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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 19 recordsLinked to original sources

Rb, whi it's not just for metazoans anymore.

The E2F family of heterodimeric transcription factors controls the expression of genes required in G1 for cell cycle progression. The retinoblastoma (Rb) family of pocket proteins which, upon binding to E2F, inhibit this complex from initiating transcription. Upon mitogen stimulation, this repression is relieved by hyperphosphorylation of Rb by the cyclin D Cdk4/6 complex. Initiation of the cell cycle in yeast is similar. The heterodimeric transcription factor SBF controls most G1-specific transcription. Its activation is dependent upon the removal of Whi5; a functional homolog of Rb. Similar to Rb, disassociation of Whi5 from SBF is controlled by G1 cyclin/Cdk-dependent phosphorylation. Although Rb and Whi5 play similar roles in regulating G1 gene expression, they exhibit no sequence homology. This review will discuss the difference and similarities between how these proteins play similar roles in controlling G1 progression.

Animals↗

A semiconductor source of triggered entangled photon pairs.

Entangled photon pairs are an important resource in quantum optics, and are essential for quantum information applications such as quantum key distribution and controlled quantum logic operations. The radiative decay of biexcitons-that is, states consisting of two bound electron-hole pairs-in a quantum dot has been proposed as a source of triggered polarization-entangled photon pairs. To date, however, experiments have indicated that a splitting of the intermediate exciton energy yields only classically correlated emission. Here we demonstrate triggered photon pair emission from single quantum dots suggestive of polarization entanglement. We achieve this by tuning the splitting to zero, through either application of an in-plane magnetic field or careful control of growth conditions. Entangled photon pairs generated 'on demand' have significant fundamental advantages over other schemes, which can suffer from multiple pair emission, or require post-selection techniques or the use of photon-number discriminating detectors. Furthermore, control over the pair generation time is essential for scaling many quantum information schemes beyond a few gates. Our results suggest that a triggered entangled photon pair source could be implemented by a simple semiconductor light-emitting diode.

Journal Article↗

A review of health care models for coronary heart disease interventions.

This article reviews models for the treatment of coronary heart disease (CHD). Whereas most of the models described were developed to assess the cost effectiveness of different treatment strategies, other models have also been used to extrapolate clinical trials, for capacity and resource planning, or to predict the future population with heart disease. In this paper we investigate the use of modelling techniques in relation to different types of health intervention, and we discuss the assumptions and limitations of these approaches. Many of the models reviewed in this paper use decision tree models for acute or short term interventions, and Markov or state transition models for chronic or long term interventions. Discrete event simulation has, however, been used for more complex whole system models, and for modelling resource-constrained interventions and operational planning. Nearly all of the studies in our review used cohort-based models rather than population based models, and therefore few models could estimate the likely total costs and benefits for a population group. Most studies used de novo purpose built models consisting of only a small number of health states. Models of the whole disease system were less common. The model descriptions were often incomplete. We recommend that the reporting of model structure, assumptions and input parameters is more explicit, to reduce the risk of biased reporting and ensure greater confidence in the model results.

Coronary Disease↗

Using simulation to estimate the cost effectiveness of improving ambulance and thrombolysis response times after myocardial infarction.

OBJECTIVES: To quantify the health gains and costs associated with improving ambulance and thrombolysis response times for acute myocardial infarction. DESIGN: A computer simulation model. PATIENTS/SETTINGS: Patients experiencing acute myocardial infarction in England. INTERVENTIONS: Improving the ambulance response time to 75% of calls reached within 8 minutes and the hospital arrival to thrombolysis time interval (door-to-needle time) to 75% receiving it within 30 minutes and 20 minutes, compared to best estimates of response times in the mid-1990s. MAIN OUTCOME MEASURES: Deaths prevented, life years saved, and discounted cost per life year saved. RESULTS: Improving the ambulance response to 75% of calls within 8 minutes resulted in an estimate of 5 deaths prevented or 57 life years saved per million population per year, with a discounted incremental cost per life year saved of 8540 pounds sterling over 20 years. The corresponding benefit of improving the door-to-needle time to 75% of myocardial infarction patients within 30 minutes was an estimated 2 deaths prevented and 15 life years saved per million population per year, with a discounted incremental cost per life year saved of between 10,150 pounds sterling to 54,230 pounds sterling over 20 years. Little further gain was associated with reaching the 20 minute target. Combining ambulance and thrombolysis targets resulted in 70 life years saved per million population per year. CONCLUSIONS: Improving ambulance response times appears to be cost effective. Reducing door-to-needle time will have a smaller effect at an uncertain cost. Further benefits may be gained from reducing the time from onset of symptoms to starting thrombolysis.

Aged↗

Pseudoactinomycotic radiate granules of the gynaecological tract: review of a diagnostic pitfall.

