Biomedical subjects

K Karjalainen

Publications and source records attributed to K Karjalainen.

At least 19 recordsLinked to original sources

PubMed2002

Multidisciplinary bio-psycho-social rehabilitation for chronic low back pain.

BACKGROUND: Chronic low back pain is, in many countries, the main cause of long term disability in middle age. Patients with chronic low back pain are often referred for multidisciplinary treatment. Previous published systematic reviews on this topic included no randomised controlled trials and pooled together controlled and non-controlled studies. OBJECTIVES: To assess the effect of multidisciplinary bio-psycho-social rehabilitation on pain, function, employment, quality of life and global assessment outcomes in subjects with chronic disabling low back pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsychLIT, CINAHL, Health STAR, and The Cochrane Library from the beginning of the database to June 1998 using the comprehensive search strategy recommended by the Back Review Group of the Cochrane Collaboration. INTERVENTION specific key words for this review were: patient care team, patient care management, multidisciplinary, interdisciplinary, multiprofessional, multimodal, pain clinic and functional restoration. We also reviewed reference lists and consulted the editors of the Back Review Group of the Cochrane Collaboration. SELECTION CRITERIA DESIGN: randomised controlled trials comparing multidisciplinary bio-psycho-social rehabilitation with a non-multidisciplinary control intervention. POPULATION: Adults with disabling low back pain of more than three months in duration. INTERVENTION: Patients had to be assessed and treated by qualified professionals according to a plan that addresses physical and at least one of psychological, or social/occupational dimensions. OUTCOMES: Only trials which reported treatment effect in at least one of pain, function, employment status, quality of life or global improvement. Exclusion: Pure educational interventions (back schools) and pure physical interventions were excluded. DATA COLLECTION AND ANALYSIS: Selection, data extraction and quality grading of studies was done by two independent reviewers using pre-tested data forms. Study quality was assessed according to the scheme recommended by the Back Review Group of the Cochrane Collaboration. Trials with internal validity scores of five or more in a ten point scale were considered high quality. Discrepancies between reviewers were resolved by consensus or by a third reviewer. Given the marked heterogeneity in study settings, interventions and control groups we decided not to pool trial results in a meta-analysis. Instead, we summarized findings by strength of evidence and nature of intervention and control treatments. The evidence was judged to be strong when multiple high quality trials produced generally consistent findings. It was judged to be moderate when multiple low quality or one high quality and one or more low quality trials produced generally consistent findings. Evidence was considered to be limited when only one randomised trial existed or if findings of existing trials were inconsistent. MAIN RESULTS: Ten trials (12 randomised comparisons) were included. They randomised a total of 1964 patients with chronic low back pain. There was strong evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary bio-psycho-social intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psycho-physical treatments did not improve pain, function or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. REVIEWER'S CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improves pain and function. Less intensive interventions did not show improvements in clinically relevant outcomes.

Back Pain↗

PubMed2001

A response calculus for immobilized T cell receptor ligands.

To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affinity determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated the importance of receptor cross-linking density in determining TCR signaling. Moreover, it was found that the functional two-dimensional affinity of TCR ligands was affected by the chemical composition of the ligand-presenting surface. This makes it possible that cell-bound TCR ligands, despite their low affinity in solution, are of optimal two-dimensional affinity thereby allowing effective TCR binding under physiological conditions, i.e. at low ligand densities in cellular interfaces.

Antibodies↗

PubMed2001

Multidisciplinary rehabilitation for chronic low back pain: systematic review.

OBJECTIVE: To assess the effect of multidisciplinary biopsychosocial rehabilitation on clinically relevant outcomes in patients with chronic low back pain. DESIGN: Systematic literature review of randomised controlled trials. PARTICIPANTS: A total of 1964 patients with disabling low back pain for more than three months. MAIN OUTCOME MEASURES: Pain, function, employment, quality of life, and global assessments. RESULTS: Ten trials reported on a total of 12 randomised comparisons of multidisciplinary treatment and a control condition. There was strong evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration improves function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary biopsychosocial intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psychophysical treatments did not improve pain, function, or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain and improves function in patients with chronic low back pain. Less intensive interventions did not show improvements in clinically relevant outcomes.

Chronic Disease↗

PubMed2001

In vivo-matured Langerhans cells continue to take up and process native proteins unlike in vitro-matured counterparts.

