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Biomedical subjects

A Peretz

Publications and source records attributed to A Peretz.

At least 19 recordsLinked to original sources
PubMed2005

The neural correlates of understanding the other's distress: a positron emission tomography investigation of accurate empathy.

The purpose of the present study was to assess the relationship between brain metabolism and empathic response. Six right-handed healthy volunteers were scanned with PET and fluorodeoxyglucose twice: during an interview about neutral story themes and during an empathic response eliciting interview about a story of a character in distress. Metabolic values in the medial and superior frontal gyrus, occipitotemporal cortices, thalamus and the cerebellum were higher during empathic response than during the neutral theme interview. Furthermore, the subjects' empathy scores were positively correlated with metabolism in the medial aspects of the superior frontal gyrus. Our results suggest that empathy consists of both affective and cognitive components and hence may involve cortices that mediate simulation of emotional processing and mental state attribution.

Adult↗
PubMed2005

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study.

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.

Adult↗
PubMed2005

Long-term tolerability of tramadol LP, a new once-daily formulation, in patients with osteoarthritis or low back pain.

INTRODUCTION: Tramadol hydrochloride is a centrally acting analgesic, which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. An oral, once a day, sustained release formulation of tramadol is thought to be advantageous compared with immediate release preparations as it prevents plasma peaks associated with increased side-effects of the drug. It may also improve compliance. The purpose of the study was to assess the long-term safety of a new sustained-release formulation of tramadol (tramadol LP) in patients with knee or hip osteoarthritis and in patients with refractory low back pain. STUDY DESIGN: The design was a phase III, open, multicentre, international, tolerability study with tramadol LP at a dose titrated by the patient between 100 and 400 mg once daily, according to the intensity of pain. The treatment was administered for a continuous period of 4 weeks followed by an intermittent intake of 5 months in 204 patients. The safety criteria for evaluation were recording of adverse events, laboratory tests, electrocardiogram, radiography, global tolerability assessed by the patient and the investigators. RESULTS: Long-term use of tramadol LP was reasonably well tolerated. Most of the reported adverse events were expected and occurred within the first month of treatment. Roughly half of the patients (49%) reported adverse events, of which 66% were related to treatment. Gastrointestinal events (nausea and vomiting) were the most frequent. Serious adverse events were reported in 6.4% of patients, from which only two cases were related to treatment. There was no sign of tolerance development and the percentage of patients presenting withdrawal symptoms after the end of treatment was low (6%). CONCLUSION: Long-term treatment with tramadol LP once daily is generally safe in patients with osteoarthritis or refractory low back pain.

Acetaminophen↗
PubMed2004

Is the WKL1 gene associated with schizophrenia?

A missense mutation Leu309Met in the WKL1 (MLC1, KIAA0027) gene, mapped to 22q13.3, was reported to co-segregate with periodic catatonic schizophrenia (SCZ) in a single large German pedigree with seven affected individuals (Meyer et al. [2001: Mol Psychiatry 6:302-306]). This report raised the following questions that were dealt with in the present study: does the Leu309Met mutation have a role in SCZ, or only in catatonic SCZ? Does the mutation Leu309Met in the WKL1 gene, encoding a putative membrane protein, non-selective cation channel, have any effect on the channel activity? Is the WKL1 gene, which is expressed exclusively in brain, expressed differently in SCZ brains compared to controls? These questions were answered by screening the Leu309Met mutation in 117 Israeli Jewish patients with SCZ (55 Ashkenazi and 62 non-Ashkenazi Jews) and 176 matched controls. In search of differences in the level of WKL1 gene expression, postmortem dorsalateral prefrontal cortex of 16 schizophrenic patients and 15 controls was checked. We also measured the putative channel activity of normal WKL1 subcloned in pcDNA3 to determine the effect of the reported Leu309Met mutation. Our results argue against the involvement of WKL1 in SCZ susceptibility.

Adult↗
PubMed2002

Unusual localisation of chronic arthropathy in lumbar facet joints after parvovirus B19 infection.

Human parvovirus B19 infection may be responsible for acute and chronic arthropathy. We present the case of a woman, who developed a severe chronic parvovirus B19 infection with persistence of DNA parvovirus B19, which was detected in the serum by polymerase chain reaction (PCR). After intravenous immunoglobulin administration she noted a disappearance of the general symptoms and the virus became undetectable by PCR in the serum. However, 1 month later back pain appeared. Magnetic resonance imaging showed bilateral effusions of the apophyseal joints of the lumbar spine (L4-L5). Spine involvement is rarely described during acute or chronic parvovirus B19 infection. In this case it was not possible to determine whether the facet joint arthropathy was reactive or due to persistent articular infection, or induced by immunoglobulin therapy.

Adult↗
PubMed2001

Zinc supplementation increases bone alkaline phosphatase in healthy men.