The filamentous bacterium actinomyces can cause serious gynaecological tract infections, including pelvic inflammatory disease (PID) and tubo-ovarian abscess. Thus, definitive diagnosis of actinomycotic granules (AMGs) in gynaecological specimens is clinically important. Non-infectious pseudoactinomycotic radiate granules (PAMRAGs) can mimic the microscopic appearance of AMGs. PAMRAGs may be more common than actinomycotic infections in specimens from patients using intrauterine devices and may be seen in patients with PID. Although the composition and aetiology of PAMRAGs is unclear and variable, a panel of histochemical stains can aid in diagnosis. On haematoxylin and eosin (H&E) stained sections, AMGs show as distinct granules with basophilic peripheral radiating filaments and a dense central eosinophilic core, whereas H&E stained sections of PAMRAGs feature refractile granules with irregular club-like peripheral projections and no central dense core. The filaments of AMGs are Gram positive on Brown and Brenn (B&B) stain and are highlighted with Gomori methenamine silver stain (GMS). They stain negatively with a modified acid fast bacillus (AFB) stain, aiding in the distinction of actinomyces from nocardia. PAMRAGs show negative or non-specific staining with B&B, GMS, and AFB stains. Therefore, knowledge of these staining properties and the distinguishing characteristics of PAMRAGs and AMGs enables recognition of this important diagnostic pitfall.

Actinomycosis↗

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Humans↗

Identification of genotype 3 hepatitis E virus (HEV) in serum and fecal samples from pigs in Thailand and Mexico, where genotype 1 and 2 HEV strains are prevalent in the respective human populations.

Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important public health concern in many developing countries. Increasing evidence indicates that hepatitis E is a zoonotic disease. There exist four major genotypes of HEV, and HEV isolates identified in samples from pigs belong to either genotype 3 or 4. Genotype 1 and 2 HEVs are found exclusively in humans. To determine whether genotype 1 and 2 HEVs also exist in pigs, a universal reverse transcription-PCR assay that is capable of detecting all four HEV genotypes was used to test for the presence of HEV RNA in serum and/or fecal samples from pigs in Thailand, where genotype 1 human HEV is prevalent, and from pigs in Mexico, where genotype 2 human HEV was epidemic. In Thailand, swine HEV RNA was detected in sera from 10/26 pigs of 2 to 4 months of age but not in sera from 50 pigs of other ages. In Mexico, swine HEV RNA was detected in 8/125 sera and 28/92 fecal samples from 2- to 4-month-old pigs. Antibodies to swine HEV were also detected in about 81% of the Mexican pigs. A total of 44 swine HEV isolates were sequenced for the open reading frame 2 gene region. Sequence analyses revealed that all swine HEV isolates identified in samples from pigs in Thailand and Mexico belong to genotype 3. Phylogenetic analyses revealed that minor branches associated with geographic origin exist among the swine HEV isolates. The results indicated that genotype 1 or 2 swine HEV does not exist in pigs from countries where the respective human HEV genotype 1 or 2 is prevalent. It is likely that only genotype 3 and 4 HEV strains have zoonotic potential.

Animals↗

Large cell neuroendocrine carcinoma of the larynx: a case report and a review of the classification of this neoplasm.

This report describes a case of large cell neuroendocrine carcinoma (LCNEC) of the larynx. A 74 year old man who presented with otalgia underwent direct laryngoscopy with biopsy, which revealed an invasive poorly differentiated carcinoma. Laryngectomy with bilateral neck dissections revealed invasion of the pre-epiglottic space by the tumour, with metastases to bilateral lymph nodes (AJCC T3N2c). The tumour was characterised by large cells with vesicular chromatin and prominent nucleoli. The cells were arranged in organoid and trabecular patterns with a background of extensive necrosis and numerous mitotic figures. Immunohistochemical and ultrastructural analyses confirmed the neuroendocrine nature of the tumour. Metastatic disease was present in the liver, and the patient died within weeks of surgery. LCNEC carcinoma is a rare tumour of the larynx. Recognition at this site is essential so that proper patient management can be initiated.

Aged↗

Bladder neck needle suspension for urinary incontinence in women.

