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Biomedical subjects

J M Watson

Publications and source records attributed to J M Watson.

At least 37 records · Page 2Linked to original sources
PubMed2003

SARS: UK public health response--past, present and future.

The emergence of severe acute respiratory syndrome (SARS) in China, the occurrence of epidemics of SARS in China and a number of Southeast Asian countries, and its spread to countries elsewhere, have presented major challenges to public health systems throughout the world. Although very few true cases of SARS were detected in the United Kingdom, the public health response to the threat of SARS was considerable. The main components of this response were the early detection, isolation and reporting of cases, and the provision of comprehensive information to health professionals, cases, their contacts and the public. The development of the response to SARS raised a number of more general issues relevant to future infectious epidemic threats. Although the World Health Organisation has now declared SARS 'contained', the possibility of re-emergence is ever present. All countries will need to be vigilant and plan their response to the possibility of a renewed SARS epidemic.

Health Planning↗
PubMed2003

Appropriateness of thresholds currently used to describe influenza activity in England.

The timing and magnitude of influenza virus activity in England each winter remain unpredictable. Nevertheless, it is important to describe levels of activity in a timely manner, using defined 'threshold values'. This informs public health practitioners and the general public of the level of influenza virus circulation, and provides an indication of when sufficient activity is occurring in the community to warrant the use of antiviral drugs. Data presented here suggest that the current numerical thresholds, and their corresponding descriptions, are no longer appropriate for the levels of activity recently observed in England. Based on integrated clinical and virological data, we suggest alternative threshold values of 'baseline' activity (0-30/100,000 population), 'normal seasonal' activity (30-200/100,000) and 'epidemic' activity (> 200/100,000).

England↗
PubMed2002

The molecular epidemiology of tuberculosis in inner London.

The study used DNA fingerprint typing (spoligotyping and Heminested-lnverse-PCR) of Mycobacterium tuberculosis from all culture-confirmed inner London patients over a 12-month period to describe transmission. The methodology was evaluated by comparison with standard IS6110 typing and by examining its ability to identify known household clusters of cases. Isolates sharing indistinguishable typing patterns using both techniques were defined as clustered. Clusters were investigated to identify epidemiological links. The methodology showed good discriminatory power and identified known household clusters of cases. Of 694 culture-confirmed cases, 563 (81%) were typed. Eleven (2%) were due to laboratory cross-contamination and were excluded. Of the remaining 552 isolates 148 (27%) were clustered. Multivariate analysis indicated that clustering was more common in those with pulmonary smear positive disease (P < 0.02); those born in the United Kingdom (P < 0.0003) and in patients living in south London (P = 0.02). There was also a trend towards clustering being more common in those not known to have HIV infection (P = 0.051). The results suggest that in inner London, recent local transmission makes an important contribution to notification rates.

Adolescent↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Prevalence, morbidity and service need among South Asian and white adults with intellectual disability in Leicestershire, UK.

BACKGROUND: Previous reports have suggested that South Asian and white UK populations have different prevalences of intellectual disability (ID), related psychological morbidity and service use. The aim of the present study was to compare these rates among South Asian and white adults in Leicestershire, UK. METHOD: This cross-sectional study is comprised of two parts. The analysis of prevalence is based on data from all South Asian and white adults known to the Leicestershire Learning Disabilities Register in 1991, with population denominators being drawn from the 1991 census. The other analyses use data collected from the most recent semi-structured home interviews, carried out between 1987 and 1998, with 206 South Asian and 2334 white adults. RESULTS: The prevalence of ID in adults in Leicestershire is 3.20 per 1000 in South Asians and 3.62 per 1000 in whites. Among adults with ID, South Asians have similar prevalences of disabilities to whites and significantly lower skill levels. South Asians show similar levels of psychological morbidity, but make significantly lower use than whites of psychiatric services, residential care and respite care. South Asians use community services as extensively as whites, but feel that they have a substantially greater unmet need, especially with regard to social services. CONCLUSION: South Asian and white populations have similar prevalences of ID and related psychological morbidity. Culturally appropriate services for South Asian adults may need to focus on skill development and community care.

Adult↗
PubMed2002

An estimate of the contribution of HIV infection to the recent rise in tuberculosis in England and Wales.

BACKGROUND: The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period. METHODS: Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection. RESULTS: In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups. CONCLUSIONS: In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age.

AIDS-Related Opportunistic Infections↗
PubMed2002

Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.

BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.

AIDS-Related Opportunistic Infections↗
PubMed2001

Structural consequences of divalent metal binding by the adenylyl cyclase toxin of Bordetella pertussis.

