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Biomedical subjects

J Weir

Publications and source records attributed to J Weir.

At least 19 recordsLinked to original sources
PubMed2000

Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat.

Vertebrate photoreceptor cells are the basic sensory apparatus of the retina, capable of converting the energy of absorbed photons into neuronal signals. The proximal portions of mammalian photoreceptor outer segments are synthesized daily by cell bodies, and outer segment tips are shed with a circadian rhythm, resulting in a complete turnover of outer segments about every 9 days. The shed outer segments are phagocytosed by adjacent retinal pigment epithelial (RPE) cells, and metabolites are recycled to photoreceptors. The Royal College of Surgeons (RCS) rat is a widely studied, classic model of recessively inherited retinal degeneration in which the RPE fails to phagocytose shed outer segments, and photoreceptor cells subsequently die. We have used a positional cloning approach to study the rdy (retinal dystrophy) locus of the RCS rat. Within a 0.3 cM genetic inclusion interval, we have discovered a small deletion of RCS DNA that disrupts the gene encoding the receptor tyrosine kinase Mertk. The deletion includes the splice acceptor site upstream of the second coding exon of Mertk and results in a shortened transcript that lacks this exon. The aberrant transcript joins the first and third coding exons, leading to a frameshift and a translation termination signal 20 codons after the AUG. The concordance of these and other data indicate that Mertk is probably the gene for rdy. Our results provide genetic evidence for an essential role of a receptor tyrosine kinase in a specialized form of phagocytosis and suggest a molecular model for ingestion of outer segments by RPE cells.

Animals↗
PubMed2000

Identification of differentiating cochlear hair cells in vitro.

HYPOTHESIS: The expression of hair cell-specific genes involved in differentiation was studied in the cell line UB/OC-1 (University Bristol/Organ of Corti). BACKGROUND: Studies of gene expression in cochlear hair cells are restricted by the small number of cells available and by their experimental inaccessibility. The cell line was derived from the H2K(b)tsA58 transgenic mouse, which harbors a conditionally expressed immortalizing gene. Two genes that are characteristic of hair cells were upregulated during differentiation of UB/OC-1 cells in vitro. They are the transcription factor Brn3.1, which is essential for hair cell differentiation, and the alpha9 subunit of the nicotinic acetylcholine receptor that is involved in olivocochlear efferent innervation. METHODS: The expression of Brn3.1 and alpha9, at different time points under differentiating conditions, was analyzed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Western blot analysis and immunofluorescence analysis were performed on the cell line with anti-Brn3.1 antibody. RESULTS: Reaction products for alpha9 were detected after 3 to 6 days under differentiating conditions. Low levels of Brn3.1 were detectable under proliferating conditions and increased under differentiating conditions. All cells expressed Brn3.1 under differentiating conditions. This temporal pattern of gene expression is very closely similar to that found in vivo. CONCLUSION: The cochlear hair cell line UB/OC-1 provides a valuable experimental system because it conditionally expresses genes essential for normal differentiation and electrophysiology. It should prove valuable in the identification and characterization of genes involved in development and may provide material for screening new therapeutic methods of stimulating recovery and regeneration of hair cells.

Animals↗
PubMed2000

Inflammatory abdominal aortic aneurysms: diagnosis with gadolinium enhanced T1-weighted imaging.

AIM: Inflammatory abdominal aortic aneurysms (IAAA) are a variant of abdominal aortic aneurysms, which are associated with an increased morbidity. The diagnosis of IAAA has traditionally been established with a combination of clinical and laboratory findings together with contrast enhanced CT. There is a high incidence of renal impairment in this group, and therefore contrast enhanced CT may be harmful. PATIENTS AND METHODS: Five patients with IAAA underwent T1-weighted spin echo and gradient echo gadolinium enhanced abdominal MRI. A total of eight examinations were performed, including three patients who underwent repeat MRI following steroid therapy. RESULTS: The inflammatory cuff was clearly identified following gadolinium administration in all eight examinations. The cuff enhanced homogeneously in all patients with no alteration in appearance following steroid therapy. The intravenous administration of gadolinium DTPA enabled clearer definition of locally involved structures. CONCLUSION: Gadolinium enhanced MRI readily demonstrates features of IAAA. In view of potential renal impairment in this patient group, we recommend this technique in preference to contrast enhanced CT in the initial investigation of inflammatory abdominal aortic aneurysms.

Aged↗
PubMed1999

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

Biopsy, Needle↗
PubMed1999

Quantifying comorbidity in a disease-specific cohort: adaptation of the total illness burden index to prostate cancer.

