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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 19 recordsLinked to original sources
PubMed2006

Unusual presentation of 22-kilogram retroperitoneal müllerian serous cystadenoma.

BACKGROUND: Müllerian cyst of the retroperitoneum is an extremely rare disease that is thought to be a subtype of urogenital cyst. It is a benign condition that can only be diagnosed and cured by surgical resection. CASE: An 80-year-old female with a huge cystic swelling, thought to be ovarian in origin, underwent laparotomy. Surgical exploration and subsequent histopathological analysis of the cyst revealed a müllerian serous cystadenoma of the retroperitoneum, 22 kg in weight. Preoperative ultrasound scan and computed tomography failed to elucidate a correct preoperative etiology. CONCLUSION: Huge retroperitoneal cysts may coexist with other pelvic pathology creating diagnostic and therapeutic dilemmas. The use of computed tomography for diagnosis may be not helpful with huge cysts. Good preoperative preparation and surgical technique are essential for managing these cases.

Aged, 80 and over↗
PubMed2006

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate.

TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

Gene Expression Regulation, Neoplastic↗
PubMed2006

Identification of prognostic signatures in breast cancer microarray data using Bayesian techniques.

We apply a new Bayesian data analysis technique (latent process decomposition) to four recent microarray datasets for breast cancer. Compared to hierarchical cluster analysis, for example, this technique has advantages such as objective assessment of the optimal number of sample or gene clusters in the data, penalization of overcomplex models fitting to noise in the data and a common latent space of explanatory variables for samples and genes. Our analysis provides a clearer insight into these datasets, enabling assignment of patients to one of four principal processes, each with a distinct clinical outcome. One process is indolent and associated with under-expression across a number of genes associated with tumour growth. One process is associated with over expression of GRB7 and ERBB2. The most aggressive process is associated with abnormal expression of transcription factor genes, including members of the FOX family of transcription factor genes.

Bayes Theorem↗
PubMed2006

Efficacy of super-oxidized water fogging in environmental decontamination.

The efficacy of decontamination using Sterilox fog was assessed against meticillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii. Ceramic tiles were inoculated with the test organisms and, once dried, were subjected to Sterilox fogging using a stationary vaporizing machine sited at a distance of 3m for 10 min and then left for a further hour. In a second experiment using the same organisms, the first 10-min fogging period was followed by a directed fogging period of 30s at a distance of 1m. Organisms were cultured from the tiles, plated on to tryptone soya agar and incubated for 48 h. Initial counts of approximately 10(9) colony-forming units/mL for both organisms were reduced approximately 10(4) fold for MRSA and 10(5.8) fold for A. baumannii when using a single fogging. The second fogging resulted in 10(6.8)-fold reductions for both organisms. Sterilox fog is safe and simple to use, and can reduce levels of nosocomial pathogens by a factor of almost 10(7). It is worthy of clinical evaluation in clinical settings to determine whether it maintains its microbicidal effects against a variety of organisms on different surfaces.

Acinetobacter↗
PubMed2005

Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk.

IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1alpha and IL1beta. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the 'ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95% CI = 0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.

Aged↗
PubMed2005

Measures of health-related quality of life and functional status in survivors of oral cavity cancer who have had defects reconstructed with radial forearm free flaps.

The aim of this study was to evaluate (by postal questionnaire) quality of life and function in patients who have had resections of oral cancer and reconstruction by radial forearm flaps. Between October 1987 and December 2002, 258 patients had reconstructions by radial forearm flaps after resection of tumours in the oral cavity. Of these, 139 surviving patients were identified from the database and were sent questionnaires comprising five sections: Functional Assessment of Cancer Therapy-General (FACT-G) and -Head and Neck (FACT-HN); University of Washington Quality of Life Scale (UWQoL); Performance Status Scale for Head and Neck Cancer (PSS-HN); and the final section addressed dental rehabilitation and morbidity at the donor site. Sixty-three questionnaires (45%) were returned. In 17 (27%), parts of the questionnaire were incomplete. The median UWQoL score was 623/900, FACT-G was 92/108, FACT-HN was 31/48, and PSS-HN showed that eating in public, understandability of speech and normality of diet were 75/100, 75/100 and 50/100, respectively. The effect of stage and site on quality of life and function did not reach statistical significance. The effect of radiotherapy on speech (p=0.036) and diet (p=0.007) was significant. Patients who worried about their cancer returning had a lower UWQoL score (p=0.016). Ninety percent regarded their arm as disfigured, but 81% felt comfortable wearing short-sleeved shirts. Sensation and function of the hand were reported as normal in 87 and 92%, respectively. We conclude that patients who have had oral cancer have a persistent reduction in quality of life and function long after completion of treatment. The effects can be assessed by postal questionnaire, but the low rate of return (45%) and difficulties with completion reduce the quality of the data. Quality of life and function are essential components of improvements in outcome.

