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S Matthews

Publications and source records attributed to S Matthews.

At least 55 records · Page 3Linked to original sources

Using an interactive framework of society and lifecourse to explain self-rated health in early adulthood.

This paper presents an integrated model of the determinants of adult health combining lifecourse factors and contemporary circumstances. Using the 1958 British Birth Cohort, it operationalises lifecourse influences in terms of factors from birth to age 33, which might act through latent, pathway, or cumulative effects. Contemporary circumstances are represented by variables at different levels of social aggregation: macro (socio-economic circumstances); meso (involvement in civil society functions); micro (personal social support); and intersecting (job insecurity and life control). Multiple regression models were fitted, using self-rated health at age 33 as the health outcome. To allow for temporal ordering of events, early life factors were entered first in the final model, followed by later childhood factors and, finally current factors. Self-rated health was predicted by variables representing both early and later stage of the lifecourse and also contemporary societal-level factors. The effects of childhood factors were not removed by including contemporary factors, and conversely, contemporary factors contributed to the prediction of self-rated health over and above lifecourse factors. The factors were not collinear; supporting the notion that each dimension was distinct from the others. Although the model accounted for only 9% of the variance in self-rated health, the general conclusion is that both lifecourse and contemporary circumstances should be considered together in explaining adult health.

Adolescent↗

Intimin and the host cell--is it bound to end in Tir(s)?

Intimate bacterial adhesion to the intestinal epithelium is a pathogenic mechanism shared by several human and animal enteric pathogens, including enteropathogenic and enterohaemorrhagic Escherichia coli. Two bacterial protein partners involved in this intimate association have been identified, intimin and Tir. Some key remaining questions include whether intimin specifically interacts with one or more host-cell-encoded molecules and whether these contacts are a prerequisite for the subsequent intimate intimin-Tir association. Recent data support the hypothesis that the formation of a stable intimin-Tir relationship is the consequence of intimin protein interactions involving both host and bacterial components.

Adhesins, Bacterial↗

Psychological distress and work and home roles: a focus on socio-economic differences in distress.

BACKGROUND: Home and work factors have been linked to psychological status, but less is known about their contribution to social inequalities in psychological status. We examine whether social inequalities in psychological distress can be explained by work-home factors and whether the impact of these potential explanatory factors is similar for men and women. METHODS: Data are from the 1958 British birth cohort study. We sought to explain social class differences in psychological distress at age 33. Explanatory factors were classified as work-home roles: i.e. employment, marital status, domestic responsibility, children and elderly care; and work-home characteristics: i.e. job-strain, insecurity, unsocial working hours, youngest child's age, number of children and level of involvement in childcare. RESULTS: A social gradient in psychological distress was found: odds ratios for classes IV and V v. I and II were 2.65 (men) and 3.02 (women). Work factors had consistently stronger associations with psychological distress and with social class among men than women. Work factors had a greater impact on class differences in psychological distress in men. Associations for home roles and characteristics were less consistent and their combined effect on class differences in distress was negligible for both sexes. CONCLUSION: Explanations for the social gradient differ for men and women. Work may be more important for men than women, but the impact of home factors was not strong during the early adulthood of this cohort.

Activities of Daily Living↗

A National Cancer Institute of Canada clinical trials group phase II study of eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous cell head and neck cancer.

