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Biomedical subjects

J M Watson

Publications and source records attributed to J M Watson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Age-related expression of PEDF/EPC-1 in human endometrial stromal fibroblasts: implications for interactive senescence.

Aging is the major risk factor for many cancers, and age-related changes in the tissue microenvironment can facilitate tumor growth. This study uses human endometrial cells to begin to test the hypothesis that age-related changes in pigment epithelium-derived factor/early population doubling cDNA-1 (PEDF/EPC-1) levels create an environment that is more permissive to tumor growth. Endometrial stromal fibroblasts (ESF) are the predominant cell type in the human endometrium and exert regulatory control over the glandular epithelial cells, which are the source of most tumors. As ESF age in vitro, their ability to regulate appropriate growth and differentiation of epithelial cells declines. Endometrial epithelial cells in primary culture expressed relatively low levels of PEDF/EPC-1 mRNA. In contrast, early passage quiescent ESF from adult donors produce higher levels of the 1.5-kb PEDF/EPC-1 mRNA and 50-kDa secreted protein than epithelial cells. As ESF age in vitro the relative abundance of PEDF/EPC-1 mRNA declines, as does the level of PEDF/EPC-1 protein secreted into cell culture medium. Treatment with PEDF/EPC-1 protein had no effect on ESF proliferation but did inhibit anchorage-dependent and anchorage-independent proliferation of endometrial carcinoma cells in a dose- and time-dependent manner. These findings imply that an age-related loss of PEDF/EPC-1 expression by ESF could eliminate a negative regulator of cancer cell growth and, thereby, contribute to the age-related increase in cancer incidence.

Adult↗
PubMed1999

Cross-modal semantic and homograph priming in healthy young, healthy old, and in Alzheimer's disease individuals.

Two experiments are reported that explore the influence of strength of the prime-target relationship on the observed priming effects in young, healthy old, and individuals diagnosed with dementia of the Alzheimer type (DAT). In Experiment 1, participants were auditorily presented primes (FURNITURE) and after varying delays presented visual targets that were (1) high-strength related (e.g., SOFA), (2) low-strength related (e.g., RUG), or (3) unrelated control words (e.g., COW or DEER). The results indicated that the DAT individuals produced relatively larger priming effects that both the young and the healthy old, but these data could be accommodated by increases in effect size due to general slowing of response latencies. In Experiment 2, the same cross-modal priming paradigm was used with ambiguous words presented as primes (e.g., BANK) and either high-dominant (e.g., MONEY) or low-dominant (e.g., RIVER) words as targets. The results of Experiment 2 produced a qualitatively distinct pattern of priming that indicated DAT individuals only produced priming for high-dominant targets and not for low-dominant targets, whereas, the healthy control groups produced equivalent priming for both high- and low-dominant targets. The discussion focuses on the implication that these results have for the interpretation of semantic priming effects, in general, along with implications for the apparent semantic memory loss in DAT individuals.

Adolescent↗
PubMed1999

Molecular characterisation and expression of a wound-inducible cDNA encoding a novel cinnamyl-alcohol dehydrogenase enzyme in lucerne (Medicago sativa L.)

A lucerne (alfalfa, Medicago sativa) stem cDNA library was screened with a cinnamyl-alcohol dehydrogenase (CAD) cDNA probe from tobacco (Nicotiana tabacum cv. Samsun). Two distinctly different cDNA clones (54% identical) were isolated and identified as putative CAD-encoding cDNAs by comparison of their nucleotide sequences with those of CAD-encoding DNA sequences from other plant species. One of the cDNAs, MsaCad2, was found to be 99.4% identical at the nucleotide level to the previously isolated lucerne cad cDNA which encodes a CAD isoform involved in lignin biosynthesis. The other cDNA, MsaCad1, has not been reported previously in lucerne, and encodes a protein related to the ELI3 class of elicitor-inducible defence-related plant proteins. The MsaCad1- and MsaCad2-encoded proteins were expressed in Escherichia coli and CAD1 was shown to be active with a range of cinnamyl, benzyl and aliphatic aldehyde substrates, while CAD2 was specific for the cinnamyl aldehydes only. Each of the respective genes is present as one or two copies. The MsaCad1 gene is expressed most actively in stem and floral tissue, whereas MsaCad2 is most actively expressed in stem, hypocotyl and root tissue. In stem tissue, expression of both genes occurs predominantly in internodes 4 and 5 (from the apex). MsaCad2, in contrast to MsaCad1, is not significantly expressed in the top three internodes of the stem. Both MsaCad1 and MsaCad2 are wound-inducible, and the wound-responsiveness of each gene is modulated by salicylic acid.

