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Biomedical subjects

J M Watson

Publications and source records attributed to J M Watson.

At least 55 records · Page 3Linked to original sources
PubMed2001

High school students' responses to dating aggression.

The purpose of this study was to identify high school students' actions in response to physical aggression in their dating relationships. The association of these actions with race/ethnicity and gender was also examined. From a sample of high school students (N = 476), a subsample who reported that they had experienced at least one episode of being victimized by physical aggression in a dating relationship (n = 183), served as the sample of interest. On average, students engaged in two help-seeking actions, with females reporting more actions than males. Overall, the most common responses to physical aggression in a dating relationship were aggressive action (e.g., fight back), informal help seeking, threatened or actual breakup, and doing nothing (males) or crying (females). Females were more likely to fight back than were males. Race was largely unrelated to students' actions. Intervention opportunities and areas for future research are discussed.

Adolescent↗
PubMed2001

Immunogenic and isotype-specific responses to Russian and US cold-adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice.

The immunogenicity of the Russian cold-adapted (ca) donor stains, A/Leningrad (Len)/134/17/57 and A/Leningrad/134/47/57, and the US strain A/Ann Arbor (AA)/6/60-ca, were compared in BALB/c mice with their respective wild-type parental viruses. Each ca donor strain was less immunogenic than its wild-type parent. The vaccinating dose, when administered twice, which prevented multiplication of a standard challenge of parental wild-type virus in 50% of mice (the 50% protective dose or PD(50)), was shown for A/Len/134/17/57-ca, A/Len/134/47/57-ca, and A/AA/6/60-ca to be 10(3.77), 10(4.32), and 10(4.70), respectively. These findings were extended by measuring the number of antibody secreting cells induced in the lungs and mediastinal lymph nodes of mice infected with the same ca donors using an ELISPOT assay. When each donor strain was administered twice at a dose of 100 PD(50) over a 3-week interval, the overall immunoglobulin isotype antibody secreting cell profiles were shown to be similar. However, A/Len/134/17/57-ca and A/Len/134/47/57-ca induced significantly higher total immunoglobulin responses in the lungs than A/AA/6/60-ca (P < 0.05). A/Len/134/17/57-ca also induced a significantly greater IgA response in the lungs than A/AA/6/60-ca (P < 0.05). These results suggest that A/Len/134/17/57-ca is a superior immunogen to A/Len/134/47/57-ca which in turn is more immunogenic than A/AA/6/60-ca.

Adaptation, Physiological↗
PubMed2001

Can calls to NHS Direct be used for syndromic surveillance?

This study assessed whether NHS Direct could be a useful source of surveillance data for communicable diseases, using influenza as a pilot condition. Data on the weekly total number of calls and the number from people reporting influenza-like symptoms to three pilot NHS Direct sites were collected between November 1999 and March 2000. NHS Direct data were compared with routinely available influenza surveillance data. The NHS Direct call rate peaked at 331 per 100,000 population in week 52 of 1999. The percentage of calls for 'influenza-like illness' (one site) peaked at 15% during week 51. Information about weekly call numbers to NHS Direct could be produced in a timely way. It was not clear whether the observed peak in calls reflected a true increase in influenza or whether it was the result of an increase in calls over the Christmas/Millennium holiday period due to more difficulty in accessing other services. The ability to assess the proportion of calls made directly by, or on behalf of, each age group will be of vital importance in interpreting seasonal respiratory disease.

Disease Outbreaks↗
PubMed2000

Inhibition of the calcium-dependent tyrosine kinase (CADTK) blocks monocyte spreading and motility.