UNLABELLED: BACKGROUND/PATIENTS AND METHODS: Thirty-two patients with recurrent head and neck cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil (10 mg/m2) and 5-fluorouracil (5-FU) (1 mg/m2) (E5F) orally twice daily for 28 days followed by a seven-day treatment free period. Thirty-five-day cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Doses were modified for toxicity. Standard toxicity and response criteria were used. RESULTS: Thirty-two patients were accrued; thirty-two and twenty-eight patients were evaluable for toxicity and response, respectively. Twelve patients received three or more cycles of E5F. Drug related toxicities were usually grade 1-2 intensity and included lethargy, nausea or diarrhea (> or = 25% of patients), and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients). Hematologic toxicity was generally mild; two patients experienced grade 3-5 leukopenia or thrombocytopenia. No significant biochemical toxicity was seen. One patient was withdrawn (severe nausea and vomiting) and one patient died because of drug related toxicity (thrombocytopenia). In the final analysis there were one complete and four partial responses for a 15.6% overall response. CONCLUSIONS: E5F demonstrates activity in chemotherapy naïve patients with advanced HNC cancer with acceptable toxicity profile. Further investigation of E5F with other active agents is warranted in HNC.

Adult↗

Can parents accurately perceive hyperactivity in their child?

In all, 1872 children were recruited as part of a larger study concerning food additives and behaviours in preschool children. This figure represented 70% of the whole population of 3 1/4 -year-old children resident on the Isle of Wight, UK. Parents completed an assessment concerning their perceptions of their child's behaviour. The results of this assessment were compared with scores on two validated parental questionnaires, the Weiss Werry Peters (WWP) hyperactivity scale and the Emotionality, Activity and Sociability Temperament Questionnaire (EAS), which were used to assess hyperactivity. The accuracy of parents in perceiving hyperactivity in their children was found to be around 50% if the child was hyperactive, and 89% if the child was not hyperactive. The implications of these findings for services are discussed. Frequencies of potential risk groups for future Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder were also suggested.

Child Behavior↗

Site-directed mutagenesis of intimin alpha modulates intimin-mediated tissue tropism and host specificity.

The hallmark of enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherchia coli adhesion to host cells is intimate attachment leading to the formation of distinctive 'attaching and effacing' lesions. This event is mediated, in part, by binding of the bacterial adhesion molecule intimin to a second bacterial protein, Tir, delivered by a type III secretion system into the host cell plasma membrane. The receptor-binding activity of intimin is localized to the C-terminal 280 amino acids (Int280) and at least five distinct intimin types (alpha, beta, gamma, delta and epsilon) have been identified thus far. In addition to binding to Tir, intimin can also bind to a component encoded by the host. The consequence of latter intimin-binding activity may determine tissue tropism and host specificity. In this study we selected three amino acids in intimin, which are implicated in Tir binding, for site-directed mutagenesis. We used the yeast two-hybrid system and gel overlays to study intimin-Tir protein interaction. In addition, the biological consequences of the mutagenesis was tested using a number of infection models (cultured epithelial cells, human intestinal explants and a mouse model). We report that while an I237/897A substitution (positions numbered according to Int280alpha/whole intimin alpha) in intimin alpha did not have any affect on its biological activity, a T255/914A substitution attenuated intimin activity in vivo. In contrast, the mutation V252/911A affected tissue targeting in the human intestinal explant model and attenuated the biological activity of intimin in the mouse model. This study provides the first clues of the molecular basis of how intimin mediates tissue tropism and host specificity.

Adhesins, Bacterial↗

Multiple courses of antenatal corticosteroids: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of multiple courses of antenatal corticosteroids on perinatal and neonatal death and neonatal, infant, and maternal disease. METHODS: MEDLINE and Embase were searched for human studies published in English. Studies that compared multiple courses of antenatal corticosteroids versus a single course were included if they were published in full and were controlled for gestational age at birth. Meta-analyses (odds ratio and 95% confidence interval) were undertaken when possible. RESULTS: Eight observational studies were included. Selection bias was present in all studies. Multiple courses of antenatal corticosteroids were associated with a decreased risk of respiratory distress syndrome (odds ratio, 0.79; 95% confidence interval, 0.64 to 0.98) and patent ductus arteriosus (odds ratio, 0.56; 95% confidence interval, 0.35 to 0.90) and were associated with an increased risk of endometritis (odds ratio, 3.42; 95% confidence interval, 1.92 to 6.11). There was no significant effect on other neonatal and maternal outcomes. CONCLUSION: It is not possible to establish the true effects of multiple courses of antenatal corticosteroids by a review of the results of observational studies because of the effect of confounding variables. Randomized controlled trials are needed to address this important issue.

