Biomedical subjects

S Reece

Publications and source records attributed to S Reece.

At least 19 recordsLinked to original sources

PubMed2002

Tissue tropism of enteropathogenic Escherichia coli strains belonging to the O55 serogroup.

Four enteropathogenic Escherichia coli (EPEC) strains belonging to the O55 serogroup (G21 and G30 [both O55:H6], G35 [O55:H-], and G58 [O55:H7]) were tested for their tissue tropism by using human intestinal in vitro organ culture. Strains showed restricted adhesion with attaching-and-effacing activity to follicle-associated epithelium of Peyer's patches, with no apparent adhesion to duodenum or colon. G35 and G58 express intimin gamma and show a similar tropism to intimin gamma-expressing enterohemorrhagic E. coli (EHEC) O157:H7. However, strains G21 and G30 were unusual because they expressed intimin alpha and had a restricted tissue tropism of intimin gamma phenotype. The amino acid sequence of the carboxy-terminal 280 amino acids of intimin from G21 was determined. Comparison with the prototype intimin alpha from strain E2348/69 (O127:H6) showed a single amino acid difference (corresponding to Val907 and Ala907 in the whole intimins). This mutation was reproduced by site-directed mutagenesis in an intimin alpha plasmid template, pCVD438, with the hypothesis that it may induce a change in tropism. However, when the mutated plasmid was placed in both EPEC and EHEC backgrounds, duodenal adhesion in a manner similar to strain E2348/69 was evident upon in vitro organ culture. Thus, additional factor(s) unrelated to intimin exist in the O55:H6 genome that influence human intestinal tissue tropism.

Amino Acid Sequence↗

PubMed2002

Intimin type influences the site of human intestinal mucosal colonisation by enterohaemorrhagic Escherichia coli O157:H7.

BACKGROUND: Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli epithelial cell adhesion is characterised by intimate attachment, and attaching and effacing (A/E) lesion formation. This event is mediated in part by intimin binding to another bacterial protein, Tir (translocated intimin receptor), which is exported by the bacteria and integrated into the host cell plasma membrane. Importantly, EPEC (O127:H6) and EHEC (O157:H7) express antigenically distinct intimin types known as intimin alpha and gamma, respectively. EHEC (O157:H7) colonises human intestinal explants although adhesion is restricted to the follicle associated epithelium of Peyer's patches. This phenotype is also observed with EPEC O127:H6 engineered to express EHEC intimin gamma. AIMS: To investigate the influence of intimin on colonisation of human intestine by E coli O157:H7, and intimin types on tissue tropism in humans. METHODS: Human intestinal in vitro organ culture with wild type and mutant strains of O157:H7 were employed. RESULTS: Introducing a deletion mutation in the eae gene encoding intimin gamma in EHEC (O157:H7) caused the strain (ICC170) to fail to colonise human intestinal explants. However, colonisation of Peyer's patches and A/E lesion formation were restored with intimin gamma expression from a plasmid (ICC170 (pICC55)). In contrast, complementing the mutation with intimin alpha resulted in a strain (ICC170 (pCVD438)) capable of colonising and producing A/E lesions on both Peyer's patch and other small intestinal explants. CONCLUSION: Intimin is necessary for human intestinal mucosal colonisation by E coli O157:H7. Intimin type influences the site of colonisation in a Tir type independent mechanism; intimin gamma appears to restrict colonisation to human follicle associated epithelium.

Adhesins, Bacterial↗

PubMed2001

Polymorphisms in glutathione S-transferases are associated with altered risk of nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis.

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and mortality among renal transplant recipients, with tumors behaving more aggressively than those in nontransplant patients. Not all immunosuppressed patients develop NMSC, however, and in those that do, the rate of accrual and numbers of lesions vary considerably. Though ultraviolet light is critical, it is unlikely that this alone explains the observed phenotypic diversity, suggesting the possible involvement of genetic factors. Furthermore, although twin studies in nontransplant patients with NMSC suggest a low genetic component, several genes associated with susceptibility and outcome in these patients have been identified. Thus, having previously shown that polymorphism in members of the glutathione S-transferase (GST) supergene family is associated with altered NMSC risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained significant after correction for age, gender, and ultraviolet light exposure (p = 0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and sunbathing score showed that the two factors were synergistic and individuals with both risk parameters demonstrated a shorter time from transplantation to development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6), particularly those with lower ultraviolet light exposure and cigarette consumption. GSTM3 and GSTT1 also demonstrated significant associations, though some genotype frequencies were low. These preliminary data suggest that genetic factors mediating protection against oxidative stress are important in NMSC development in immunosuppressed patients and may be useful in identifying high-risk individuals.

Adult↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients.

A single-center, cross-sectional, longitudinal study was conducted to determine the prevalence, annual incidence, and clinical risk factors for skin cancer in a white renal transplant population. One hundred eighty-two white patients (95% of population) with functioning allografts, a mean age at transplantation of 38.9 +/- 15. 6 (SD) years, and a mean follow-up of 8.5 +/- 6.3 years were interviewed and examined between May 1997 and June 1999. All case notes were carefully reviewed. Since transplantation, 16.5% of the patients had developed nonmelanoma skin cancer; 15.4%, actinic keratoses (AK); 53%, viral warts; and 1.6%, lentigo maligna melanoma (n = 3). Thirty-nine percent of the tumors were detected as a consequence of this study, and 20% of these occurred on covered body sites. The squamous cell (SCC)-basal cell carcinoma (BCC) ratio was 3.8:1. Eighty-two percent of the patients were examined a second time 12 months after the initial assessment. Using these data to identify new lesions, the annual incidence was calculated at 6.5%, increasing to 10.5% at more than 10 years posttransplantation. Duration of immunosuppression, older age at transplantation, presence of AK, male sex, and outdoor occupation were significantly associated with both SCC and BCC; SCC alone was associated with a history of having smoked tobacco. Early identification of those at greatest risk using a clinical risk profile may allow the development of more structured preventative and surveillance strategies than currently exist.

