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A novel immunoglobulin superfamily receptor (19A) related to CD2 is expressed on activated lymphocytes and promotes homotypic B-cell adhesion.

A novel lymphocyte-specific immunoglobulin superfamily protein (19A) has been cloned. The predicted 335-amino-acid sequence of 19A represents a Type 1 membrane protein with homology with the CD2 family of receptors. A molecular model of the two predicted extracellular immunoglobulin-like domains of 19A has been generated using the crystal structure of CD2 as a template. In isolated lymphocytes, expression of 19A is induced by various activation stimuli, and enforced expression of the 19A gene promotes homotypic cell adhesion in a B-cell-line model. Collectively these data imply that the 19A protein plays a role in regulation of lymphocyte adhesion.

Amino Acid Sequence↗

Dermatitis caused by physical irritants.

BACKGROUND: Although physical irritant contact dermatitis (PICD) is a common occupational dermatosis, it is one of the least well understood because of its multiple types, lack of diagnostic test, and the many mechanisms involved in its production. OBJECTIVES: To characterize the materials and mechanisms of physical irritation of the skin. METHODS: We did a retrospective analysis over the past 20 years of all patients with a diagnosis of PICD at St John's Institute of Dermatology Contact Dermatitis Clinic. RESULTS: Of the 29,000 patients who attended the clinic over the study period, 392 patients were diagnosed with PICD and of these, 335 files were analysed. CONCLUSIONS: Our findings show that PICD accounted for 1.15% of all patients attending the contact clinic over the study period. Diverse occupations and materials were implicated. The most common cause of PICD was low humidity due to air-conditioning, which caused dermatitis of the face and neck in office workers due to drying out of the skin.

Adolescent↗

The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation.

Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case-control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged < or =75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2.51, 95% confidence interval (CI) 1.02-12.01], particularly for woodworm treatment (OR = 5.1, 95% CI 1.5-17.4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.

Adolescent↗

Who uses welfare benefits advice services in primary care?

There is considerable interest among organisations such as primary care trusts and health action zones in commissioning welfare benefits advice services in primary healthcare settings as part of local strategies to reduce health inequalities. However, very little is known about the contribution to health of such services or about the health status of those who use them. The present study reports on a longitudinal study of the contribution to individual health of welfare benefits advice in primary care that has gathered baseline demographic and health data on 345 research subjects. The average age of the subjects was 54 years, and they were likely to be unemployed or retired. Over 85% were advised to apply for welfare benefits or to appeal against the loss of a benefit, the most common benefit being Disability Living Allowance (over 50% of all subjects). Three-quarters reported a physical disability or long-term illness that limited their daily activity, and over half reported arthritis or rheumatism. Scores on the short form 36 (SF-36) which quantify self-reported physical and psychosocial aspects of health, were much lower than population norms, indicating poorer health. The burden of illness borne by users of these services is not surprising. However, reliable data has not previously been available. It appears that primary care provides good access to advice services for people in middle and old age, but not to other groups (e.g. families with young children, substance misusers or those with mental health problems). Better data collection by advice services, wherever located, would strengthen their understanding of the needs of those whom they serve, and help them to identify under-served groups. These data could be used to support requests for continued or extended funding.

Adolescent↗

Specific phosphatidylethanolamine dependence of Serratia marcescens cytotoxin activity.