Zinc takes part in the metabolism of bone as a constituent of the matrix and as an activator of several metallo-enzymes. Animal in vitro and in vivo studies strongly suggest that zinc supplementation could stimulate bone formation and inhibit bone resorption but data in humans remain rare. The biological effects of 50 mg zinc given orally as gluconate in 20 healthy male volunteers were investigated in a 12 weeks double-blind placebo-controlled randomized trial. To investigate bone turnover, total alkaline phosphatases activity (ALP), bone specific alkaline phosphatase activity (BAPE) and BAP mass (BAP-M) concentration were measured as parameters of bone formation while urine calcium and C-terminal collagen peptide were determined as parameters of bone resorption. Samples were obtained in fasting subjects at baseline and after 6 and 12 weeks. In zinc treated subjects, a significant increase was observed at least after 12 weeks in total ALP (p < 0.01), BAP-M (p < 0.05) and BAP-E (p < 0.02). These parameters did not significantly change in the placebo group. Urine zinc/creatinine ratio significantly increased after 6 (p < 0.03) and 12 weeks (p < 0.04) in the zinc-treated group and was significantly different from the placebo group (p < 0.002). There was no significant effect of zinc supplementation on parameters of bone resorption. In conclusion, zinc supplementation at supraphysiological doses increased parameters of bone formation in healthy men while parameters of bone resorption remained unchanged.

Adult↗
PubMed2001

Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial.

INTRODUCTION: Selenium is an essential trace element with antioxidant properties. Trials with selenium have been conducted in rheumatoid arthritis (RA) to correct impaired selenium status and increase defences against deleterious oxidant species. AIM OF THE STUDY: To investigate in a double blind multi-centric placebo-controlled study the effects of selenium supplementation in RA. METHODS: Fifty five patients with moderate RA received during 90 days either capsules containing selenium-enriched yeast (200 microg/d) or a placebo. RESULTS: The visual analog scale, the Ritchie index, the number of swollen and painful joints, and morning stiffness significantly decreased with time in both groups (p<0.001), but no difference between groups could be identified. When examining the quality of life a significant (p<0.01) improvement in arm movements and health feeling was evidenced in selenium-treated patients. CONCLUSION: Selenium treatment did not show clinical benefit on RA. Interestingly, the improval in both groups demonstrated a placebo effect of the intervention trial.

Adolescent↗
PubMed2001

[COX-2 inhibitor non-steroidal anti-inflammatory drugs, myth or reality?].

The discovery of two isoforms of cyclooxygenase, Cox-1 constitutive and Cox-2 inducible, has prompted the development of new molecules with high Cox-2 selectivity. These new NSAIDs belong to the coxib class and have theoretically a better digestive tolerability than classical NSAID have. In Belgium, rofecoxib ((Vioxx) and celecoxib (Celebrex) are commercialized. Rofecoxib is indicated in the symptomatic treatment of osteoarthritis (12.5 to 25 mg/d) and celecoxib is indicated in osteoarthritis (200 mg/d) and in rheumatoid arthritis (200 to 400 mg/d). Several studies have demonstrated their efficacy, similarly to classical NSAID as diclofenac (Voltaren), naproxen (Naprosyne), ibuprofen (Brufen) and their superiority compared to placebo. Their safety profile for gastrointestinal events is proven in patients without ulcer history compared to classical NSAID. However, the concomitant use of aspirin decreases the benefit as demonstrated for celecoxib at 400 mg/d but not investigated for rofecoxib. The selective inhibition of Cox-2 with no effect on Cox-1 favors cardiovascular events in patients at risk. Other side effects are similar to classical NSAID. Thus Cox-2 inhibitors NSAID are interesting molecules for their sparing gastrointestinal activity. They must be used with caution in patients with ulcer history, in the elderly and in patients requiring aspirin for cardiovascular prophylaxis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Diagnostic specificities and sensitivities of anti dsDNA, anti membrane DNA and anti nucleosomes autoantibodies.

The aim of this study is to evaluate, from 369 routine sera of SLE and control patients, the worth of anti double stranded nuclear DNA, anti nucleosomes autoantibodies and anti membrane DNA for the diagnosis of SLE. Cell membrane associated DNA (mDNA) has been described on B lymphocytes and monocytes, but not on T cells. Antibodies to mDNA were identified by an indirect immunofluorescence assay using a B cell line fixed but not permeabilised. At a 1:40 serum dilution, anti mDNA is almost associated with the diagnosis of systemic lupus erythematosus (SLE). Anti mDNA were shown to be different in specificity as compared with anti double stranded nuclear DNA. We compare its characteristics as diagnostic procedure to the conventional anti dsDNA antibody detection and to the recently introduced anti nucleosome antibody test documented as associated with SLE. It appears that the best sensitivity (0.65) and specificity (0.98) is given by the anti mDNA test.