Adrenal Cortex Hormones↗

Self-rated health and limiting longstanding illness: inter-relationships with morbidity in early adulthood.

BACKGROUND: Self-rated health and limiting longstanding illness are both widely used global measures of health, but understanding is poor of their meaning and validity at younger ages. METHODS: We examined the association between self-rated health and limiting longstanding illness and specific health problems at two ages (23 and 33 years), and assessed change over the 10-year period for each health measure relative to another. Longitudinal data were taken from the nationally representative British birth cohort for which health measures were obtained at ages 23 and 33. RESULTS: Self-rated health and limiting longstanding illness were strongly associated with each other as well as with specific health problems, particularly with serious conditions (e.g. epilepsy, cancer, diabetes) and more weakly with less serious conditions (e.g. eczema and hay fever). Rating of overall health and limiting longstanding illness was highly stable during the 10-year period with most, but not all, health change reflecting a deterioration in health status. Deterioration in limiting illness corresponded to an even greater health decline in specific conditions. CONCLUSIONS: Self-rated health and limiting longstanding illness are valid health measures appropriate for use in general health surveys.

Adult↗

Peritonitis associated with Actinobacillus equuli in horses: 51 cases.

OBJECTIVE: To review the clinical findings, diagnosis and treatment of 51 horses with peritonitis attributed to Actinobacillus equuli. DESIGN: Retrospective study of clinical cases. METHODS: Breed, age and gender of horse, history, physical examination findings, treatment and outcome were determined from the hospital records of 51 horses in which a diagnosis of peritonitis attributed to A. equuli was made between January 1993 and June 1999. Results of abdominal fluid cytology and bacteriology, antimicrobial sensitivity patterns, haematology and faecal egg counts, when performed, were also retrieved. RESULTS: There was a variety of breeds of horses affected. There were 35 male and 17 female horses, aged from 9 months to 22 years, presented. Lethargy, signs of depression with mild to moderate signs of abdominal pain and inappetence were the most common reasons for presentation. Most horses had elevated heart and respiratory rates, an elevated rectal temperature and reduced intestinal borborygmi heard on auscultation of the abdomen. Abnormal colour with an elevated protein were features of an abdominal fluid sample in 98% of horses and a marked elevation in nucleated cell count was present in all samples. Pleomorphic gram-negative rods were seen on cytology in 53% of samples and a positive culture of A. equuli was returned in 72% of samples. Other laboratory findings in some horses included mild haemoconcentration, hypoproteinaemia, an elevated circulating nucleated cell count with a left shift, an elevation in fibrinogen concentration and an elevated faecal egg count. All horses demonstrated a rapid response to treatment with procaine penicillin alone, or a combination of procaine penicillin and gentamicin sulphate. Where antimicrobial sensitivity tests were performed, all but two isolates were sensitive to procaine penicillin. All horses responded to antimicrobial and supportive therapy and were discharged from hospital. CONCLUSION: Horses with A. equuli peritonitis present with similar clinical signs as horses with other causes of abdominal pain. However, these signs, when evaluated in conjunction with the results of abdominal fluid analysis and response to treatment, are characteristic of A. equuli peritonitis. Pleomorphic gram-negative bacteria may be seen on a cytological preparation of the abdominal fluid sample, and a positive bacterial culture may be obtained in some, but not all, cases. Most isolates are sensitive to procaine penicillin, so treatment with procaine penicillin and gentamicin sulphate is recommended until antimicrobial sensitivity is known.

Actinobacillus↗

Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study.