Freshly isolated peripheral blood monocytes lack focal adhesion kinase (p125(FAK)) but activate a second member of this kinase family, calcium-dependent tyrosine kinase (CADTK; also known as Pyk2/CAKbeta/RAFTK/FAK2), upon adhesion or stimulation with chemokines. To study the role of CADTK in monocyte adherence and motility, we performed immunocytochemical localization that showed CADTK at the leading edge and ruffling lamellipodial structures in freshly isolated, adhered human monocytes. We next introduced CADTK/CAKbeta-related non-kinase (CRNK), the C-terminal noncatalytic domain of CADTK, into monocytes by electroporation and showed that it inhibited CADTK autophosphorylation. Introduction of the fusion protein glutathione S-transferase (GST)-CRNK also reduced (i) cell spreading, as reflected in a reduced cell area 30 min after adhesion, (ii) adhesion-induced phosphotyrosine increases and redistribution into lamellipodia, and (iii) adhesion-induced extracellular signal-regulated protein kinase (ERK) activation. In control experiments, introduction of GST or GST-C3 transferase (an inhibitor of RhoA GTPase activity) by electroporation did not affect these parameters. Monocytes adhered in the presence of autologous serum were highly motile even after introduction of GST (83% motile cells). However, only 26% of monocytes with introduced GST-CRNK were motile. In contrast, GST-CRNK-treated monocytes were fully capable of phagocytosis and adhesion-induced cytokine gene induction, suggesting that CADTK is not involved in these cellular activities and that GST-CRNK introduction does not inhibit global monocyte functions. These results suggest that CADTK is crucial for the in vitro monocyte cytoskeletal reorganization necessary for cell motility and is likely to be required in vivo for recruitment to sites of inflammation.

Cell Adhesion↗
PubMed2000

Cellular differentiation causes a selective down-regulation of interleukin (IL)-1beta-mediated NF-kappaB activation and IL-8 gene expression in intestinal epithelial cells.

Interleukin (IL)-1beta signals through various adapter proteins and kinases that lead to activation of numerous downstream targets, including the transcription factors including NF-kappaB. In this study, we analyzed and characterized the effect of the differentiation of intestinal epithelial cells on IL-1beta-mediated NF-kappaB activation and IL-8 gene expression. We report that IL-8 mRNA accumulation and protein secretion were down-regulated in IL-1beta- and lipopolysaccharide-stimulated differentiated HT-29 cells (HT-29/MTX, where MTX is methotrexate) compared with undifferentiated cells (HT-29/p), whereas no differential effects were found following tumor necrosis factor (TNF)-alpha or phorbol myristate acetate stimulation. Cross-linking and affinity binding studies reveal that IL-1beta exclusively binds the type I receptor (IL-1RI) and not IL-1RII in both HT-29/p and HT-29/MTX cells. IL-1beta-mediated IkappaB kinase and c-Jun N-terminal kinase (JNK) activity were both diminished in differentiated HT-29 cells. DNA binding activity in differentiated HT-29 cells relative to HT-29/p cells was strongly reduced following IL-1beta exposure but not after TNF-alpha stimulation. The proximal IL-1 signaling molecule IL-1 receptor-associated kinase was not degraded in IL-1beta-stimulated HT-29 cells, in contrast to Caco-2 cells. kappaB-luciferase reporter gene activity was 16-fold higher following TNF receptor-associated factor-6 transfection after IL-1beta stimulation in HT-29/MTX cells. We conclude that cellular differentiation of HT-29 cells selectively impairs the IL-1beta signaling pathway inhibiting both NF-kappaB and JNK activity in response to IL-1beta. This relative unresponsiveness to IL-1beta may represent an important regulatory mechanism of differentiated intestinal epithelial cells.

Cell Differentiation↗
PubMed2000

A G protein-coupled receptor for UDP-glucose.

Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism.

GTP-Binding Proteins↗
PubMed2000

Differential role of tyrosine phosphorylation in adhesion-induced transcription, mRNA stability, and cytoskeletal organization in human monocytes.

Monocyte adhesion resulted in rapid tyrosine phosphorylation and subsequent cytokine mRNA induction. The objective of this study was to determine the role of specific tyrosine phosphorylation events, particularly those involving members of the MAP kinase family, in regulating adhesion-induced cytokine expression. Using nuclear run-on analyses, we demonstrated that on adhesion, monocytes rapidly transcriptionally activated numerous cytokine mRNAs, coincident with the activation of the transcription factors NF-KB and AP-1. Both an inhibitor of tyrosine phosphorylation, genistein, and the cytoplasmic tyrosine phosphatase PTP1B, were unable to prevent adhesion-mediated transcriptional activation. However, both blocked adhesion-induced ERK and JNK but not p38 kinase activation and at the same time decreased the stability of interleukin-1beta (IL-1beta) and IL-8 transcripts. In addition, whereas adhesive events occurred in the presence of genistein and PTP1B, monocyte spreading was markedly inhibited. Our results suggest that the majority of protein phosphorylation events are associated with adhesion-induced cytokine expression through transcript stabilization and cytoskeletal organization. A minority of protein phosphorylation events, not sensitive to genistein or PTP1B exposure, may be instrumental in regulating transcription. Thus the spectrum of protein tyrosine kinases required for transcription appear distinct from those involved in maintaining the stability of some cytokine mRNAs and the integrity of the cytoskeleton to which mRNA destined for translation must be associated.