We have been able to identify the cell subset derived from Langerhans cells in the total dendritic cell population of the peripheral lymph node and hence to follow their trafficking under normal physiological conditions as well as upon skin irritation. As expected, the rapid mobilization of Langerhans cells triggered by inflammatory signals into the draining lymph node correlated with an up-regulation of costimulatory molecules and with an enhanced immunostimulatory capacity. Surprisingly, however, these cells, instead of shutting down, maintain the capacity to capture and process protein Ags during the couple of days they stay alive in stark contrast to in vitro-matured dendritic cells.

Animals↗

PubMed2001

Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens.

Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3 (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands. Comparable studies using anti-TCR antibodies of known affinity confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength.

Animals↗

PubMed2001

Multidisciplinary biopsychosocial rehabilitation for subacute low back pain in working-age adults: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

STUDY DESIGN: A systematic review of randomized controlled trials was performed. OBJECTIVE: To evaluate the effectiveness of multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working-age adults. SUMMARY OF BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for patients with chronic low back pain. The multidisciplinary biopsychosocial approach for prolonged low back pain could be considered to prevent chronicity. Work site visits and a close relationship with occupational health care might produce results in terms of patients working ability. METHODS: Reviewed randomized controlled trials as well as controlled trials were identified from electronic bibliographic databases, reference checking, and consultation with experts in the rehabilitation field. Four blinded reviewers selected the trials. Two rehabilitation specialists evaluated the clinical relevance. Two other blinded reviewers extracted the data and assessed the main results along with the methodologic quality of the studies. A qualitative analysis was performed to evaluate the level evidence. RESULTS: Of 1808 references, only 2 relevant studies were included. Both were considered to be methodologically low-quality randomized controlled trials. The clinical relevance of the studies was sufficient. The level of scientific evidence was moderate, showing that multidisciplinary rehabilitation involving work site visit or more comprehensive occupational health care intervention helps patients return to work faster, makes sick leaves less, and alleviates subjective disability. CONCLUSIONS: There is moderate evidence showing that multidisciplinary rehabilitation for subacute low back pain is effective, and that work site visit increases the effectiveness, but because the analyzed studies had some methodologic shortcomings, an obvious need still exists for high-quality trials in this field.

Humans↗

PubMed2001

Multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVES: To evaluate the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults. SUMMARY OF BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs for neck and shoulder pain require substantial staff and financial resources. They are widely used, despite questionable evidence of their effectiveness. METHODS: The reviewed randomized controlled and controlled trials appraising the effectiveness of biopsychosocial rehabilitation for working age patients with neck and shoulder pain were identified by searching electronic bibliographic databases, checking references, and consulting experts in the rehabilitation field. Four blinded reviewers selected the trials. Two specialists on rehabilitation evaluated the clinical relevance. Two other blinded reviewers extracted the data and assessed the main results and the methodologic quality of the studies. A qualitative analysis was performed to evaluate the level of scientific evidence. RESULTS: After 1808 abstracts and the references of 65 reviews were screened, only two relevant studies were found that satisfied the criteria. One of these was considered a methodologically low-quality randomized controlled trial, and the other was a methodologically low-quality controlled clinical trial. The clinical relevance of included studies was satisfactory. The level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain was limited. CONCLUSIONS: There appears to be little scientific evidence for the effectiveness on neck and shoulder pain of multidisciplinary biopsychosocial rehabilitation compared with other rehabilitation methods. There is an urgent need for high-quality trials in this field.

Adult↗

PubMed2001

TARPP, a novel protein that accompanies TCR gene rearrangement and thymocyte education.

Studies on thymic T cell development have usually concentrated on cell surface molecules. However, intracellular proteins expressed only in thymocytes have never been described. Here we report the discovery of a novel thymocyte-specific protein, named TARPP, which represents a high molecular mass ( approximately 100 kDa) variant of the previously identified protein ARPP-21 ( approximately 21 kDa). TARPP is a cytosolic protein that is expressed at high levels in immature thymocytes. It appears concomitant with the commitment to T cell lineage, and its expression is switched off as a consequence of TCR engagement during positive selection. Such an expression pattern, correlating with the rearrangement of the TCR genes and thymocyte education, suggests a role for TARPP during this important phase of thymocyte development.

Aging↗

PubMed2000

Anatomical origin of dendritic cells determines their life span in peripheral lymph nodes.