The cytolytic and haemolytic activity of Serratia marcescens is determined by the ShlA protein, which is secreted across the outer membrane with the aid of the ShlB protein. In the absence of ShlB, inactive ShlA* remains in the periplasm of Escherichia col transformed with an shlA-encoding plasmid, which indicates that ShlB converts ShlA* to active ShlA. ShlA* in a periplasmic extract and partially purified ShlA* were activated in vitro by partially purified ShlB. When both proteins were highly purified, ShlA* was only activated by ShlB when phosphatidylethanolamine (PE) or phosphatidylserine was added to the assay, while phosphatidylglycerol contributed little to ShlA* activation. Lyso-PE, cardiolipin, phosphatidylcholine, phosphatidic acid, lipopolysaccharide and various detergents could not substitute for PE. Although radioactively labelled PE was so tightly associated with ShlA that it remained bound to ShlA after heating and SDS-PAGE, it was not covalently linked to ShlA as PE could be removed by thin-layer chromatography with organic solvents. The number of PE molecules associated per molecule of ShlA was 3.9 +/- 2.2. Active ShlA was inactivated by treatment with phospholipase A2, which indicated that PE is also required for ShlA activity. ShlA-255 (containing the 255 N-terminal amino acids of ShlA) reversibly complemented ShlA* to active ShlA and was inactivated by phospholipase A2, which demonstrated that PE binds to the N-terminal portion of ShlA; this region has previously been found to be involved in ShlA secretion and activation. Electrospray mass spectroscopy of ShlA-255 determined a molar mass that corresponded to that of unmodified ShlA-255. An E. coli mutant that synthesized only minute amounts of PE did not secrete ShlA but contained residual cell-bound haemolytic activity. Since PE binds strongly to ShlA* in the absence of ShlB without converting ShlA* to haemolytic ShlA, ShlB presumably imposes a conformation on ShlA that brings PE into a position to mediate interaction of the hydrophilic haemolysin with the lipid bilayer of the eukaryotic membrane.

Agar↗

YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-alpha production and downregulation of the MAP kinases p38 and JNK.

Exposure of macrophages to lipopolysaccharide (LPS) leads to production of the pro-inflammatory cytokine, tumour necrosis factor alpha (TNF-alpha). Previous studies have suggested that pathogenic Yersinia spp. inhibit LPS-mediated production of TNF-alpha in macrophages, and that one of the Yop proteins secreted by the plasmid-encoded type III pathway is required for this activity. We found that TNF-alpha production was inhibited when J774A.1 murine macrophages were infected with wild-type Y. pseudotuberculosis but not with an isogenic ysc mutant defective for Yop secretion. We inactivated multiple yop genes to identify which of these factors are required for the inhibition of TNF-alpha production. A mutant unable to express yopJ was defective for the inhibition of TNF-alpha production. Production of TNF-alpha is regulated at the transcriptional and translational levels by several mitogen-activated protein (MAP) kinases. The MAP kinases p38 and JNK underwent sustained activation in macrophages infected with the yopJ mutant. Conversely, p38 and JNK were downregulated in macrophages infected with the wild-type strain. The ability of the yopJ mutant to downregulate p38 and JNK and to inhibit production of TNF-alpha was restored by the expression of yopJ+ in trans. Therefore, YopJ is required for Y. pseudotuberculosis to downregulate MAP kinases and inhibit the production of TNF-alpha in macrophages.

Animals↗

The haemolysin-secreting ShlB protein of the outer membrane of Serratia marcescens: determination of surface-exposed residues and formation of ion-permeable pores by ShlB mutants in artificial lipid bilayer membranes.

The ShlB protein in the outer membrane of Serratia marcescens is the only protein known to be involved in secretion of the ShlA protein across the outer membrane. At the same time, ShlB converts ShlA into a haemolytic and a cytolytic toxin. Surface-exposed residues of ShlB were determined by reaction of an M2 monoclonal antibody with the M2 epitope DYKDDDDK inserted at 25 sites along the entire ShlB polypeptide. The antibody bound to the M2 epitope at 17 sites in intact cells, which indicated surface exposure of the epitope, and to 23 sites in isolated outer membranes. Two insertion mutants contained no ShlB(M2) protein in the outer membrane. The ShlB derivatives activated and/or secreted ShlA. To gain insights into the secretion mechanism, we studied whether highly purified ShlB and ShlB deletion derivatives formed pores in artificial lipid bilayer membranes. Wild-type ShlB formed channels with very low single channel conductance that rarely assumed an open channel configuration. In contrast, open channels with a considerably higher single channel conductance were observed with the deletion mutants ShlB(Delta65-186), ShlB(Delta87-153), and ShlB(Delta126-200). ShlB(Delta126-200) frequently formed permanently open channels, whereas the conductance caused by ShlB(Delta65-186) and ShlB(Delta87-153) did not assume a stationary value, but fluctuated rapidly between open and closed configurations. The results demonstrate the orientation of large portions of ShlB in the outer membrane and suggest that ShlB may function as a specialized pore through which ShlA is secreted.