Adult↗
PubMed2000

Reversal of caffeine withdrawal by ingestion of a soft beverage.

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Adult↗
PubMed2000

Clusters of new tuberculosis cases in North-west London: a survey from three hospitals based on IS6110 RFLP typing.

OBJECTIVES: The relative contributions of reactivation of latent infection and clusters of new infections to the overall incidence of tuberculosis in the U.K. is unknown. A study was carried out in North-West London to determine the feasibility of IS6110 RFLP strain typing as a tool to investigate the relative contributions of these two sources. METHODS: All available isolates of M. tuberculosis from specimens collected over a calendar year at three participating hospitals were typed by RFLP using an IS6110 probe. Isolates exhibiting a single band pattern were subject to further typing using an oligonucleotide direct repeat probe. Demographic and clinical information on cases was obtained from the National Survey of Tuberculosis Notifications in England and Wales and further information sought on clustered cases as identified by RFLP typing. RESULTS: Twenty-seven (23%) of the 118 cases had shared IS6110 RFLP patterns. Strains from nine cases had single band patterns, but these were all distinguishable from each other when subjected to further typing by direct repeat probe. The remaining 18 cases belonged to eight clusters. Epidemiological links were established between all the patients in each cluster. The likelihood of being in a cluster was increased in cases with pulmonary smear-positive disease. It was lower in cases of Indian Sub-continent ethnic origin. For 10 of the 18 clustered cases epidemiological links had not been established by conventional contact tracing. CONCLUSIONS: Investigation of the relative contributions of reactivation of latent infection and new infection is feasible in a UJK population, using IS6110 RFLP typing of M. tuberculosis isolates and epidemiological enquiries. This study in London identified clustered, presumably new cases, the majority of whom had not been linked epidemiologically. Comprehensive IS6110 RFLP typing of UK isolates would probably identify many clusters of incident tubercular infection.

Adolescent↗
PubMed2000

Tuberculosis drug resistance in England and Wales. How much is 'home-grown'?

The fact that a substantial proportion of tuberculosis drug resistance (especially multidrug resistance) is due to transmission of resistant strains or treatment failure in the UK underlines the need to strengthen control in this country. Early identification and effective treatment of cases (including measures to support adherence and appropriate use of initial treatment regimes involving at least four drugs in those at risk of isoniazid resistance) would help to control the problem [1].

Antitubercular Agents↗
PubMed2000

Socioeconomic status, ethnicity, and environmental tobacco exposure among non-smoking females.

This study examined the relationship between socioeconomic status (SES) and environmental tobacco smoke (ETS) exposure among non-smoking females, determined which SES variable(s) were most strongly associated with ETS exposure, and examined whether the relationship between SES and ETS exposure was the same for Blacks and Whites. Participants were 404 never-smoker females recruited in the community. Independent variables included income, education, occupation, median income within zip code of participants' residence, and ethnicity. Number of days per week exposed to ETS in the past year was the dependent variable. There was a significant correlation between CO levels (parts per million, ppm) and self-reported ETS exposure (r = 0.22, p < 0.001). The mean CO level exposure was 1.81 +/- 1.19 ppm, and the mean number of days per week of ETS exposure was 4.72 +/- 4.71. The most frequent source of ETS exposure was at public places (64.4%). Although Blacks tended to report higher ETS exposure than Whites (p = 0.08), this tendency disappeared when SES indicators were entered in the model. Correlations among SES indicators were either non-significant or very modest suggesting that different SES indicators may not measure the same construct. Education was the only SES variable that was significantly associated with ETS exposure in this population. The relationship between SES and ETS exposure was similar for both Blacks and Whites. These findings suggest that education may be the most important factor to be considered when designing interventions to decrease ETS exposure among young non-smoking females (e.g., public education of the hazards of ETS exposure and awareness of existing tobacco-control laws and regulations).

Adolescent↗
PubMed2000

Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes.

