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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 19 recordsLinked to original sources
PubMed2006

Anatomy and ultrasonographic appearance of the tympanic bulla and associated structures in the rabbit.

Otitis media is a relatively common condition in the rabbit although it can be difficult to evaluate clinically. Diagnostic imaging of the rabbit has traditionally involved radiography and there are few reports regarding the use of ultrasound. The aim of this study was to determine if the tympanic bulla (TB) and associated structures could be evaluated in the rabbit using currently available ultrasound equipment. The normal anatomy of the region was established using gross dissection and emascerated specimens and compared with the dog and cat. Ten New Zealand white rabbit cadavers were examined using two ultrasound machines and four transducers from a variety of locations. A 12 MHz linear transducer was found to be most appropriate. From a lateral approach the external ear canal could be visualized to the level of the external acoustic meatus while the TB itself could only be visualized from a ventral approach. The jugular and mastoid processes in the rabbit are very prominent and interfered with imaging of the TB from all approaches. Water-soluble lubricant introduced into the TB could be identified through the ventral bone wall of the TB and allowed the lumen and far wall to be visualised. Further work is required to determine whether ultrasound examination of the TB can be performed in live rabbits and to evaluate its benefits in the evaluation of clinical cases of otitis media.

Animals↗
PubMed2006

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies.

The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined.

Adult↗
PubMed2006

Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone.

Testosterone has marked beneficial cardiovascular effects, many of which have been attributed to a vasodilatory action. However, the molecular target of testosterone underlying this effect is subject to debate. In this study, we have used microfluorimetry as a noninvasive means of examining whether testosterone could exert dilatory effects via inhibition of voltage-gated Ca2+ entry in the model vascular smooth muscle cell line, A7r5. Rises of [Ca2+]i evoked by 50 mm K+ -containing solution were suppressed in a concentration-dependent manner by testosterone (IC50, 3.1 nm) and by the nonaromatizable analog, 5beta-dihydrotestosterone (IC50, 6.9 nm). The effects of testosterone were apparent in the presence of pimozide (to block T-type Ca2+ channels) but not nifedipine (to block L-type Ca2+ channels). Testosterone did not alter Ca2+ mobilization from intracellular stores by the prostaglandin analog U46619 or capacitative Ca2+ entry in cells pretreated with thapsigargin. Our results indicate that testosterone, at physiological concentrations, can selectively suppress Ca2+ entry into A7r5 cells via L-type Ca2+ channels. We suggest this effect is a likely mechanism underlying its vasodilatory actions and beneficial cardiovascular effects.

Animals↗
PubMed2006

Role of Rab5 in insulin receptor-mediated endocytosis and signaling.

Activated insulin receptors recruit various intracellular proteins leading to signal generation and endocytic trafficking. Although activated receptors are rapidly internalized into the endocytic compartment and subsequently degraded in lysosomes, the linkage between insulin receptor signaling and endocytosis is not well understood. This study utilizes both overexpression and depletion of Rab5 proteins to show that they play a critical role in both insulin-stimulated fluid phase and receptor-mediated endocytosis. Specifically, Rab5:WT and Rab5:Q79L (a GTP-hydrolysis defective mutant) enhance both types of endocytosis in response to insulin, while Rab5:S34N (a GTP-binding defective mutant) has the opposite effect. Morphological analysis indicates that both Rab5 and insulin receptor are found on early endosomes, but not at the plasma membrane. In addition, expression of Rab5:WT and Rab5:Q79L enhance both Erk1/2 and Akt activation without affecting JN- and p38-kinase activities, while the expression of Rab5:S34N blocks both Erk1/2 and Akt activation. Consistent with these observations, DNA synthesis is also altered by the expression of Rab5:S34N. Taken together, these results demonstrate that Rab5 is required for insulin receptor membrane trafficking and signaling.

Animals↗
PubMed2006

Rin1 regulates insulin receptor signal transduction pathways.

Rin1 is a multifunctional protein containing several domains, including Ras binding and Rab5 GEF domains. The role of Rin1 in insulin receptor internalization and signaling was examined by expressing Rin1 and deletion mutants in cells utilizing a retrovirus system. Here, we show that insulin-receptor-mediated endocystosis and fluid phase insulin-stimulated endocytosis are enhanced in cells expressing the Rin1:wild type and the Rin1:C deletion mutant, which contain both the Rab5-GEF and GTP-bound Ras binding domains. However, the Rin1:N deletion mutant, which contains both the SH2 and proline-rich domains, blocked insulin-stimulated receptor-mediated and insulin-stimulated fluid phase endocytosis. In addition, the expression of Rin1:delta (429-490), a natural occurring splice variant, also blocked both receptor-mediated and fluid phase endocystosis. Furthermore, association of the Rin1 SH2 domain with the insulin receptor was dependent on tyrosine phosphorylation of the insulin receptor. Morphological analysis indicates that Rin1 co-localizes with insulin receptor both at the cell surface and in endosomes upon insulin stimulation. Interestingly, the expression of Rin1:wild type and both deletion mutants blocks the activation of Erk1/2 and Akt1 kinase activities without affecting either JN or p38 kinase activities. DNA synthesis and Elk-1 activation are also altered by the expression of Rin1:wild type and the Rin1:C deletion mutant. In contrast, the expression of Rin1:delta stimulates both Erk1/2 and Akt1 activation, DNA synthesis and Elk-1 activation. These results demonstrate that Rin1 plays an important role in both insulin receptor membrane trafficking and signaling.