Adult↗
PubMed2005

A simple approach for estimating gene expression in Candida albicans directly from a systemic infection site.

Gene expression analysis after the host-pathogen interaction is revolutionizing our understanding of the host response to infection. Numerous studies have utilized microarray analysis to follow host cell transcriptome alterations in response to interactions with infectious pathogens. However, similar analyses of pathogen transcriptional adaptation at the infection site have been limited. Understanding the nature of this interaction from the pathogen perspective at different sites and stages of infection is central to strategies for development of new anti-infective therapies. Toward this end, we developed a protocol to analyze changes in gene expression for a eukaryotic pathogen, Candida albicans, during systemic infection in mice. The experimental approach takes advantage of the resistance of the cell wall of many fungal pathogens to cell lysis, relative to mammalian cells. After lysis of mammalian cells, the tissue mixture containing fungal cells is depleted of mammalian RNA by centrifugation, followed by enzymatic digestion. RNA-digesting enzymes are then inhibited before eukaryotic cell lysis and RNA isolation. The protocol provides a reproducible quantity of RNA based on pathogen cell number. The quality of the RNA allowed reliable downstream transcriptional analysis using reverse-transcription polymerase chain reaction and microarrays. The in vivo gene expression data confirmed involvement of several putative pathogenesis genes. More importantly, the results provided a wealth of biologically interesting hypotheses to direct future investigation.

Animals↗
PubMed2005

Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer.

In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types.

Biomarkers, Tumor↗
PubMed2005

Seroma formation after axillary lymphadenectomy with and without the use of drains.

Seroma formation after axillary lymphadenectomy is common. We performed a randomised controlled trial comparing seroma rate and volume after axillary lymphadenectomy with and without use of drains. In this study, there was no difference in incidence of seroma formation between patients who did and did not have a drain inserted after axillary lymphadenectomy for breast cancer. Undrained patients, however, had larger volume seromas of longer duration which required more aspirations. There was a tendency for undrained patients to have fewer complications when compared to patients with drains.

Axilla↗
PubMed2005

What does tumour necrosis factor excess do to the immune system long term?

Members of the tumour necrosis factor (TNF)/TNF-receptor (TNF-R) superfamily coordinate the immune response at multiple levels. For example, TNF, LTalpha, LTbeta and RANKL provide signals required for lymphoid neogenesis, CD27, OX-40, 4-1BB and CD30 deliver costimulatory signals to augment immune responses, while pro-apoptotic members such as TNF, CD95L and TRAIL may contribute to the termination of the response. Biological identity of individual family members has been revealed through studies of gain of function or gene deficient mutants. Most notable are the development of spontaneous inflammatory polyarthritis in human TNF-globin transgenic mice, the auto-inflammatory syndromes resulting from mutations in the 55-kDa TNF-R, and, in particular, the obligatory role for the RANKL/RANK axis in osteoclastogenesis and bone remodelling. A growing appreciation of the molecular basis of signalling pathways transduced by TNF-R has provided a framework for better understanding the biology of this expanding family. For while the rapid and robust activation of NF-kappaB and MAPK pathways is typical of acute TNF-R engagement, the molecular basis of sustained receptor signalling remains a mystery, in spite of its relevance to chronic inflammatory and immune responses. Focusing on T cells, this report describes some of the molecular footprints of sustained TNF-R engagement and illustrates how these may influence immune function. A common theme arising is that prolonged TNF stimulation alters signalling thresholds over time. The authors propose that one major outcome of long term exposure to TNF is a state of localised IL-2 deficiency at sites of inflammation. The implications of this deficiency are discussed.

