrocyte sedimentation rate (ESR) declined but not significantly. By contrast, HAQ scores and radiographs worsened between 0 and 10 years (p = 0.0004, p = 0.0001, respectively). There was a trend toward lower ESR values and less disability and the lower radiographic scores in those with 10-15 years' disease duration in 1996 compared with those of similar duration in 1986. However, worsening of radiographs occurred in patients with short, medium, and long histories of RA. Correlations between disability, radiographic scores, and joint tenderness were apparent at the start and conclusion of the study. At 10 years, 54 (19%) of the original cohort had undergone at least one large joint replacement. Significantly more women required joint replacement surgery (chi-square 5.44, p = 0.02). CONCLUSION: Over a 10 year period patients with RA exhibited an excess of deaths and a deterioration of radiographs and function despite regular DMARD treatment and apparent clinical containment. Worsening of radiographs occurred in both relatively early and late disease. There was a steady requirement for surgical large joint replacement with time. This study suggests that in the long term. the effect of DMARD treatments may be less than the expectations derived from short term studies.

Adult↗
PubMed2000

Altered HOX and WNT7A expression in human lung cancer.

HOX genes encode transcription factors that control patterning and cell fates. Alterations in HOX expression have been clearly implicated in leukemia, but their role in most other malignant diseases remains unknown. By using degenerate reverse transcription-PCR and subsequent real-time quantitative assays, we examined HOX expression in lung cancer cell lines, direct tumor-control pairs, and bronchial epithelial cultures. As in leukemia, genes of the HOX9 paralogous group and HOXA10 were frequently overexpressed. For HOXB9, we confirmed that elevated RNA was associated with protein overexpression. In some cases, marked HOX overexpression was associated with elevated FGF10 and FGF17. During development, the WNT pathway affects cell fate, polarity, and proliferation, and WNT7a has been implicated in the maintenance of HOX expression. In contrast to normal lung and mortal short-term bronchial epithelial cultures, WNT7a was frequently reduced or absent in lung cancers. In immortalized bronchial epithelial cells, WNT7a was lost concomitantly with HOXA1, and a statistically significant correlation between the expression of both genes was observed in lung cancer cell lines. Furthermore, we identified a homozygous deletion of beta-catenin in the mesothelioma, NCI-H28, associated with reduced WNT7a and the lowest overall cell line expression of HOXA1, HOXA7, HOXA9, and HOXA10, whereas HOXB9 levels were unaffected. Of note, both WNT7a and beta-catenin are encoded on chromosome 3p, which undergoes frequent loss of heterozygosity in these tumors. Our results suggest that alterations in regulatory circuits involving HOX, WNT, and possibly fibroblast growth factor pathways occur frequently in lung cancer.

Blotting, Western↗
PubMed2000

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Amino Acid Sequence↗
PubMed2000

Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time.

Vernalization, the acceleration of flowering by a long period of cold temperature, ensures that many plants overwinter vegetatively and flower in spring. In Arabidopsis, allelic variation at the FRIGIDA (FRI) locus is a major determinant of natural variation in flowering time. Dominant alleles of FRI confer late flowering, which is reversed to earliness by vernalization. We cloned FRI and analyzed the molecular basis of the allelic variation. Most of the early-flowering ecotypes analyzed carry FRI alleles containing one of two different deletions that disrupt the open reading frame. Loss-of-function mutations at FRI have thus provided the basis for the evolution of many early-flowering ecotypes.

Alleles↗