OBJECTIVES: Numerous studies have demonstrated the importance of comorbid illness when analyzing medical outcomes. The purpose of this study was to adapt a generic comorbidity index, the Total Illness Burden Index (TIBI), for use in men with prostate cancer, and to evaluate the usefulness of the new instrument in adjusting for the impact of comorbidity on functional outcomes in a prostate cancer cohort. METHODS: The TIBI uses patients' self-report of symptoms and diagnoses to determine not only the presence but also the severity of comorbidities in each of 16 body system domains. To create the TIBI-P (prostate cancer modification), some domains were added and others were modified according to clinical criteria. The TIBI-P was completed by 1638 men with prostate cancer followed up longitudinally in 29 urology practices in the United States. TIBI-P scores were calculated for each patient and analyzed with scores on the SF-36 quality-of-life questionnaire and with patient report of days confined to bed. RESULTS: After adjusting for age and income, lower SF-36 scale scores and increases in confinement to bed were associated with a greater burden of comorbid illness as measured by the TIBI-P, independent of the extent of prostate cancer. The TIBI-P explained 24% of the variance in the SF-36 physical functioning domain score. CONCLUSIONS: The TIBI-P is a powerful measure of the impact of comorbid illness on the quality of life and functioning among patients with prostate cancer. This index may prove valuable in research on clinical and economic outcomes of prostate cancer.

Aged↗
PubMed1999

The structure and paramutagenicity of the R-marbled haplotype of Zea mays.

Paramutation is the meiotically heritable silencing of a gene that can occur in particular heterozygous combinations. The R-marbled (R-mb) haplotype is paramutagenic: it causes paramutable r1 haplotypes like R-r to become heritably silenced. R-mb was found to comprise three distinct r1 genes arranged as direct repeats. The most distal gene of R-mb, Scm, contains a novel transposable element, Shooter (Sho). Excision of the Sho element early in aleurone development results in the characteristic "marbled" aleurone pigmentation pattern conferred by R-mb. The effect of gene copy number on the paramutagenic strength of R-mb was tested. Paramutagenic strength of R-mb is directly correlated with r1 gene copy number. Paramutagenic strength of R-mb is directly correlated with r1 gene copy number. Paramutagenic strength of R-mb was not affected by removal, through crossing over, of the Sho transposon. Finally, R-mb does not appear to contain the transposable element, Doppia, which is associated with paramutability of R-r, and has been suggested to play a role in paramutagenicity of another paramutagenic haplotype, R-stippled.

Base Sequence↗
PubMed1999

Prevalence of protein-energy malnutrition at diagnosis in children with acute lymphoblastic leukemia.

BACKGROUND: The purpose of the present study was to test the hypothesis that protein-energy undernutrition is common in patients with acute lymphoblastic leukemia at diagnosis. Previous studies have failed to establish whether undernutrition is a common feature at diagnosis. METHODS: Body mass index (BMI, weight/height2), expressed as a standard deviation score (SDS) relative to contemporary United Kingdom reference data, was used as the index of nutritional status. The index was calculated in a national cohort of standard-risk patients (n = 1019) treated in the same protocol in the United Kingdom. RESULTS: Prevalence of undernutrition (defined as BMI SDS <-2.0) exceeded expected frequencies in boys (7.6%) and girls (6.7%). These differences were statistically significant (p < 0.001), with a 95% confidence interval for the prevalence of undernutrition of 5.8% to 9.0%. CONCLUSIONS: Undernutrition is relatively common in patients with newly diagnosed acute lymphoblastic leukemia, with a threefold excess of patients below the cutoff used to define undernutrition. Screening for undernutrition at diagnosis of acute lymphoblastic leukemia is indicated, and the BMI SDS is a simple index of nutritional status that could be readily calculated using measurements routinely made at diagnosis. The same simple screening technique could also be used clinically to detect and manage or prevent overnutrition (obesity), which is common in these patients after diagnosis.

Adolescent↗
PubMed1999

Patient selection criteria in the surgical treatment of veno-occlusive dysfunction.

PURPOSE: We evaluated short and long-term results of simple and complex venous surgery in patients with veno-occlusive dysfunction unresponsive to maximum recommended doses of intracavernous alprostadil, who were selected with newly developed diagnostic indicators. MATERIALS AND METHODS: A total of 23 impotent men with a mean age of 41 years (range 20 to 50) underwent complex penile venous surgery. Only patients fulfilling at least 3 criteria were included in study. The criteria were mild cavernous leak assessed by cavernosometry (grades 1 and 2), more than 30% cavernous smooth muscle tissue (histomorphometric analysis), normal analogical corpus cavernosum electromyography recordings according to international standards, cavernosal oxygen tension greater than 65 mm. Hg at erection and age younger than 50 years. RESULTS: Of 23 patients 17 (74%) had normal erections within a year after surgery, and 5 of them (29%) complained of recurrent erectile dysfunction. At long-term followup 6 of 12 patients had spontaneous erections. CONCLUSIONS: Careful selection with advanced diagnostic techniques should be mandatory before performing venous surgery in patients with high degree veno-occlusive dysfunction as the only alternatives are major therapeutical solutions.

Adult↗
PubMed1998

Extracellular levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid measured by microdialysis in the corpus striatum of conscious AS/AGU mutant rats.