Animals↗
PubMed2004

Human midbrain sensitivity to cognitive feedback and uncertainty during classification learning.

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the "prediction error") and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.

Adult↗
PubMed2004

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Animals↗
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

Management of the neck in patients with T1 and T2 cancer in the mouth.

UNLABELLED: Our aim in this retrospective study was to evaluate the extent of control of metastatic disease in the neck and the survival of patients with T1 and T2 oral cancer. METHODS: All 171 patients with T1 and T2 squamous cell carcinoma (SCC) in the mouth were identified from our computerised database. All had had primary tumours resected and 21 patients with palpable neck nodes had therapeutic neck dissections. Among 150 patients with no palpable nodes, 75 had elective neck dissections, and 75 were observed. The decision to do an elective neck dissection was based on clinical criteria and was not randomised. RESULTS: Cervical nodes contained metastases in 17 of 21 patients who had therapeutic, and 27 of 75 who had elective, neck dissections. Neck metastases developed subsequently in 15 of 75 patients in the observed group, and 9 of these were salvaged by therapeutic neck dissection. The 5-year disease free survival was 19/21 after therapeutic dissection, 72/75 after elective dissection, and 69/75 in the observed group. Patients with cervical nodal metastases had significantly reduced 5-year survival compared with those without (63% and 91%, P = 0.003).

Adult↗
PubMed2004

Motor balance and coordination training enhances functional outcome in rat with transient middle cerebral artery occlusion.

The goal of this study was to determine if relatively complex motor training on Rota-rod involving balance and coordination plays an essential role in improving motor function in ischemic rats, as compared with simple locomotor exercise on treadmill. Adult male Sprague-Dawley rats with (n=40) or without (n=40) ischemia were trained under each of three conditions: (1) motor balance and coordination training on Rota-rod; (2) simple exercise on treadmill; and (3) non-trained controls. Motor function was evaluated by a series of tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and at 14 or 28 days after training procedures in both ischemic and normal animals. Infarct volume in ischemic animals was determined with Nissl staining. Compared with both treadmill exercised and non-trained animals, Rota-rod-trained animals with or without ischemia significantly (P<0.01) improved motor performance of all tasks except for foot fault placing after 14 days of training, with normal rats having better performance. Animals trained for up to 28 days on the treadmill did not show significantly improved function. With regard to foot fault placing task, performance on foot placing was improved in ischemic rats across the three measurements at 0, 14 and 28 days regardless of training condition, while the normal group reached their best performance at the beginning of measurement. No significant differences in infarct volume were found in rats trained either with Rota-rod (47+/-4%; mean+/-S.E.), treadmill (45+/-5%) or non-exercised control (45+/-3%). In addition, no obvious difference could be detected in the location of the damage which included the dorso-lateral portion of the neostriatum and the frontoparietal cortex, the main regions supplied by the middle cerebral artery. The data suggest that complex motor training rather than simple exercise effectively improves functional outcome.

Animals↗
PubMed2004

Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood.

The optimal therapy for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We therefore reviewed our institutional outcomes for children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for advanced APL. Between 1986 and 2003, 12 allogeneic HSCTs (five related donor, seven unrelated donor) were performed for 11 patients (median age, 13 years) with relapsed (n = 8) or refractory (n = 3) APL. All patients engrafted, after a median of 18.5 days. Grade B-D acute graft-versus-host disease (GVHD) developed after five transplants (42%; 90% CI, 18-68%), and the cumulative incidence of chronic GVHD was 45% (90% CI, 19-71%). The cumulative incidence of overt relapse post-HSCT was 10% (90% CI, 0-28%). The overall 5-year survival was 73% (90% confidence interval (CI), 51-95%), with a median post-HSCT follow-up of 64 months. The Lansky/Karnofsky performance scores are 100% in six of eight survivors. In view of the low risk of subsequent relapse and favorable survival suggested by other reports and our own experience, we continue to recommend allogeneic HSCT for children with advanced APL for whom a suitably HLA-matched donor is identified.

Acute Disease↗