Dendritic cells (DCs) exhibit considerable heterogeneity in their anatomical location, surface phenotype, and functional properties. In this study, we demonstrate that peripheral lymph nodes contain at least four major, functionally separable, and independently derived, DC subsets, which can be clearly demarcated by their CD11c, CD40, and CD8 expression pattern. Surprisingly, all DCs derived directly from the bone marrow, the myeloid- and the lymphoid-related subsets, turned over fast with t(1/2) of a couple of days. In contrast, DCs exported from the skin, both dermal and epidermal, accumulated 3- to 4-fold slower, turnover that is dramatically increased by cutaneous inflammation.

Administration, Cutaneous↗

PubMed2000

Multidisciplinary rehabilitation for fibromyalgia and musculoskeletal pain in working age adults.

BACKGROUND: Non-malignant musculoskeletal pain is an increasing problem in western countries. Fibromyalgia syndrome is an increasing recognised chronic musculoskeletal disorder. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for fibromyalgia and widespread musculoskeletal pain among working age adults. SEARCH STRATEGY: An electronic search was conducted and included Medline from 1966, PsycLIT from 1967 and EMBASE from 1980 to April 1998. The Cochrane Musculoskeletal Group Trials Register was searched as well as, the Cochrane Controlled Trials Register (CCTR). The references of identified articles and reviews were checked, studies published in the Finnish medical database Medic from 1978 to 1998 screened and the Science Citation Index searched. Content experts were also contacted for additional or unpublished studies. SELECTION CRITERIA: From all references found in our original search, we selected all randomized controlled trials (RCTs) and clinical controlled trials (CCTs). Trials had to assess the effectiveness of multidisciplinary rehabilitation for patients suffering from fibromyalgia and widespread musculoskeletal pain among working age adults. The rehabilitation program was required to be multidisciplinary; that is, it had to consist of a physician's consultation, plus a psychological, social or vocational intervention, or a combination of both. DATA COLLECTION AND ANALYSIS: Four reviewers independently selected the RCTs and CCTs that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the relevance and applicability of the findings of the selected studies to actual clinical use. Two other reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only seven relevant studies (1050 patients) that met our inclusion criteria. None of these were considered, methodologically, a high quality randomized controlled trial. Four of the included RCTs on fibromyalgia were graded low quality and suggest no quantifiable benefits. The three included RCTs on widespread musculoskeletal pain showed that based on limited evidence, overall, no evidence of efficacy was observed. However, behavioral treatment and stress management appear to be important components. Education combined with physical training showed some positive effects in long term follow up. REVIEWER'S CONCLUSIONS: We conclude that there appears to be little scientific evidence for the effectiveness of multidisciplinary rehabilitation for these musculoskeletal disorders. However, multidisciplinary rehabilitation is a commonly used intervention for chronic musculoskeletal disorders, which cause much personal suffering and substantial economic loss to the society. There is a need for high quality trials in this field.

Adult↗

PubMed2000

Multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working age adults.

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for chronic low back pain patients. The biopsychosocial approach for low back pain could also be considered to prevent chronicity by carrying out the rehabilitation if the acute pain is prolonged. Nevertheless multidisciplinary treatment programmes are often laborious and long processes and require good collaboration between the patient, the rehabilitation team and the work place. By workplace visits and close relationship with occupational health care one might expect results in terms of patients working ability. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for subacute low back pain among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on subacute low back pain were separated afterwards. SELECTION CRITERIA: From all references found in our original search we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of multidisciplinary rehabilitation for working age patients suffering from subacute low back pain (more than 4 weeks but less than 3 months). The rehabilitation program was required to be multidisciplinary, i.e.; it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the randomized controlled trials and controlled trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only 2 relevant studies that satisfied our criteria on subacute low back pain. They were both considered to be methodologically low quality randomized controlled trials. The clinical relevance of included studies was sufficient. The level of scientific evidence for the effectiveness of multidisciplinary rehabilitation was moderate on subacute low back pain showing that multidisciplinary rehabilitation which includes workplace visit or more comprehensive occupational health care intervention helps patients to return to work faster, makes sick leaves less and alleviates subjective disability. REVIEWER'S CONCLUSIONS: We conclude that there is moderate evidence of positive effectiveness of multidisciplinary rehabilitation for subacute low back pain and workplace visit increases the effectiveness. But because this evidence is based on the trials that had some methodological shortcomings and several expensive multidisciplinary rehabilitation programmes are commonly used for common subacute low back problems, there is an obvious need for high quality trials in this field.