Alcohol Oxidoreductases↗
PubMed1999

Epidemiological features of parainfluenza virus infections: laboratory surveillance in England and Wales, 1975-1997.

Hospital laboratory reports of parainfluenza virus (PIV) infections from England and Wales between 1975 and 1997 were analysed with regard to PIV type and seasonality, and in addition, those between 1985 1997 with regard to age, sex and clinical features. Laboratory-based surveillance data highlight striking differences in the seasonality of different PIV types. PIV-3 reports demonstrated a clear annual epidemic cycle, with a peak usually occurring in late spring or summer, whereas peaks of PIV-1 and PIV-2 occurred at one or two year intervals, in the late autumn or early winter. PIV-4 also occurred most frequently in the late autumn or early winter, but a clear epidemic cycle could not be identified. Laboratory surveillance data also provide insight into the age and disease distribution of PIV infection in children and indicate severity of PIV infection in immunosuppressed adults. Of 8221 PIV reports received between 1985-1997, PIV-3 accounted for 70.8%, PIV-1 for 17.2%, PIV-2 for 7.5%, and PIV-4 for 1.1%; 64.1% of reports came from infants under one year, 24.4% from children aged 1-4 years and 7.2% from individuals aged 5 years or older, with an excess of males in all age groups. Bronchiolitis, croup and pneumonia occurred in association with all PIV types. In children under 1 year, PIV-2 infections were more likely to be associated with bronchiolitis than infections with other PIV types. In children under 15 years, croup was more frequently associated with PIV-1 and PIV-2 than with PIV-3 or PIV-4. In 392 (7.2%) of the reported PIV infections between 1989 and 1997 an underlying condition was implicated, which included immunosuppression or chronic cardiac or pulmonary disease. Considerable morbidity is associated with PIV infections in infants and young children and would make the widescale use of a vaccine a valuable public health intervention. Surveillance information is essential to guide the development and use of preventive measures as well as to monitor their effectiveness.

Adolescent↗
PubMed1999

Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry.

1. This study describes the pharmacological comparison of the muscarinic partial agonists sabcomeline, xanomeline and milameline at human cloned muscarinic receptor subtypes (hM1-5). 2. Radioligand binding studies at the hM1-5 muscarinic receptor subtypes were compared with functional studies using microphysiometry using carbachol as the standard full agonist. 3. In binding assays none of the compounds studied displayed preferential affinity for the M1,3,4 or M5 subtypes although carbachol was less potent at hM1 than hM3,4,5. 4. In functional studies, all of the compounds studied displayed similar levels of efficacy across the muscarinic receptors with the exception of M3, where there was a large apparent receptor reserve and the compounds behaved essentially as full agonists. 5. Sabcomeline was the most potent agonist in functional studies but also showed the lowest efficacy. In terms of potency, xanomeline showed some selectivity for M1 over M2 receptors and milameline showed some selectivity for M2 over M1 receptors. 6. These results show the value of microphysiometry in being able to compare receptor pharmacology across subtypes irrespective of the signal transduction pathway. 7. None of the partial agonists showed functional selectivity for M1 receptors, or indeed any muscarinic receptor, in the present study.

Animals↗
PubMed1999

Influenza activity in England and Wales: October 1998 to June 1999.