Amino Acid Sequence↗

The axr4 auxin-resistant mutants of Arabidopsis thaliana define a gene important for root gravitropism and lateral root initiation.

To understand the molecular mechanism of auxin action, mutants of Arabidopsis thaliana with altered responses to auxin have been identified and characterized. Here the isolation of two auxin-resistant mutants that define a new locus involved in auxin response, named AXR4, is reported. The axr4 mutations are recessive and map near the ch1 mutation on chromosome 1. Mutant plants are specifically resistant to auxin and defective in root gravitropism. Double mutants between axr4 and the recessive auxin-resistant mutants axr1-3 and aux1-7 were characterized to ascertain possible genetic interactions between the mutations. The roots of the axr4 axr1-3 double mutant plants are less sensitive to auxin, respond more slowly to gravity, and form fewer lateral roots than either parental single mutant. These results suggest that the two mutations have additive or even synergistic effects. The AXR1 and AXR4 gene products may therefore act in separate pathways of auxin response or perhaps perform partially redundant functions in a single pathway. The axr4 aux1-7 double mutant has the same sensitivity to auxin as the aux1-7 mutant but forms far fewer lateral roots than either parental single mutant. The aux1-7 mutation thus appears to be epistatic to axr4 with respect to auxin-resistant root elongation, whereas in lateral root formation, the effects of the two mutations are additive. The complexity of the genetic interactions indicated by these results may reflect differences in the mechanism of auxin action during root elongation and the formation of lateral roots. The AXR4 gene product, along with those of the AXR1 and AUX1 genes, is important for normal auxin sensitivity, gravitropic response in roots and lateral root formation.

Arabidopsis↗

An implantable two channel drop foot stimulator: initial clinical results.

This article reports preliminary results of pilot studies of a new implantable two channel drop foot stimulator. The stimulator consists of an externally worn transmitter inductively coupled to an implanted receiver unit located in the lower leg, lateral and distal to the knee. The receiver is connected to electrodes located under the epineurium of the deep and the superficial peroneal nerves. Stimulation is triggered by detection of heel lift and terminated at heel strike in a manner similar to surface mounted systems. The location of the electrodes allows for a degree of selectivity over the resultant moment about the ankle joint that is not possible with surface stimulation of the common peroneal nerve. The two subjects used the stimulator on a regular basis and showed increases in walking speed of between 10% and 44% when compared to their baseline measurements. Isometric tests have demonstrated that the stimulator allows selective and repeatable stimulation of ankle joint muscles.

Electric Stimulation Therapy↗

Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: a multicenter study.

OBJECTIVE: To evaluate an implanted neuroprosthesis that allows tetraplegic users to control grasp and release in 1 hand. DESIGN: Multicenter cohort trial with at least 3 years of follow-up. Function for each participant was compared before and after implantation, and with and without the neuroprosthesis activated. SETTING: Tertiary spinal cord injury (SCI) care centers, 8 in the United States, 1 in the United Kingdom, and 1 in Australia. PARTICIPANTS: Fifty-one tetraplegic adults with C5 or C6 SCIs. INTERVENTION: An implanted neuroprosthetic system, in which electric stimulation of the grasping muscles of 1 arm are controlled by using contralateral shoulder movements, and concurrent tendon transfer surgery. Assessed participants' ability to grasp, move, and release standardized objects; degree of assistance required to perform activities of daily living (ADLs), device usage; and user satisfaction. MAIN OUTCOME MEASURES: Pinch force; grasp and release tests; ADL abilities test and ADL assessment test; and user satisfaction survey. RESULTS: Pinch force was significantly greater with the neuroprosthesis in all available 50 participants, and grasp-release abilities were improved in 49. All tested participants (49/49) were more independent in performing ADLs with the neuroprosthesis than they were without it. Home use of the device for regular function and exercise was reported by over 90% of the participants, and satisfaction with the neuroprosthesis was high. CONCLUSIONS: The grasping ability provided by the neuroprosthesis is substantial and lasting. The neuroprosthesis is safe, well accepted by users, and offers improved independence for a population without comparable alternatives.