Cell Line↗
PubMed2006

Sweat-gland tumours: a clinical review of cases in one centre over 20 years.

AIMS: Sweat-gland tumours (SGTs) are uncommon, but malignant varieties are very rare. We have added our data on 30 new cases seen at the Royal Marsden NHS Foundation Trust to the published literature, particularly concentrating on clinical issues. We include a literature review. MATERIALS AND METHODS: The Royal Marsden NHS Foundation Trust database was searched for cases of SGT from 1972. Data were collected on all cases, including patient demographics and tumour characteristics, treatment and outcome. RESULTS: Thirty cases were confirmed histologically to be SGTs. Fourteen were malignant, 15 benign and the degree of malignancy in one was histologically indistinguishable. Mean age was 55 years (64 for malignant, 47 for benign tumours). The 15 patients with benign tumours were almost all treated with complete excision. Those with local relapse underwent successful re-excision. Their 5-year disease-free survival was 78% and cause-specific survival was 100%. Twelve of the 14 malignant tumours had localised disease at diagnosis, one had nodal disease and one had metastatic tumour nodules. All except one were treated with wide local excision. The patient with nodal involvement also had a lymph-node dissection. Two received adjuvant radiotherapy to the tumour bed. One received a melphalan limb perfusion. Eight of the 14 had no relapse. Six had locoregional relapse, and four of these also developed distant metastases. Visceral disease was always fatal. Radiotherapy and chemotherapy at relapse were unsuccessful. Five-year disease-free survival was 45%, and cause-specific survival was 57%. CONCLUSION: These rare tumours should be treated initially with complete wide local excision. In malignant tumours, lymph-node involvement is a poor prognostic sign. Wide local excision remains the primary treatment. Adjuvant radiotherapy may be useful in high-risk cases.

Antineoplastic Agents↗
PubMed2006

Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease?

MicroRNAs (miRNAs) are endogenous 19-25 nucleotide RNAs that have recently emerged as a novel class of important gene-regulatory molecules involved in many critical developmental and cellular functions. miRNAs have been implicated in the pathogenesis of several human diseases, such as neurodegenerative disorders, cancer, and more recently in viral and metabolic diseases. Unraveling the roles of miRNAs in cellular processes linked to human diseases will lead to novel opportunities for the regulation of protein function and will help to evaluate their potential for therapeutic intervention. Approaches to interfere with miRNA function in vitro and in vivo based on synthetic anti-miRNA oligonucleotides (AMOs) are discussed in this review.

Animals↗
PubMed2006

Characterization of AWAP IV, the C-terminal domain of the avian protein AWAK.

AWAP IV constitutes the C-terminal domain of the larger 81 kDa protein AWAK [Avian WAP (whey acidic protein) domain- and Kunitz domain-containing], which is predicted, through conserved domain database searching, to contain at least four WAP domains and one Kunitz domain. RT (reverse transcription)-PCR analyses revealed mRNA transcripts encoding AWAP IV in the small intestinal and kidney tissues of 5-day-old Salmonella-infected chicks. Time-kill antimicrobial assays using rAWAP IV (recombinant AWAP IV) cell lysate indicated antimicrobial activity against gram-positive and gram-negative bacteria including Salmonella, Streptococcus and Staphylococcus spp. In addition, permeabilization of the outer membrane of Salmonella, as shown by the NPN (N-phenyl-1-naphthylamine) fluorescent probe assay, supported the ability of rAWAP IV to disrupt prokaryotic membranes. WAP domains can function as inhibitors of serine protease activity, and the microbial serine proteases subtilisin and proteinase K were inhibited by rAWAP IV cell lysate. However, at comparable concentrations, no significant inhibition of the mammalian serine protease elastase was observed. The combined broad-spectrum antibacterial and anti-protease activities of AWAP IV suggest a novel role in the avian innate defence mechanisms operating against microbial infection.

Animals↗
PubMed2006

Homicide of children aged 0-4 years, 2003-04: results from the National Violent Death Reporting System.