Influenza activity in England and Wales in the winter of 1998/1999 reached the highest weekly levels seen since the epidemic of 1989/1990. Activity peaked at Christmas and the New Year, adding to the winter pressures on general practitioner and hospital services. Adults aged 65 years and over consulted with general practitioners at the highest rates. Outbreaks of influenza or flu-like illness occurred in several schools and nursing homes and, in June 1999, on a British cruise ship in the Mediterranean. Deaths from all causes reached a higher peak in week 1 of 1999 than occurred in the peak week of the influenza epidemic of 1989/90.

Adolescent↗
PubMed1998

Selective potentiation of gynecologic cancer cell growth in vitro by electromagnetic fields.

OBJECTIVE: Epidemiological data suggest that exposure to electromagnetic fields (EMF) may increase the risk of various cancers. We evaluated EMF effects on the in vitro growth response of human cell lines isolated from various reproductive tract tissues. We also assessed the effects of EMF on cisplatin- or paclitaxel-induced cytotoxicity. METHODS: Endometrial, ovarian, and prostate cancer cell lines as well as immortalized endometrial stromal cells and immortalized ovarian epithelial cells were exposed continually to EMF. Proliferation was assessed by the metabolic activity assay, MTT, direct cell counting, and anchorage-independent colony formation in soft agar. Cytotoxicity induced by cisplatin or paclitaxel was assessed using the MTT assay. RESULTS: Continuous exposure to EMF at field strengths of 2 G enhanced proliferation of two human prostate and three endometrial, but only one ovarian, cancer cell lines. EMF enhanced metabolic activity of cancer cells within 96 h and increased absolute cell number (anchorage-dependent proliferation) and colony-forming efficiency (anchorage-independent proliferation) over sham-treated controls. EMF had no effect on cytotoxicity induced by the chemotherapeutic agents Taxol or cisplatin. CONCLUSIONS: Continuous exposure to EMF can enhance growth rates of transformed cells for some human epithelial cancers. Cancer cells from the steroid sex hormone regulated tissues of endometrium and prostate appeared to be more responsive to EMF than cells from ovarian cancers.

Cell Division↗
PubMed1998

Identification of the structural region of taxol that may be responsible for cytokine gene induction and cytotoxicity in human ovarian cancer cells.

PURPOSE: Interleukin-8 (IL-8) is a pleiotropic chemokine with both chemoattractant and angiogenic properties. In addition to its cytotoxic effects on ovarian cancer cells, taxol can transcriptionally activate genes such as IL-8 that may play a role in tumorigenesis. Utilizing IL-8 as a prototypic marker of tumor-derived modulators of growth, we undertook a systematic study of taxol and 11 structurally modified taxol analogs to identify the region of the taxane skeleton responsible for IL-8 gene induction. METHODS: The human ovarian cancer cell line OVCA-420 was exposed to taxol or taxol analogs. IL-8 gene induction was assessed by Northern blot analysis after 6 h and cytotoxicity after 72 h. RESULTS: Changes in the southern hemisphere (C-1 to C-4) of the taxane skeleton had greater effects on IL-8 induction than changes in the northern hemisphere (C-7 to C-11). Some of the taxol analogs modified at positions C-1 and/or C-2 with increased hydrophobicity induced IL-8 expression more than threefold over that induced by taxol or taxotere and more than 20-fold over control cells. Cells that failed to induce IL-8 gene expression in response to taxol were only marginally responsive to the analogs unless first primed with IL-1beta. Modifications to the northern hemisphere did not alter taxol's effect on IL-8 expression in human cells, but did influence TNFalpha expression in murine macrophage cells, suggesting species and/or gene specificity. We found a direct correlation between IL-8 induction and cytotoxicity, in that analogs that dramatically upregulated IL-8 expression proved to be the most cytotoxic, inhibiting cell survival by > 90%. CONCLUSION: Taken together our results demonstrate that changes in the southern hemisphere of the taxane skeleton influence both the gene induction and cytotoxic potential of taxol in human ovarian cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed1998

The origin and loss of the ubiquitin activating enzyme gene on the mammalian Y chromosome.