Adult↗

Dimensionality and clinical importance of pain and disability in hand osteoarthritis: Development of the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index.

OBJECTIVE: To develop a reliable, valid, and responsive self-administered questionnaire to probe pain, stiffness and physical disability in patients with osteoarthritis (OA) of the hand. DESIGN: In order to assess the dimensionality of the symptomatology of hand OA, a self-administered questionnaire was developed to probe various aspects of pain (10 items), stiffness (two items), and physical function (83 items). The question inventory was generated from eight existing health status measures and an interactive process involving four rheumatologists, two physiotherapists, and an orthopaedic surgeon. RESULTS: Face-to-face interviews were conducted with 50 OA hand patients; 39 females and 11 males with mean age 62.8 years and mean disease duration 9.4 years. Items retained were those which fulfilled specified selection criteria: prevalence > or =60% and mean importance score approximating or exceeding 2.0 Item exclusion criteria included low prevalence, gender-based, ambiguous, duplicates or similarities, alternatives, composite items, and items that were too restrictive. This process resulted in five pain, one stiffness and nine function items which have been proposed for incorporation in the AUSCAN Index. CONCLUSIONS: Using a traditional development strategy, we have constructed a self-administered multi-dimensional outcome measure for assessing hand OA. The next stage includes reliability, validity and responsiveness testing of the 15-item questionnaire.

Activities of Daily Living↗

Clinimetric properties of the AUSCAN Osteoarthritis Hand Index: an evaluation of reliability, validity and responsiveness.

OBJECTIVE: To assess the reliability, validity and responsiveness of the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index in both Likert (LK) and Visual Analogue (VA)-scaled formats. METHODS: Two separate studies were conducted; the first addressing reliability and validity issues and the second addressing index responsiveness. In a group of 50 patients with osteoarthritis (OA) of the hand, test-retest reliability was assessed at a 1-week interval and internal consistency from single administrations of the Index. Construct validity was evaluated against several other outcome measures including the Functional Index for Hand Osteoarthritis (FIHOA), separate patient and physician global assessments, Doyle Index, grip strength, pinch grip, and Health Assessment Questionnaire. A 6-week washout retreatment design was used in a group of 44 OA hand patients to assess index responsiveness and comparative responsiveness against the FIHOA. RESULTS: Reliability and construct validity coefficients confirm the reliability and construct validity of both the AUSCAN LK3.0 and AUSCAN VA3.0 Indices. The washout retreatment study establishes index responsiveness and suggests that the AUSCAN LK3.0 and AUSCAN VA3.0 Indices may be more responsive than the FIHOA. CONCLUSIONS: The patient self-completed AUSCAN LK3.0 and AUSCAN VA3.0 Indices are reliable, valid and responsive and can be recommended as primary outcome measures for future hand OA clinical trials.

Adult↗

The relationship of resiliency to decision making and risk behaviors of cancer-surviving adolescents.

Adolescents with a history of cancer frequently engage in risk behaviors. The purpose of this correlational study was to explore factors that affect decision making and risk behaviors (smoking, alcohol use, and illicit drug use) of cancer-surviving adolescents. A sample of 52 teen survivors participated at two cancer centers. In addition to a medical record review and IQ testing, several psychosocial measures were administered in a semistructured interview with the teen survivor. Three antecedent factors (cognitive function, resiliency, and role modeling of risk behaviors by parents and peers) were examined in a hierarchical regression model to predict decision making. These same factors, with an additional mediating variable (decision making), were examined in a hierarchical logistic regression model to predict risk behaviors in teen survivors. In the decision-making model, adjusted for demographic covariates, resiliency was a marginally significant predictor of decision making. As non-resiliency increases, quality of decision making may decrease for teen survivors. In the model to predict risk behaviors, four factors (cognitive function, resiliency, role modeling, and decision making) were added to the basic model, controlling for the same covariates. Resiliency and decision making were highly significant predictors of one or more risk behaviors. Non-resilient teen survivors with poor-quality decision making are more likely to engage in risk behaviors of substance use and need intervention that is aimed at improving decision-making skills to reduce these behaviors.