OBJECTIVE: To examine the influence of caffeine on the frequency and perception of hypoglycemia in "free-living" patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 34 patients with type 1 diabetes were recruited for a prospective randomized placebo-controlled double-blind study. After a lead-in phase and while adhering to a low-caffeine diet, subjects were randomized to capsules containing either 200 mg caffeine or matched placebo with crossover at 3 months. Hypoglycemic episodes were monitored throughout with capillary blood glucose readings and a symptom questionnaire. During the study, measurements of blood pressure, middle cerebral artery blood velocity (a surrogate measure of cerebral blood flow), cognitive function (via a four-choice reaction time test), HbAlc levels, and lipid profiles were taken at the beginning and end of each phase. RESULTS: Throughout the study, no changes were evident regarding glycemic control or lipid profile. The number of symptomatic episodes was greater with caffeine (1.3 vs. 0.9 episodes/week; P < 0.03) and was associated with more intense warning symptoms (29 vs. 26 total symptom score; P < 0.05). For women, caffeine ingestion caused a modest pressor response (115 vs. 110 mmHg; P < 0.01). Four-choice reaction time improved slightly with caffeine supplementation (P < 0.05). CONCLUSIONS: Ingestion of modest amounts of caffeine enhances the intensity of hypoglycemia warning symptoms in patients with type 1 diabetes without altering the prevailing standard of glycemic control or increasing the incidence of severe hypoglycemic episodes.

Adult↗
PubMed2000

Influenza surveillance in England and Wales: October 1999 to May 2000.

The period of increased influenza activity in England and Wales in the winter of 1999/2000 was associated with considerable morbidity and mortality and well-publicized pressure on hospital services. The influenza activity coincided with the regular annual increase in respiratory syncytial virus infections and the Christmas and New Year holiday period. Consultation rates with general practitioners for influenza-like illness did not reach 'epidemic' levels but were higher than seen in many winters and comparable with those seen in two out of the previous three winters. In common with those winters, attack rates for influenza-like illness and acute bronchitis were especially high in elderly people among whom complications of acute infection and hospital admissions increased. Excess mortality due to influenza during this period appeared to be substantial but was not as high as seen in the last epidemic (1989/90).

Adolescent↗
PubMed2000

Final report about Stage II Collaboration Project on Leprosy Rehabilitation.

OBJECTIVE: To undertake the pilot experiments of prevention of disability (POD) in 14 different geographical areas to serve as examples for future development of rehabilitation work in China and in Asia. METHODS: According to the principles and national criterion, 27 000 people affected by leprosy were selected and assessed using disability record forms at beginning and followed up regularly for observing changes of different indicators. RESULTS: A total of 197 neuritis cases were detected and treated with prednisolone out of 1 407 new or active cases. Self-care training of eyes, hands and feet were conducted for 10 500 disabled people affected by leprosy. Comprehensive therapy was given to 1 804 cases having complicated ulcers of which 1 055 cases have got their ulcers healed. Out of 706 prostheses, 613 were given to patients with satisfactory results. Surgical treatment was given to 269 cases and 251 have shown good progress. CONCLUSION: Most of patients have got benefit from the project in function or appearance which is very helpful for their going back to the society and agreed by foreign experts during the final evaluation. The experiences from the project can be implemented in the whole country.

China↗
PubMed1999

Cisplatin inhibits paclitaxel-induced apoptosis in cisplatin-resistant ovarian cancer cell lines: possible explanation for failure of combination therapy.