Acute Disease↗

PubMed2000

Multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults.

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs for neck and shoulder pain require substantial staff and financial resources. Despite questionable scientific evidence of their effectiveness, they are widely used. Neck and shoulder complaints are common among working age adults and they are often associated with physical work load and stress. Pain in the neck and shoulder area cause biopsychosocial difficulties for the patient especially if disability due to pain is prolonged. To help patients with biopsychosocial problems or to prevent their development, multidisciplinary biopsychosocial programs are applied on rehabilitation for neck and shoulder pain patients. Nevertheless multidisciplinary treatment programmes are often laborious and rather long processes and require good collaboration between the patient, the rehabilitation team and the work place. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on neck and shoulder pain were separated afterwards. SELECTION CRITERIA: From all references found in our original search we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of biopsychosocial rehabilitation for patients suffering from neck and shoulder pain among working age adults. The rehabilitation program was required to be multidisciplinary, i.e.; it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the randomized controlled trials and controlled trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only 2 relevant studies that satisfied our criteria. One of these was considered methodologically low quality randomized controlled trial and the other one was a methodologically low quality controlled clinical trial. The clinical relevance of included studies was satisfactory. The level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation was limited for neck and shoulder pain. REVIEWER'S CONCLUSIONS: We conclude that there appears to be little scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation compared with other rehabilitation facilities on neck and shoulder pain. Multidisciplinary rehabilitation is a commonly used intervention for chronic neck and shoulder complaints, therefore we see an urgent need for high quality trials in this field.

Adult↗

PubMed2000

Biopsychosocial rehabilitation for upper limb repetitive strain injuries in working age adults.

BACKGROUND: Upper limb repetitive strain injury is a common problem in western countries, causing human suffering and huge economical losses. Patients with prolonged pain associated with repetitive tasks in the work place can face both psychological and physical difficulties. Different treatment programmes, physical, psychological, behavioural, social and occupational treatments have been developed and used to help these patients. OBJECTIVES: The objective of this systematic review is to determine the effectiveness of biopsychosocial rehabilitation for upper limb repetitive strain injuries among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for a more broad area of musculoskeletal disorders. Trials on repetitive strain injuries were separated afterwards. SELECTION CRITERIA: Randomised controlled trials and controlled trials comparing biopsychosocial measures for the treatment of repetitive upper limb strain injury in working age adults DATA COLLECTION AND ANALYSIS: Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of biopsychosocial rehabilitation. MAIN RESULTS: We found only two relevant studies that satisfied our criteria. They assessed the effectiveness of two specific interventions and were both considered as low quality trials. The clinical relevance of the included studies was also unsatisfactory. The level of scientific evidence for the effectiveness of biopsychosocial rehabilitation for repetitive strain injuries was limited. One small trial found that hypnosis supplementary to comprehensive treatment can decrease the intensity of pain for acute RSI in six weeks follow-up. REVIEWER'S CONCLUSIONS: We conclude that presently there appears to be little scientific evidence for the effectiveness of biopsychosocial rehabilitation on repetitive strain injuries. As RCTs on more intensive and comprehensive biopsychosocial treatment programmes for RSI are lacking, there does not seem to be reliable data for these interventions. There is a need for high quality trials in this field.

Adult↗

PubMed2000

Alveolar bone loss in type 1 diabetic subjects.

UNLABELLED: AIM, BACKGROUND: The aim of this study was to assess the degree of marginal alveolar bone loss in a group of young subjects with type 1 diabetes mellitus (DM) (n=35, age range 24-36 years) and age-matched non-diabetic control subjects (n=10). METHOD: The diabetic group was divided into 3 subgroups (D1, D2, D3) according to the severity of the diabetic state. The level of alveolar bone was measured on panoramic radiographs of maxillary and mandibular molars as the % of the distance between the cemento-enamel junction (CEJ) and the bone crest along the total length of the root. All mesial and distal sites with a distance of > 15% (BL>15%) were picked, and calculations were performed using the individual %s of sites with BL> 15%. RESULTS: Based on the present findings, we conclude that type 1 DM has a modifying effect on marginal loss of alveolar bone. A clear trend towards increased marginal bone loss was seen in the subjects with complicated DM (D3). The subjects with good metabolic control and no complications of DM (D1) are no more susceptible to marginal bone loss than non-diabetic controls of the same age. CONCLUSIONS: The present findings confirm our previous results on increased loss of periodontal support in subjects with complicated DM already at an early age.