BACKGROUND: Atopy is defined as the genetic propensity to develop immunoglobulin E antibodies in response to exposure to allergens and assessed by skin prick test responses to common allergens. Although it is generally agreed that atopy is an important risk factor for allergic diseases such as asthma, rhinitis, and eczema, the extent to which atopy accounts for these diseases is controversial. OBJECTIVE: We aim to describe the prevalence of sensitization to common allergens and investigate the degree of association of atopy (as defined by positive skin prick test to 1 or more common allergens) to asthma, rhinitis, and eczema in a birth cohort at the age of 4 years. METHODS: A birth cohort of 1456 children was recruited over a 14-month period (1989-1990). These children have been seen previously at 1 and 2 years of age. At 4 years, 1218 children were reviewed and an interview was administered or postal questionnaire was completed for the presence of allergic diseases (asthma, rhinitis, and eczema). Additionally, in 981 children, skin prick tests with a battery of 12 common allergens were performed. Allergens were house dust mite (Dermatophagoides pteronyssimus), grass pollen mix, cat, dog, Alternaria alternata, Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut. A mean wheal diameter of at least 3 mm greater than the negative control was taken as positive. This analysis is confined to the 981 (67% of the original population) who also had skin prick tests to the standard battery. chi(2) tests were used to test the univariate association between each allergic disease and positive skin test. Multiple logistic regression analysis was performed to obtain the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the independent effect of sensitization to each allergen on allergic disease, adjusting for the effect of sensitization to other allergens. To ascertain how much of allergic disease is attributable to atopy, we estimated the population-attributable risk. This was calculated with the formula: P(R - 1) where R is the OR for the allergic disease under consideration and P is the proportion of atopy in children with that disease. RESULTS: Children who were skin prick-tested at 4 years were similar in most characteristics to the rest of the population, except that they had a higher prevalence of allergic disease. Allergic disorders (asthma, rhinitis, and eczema) were present in 276 (28.1%) of 981. One hundred ninety-two (19.6%) children were atopic (positive reaction to 1 or more allergens). Sensitization to inhalant allergens was relatively common (19.2%) as compared with food allergens (3.5%). House dust mite (11.9%), grass pollen (7.8%), and cat (5.8%) were the most common positive reactions. A test to the 4 most common allergens (house dust mite, grass pollen, cat, and A alternata) could detect 94% of the atopic children. Sensitization to the 4 most common allergens was strongly associated with the presence of allergic disorders. There was a graded effect with the potent allergens, such as house dust mite, having the greatest impact. For example, 50% of children sensitized to house dust mite had asthma as opposed to 44% sensitized to cat, 42% sensitized to grass pollen, and 32% sensitized to A alternata. Overall, 68.4% of children sensitized to house dust mite had asthma, eczema, and/or rhinitis. The respective figures for grass pollen, cat, and A alternata were 64.9%, 66.7%, and 57.4%. The proportion of children sensitized to cat was not higher in households with cat ownership (households with cats: 5.1% [19/374]; households without cats: 6.2% [36/580]; not significant [NS]). Similarly, no difference was seen in sensitization to dog in households with and without dogs (households with dogs: 1.8% [5/282]; households without dogs: 2.8% [19/673]; NS). Boys were atopic more often than girls at this age (male: 112 of 497 [22.5%] vs female: 80 of 484 [16.5%]; OR: 1.47, 95% CI: 1.07-2.02). Male preponderance was observed with most allergens, but this was statistically significant only for house dust mite (male: 75/497 [15.1%] vs female: 42/484 [8.7%]; OR: 1.87; CI: 1.25-2.79) and grass pollen (male: 51/497 [10.3%] vs female: 26/484 [5.4%]; OR: 2.01; CI: 1.23-3.29). An independent effect of allergen sensitization on asthma was observed only with house dust mite with an OR of 8.07 (CI: 4.60-14.14). The highest independent risk for rhinitis was sensitization to grass pollen (OR: 5.02; CI: 2.21-11.41), and for eczema, sensitization to peanut (OR: 4.65; CI: 1.02-21.34). The majority of children (98/192) were sensitized to >1 allergen. A graded effect was observed with the risk of allergic disease in the child increasing with the number of positive skin prick test reactions. This effect was consistent throughout the spectrum of allergic diseases (asthma, eczema, and rhinitis). (ABSTRACT TRUNCATED)

Allergens↗

Registered male: a discussion on men in the nursing profession.