Adenylyl cyclase toxin of Bordetella pertussis has been shown by several investigators to require Ca(2+) for its actions on target cells, but little is known about the nature and specificity of divalent metal binding to this novel toxin. Calcium is the preferred divalent metal since toxic actions are markedly reduced in the presence of divalent species other than calcium. Mn(2+) EPR was used to quantitate and characterize divalent metal binding and revealed that the toxin contains approximately 40 divalent metal sites, consisting of at least one class of high-affinity sites that bind Mn(2+) with a K(D) of 0.05 to 0.35 microM and one or more classes of lower affinity sites. Water proton relaxation data indicate that approximately 30 of these sites are completely inaccessible to bulk solvent. Our observations, together with the sequence homology between adenylyl cyclase toxin and the alkaline protease of Pseudomonas aeruginosa, indicate that the formation of five beta-sheet helices within the repeat domain of the toxin upon binding Ca(2+) is required for cell intoxication.

Adenylate Cyclase Toxin↗
PubMed2001

RhoA is required for monocyte tail retraction during transendothelial migration.

Transendothelial migration of monocytes is the process by which monocytes leave the circulatory system and extravasate through the endothelial lining of the blood vessel wall and enter the underlying tissue. Transmigration requires coordination of alterations in cell shape and adhesive properties that are mediated by cytoskeletal dynamics. We have analyzed the function of RhoA in the cytoskeletal reorganizations that occur during transmigration. By loading monocytes with C3, an inhibitor of RhoA, we found that RhoA was required for transendothelial migration. We then examined individual steps of transmigration to explore the requirement for RhoA in extravasation. Our studies showed that RhoA was not required for monocyte attachment to the endothelium nor subsequent spreading of the monocyte on the endothelial surface. Time-lapse video microscopy analysis revealed that C3-loaded monocytes also had significant forward crawling movement on the endothelial monolayer and were able to invade between neighboring endothelial cells. However, RhoA was required to retract the tail of the migrating monocyte and complete diapedesis. We also demonstrate that p160ROCK, a serine/threonine kinase effector of RhoA, is both necessary and sufficient for RhoA-mediated tail retraction. Finally, we find that p160ROCK signaling negatively regulates integrin adhesions and that inhibition of RhoA results in an accumulation of beta2 integrin in the unretracted tails.

Amides↗
PubMed2001

A statewide outbreak of cryptosporidiosis in New South Wales associated with swimming at public pools.

From December 1997 to April 1998, 1060 laboratory-confirmed cryptosporidiosis cases were reported in New South Wales, Australia. In a case-control study, compared with 200 controls, the 100 cases were younger (mean age 42 versus 71 years; P < 0.0001), more likely to report swimming at a public pool (59% versus 38%; adjusted OR and 95% CI = 27; 1.4-5.1) and swimming in a dam, river or lake (OR = 48; 1.1-20.3) but less likely to report drinking bottled water (OR = 0.4; 0.2-0.9). In subgroup analyses, in rural areas illness was associated mainly with contact with another person with diarrhoea, and in urban areas illness was associated with swimming in a public pool. Cryptosporidium oocysts were more commonly detected in pools to which at least two notified cases had swum (P = 004). Outbreaks of cryptosporidiosis can be prolonged, involve multiple pools and be difficult to control.

Adolescent↗
PubMed2001

Expression and localization of IL-1beta mRNA is interrelated with cytoskeletal rearrangement in monocytes stimulated by adherence: a light microscopy in situ hybridization study.

Differences in IL-1beta mRNA expression, stability and translation between non-adherent monocytes and those stimulated by adherence suggest that cytokine regulation is coupled to the function and assembly of cytoskeletal structures. In situ hybridization studies were performed to visualize expression and positioning of IL-1beta mRNA in adherently cultivated monocytes. IL-1beta mRNA expression was heterogeneous with high transcript levels found in spread or polarized cells. Transcripts were compartmentalized to the perinuclear region in spread cells, and partially redistributed with polarization. In contrast to mRNA distribution in other motile cell populations, IL-1beta mRNA did not localize to the distal or proximal actin cytoskeleton. Perinuclear confinement of transcripts required intact actin microfilaments. Treatment with cytoskeleton disruption and detergent extraction suggested that most non-translated IL-1beta mRNA was associated with intermediate filaments. In monocytes stimulated by LPS, IL-1beta, but not IL-1Ra transcripts were redistributed and partially associated, yet not bound to actin microfilaments. The present study demonstrates that IL-1beta mRNA expression and localization in adherent monocytes is interrelated with the cytoskeletal rearrangement upon adherence, spreading and polarization.

Actins↗
PubMed2001

Tuberculosis at the end of the 20th century in England and Wales: results of a national survey in 1998.