Combination chemotherapy using paclitaxel with a platinum-based regimen is currently the standard first-line therapy for ovarian cancer after surgical cytoreduction. Whereas cisplatin-paclitaxel combination chemotherapy has shown significant efficacy over previous drug combinations in ovarian cancer, 20-30% of patients fail to respond to this combination. These patients are deemed cisplatin-paclitaxel resistant, although it is unclear whether the tumors are resistant to one or both drugs. Because the options available to ovarian cancer patients for second-line therapy are limited, and knowing that mechanistic differences exist between cisplatin and paclitaxel, we assessed the efficacy of combination drug therapy on cisplatin-resistant (cisplatinR) ovarian cancer cells. We found that paclitaxel induced apoptosis in cisplatinR cells as well as in the cisplatin-sensitive parental cell lines. In cisplatinR C-13 cells, the concomitant addition of cisplatin blocked paclitaxel-induced apoptosis as determined by DNA fragmentation assays, fluorescence microscopy, and flow cytometry. Paclitaxel-induced multimininucleation was also inhibited when the cells were exposed sequentially to paclitaxel and then cisplatin. Cisplatin did not block paclitaxel-induced stabilization of microtubules or prevent paclitaxel-induced loss of Bcl-2 expression in cisplatinR cells. Conversely, paclitaxel did not inhibit p53 protein accumulation by cisplatin. These results suggest that cisplatin blocks paclitaxel-induced apoptosis at a point downstream of Bcl-2 degradation and independent of microtubule stabilization. Our research shows that cisplatin can inhibit the effectiveness of paclitaxel in cispatinR cell lines. Therefore, the establishment of a clinical protocol to evaluate the efficacy of paclitaxel alone versus another second-line regimen in patients with cisplatin-paclitaxel-resistant ovarian cancer is warranted.

Antineoplastic Agents↗
PubMed1999

The role of interleukin-1 in interactive senescence and age-related human endometrial cancer.

The causes of the age-related increase in cancer rates are poorly understood. One cause could be age-related changes in the stromal/epithelial cell interactions that facilitate tumorigenesis. We tested the hypothesis that aging of human endometrial stromal fibroblasts (ESF) alters their influence over endometrial epithelial cells. ESF from adults were found to inhibit anchorage-independent proliferation, to restrain colony outgrowth, and to induce formation of normal tissue architecture by human endometrial cancer cells. As ESF age, these inhibitory influences on malignant-like behaviors by epithelial cells are altered, becoming stimulatory. Age-related change in interleukin-1alpha (IL-1alpha) expression is a molecular determinant of ESF/epithelial cell interactions. Levels of IL-1alpha and IL-1-induced mRNAs increase in ESF with age. Treatment with IL-1 accelerates age-related changes in mRNA abundance and loss of ESF restraint over malignancy-associated behaviors by epithelial cells. Transfection of ESF with the intracellular IL-1 receptor antagonist preserved the young phenotype with respect to interactions with epithelial cells and prevented age-associated increases in groalpha and IL-8 mRNA levels. Our results indicate that aging of ESF is accompanied by an interactive senescence that alters ESF signaling to cancer cells and could contribute to increased cancer rates by providing a microenvironment that is more conducive to tumorigenesis.

Adenocarcinoma↗
PubMed1999

In vitro characterisation of the muscarinic receptor partial agonist, sabcomeline, in rat cortical and heart membranes.

We have investigated the pharmacology of the functionally selective muscarinic M1 receptor partial agonist, sabcomeline [SB-202026 (R-(Z)-(+)-alpha-(methoxyamino)-1-azabicyclo[2.2.2] octane-3-acetonitrile)], in rat cortex and heart using radioligand binding and functional studies. The Quinuclidinyl benzilate/Oxotremorine-M acetate ratio from radioligand binding studies suggested that sabcomeline and xanomeline [3(3-hexyloxy-1,25-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-met hylpyridine] are muscarinic receptor partial agonists in cortical and heart membranes. In [35S]GTPgammaS binding studies in rat cortex, carbachol stimulated binding via muscarinic M2/M4 receptors which could be blocked by sabcomeline with a pA2 of 7.2. In rat heart membranes, carbachol also stimulated [35S]GTPgammaS binding studies through muscarinic M2 receptors. Sabcomeline caused a small stimulation of basal [35S]GTPgammaS binding in both rat and heart tissues. Sabcomeline did not stimulate phosphoinositide hydrolysis in rat cortical slices, but did block the muscarinic M1 receptor-mediated response caused by carbachol with apparent pKb of 6.9. Xanomeline and milameline also had no effect on phosphoinositide hydrolysis up to 100 microM. In adenylyl cyclase studies in rat atria, sabcomeline inhibited forskolin-stimulated adenylyl cyclase activity to a similar extent to that of carbachol, xanomeline and milameline. The present study, using the techniques of radioligand binding, supports previous publications which have claimed that sabcomeline is a muscarinic receptor partial agonist. As expected, this study shows that the functional actions of this compound at muscarinic receptor subtypes and in different tissues will depend on receptor reserve.

Adenylyl Cyclases↗