The aim of this discussion paper is to alert the profession to issues surrounding men in nursing. There is a historical connection between men and the nursing profession; men having served as nurses long before Florence Nightingale. Literature suggests that women and men enter the nursing profession for the same reasons, however the paths which lead men to nursing differ. Feminist sociologists express alarm at the disproportionate number of males in managerial nursing positions and hold that this may have negative consequences for the profession. Male and female patients have a definite preference in regards to the gender of their nurse. Issues surrounding this preference will be explored.

Australia↗

Adult neurogenesis in natural populations.

The dogma that the adult brain produces no new neurons has been overturned, but the critics are still asking, so what? Is adult neurogenesis a biologically relevant phenomenon, or is it perhaps harmful because it disrupts the existing neuronal circuitry? Considering that the phenomenon is evolutionarily conserved in all mammalian species examined to date and that its relevance has been well documented in non-mammalian species, it seems self-evident that neurogenesis in adult mammals must have a role. In birds, it has been established that neurogenesis varies dramatically with seasonal changes in song production. In chickadees, the learning behaviour related to finding stored food is also correlated with seasonal adult neurogenesis. Such studies are still nonexistent in mammals, but the related evidence suggests that neurogenesis does vary seasonally in hamsters and shows sexual differences in meadow voles. To promote studies on natural populations asking fundamental questions of the purpose and function of neurogenesis, we organized a Workshop on "Hippocampal Neurogenesis in Natural Populations" in Toronto in May 2000. The Workshop highlighted recent discoveries in neurogenesis from the lab, and focused on its functional consequences. The consensus at the Workshop was that demonstration of a role for neurogenesis in natural behaviours will ultimately be essential if we are to understand the purpose and function of neurogenesis in humans.

Adult↗

Association of allergy-related symptoms with sensitisation to common allergens in an adult European population.

BACKGROUND: Atopy is an important risk factor for asthma and allergic diseases. However, the relationship between atopy and allergic symptoms is not fully understood, and may not be the same for different allergy related symptoms and in differing environmental conditions. OBJECTIVE: To study the differences in the association of allergy-related symptoms and atopy, in an adult population from five European countries. METHODS: A prospective, multi-national study was conducted. Centres included Isle of Wight (UK), Vienna (Austria), Freiburg (Germany), Athens (Greece), and Kaunas (Lithuania). We used five questions derived from the ISAAC (International Study of Asthma and Allergy in Children) and other validated questionnaire, to evaluate the presence of allergic symptoms in a selected adult population. Atopy was assessed by SPT or IgE measurement to 3 core allergens (dust mite, cat and grass pollen) in all centres and 1-2 additional allergens relevant to each area (parietaria, olive, birch pollen, tree pollen mix, dog). RESULTS: Of 3985 subjects, 2478 (62%) responded positively to one or more core ISAAC questions. Sensitisation rate was high in Austria and UK and relatively low in Greece. Dust mite and cat were important allergens for asthma, odds ratio (OR): 2.24, 95% confidence interval (CI): 1.63-3.08 and OR: 2.31, CI: 1.69-3.14, respectively. Grass pollen was strongly associated with hay fever in all centres (OR: 3.62 CI: 2.81-4.66) and with birch pollen in Austria (OR: 3.57, CI: 2.09-6.09) and with parietaria in Greece (4.61 (2.99-7.12). In the comparative analysis, using UK as a reference, Lithuanians had a 10-20-fold reduced risk of asthma and hay fever, but were twice more likely to report chronic itching. The risk of dust mite allergy was 3- and 10-fold lower in Lithuania and Greece, respectively, whereas the risk of cat and grass pollen allergy was one and half times higher in Austria. CONCLUSION: The risk of allergic symptoms and sensitisation and their association vary widely in different European countries.