Mammalian sex chromosomes are thought to be descended from a homologous pair of autosomes: a testis-determining allele which defined the Y chromosome arose, recombination between the nascent X and Y chromosomes became restricted and the Y chromosome gradually lost its non-essential genetic functions. This model was originally inferred from the occurrence of few Y-linked genetic traits, pairing of the X and Y chromosomes during male meiosis and, more recently, the existence of X-Y homologous genes. The comparative analysis of such genes is a means by which the validity of this model can be evaluated. One well-studied example of an X-Y homologous gene is the ubiquitin activating enzyme gene ( UBE1 ), which is X-linked with a distinct Y-linked gene in many eutherian ('placental') and metatherian (marsupial) mammals. Nonetheless, no UBE1 homologue has yet been detected on the human Y chromosome. Here we describe a more extensive study of UBE1 homologues in primates and a prototherian mammal, the platypus. Our findings indicate that UBE1 lies within the X-Y pairing segment of the platypus but is absent from the human Y chromosome, having been lost from the Y chromosome during evolution of the primate lineage. Thus UBE1 illustrates the key steps of 'autosomal to X-specific' evolution of genes on the sex chromosomes.

Animals↗
PubMed1998

Geographical distribution of tuberculosis notifications in national surveys of England and Wales in 1988 and 1993: report of the Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group.

BACKGROUND: The geographical distribution of tuberculosis in England and Wales and changes since 1983 were examined using data from the 1988 and 1993 national surveys of tuberculosis notifications. METHODS: Notification rates for England and Wales in 1988 and 1993 were calculated for geographical areas using Office for National Statistics (ONS) mid year population estimates. Those for the standard regions and the Greater London boroughs were calculated for the main ethnic groups. Those for the counties and local authorities were calculated for all ethnic groups combined. These were compared using data from the 1983 national survey as a baseline. RESULTS: Wide regional variations in notification rates persist with Greater London having the highest rates. Rates in the ethnic group from the Indian subcontinent (ISC) were high in all regions, whilst those of the white ethnic group varied fourfold. Twenty seven of the 33 London boroughs showed increased rates in 1993 compared with 1988. In general, those local authority areas with high rates had high proportions of notifications in individuals of ISC ethnic origin, emphasising the continuing important contribution of ethnic minority groups to local tuberculosis rates. The number of local authority areas with notification rates four times the national average increased, but the number of areas with low or zero rates increased even more. CONCLUSIONS: The distribution of tuberculosis in England and Wales continues to vary markedly by geographical area. The distribution is becoming increasingly polarised with a growth in the number of areas with very high rates of notifications and a greater increase in the number of areas with very few notifications. Patients from ethnic minorities continued to contribute a substantial and increasing proportion of all reported tuberculosis cases in most regions in 1988 and 1993. These findings have important implications for the provision of tuberculosis services in England and Wales.

Demography↗
PubMed1998

A field trial of detection and treatment of nerve function impairment in leprosy--report from national POD pilot project.

As part of a collaborative project between the Ministry of Health of China (MOH) and The Leprosy Mission International (TLMI) on leprosy rehabilitation and prevention of disability (POD), a total of 1407 patients was monitored for possible nerve function impairment (NFI) through standardized clinical nerve function assessment between May 1995 and February 1998. Of these, 191 patients were found to have NFI and were put on a fixed regimen of prednisolone. In this study, 36.7% of NFI occurred before diagnosis of leprosy, 35.6% developed during MDT and 25.7% after their release from MDT. Overall, 7.5% (105 out of 1407) of all patients, or 55.9% of patients with NFI, suffered from silent neuropathy. Of the affected nerves, 62.6% had silent neuropathy. Sensory impairment responded to prednisolone satisfactorily, giving a recovery rate of 73.8%, 76.5% and 81.0% in ulnar, median and posterior tibial nerve, respectively. Sensibility in patients even with a NFI duration longer than 6 months made significant improvement (p < 0.05). Motor function improvement was less satisfactory, especially in ulnar and c. popliteal nerve. The possible reasons are analysed. Our findings with regard to sensibility changes confirm that once it becomes clinically detectable, NFI is no longer at the 'early' stage. More sensitive tests are necessary to detect real 'early' sensory impairment in the field. Our study also indicates that with well-trained field staff and proper equipment for nerve function assessment, early detection and treatment of NFI can be practical and effective.