Adult↗

PubMed1999

Impaired NK1.1 T cell development in mice transgenic for a T cell receptor beta chain lacking the large, solvent-exposed cbeta FG loop.

A striking feature of the T cell receptor (TCR) beta chain structure is the large FG loop that protrudes freely into the solvent on the external face of the Cbeta domain. We have already shown that a transgene-encoded Vbeta8.2(+) TCR beta chain lacking the complete Cbeta FG loop supports normal development and function of conventional alpha/beta T cells. Thus, the FG loop is not absolutely necessary for TCR signaling. However, further analysis has revealed that a small population of alpha/beta T cells coexpressing NK1.1 are severely depleted in these transgenic mice. The few remaining NK1.1 T cells have a normal phenotype but express very low levels of TCR. We find that the TCR Vbeta8.2(+) chain lacking the Cbeta FG loop cannot pair efficiently with the invariant Valpha14-Jalpha281 TCR alpha chain commonly expressed by this T cell family. Consequently, fewer NK1.1 T cells develop in these mice. Our results suggest that expression of the Valpha14(+) TCR alpha chain is particularly sensitive to TCR-beta conformation. Development of NK1.1 T cells appears to need a TCR-beta conformation dependent on the presence of the Cbeta loop that is not necessarily required for assembly and function of TCRs on most alpha/beta T cells.

Animals↗

PubMed1999

T cell receptor beta chain lacking the large solvent-exposed Cbeta FG loop supports normal alpha/beta T cell development and function in transgenic mice.

The striking and unique structural feature of the T cell receptor (TCR) beta chain is the bulky solvent-exposed FG loop on the Cbeta domain, the size of almost half an immunoglobulin domain. The location and size of this loop suggested immediately that it could be a crucial structural link between the invariant CD3 subunits and antigen-recognizing alpha/beta chains during TCR signaling. However, functional analysis does not support the above notion, since transgene coding for TCR beta chain lacking the complete FG loop supports normal alpha/beta T cell development and function.

Animals↗

PubMed1999

Role of the T cell receptor alpha chain in stabilizing TCR-superantigen-MHC class II complexes.

Superantigens (SAGs) activate T cells by simultaneously binding the Vbeta domain of the TCR and MHC class II molecules on antigen-presenting cells. The preferential expression of certain Valpha regions among SAG-reactive T cells has suggested that the TCR alpha chain may modulate the level of activation through an interaction with MHC. We demonstrate that the TCR alpha chain is required for maximum stabilization of the TCR-SAG-MHC complex and that the alpha chain increases the half-life of the complex to match those of TCR-peptide/MHC complexes. The site on the TCR alpha chain responsible for these effects is CDR2. Thus, the overall stability of the TCR-SAG-MHC complex is determined by the combination of three distinct interactions: TCR-SAG, SAG-MHC, and MHC-TCR.

Amino Acid Substitution↗

PubMed1999

Transient neurological symptoms after spinal anaesthesia with hyperbaric 5% lidocaine or general anaesthesia.

Transient neurotoxicity of concentrated local anaesthetics has been thought to be the main reason for transient neurological symptoms after spinal anaesthesia. Profound musculoligamental relaxation by high doses of local anaesthetics may contribute to the development of postoperative musculoskeletal pain. In order to evaluate the role of the loss of strength of the supportive structures of the spine in the development of transient neurological symptoms, 60 patients (ASA I-II) undergoing minor orthopaedic, varicose vein or inguinal hernia operations were allocated randomly to receive spinal anaesthesia with hyperbaric lidocaine 50 mg ml-1 (85-100 mg) or balanced general anaesthesia with neuromuscular block. Patients were interviewed 24 h later and after 1 week they returned a written questionnaire. Transient neurological symptoms, consisting of pain in the buttocks or pain radiating symmetrically to the lower extremities, occurred in eight patients (27%) receiving spinal anaesthesia and in one patient (3%) receiving general anaesthesia (P < 0.05). We conclude that a transient neurotoxic effect of hyperbaric lidocaine 50 mg ml-1 is probably the main reason for transient neurological symptoms after spinal anaesthesia but musculoligamental relaxation may contribute to the development of low back or leg pain after both anaesthetic techniques.

Adult↗