BACKGROUND: Bladder neck needle suspension is an operation traditionally used for moderate or severe stress urinary incontinence in women. About a third of adult women experience some urinary incontinence, and about a third of them have moderate or severe symptoms. OBJECTIVES: To determine the effects of needle suspension on stress or mixed urinary incontinence in comparison with other management options. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (searched 18 September 2003). The reference lists of relevant articles were also searched. SELECTION CRITERIA: Randomised or quasi-randomised trials that included needle suspension for the treatment of urinary incontinence. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted independently by at least two reviewers. Two trial investigators provided additional information. MAIN RESULTS: Nine trials were identified which included 347 women having six different types of needle suspension procedures and 437 who received comparison interventions. Needle suspensions were more likely to fail than open abdominal retropubic suspension (higher subjective failure rate after the first year (91/313, 29% failed versus 47/297, 16% failed after open abdominal retropubic suspension: the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.47 to 2.72) although the difference in peri-operative complications was not significant (17/75, 23% versus 12/77, 16%; RR 1.44, 95% CI 0.73 to 2.83): there were no significant differences for other outcome measures. This effect was seen in both women with primary incontinence and women with recurrent incontinence after failed primary operations. Needle suspensions may be as effective as anterior vaginal repair (46/128, 36% failed after needles versus 50/129, 39% after anterior repair; RR 0.93, 95% CI 0.68 to 1.26) but there was little information about morbidity. Data for comparison with suburethral slings were inconclusive because they came from a small and atypical population. No trials compared needle suspensions with conservative management, peri-urethral injections, sham or laparoscopic surgery. REVIEWERS' CONCLUSIONS: Bladder neck needle suspension surgery is probably not as good as open abdominal retropubic suspension for the treatment of primary and secondary urodynamic stress incontinence because the cure rates were lower in the trials reviewed. However, the reliability of the evidence was limited by poor quality and small trials. There was not enough information to comment on comparisons with suburethral sling operations. Although cure rates were similar after needle suspension compared with after anterior vaginal repair, the data were insufficient to be reliable and inadequate to compare morbidity.

Female↗

Immunostaining patterns of myoepithelial cells in breast lesions: a comparison of CD10 and smooth muscle myosin heavy chain.

BACKGROUND: Recent studies have reported CD10 expression in myoepithelial cells (MEC) of the breast, supporting its use as a marker to help distinguish invasive breast carcinoma (IC) from ductal carcinoma in situ (DCIS). AIM: To compare the effectiveness of CD10 with smooth muscle myosin heavy chain (SMMHC) in the detection of MEC in benign and malignant breast lesions. METHODS: Histological material from 25 patients with DCIS and 21 with IC were immunostained for CD10 and SMMHC. Staining was scored on a scale of 0 to 3+ (0, no staining; 3+, intense) and the staining distribution was documented as focal, partial, or circumferential. RESULTS: Uniform, 3+ circumferential CD10 and SMMHC staining of MEC was seen in normal breast ducts and lobules, and in ducts and acini involved in sclerosing adenosis and apocrine metaplasia. In an analysis of total ducts involved by DCIS, 3+ circumferential staining was seen in 65 of 366 ducts (17.7%) stained for CD10 versus 190 of 396 ducts (48%) stained for SMMHC. MEC were not detected immunohistochemically in 116 of 366 ducts (31.7%) with anti-CD10 and 50 of 396 (12.7%) with anti-SMMHC. In contrast, all ICs were negative for both CD10 and SMMHC. Focal background staining of stromal myofibroblasts was seen with both CD10 and SMMHC, but CD10 showed a higher rate of non-specific staining of epithelial cells. CONCLUSION: Although CD10 can aid in the distinction between IC and DCIS, SMMHC is a more sensitive and specific marker of MEC and shows less heterogeneity of immunostaining patterns.

Adenocarcinoma↗

Declining prevalence of STI in the London sex industry, 1985 to 2002.

OBJECTIVES: To describe major changes in the London sex industry between 1985 and 2002 and assess the implications for sexually transmitted infection (STI) risk. METHOD: A descriptive study comparing women who first attended a sex work clinic between 1996 and 2002 and those first attending from 1985 to 1992; a nested case-control study. 1050 female sex workers took part. The setting was a specialist clinical service for sex workers based in a London genitourinary medicine (GUM) clinic, and fieldwork in west London. The main outcome measures were reported condom use and prevalent STI. RESULTS: Over the period of the study there was a significant increase in the proportion of sex workers not born in the United Kingdom (from 25% to 63%, p < 0.001), and women entered sex work at an older age (median 24 years compared with 20 years, p < 0.001). Condom use increased (with the exception of oral sex). There was a significant decline in the proportion of participants reporting a previous STI (32% compared with 80%, p < 0.001) and the prevalence of acute STI declined from 25% to 8% (p < 0.001). Acute STI was associated with younger age, younger age at first sex work, being new to sex work, and inconsistent condom use. In a multivariate analysis unprotected sex with clients was the only significant risk. CONCLUSION: Major restructuring of the sex industry, including the shift to a primarily migrant workforce, has been associated with a steep decline in acute STI, undermining popular assumptions that migrant sex workers are central to the ongoing STI epidemic. We attribute the decline in acute STI to an increase in safer sex.

Adolescent↗