Adolescent↗
PubMed1998

Advance directives in a correctional setting.

Using advance directives to preconsent to mental health treatment is a promising approach to contending with the quandary posed by patients suffering from severe mental health illness, particularly those in a prison setting. The implementation of advance directives represents unfamiliar territory because it focuses on the patient's ability to preconsent to treatment rather than the commonly interpreted prerefusal of treatment. The challenge of consenting in the prison system generates a set of unique problems. The environment in which the instrument is signed can impose significant pressures and therefore result in a viable legal challenge. The prison setting is the most coercive environment in which a patient can be treated, particularly when the patient is mentally ill. Mentally ill prisoners signing preconsent for treatment advance directives have an opportunity for unprecedented relief yet may also experience pressure to select treatments desirable to the prison staff.

Advance Directives↗
PubMed1998

Influenza surveillance in England and Wales: October 1997 to June 1998.

Influenza caused low levels of mortality and morbidity in England and Wales in the 1997/98 season. Influenza viruses of the H3N2 and H1N1 subtypes were isolated in small numbers from community and hospital patients in November and December. Their numbers subsequently increased to peak in February, H1N1 a week or two before H3N2. Most of the H1N1 isolates were similar to the A/Bayern/7/95-like virus, included in the vaccine recommended for 1997-98, whereas most H3N2 isolates were A/Sydney/5/97-like, a virus not covered by the season's vaccine but recommended for 1998/99. Consultation rates in general practice for influenza-like illnesses remained low until early February, when a small increase coincided with the increase in laboratory confirmed influenza. Fewer deaths directly attributed to influenza were registered during the surveillance period than in recent years. Localised outbreaks occurred in schools and nursing homes towards the end of the winter.

Disease Outbreaks↗
PubMed1997

Influenza surveillance in England and Wales: October 1996 to June 1997.

This report summarises information collected for the surveillance of influenza in England and Wales during the winter of 1996/97. Consultations for 'influenza and influenza-like illness' with sentinel general practitioners in England and Wales began to increase towards the end of November and peaked at the start of January. In England, consultations for 'aggregated respiratory disease' (ARD) began to increase a little earlier, perhaps as a result of increased respiratory syncytial virus activity, but also peaked in early January. Influenza A (H3N2) viruses were first detected in early October, but rarely until November, and activity peaked in early January, coinciding with the peak in consultations for flu-like illness. A few influenza B viruses were detected in late November and early December, and substantial activity was recorded in mid-January. Approximately equal numbers of influenza A(H3N2) and B viruses were identified over the winter as a whole, and circulating strains were antigenically similar to those included in the vaccine for 1996/97. Although influenza activity was 'moderate' in terms of consultations and laboratory confirmed infections, a large peak in death registrations occurred at the same time as influenza A(H3N2) virus activity peaked. The number of deaths during the winter was similar to that seen in 1989/90, when the last severe influenza epidemic occurred in England and Wales.

Disease Outbreaks↗
PubMed1997

PHLS work on the surveillance and epidemiology of tuberculosis.

The re-emergence worldwide of tuberculosis as a major threat to public health and continuing and changing challenges in the control of tuberculosis in England and Wales provide the basis for the designation, by the PHLS, of tuberculosis as a priority area. In addition to the mycobacteriology reference services provided by the PHLS in England and Wales (summarised in an accompanying article) the PHLS contributes to the control of tuberculosis through its surveillance and other epidemiological work. This article summarises the range of this work, emphasising the collaborative nature of the effort required for surveillance, prevention, and control of tuberculosis.

England↗