Adolescent↗

Transitional care for young adult survivors of childhood cancer.

OBJECTIVES: To review the obstacles and barriers to providing optimal care to young adult cancer survivors and discuss the transition from pediatric to adult health care system. DATA SOURCES: Published articles and textbook chapters. CONCLUSIONS: More than 70% of children diagnosed with cancer between birth and 14 years of age will be cured of their primary disease. Because of multiple physical and psychosocial risk factors imposed by their therapy and previous disease, childhood cancer survivors require life-long care. IMPLICATIONS FOR NURSING PRACTICE: Health care providers must be aware of the unique needs of these individuals for life-long follow-up and assist in facilitating this transition process.

Adolescent↗

Laurin-Sandrow syndrome--a surgical challenge.

We describe the sixth reported case of Laurin-Sandrow syndrome. This spectrum of congenital abnormalities includes complex syndactyly, often associated with ulnar duplication, mirror feet and columella deformities. We discuss Laurin-Sandrow syndrome and report on its surgical management.

Clubfoot↗

Choices and information offered to patients undergoing immediate post-mastectomy breast reconstruction: a survey of patient opinion and self-assessed outcome.

For those patients who request breast reconstruction after mastectomy, the immediate procedure is becoming increasingly common. Whilst this option results in resource cost savings, and may have benefits for patients, little is known about the information offered to patients who are faced with a mastectomy/reconstruction decision. To investigate these concerns, and also to determine patients' own assessment of their outcome after immediate reconstruction, we carried out a retrospective survey of all patients who underwent an immediate breast reconstruction at this Centre over a 3-year period, utilizing a detailed study-specific questionnaire, together with two widely used health status instruments. The response rate was 92% (57 patients). Nearly all patients were found to have been offered the choice of a delayed procedure, should they wish it, but information about type and choice of prosthesis was considered by patients to be inadequate. Steps to address this have been implemented. Scores from the SF-36 Health Survey Questionnaire showed that this patient group was comparable with a normal female population for the dimensions of physical function, mental health, energy, and general health. However, social function was found to be significantly lower, and a substantial minority (46%) exhibited some anxiety as assessed by the Hospital Anxiety and Depression (HAD) Scale.

Journal Article↗

Restoration of tetraplegic hand function by use of the neurocontrol freehand system.

Nine tetraplegic patients with C5 or C6 level spinal cord lesions had the Freehand System, an eight channel Functional Electrical Stimulation device, implanted to allow of hand opening and grasp. This paper describes the surgical implementation of the system and the challenges encountered. Seven of the subjects are currently daily users of the device. One subject is unable to use the system due to disruption of bowel function when the system is used. A second subject suffered a lesion of the posterior interosseous nerve, but this was not thought to be related to system use. Additionally, one subject exhibited symptoms of autonomic dysreflexia, which were alleviated by reduction of the strength of the stimulus. Despite such problems, the Freehand system can significantly improve the functional ability of C5 and C6 lesion tetraplegics.

Activities of Daily Living↗

[Current status of the rehabilitation of post-mastectomy women in the Federal Republic of Germany].

The effectiveness of rehabilitation measures in acute in-patient clinics was assessed by questioning 220 women who had had a mastectomy. As criteria were used: function of the shoulder-arm region on the operated side; prevention of oedema and infection on the operated side; emotional support; supply of an external breast prosthesis. The results indicate that rehabilitation measures need to be improved. Deficiencies in counselling and supervision were noted with regard to oedema and infection prevention in 71%, emotional support in 69%, and supply of a prosthesis in 56%. The interviews also revealed that rehabilitation depended primarily on personal engagement of the medical personnel, less on the size and type of clinic. Increasing importance is ascribed to subsequent (long-term) medical care and supervision, as is provided in the FRG under insurance regulations.

Activities of Daily Living↗