BACKGROUND: A national survey of tuberculosis was conducted in England and Wales in 1998 to obtain detailed information on the occurrence of the disease and recent trends. This survey also piloted the methodology for enhanced tuberculosis surveillance in England and Wales and investigated the prevalence of HIV infection in adults with tuberculosis. METHODS: Clinical and demographic data for all cases diagnosed during 1998 were obtained, together with microbiological data where available. Annual incidence rates in the population were estimated by age, sex, ethnic group, and geographical region using denominators from the 1998 Labour Force Survey. Incidence rates in different subgroups of the population were compared with the rates observed in previous surveys. The tuberculosis survey database for 1998 was matched against the Communicable Disease Surveillance Centre HIV/AIDS database to estimate the prevalence of HIV co-infection in adult patients with tuberculosis. RESULTS: A total of 5658 patients with tuberculosis were included in the survey in England and Wales (94% of all formally notified cases during the same period), giving an annual rate of 10.93 per 100 000 population (95% CI 10.87 to 10.99). This represented an increase of 11% in the number of cases since the survey in 1993 and 21% since 1988. In many regions case numbers have remained little changed since 1988, but in London an increase of 71% was observed. The number of children with tuberculosis has decreased by 10% since 1993. Annual rates of tuberculosis per 100 000 population have continued to decline among the white population (4.38) and those from the Indian subcontinent, although the rate for the latter has remained high at 121 per 100 000. Annual rates per 100 000 have increased in all other ethnic groups, especially among those of black African (210) and Chinese (77.3) origin. Over 50% of all patients were born outside the UK. Recent entrants to the UK had higher rates of the disease than those who had been in the country for more than 5 years or who had been born in the UK. An estimated 3.3% of all adults with tuberculosis were co-infected with HIV. CONCLUSIONS: The epidemiology of tuberculosis continues to change in England and Wales and the annual number of cases is rising. More than one third of cases now occur in young adults and rates are particularly high in those recently arrived from high prevalence areas of the world. The geographical distribution is uneven with urban centres having the highest rates. The increase in the number of cases in London is particularly large. Tuberculosis in patients co-infected with HIV makes a small but important contribution to the overall increase, particularly in London. To be most effective and to make the most efficient use of resources, tuberculosis prevention and control measures must be based on accurate and timely information on the occurrence of disease. A new system of continuous enhanced tuberculosis surveillance was introduced in 1999, based on the methodology developed in this national survey.

AIDS-Related Opportunistic Infections↗
PubMed2001

Factors that determine false recall: a multiple regression analysis.

In the Deese-Roediger-McDermott (DRM) paradigm, subjects study lists of words that are designed to elicit the recall of an associatively related critical item. The 55 lists we have developed provide levels of false recall ranging from .01 to .65, and understanding this variability should provide a key to understanding this memory illusion. Using a simultaneous multiple regression analysis, we assessed the contribution of seven factors in creating false recall of critical items in the DRM paradigm. This analysis accounted for approximately 68% of the variance in false recall, with two main predictors: associative connections from the study words to the critical item (r = +.73; semipartial r = +.60) and recallability of the lists (r = -.43; semipartial r = -.34). Taken together, the variance in false recall captured by these predictors accounted for 84% of the variance that can be explained, given the reliability of the false recall measures (r = .90). Therefore, the results of this analysis strongly constrain theories of false memory in this paradigm, suggesting that at least two factors determine the propensity of DRM lists to elicit false recall. The results fit well within the theoretical framework postulating that both semantic activation of the critical item and strategic monitoring processes influence the probability of false recall and false recognition in this paradigm.

Adult↗
PubMed2001

Socioeconomic status, ethnicity, and health care access among young and healthy women.

This study examined: (a) the relationship between socioeconomic status (SES) and health care access among healthy women; (b) which SES variable(s) were most strongly associated with HCA; and (c) whether the SES/HCA relationship was the same for Black and White women. A total of 383 women (57.4% Whites and 42.6% Blacks) participated in the study. Independent variables included family income, education levels, occupation, median income within zip code of participants' residence, and ethnicity. Dependent variables were the total and subscale scores (accessibility, accommodation, and affordability) on a measure of health care access. Family income was the SES variable that showed the strongest positive association with total health care access, and there was a significant interaction between occupation and ethnicity for total health care access. Unique relationships were observed between each SES variable and each subscale on the health care access measure. The overall patterns between SES and health care access were similar for Blacks and Whites. Results suggest that the relationship between health care access and SES should be investigated through a multi-dimensional approach, and that an array of SES variables must be considered when designing interventions to improve health care access among healthy women.

Adolescent↗
PubMed2001

Semantic, phonological, and hybrid veridical and false memories in healthy older adults and in individuals with dementia of the Alzheimer type.

Five groups of participants (young, healthy old, healthy old-old, very mild dementia of the Alzheimer type [DAT], and mild DAT) studied 12-item lists of words that converged on a critical nonpresented word (cold) semantically (chill, frost, warm, ice), phonologically (code, told, fold, old), or in a hybrid list of both (chill, told, warm, old). The results indicate that (a) veridical recall decreased with age and dementia; (b) recall of the nonpresented items increased with age and remained fairly stable across dementia; and (c) false recall varied by list type, with hybrid lists producing superadditive effects. For hybrid lists, individuals with DAT were 3 times more likely to recall the critical nonpresented word than a studied word. When false memory was considered as a proportion of veridical memory, there was an increase in relative false memory as a function of age and dementia. Results are discussed in terms of age- and dementia-related changes in attention and memory.

Adolescent↗