INTRODUCTION: To better understand, and ultimately prevent, infant/child homicide, it is imperative to more thoroughly elucidate the circumstances and conditions related to such instances. Data were obtained from the US National Violent Death Reporting System (NVDRS) to illuminate circumstances related to homicide among children aged 4 years or less, and to identify demographic groups which may be at increased risk. METHODS: The NVDRS is an active surveillance system that provides comprehensive information on all violent deaths that occur within participating states within the US. Standard statistical tests were conducted to determine homicide rates among children ages 0-4 across states that provided data for both 2003 and 2004 (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia). These data were further used to investigate infant/child homicides by race, gender, and other relevant circumstances (for example, victim-suspect relationship, weapon type, and location of homicide). A Poisson regression model was fitted to the sample data to investigate the multivariate relationship between the infant/child homicide rate and available demographic information. RESULTS: The 2003 homicide rate for children ages 0-4 was 3.0 per 100,000 population. The 2004 homicide rate was 2.5 per 100,000 population. African Americans were 4.2 times as likely as whites to be victims of homicide. Suspects were commonly parents/caregivers. The vast majority of infant/child homicides occurred in houses or apartments, using weapons that include household objects. CONCLUSION: Homicides of infants and young children are most often committed in the home, by parents/caregivers, using "weapons of opportunity". This suggests that the risk of infant/child homicide is greatest within the primary care giving environment. Moreover, the use of "weapons of opportunity" may be indicative of maladaptive stress responses. Prevention and intervention strategies to reduce infant/child homicide should target the home environment and attend to maladaptive stress responses.

Black or African American↗
PubMed2005

Surveillance for mupirocin resistance following introduction of routine peri-operative prophylaxis with nasal mupirocin.

The authors have previously described the successful use of a five-day peri-operative prophylaxis regimen using nasal mupirocin and topical triclosan (PPNMTT) to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection. The present article describes the results of repeated point-prevalence surveillance for four years to determine whether mupirocin resistance has emerged in surgical units using empirical, short-term, peri-operative prophylaxis with nasal mupirocin. Before starting PPNMTT and every six months thereafter for four years, point-prevalence surveillance was performed for nasal S. aureus carriage in all patients on five orthopaedic surgery wards, one vascular surgery ward and one elderly medicine control ward. S. aureus screening and clinical isolates (surgical patients) were undertaken for low- [minimum inhibitory concentration (MIC) 8-128 mg/L] and high-level (MIC > 128 mg/L) mupirocin resistance. All isolates were phage typed to determine whether there was evidence of the spread of clonal mupirocin-resistant strains. Of 593, 139 and 206 nasal screening swabs (taken after the regimen had started) from orthopaedic, vascular and control patients, 28%, 24% and 48% (orthopaedic/vascular surgery vs elderly medicine, P < 0.001) yielded S. aureus isolates, respectively, and 12%, 11% and 30% (P < 0.001) were MRSA positive, respectively. Of the S. aureus nasal screen isolates from orthopaedic/vascular surgery and control patients, 5% and 4%, respectively, were low-level mupirocin resistant (P > 0.1). Of 286 (orthopaedic/vascular surgery) and 68 (elderly medicine) clinical S. aureus isolates obtained after the regimen had started, 7% and 9% (P > 0.1), respectively, were low-level mupirocin resistant. No high-level mupirocin-resistant isolates were isolated from mupirocin (orthopaedic/vascular surgery) or elderly medicine control ward patients. There was no trend towards increasing prevalence of low-level mupirocin resistance during the four-year study period. The results of phage typing did not support the clonal spread of resistant strains. Long-term follow-up confirmed the efficacy of PPNMTT in reducing the prevalence of nasal carriage of S. aureus and MRSA in orthopaedic and vascular surgery patients. Despite four years of use of PPNMTT, there was no evidence of sustained emergence or spread of mupirocin resistance.

Administration, Intranasal↗
PubMed2005

Factors associated with the wastage and achievements in competition of event horses registered in the United Kingdom.