Adolescent↗

Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer.

PURPOSE: To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI). METHODS AND MATERIALS: Between 1989-1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores >or =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was < or =10.0 ng/mL and Gleason score < or = 6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126 months). RESULTS: Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0. 4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication. CONCLUSIONS: Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.

Aged↗

A clinical evaluation of an Erbium:YAG laser for dental cavity preparation.

OBJECTIVE: A randomised controlled trial to determine the acceptability to dentists and patients of cavity preparation with an Erbium:YAG laser as compared with conventional handpieces. METHODS: Fifteen dentists (9 GDPs, 1 community dentist and 5 hospital dentists) treated 77 patients (age range 3.5-68 years old) who had two matched cavities, in a split mouth, randomised trial. One cavity was prepared conventionally, the other with the laser, with dentist and patient preference determined by questionnaire. RESULTS: In the majority of cases, where dentists expressed a preference, it was for conventional cavity preparation, and this was significant (P < 0.001). In more than half of the laser appointments, dentists had to use conventional handpieces to complete the cavity. Principle difficulties reported with the laser were access (25 cases) and slow speed of cutting (11 cases). Patients aged > or = 10 years who expressed a preference, preferred laser treatment, and this was significant (P < 0.001). Patients aged < 10 years, assessed using a simplified pictorial questionnaire, did not show a significant preference for either technique. CONCLUSIONS: Dentists preferred conventional handpieces for cavity preparation while patients aged > or = 10 years old preferred laser treatment. Patients < 10 years old did not express a preference.

Adolescent↗

Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold.

Polypyrimidine tract binding protein (PTB), an RNA binding protein containing four RNA recognition motifs (RRMs), is involved in both pre-mRNA splicing and translation initiation directed by picornaviral internal ribosome entry sites. Sequence comparisons previously indicated that PTB is a non-canonical RRM protein. The solution structure of a PTB fragment containing RRMs 3 and 4 shows that the protein consists of two domains connected by a long, flexible linker. The two domains tumble independently in solution, having no fixed relative orientation. In addition to the betaalphabetabetaalphabeta topology, which is characteristic of RRM domains, the C-terminal extension of PTB RRM-3 incorporates an unanticipated fifth beta-strand, which extends the RNA binding surface. The long, disordered polypeptide connecting beta4 and beta5 in RRM-3 is poised above the RNA binding surface and is likely to contribute to RNA recognition. Mutational analyses show that both RRM-3 and RRM-4 contribute to RNA binding specificity and that, despite its unusual sequence, PTB binds RNA in a manner akin to that of other RRM proteins.

Amino Acid Motifs↗

Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli.

Intimin is a bacterial adhesion molecule involved in intimate attachment of enteropathogenic and enterohaemorrhagic Escherichia coli to mammalian host cells. Intimin targets the translocated intimin receptor (Tir), which is exported by the bacteria and integrated into the host cell plasma membrane. In this study we localized the Tir-binding region of intimin to the C-terminal 190 amino acids (Int190). We have also determined the region's high-resolution solution structure, which comprises an immunoglobulin domain that is intimately coupled to a novel C-type lectin domain. This fragment, which is necessary and sufficient for Tir interaction, defines a new super domain in intimin that exhibits striking structural similarity to the integrin-binding domain of the Yersinia invasin and C-type lectin families. The extracellular portion of intimin comprises an articulated rod of immunoglobulin domains extending from the bacterium surface, conveying a highly accessible 'adhesive tip' to the target cell. The interpretation of NMR-titration and mutagenesis data has enabled us to identify, for the first time, the binding site for Tir, which is located at the extremity of the Int190 moiety.

Adhesins, Bacterial↗