The AS/AGU rat is a mutant derived from the Albino Swiss (AS) strain. It is characterized by an ungainly, staggering gait, hind limb rigidity, whole body tremor and, in older animals, difficulty in initiating movement. As and AS/AGU males aged three, six and nine months (n=6 per group) were used to estimate the levels of dopamine and its metabolites in the extracellular fluid of the caudate-putamen. The results indicate a profound loss of dopamine in the extracellular fluid at all age points examined, together with an increase in the concentration of the metabolite 3,4-dihydroxyphenylacetic acid. It is suggested that these changes reflect a defect of dopaminergic neuron function which may underlie the motor disorder seen in these animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Partial regression in primary carcinoma of the lung: does it occur?

AIMS: To study immunohistochemically a group of 28 primary lung cancers which demonstrated histological features reminiscent of those characteristic of regression in malignant melanoma, to determine the phenotype of their immune cell infiltrates. METHODS AND RESULTS: Using a standard s-ABC immunoperoxidase method then quantification by the Leica Q500 MC image analyser, the cellular infiltrate in these tumours, when compared to 67 control cases, showed excess CD3 + T lymphocytes (P < 0.007), with an increase in CD4:CD8 ratio and increased CD68 + macrophages (P = 0.00001). CD57 + natural killer cells and S100 + Langerhans cells were also increased, but not quite significantly (P = 0.048 and P = 0.072, respectively). CONCLUSIONS: This immunophenotype resembles that shown in regressing skin malignancies and suggests a similar process occurring in lung cancer. Regressing lung cancers are associated with a better prognosis than matched controls (P = 0.0034), some showed radiological evidence of growth retardation and the group had an excess of the large cell undifferentiated histological type.

Antigens, CD↗
PubMed1997

Sale of cigarettes to school children aged 14 and 15 years in New Zealand.

AIMS: To determine the sources of cigarettes and extent of illegal sales to 14 and 15 year old children, and to examine associated risk factors in order to more effectively reduce tobacco access to children. METHOD: Nationwide cross sectional survey of fourth form school children in New Zealand by means of an anonymous self administered questionnaire. RESULTS: Questionnaires from 14,097 fourteen and fifteen years olds were analysed, with over one third smokers. Twenty four percent of the whole group (3432) had bought cigarettes in the last year. Of smokers, 59.9% bought their own, with the great majority (68.9%) from dairies, particularly females. Ninety five percent said it was "easy" or "very easy" to buy cigarettes, and this was a major risk factor for this behaviour (relative risk (RR) = 2.01, 95% confidence interval (CI) 1.74, 2.32, RR = 2.54, CI 2.28, 2.83, respectively). Only 24.6% children had ever been refused cigarettes because of age and all points of sale were comparable in this respect. Heavy smokers and males were more likely to have been refused. While refusal was associated with a fourfold increase in the perception that it was difficult to buy cigarettes, there was only a minimal reduction in the risk of children buying their own cigarettes (RR = 0.95, CI 0.91, 1.00). CONCLUSION: We have shown that the illegal sale of cigarettes to children is unacceptably easy and accurately perceived as such by children who smoke. The active enforcement of existing or future legislation is essential, with prosecution of offending retailers, if we are to make any progress to reduce the high prevalence of smoking in New Zealand children.

Adolescent↗
PubMed1995

A national survey of cigarette smoking in fourth-form school children in New Zealand.

AIMS: To determine the prevalence of cigarette smoking in 14 and 15 year old school children in New Zealand and to examine associated risk factors. METHODS: Nationwide cross-sectional survey of fourth-form school children in New Zealand by means of an anonymous self administered questionnaire in November 1992. RESULTS: Questionnaires from 14,097 fourteen and fifteen year-olds were analysed. 65.6% had tried smoking, and 36.1% regarded themselves as smokers. Females and Maori had significantly higher prevalence rates. Of Maori females 44.6% were current smokers (more than one per month) compared to 24.0% for the whole group, and 33.0% were daily smokers. Pacific Island students, who have similar socioeconomic disadvantage to Maori, have a lower relative risk of smoking (RR) 0.79, (95% confidence interval (CI) 0.68, 0.91), than Europeans. Major independent risk factors were identified and population attributable risk was calculated for parental smoking (22.9%), poor knowledge of adverse health effects (7.3%) and watching televised sports (13.4%). These three modifiable factors accounted for 36.1% of the total smoking prevalence in these children. CONCLUSION: The continued high prevalence of smoking in New Zealand children, especially in Maori and in females, prove current public health measures to be inadequate. Our results suggest that strategies aimed at decreasing parental smoking, improving student knowledge of adverse health effects and preventing tobacco sponsorship of television sports could greatly decrease the smoking prevalence in this age group.

Adolescent↗
PubMed1995

Supraglottic transection: results of repair and functional outcome.

We present two cases of supraglottic transection, with concomitant neurotemesis of the superior laryngeal nerve. Both cases were repaired primarily and a temporary tracheostomy was used to protect the airway. In both cases subsequent decannulation was achieved within four weeks, following the initial injury. No long-term swallowing or voice disturbance was noted in either case. We recommend that in such cases it is unnecessary to repair the nerves directly, but that careful repair of the wound itself will achieve a functional result.

Adult↗