The aims of this study were to estimate the wastage of horses registered for eventing in Britain, to investigate the reasons for this wastage and to evaluate factors affecting the horses' achievement of grade I status (at least 61 points) while registered. An analysis of the database of the British Eventing register found that 33.7 per cent of horses registered for the first time in 1999 were not re-registered for eventing in subsequent years. By using multivariable logistic regression analysis, it was shown that horses that were kept at an event yard were more likely to be re-registered than those kept on other premises (odds ratio [or] 2.0, 95 per cent confidence interval [ci] 1.2 to 3.2), and those that took part in showjumping while registered were also more likely to be re-registered (or 1.5, 95 per cent ci 1.1 to 2.2). Horses that took part in unaffiliated eventing while registered were less likely to be re-registered the following year (or 0.7, 95 per cent ci 0.5 to 0.9), as were those that were not insured (or 0.7, 95 per cent ci 0.5 to 1.0) and those from outside the British Isles (or 0.6, 95 per cent ci 0.3 to 1.0). Veterinary problems were the most commonly cited explanation (35.1 per cent) why horses that remained in their original ownership were not re-registered with British Eventing the following year. Horses from Australia were more likely to achieve grade I status than horses from the British Isles (or 9.7, 95 per cent ci 7.1 to 13.2), as were horses from New Zealand (or 6.4, 95 per cent ci 5.0 to 8.2), the usa (or 5.2, 95 per cent ci 3.8 to 7.2) and France (or 2.8, 95 per cent ci 2.1 to 3.7), but horses from the Netherlands (or 0.5, 95 per cent ci 0.3 to 0.9) and Belgium (or 0.3, 95 per cent ci 0.1 to 0.9) were less likely to achieve grade I status. Mares were less likely to achieve grade I status than geldings (or 0.4, 95 per cent ci 0.4 to 0.5).

Animals↗
PubMed2005

Dealing with lead in Broken Hill--trends in blood lead levels in young children 1991-2003.

The objective of the study was to investigate trends in blood lead concentrations in preschool children between 1991 and 2003, as part of the evaluation strategy of a public health lead management program in Broken Hill, Australia. Since 1991, all Broken Hill children aged 1-4 years have been offered at least annual blood lead screening as part of a community-wide lead management program. Recruitment of children was promoted throughout the period using local media and distribution of promotional material from health care centres and preschool, childcare, and educational facilities around the city. Venous blood samples were collected using standard procedures and analyses were subjected to internal and external quality control programs. Because the frequency distribution of blood lead levels are skewed, geometric rather than arithmetic means were used for comparative purposes. Trend analysis was based on age and sex standardised mean blood lead levels. The number of 1- to 4-year-old children screened ranged between 496 and 948 in any one year and response rates varied between 39% and 73%. The age-sex standardised mean blood lead level decreased from 16.3 microg/dL to 7.1 microg/dL between 1991 and 2003. Overall, blood lead levels declined by 56% over 13 years. These reductions were consistently observed irrespective of age or where a child lived in the town. The rate of decline has slowed since 1997. We conclude that substantial progress has been made in dealing with the lead problem in Broken Hill children, although the rate of decline of blood lead levels has slowed. Continued public health action is still needed to bring the proportion of young children with significantly elevated blood lead levels (>15 microg/dL) down from the 2003 figure of 12% to the NHMRC community-based target for lead in young Australians of 5%.

Child, Preschool↗
PubMed2005

Cancer risk according to type and location of ATM mutation in ataxia-telangiectasia families.

Epidemiological studies have indicated that ataxia-telangiectasia (AT) heterozygotes in AT families have an increased risk of cancer, particularly of breast cancer (BC). However, in BC case-control studies, no significant differences were found in the frequency of ATM mutations between patients and controls. In such studies missense mutations were found more frequently than truncating mutations, suggesting that the cancer risk depends on mutation type. To investigate this possibility, we assessed the risk of BC according to the type and position of the ATM truncating mutation in extended AT families. DNA or RNA that had been isolated from blood or buccal cells of AT children and their relatives was screened for ATM germ-line mutations using restriction endonuclease fingerprinting, the protein truncation test, fluorescence-assisted mismatch analysis, and direct sequencing. The standardized incidence ratio of cancer associated with ATM heterozygosity status and type of mutation was estimated. We tested for genotype-phenotype correlations by simulations, permuting mutations among parental branches. No significant difference was found in the relative risk of breast cancer or any other type of cancer based on mutation type. However, the occurrence of BC may be associated with truncating mutations in certain binding domains of the ATM protein (e.g., P53/BRCA1, beta-adaptin, and FAT domains; P = 0.006). In this limited sample set, the presence of missense or truncating ATM mutations was not associated with different cancer risks. The risk of BC appeared to be associated with the alteration of binding domains rather than with the length of the predicted ATM protein.

Ataxia Telangiectasia↗
PubMed2005

Cyclic bisphosphonate therapy in osteogenesis imperfecta type V.

The clinical and radiographic features and management of a young person with recently delineated Osteogenesis Imperfecta Type V is described. A female aged 9 years presented with a history of multiple fractures since 3 years of age and bilateral dislocation of the elbows from infancy. She was commenced on a low dose frequent regimen of cyclic intravenous pamidronate, which resulted in progressive improvement in bone density, reduced fracture frequency and remission of symptoms of osteoporosis.

Anti-Inflammatory Agents↗