Adult↗

PubMed1999

Chimpanzee thumb muscle cross sections, moment arms and potential torques, and comparisons with humans.

This study investigates the morphological basis of differences between humans and chimpanzees in the kinematical and dynamical parameters of the musculature of the thumb. It is partly intended to test an hypothesis that human thumb muscles can exert significantly greater torques, due to larger muscle cross-sectional areas or to longer tendon moment arms or to both. We focus on the estimation of the potentials of thumb muscles to exert torques about joint axes in a sample of eight chimpanzee cadaver hands. The potential torque of a muscle is estimated by taking the product of a muscle's physiological cross-sectional area (an estimator of force) with its dynamical moment arm (derived from the slope of tendon excursion versus joint angular displacement, obtained during passive movements of cadaver thumb joints). Comparison of our results with similar data obtained for humans at the same Mayo Clinic laboratory shows significant differences between humans and chimpanzees in potential torque of most thumb muscles, those of humans generally exhibiting larger values. The primary reason for the larger torques in humans is that their average moment arms are significantly longer, permitting greater torque for a given muscle size. An additional finding is that chimpanzees and humans differ in the direction of secondary thumb metacarpal movements elicited by contraction of some muscles, as shown by differences in moment arm signs for a given movement in the same muscle. The differences appear to be related to differences in the musculo-skeletal structures of the trapeziometacarpal joint.

Animals↗

PubMed1998

EMG study of hand muscle recruitment during hard hammer percussion manufacture of Oldowan tools.

The activity of 17 hand muscles was monitored by electromyography (EMG) in three subjects during hard hammer percussion manufacture of Oldowan tools. Two of the subjects were archaeologists experienced in the replication of prehistoric stone tools. Simultaneous videotapes recorded grips associated with the muscle activities. The purpose of the study was to identify the muscles most likely to have been strongly and repeatedly recruited by early hominids during stone tool-making. This information is fundamental to the identification of skeletal features that may reliably predict tool-making capabilities in early hominids. The muscles most frequently recruited at high force levels for strong precision pinch grips required to control the hammerstone and core are the intrinsic muscles of the fifth finger and the thumb/index finger regions. A productive search for skeletal evidence of habitual Oldowan tool-making behavior will therefore be in the regions of the hand stressed by these intrinsic muscles and in the joint configurations affecting the relative lengths of their moment arms.

Animals↗

PubMed1998

Concurrent and predictive validity of an early language screening program.

The efficacy of screening 2-year-old children for language delay using a parent-report questionnaire was investigated in three studies. The Language Development Survey (Rescorla, 1989) was mailed to 650 families at the time of their child's second birthday. Fifty-three percent of the surveys received by parents were completed and returned. Screening outcomes were then compared, in double-blind fashion, with the results of comprehensive clinical evaluations at ages 2 (N = 64) and 3 (N = 36). Parents' report of the size of their children's expressive vocabularies was highly correlated with clinical language measures at age 2. Children who screened positive performed significantly poorer than children who screened negative on standardized language tests and on measures taken from spontaneous conversation. The screening program demonstrated excellent sensitivity and specificity for identifying language delay at age 2 but somewhat lower levels for predicting developmental status one year later.

Age Factors↗

PubMed1983

Macro--creatine kinase 2: a possible marker of gastrointestinal cancer?

Creatine kinase (CK) is an enzyme found in many body organs. It is used clinically in the diagnosis of myocardial infarction. Recently an atypical isoenzyme, macro-CK2, not found in the sera of healthy individuals, has been reported in patients with gastrointestinal malignancies. This study is a report of our findings in serum samples obtained from 200 patients from November 1981 until December 1982. Twenty-eight patients had gastrointestinal complaints but did not have malignant disease. One hundred seventy-two patients had malignancy. Samples of serum were studied for macro-CK2 with a standard laboratory agarose gel electrophoresis technique. The tests were done without knowledge of the patients' diagnoses. The results show no detectable macro-CK2 in sera from patients without malignancy. It was present before operation in nine of 13 patients with colorectal cancer and 16 of 21 patients with metastases from colorectal cancer or gastric cancer. This preliminary study suggests that the presence of macro-CK2 in serum may be an indicator of malignancy of the gastrointestinal tract and in particular of colorectal cancer.

Adult↗

PubMed1982

The Psychiatric Status Schedule for Asian Americans.

Because Asian Americans who need to be diagnosed often do not speak English, the authors translated the Psychiatric Status Schedule into several Asian languages and devised an audiovisual version of the schedule. They tested the validity of the audiovisual version by comparing the computer diagnoses derived from interviews by mental health professionals who used the standard translated version with the computer diagnoses of mental health professionals and volunteers who used the audiovisual version. Sixty subjects were diagnosed: 20 Chinese-speaking patients, 20 Korean-speaking patients, and 20 Japanese-speaking subjects. Moderate reliability was found between those who used the standard translated version and those who used the audiovisual version.

Asian↗

PubMed1982