Antibodies, Antinuclear↗
PubMed2000

Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization.

Previous studies have demonstrated the presence of apamin-sensitive, small-conductance Ca(2+)-activated K(+) currents in human leukemic Jurkat T cells. Using a combined cDNA and reverse transcriptase-polymerase chain reaction cloning strategy, we have isolated from Jurkat T cells a 2.5-kilobase cDNA, hSK2, encoding the human isoform of SK2 channels. Northern blot analysis reveals the presence of a 2.5-kilobase hSK2 transcript in Jurkat T cells. While present in various human tissues, including brain, heart, skeletal muscle, kidney, and liver, no hSK2 mRNA could be detected in resting and activated normal human T cells. The hSK2 gene is encoded by 8 exons and could be assigned to chromosome 5 (q21.2-q22.1). The protein encoded by hSK2 is 579 amino acids long and exhibits 97% identity with its rat counterpart rSK2. When expressed in Chinese hamster ovary cells, hSK2 produces Ca(2+)-activated K(+) currents with a unitary conductance of 9.5 pS and a K(0.5) for calcium of 0.7 microm; hSK2 currents are inhibited by apamin, scyllatoxin, and d-tubocurarine. Overexpression of the Src family tyrosine kinase p56(lck) in Jurkat cells, up-regulates SK2 currents by 3-fold. While IKCa channels are transcriptionally induced upon activation of normal human T cells, our results show that in Jurkat cells SK2 channels are constitutively expressed and down-regulated following mitogenic stimulation.

Amino Acid Sequence↗
PubMed2000

Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon.

Protein tyrosine phosphatase epsilon (PTP epsilon) is strongly expressed in the nervous system; however, little is known about its physiological role. We report that mice lacking PTP epsilon exhibit hypomyelination of sciatic nerve axons at an early post-natal age. This occurs together with increased activity of delayed- rectifier, voltage-gated potassium (Kv) channels and with hyperphosphorylation of Kv1.5 and Kv2.1 Kv channel alpha-subunits in sciatic nerve tissue and in primary Schwann cells. PTP epsilon markedly reduces Kv1.5 or Kv2.1 current amplitudes in Xenopus oocytes. Kv2.1 associates with a substrate-trapping mutant of PTP epsilon, and PTP epsilon profoundly reduces Src- or Fyn-stimulated Kv2.1 currents and tyrosine phosphorylation in transfected HEK 293 cells. In all, PTP epsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects Schwann cell function during a critical period of Schwann cell growth and myelination.

Animals↗
PubMed2000

Extracellular K(+) and opening of voltage-gated potassium channels activate T cell integrin function: physical and functional association between Kv1.3 channels and beta1 integrins.

Elevated extracellular K(+) ([K(+)](o)), in the absence of "classical" immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell beta1 integrin moieties, and to induce integrin-mediated adhesion and migration. Gating of T cell voltage-gated K(+) channels (Kv1.3) appears to be the crucial "decision-making" step, through which various physiological factors, including elevated [K(+)](o) levels, affect the T cell beta1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1beta, the neuropeptide calcitonin gene-related peptide (CGRP), as well as elevated [K(+)](o) levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the beta1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K(+)](o)). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.

Cell Adhesion↗
PubMed2000

A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly.

The LQT1 locus (KCNQ1) has been correlated with the most common form of inherited long QT (LQT) syndrome. LQT patients suffer from syncopal episodes and high risk of sudden death. The KCNQ1 gene encodes KvLQT1 alpha-subunits, which together with auxiliary IsK (KCNE1, minK) subunits form IK(s) K(+) channels. Mutant KvLQT1 subunits may be associated either with an autosomal dominant form of inherited LQT, Romano-Ward syndrome, or an autosomal recessive form, Jervell and Lange-Nielsen syndrome (JLNS). We have identified a small domain between residues 589 and 620 in the KvLQT1 C-terminus, which may function as an assembly domain for KvLQT1 subunits. KvLQT1 C-termini do not assemble and KvLQT1 subunits do not express functional K(+) channels without this domain. We showed that a JLN deletion-insertion mutation at KvLQT1 residue 544 eliminates important parts of the C-terminal assembly domain. Therefore, JLN mutants may be defective in KvLQT1 subunit assembly. The results provide a molecular basis for the clinical observation that heterozygous JLN carriers show slight cardiac dysfunctions and that the severe JLNS phenotype is characterized by the absence of KvLQT1 channel.

Amino Acid Sequence↗
PubMed2000

A 'made in one piece' skeleton in a 22-year-old man suffering from sickle cell anaemia.

A 22-year-old African male with known sickle cell anaemia was referred by a Congolese medical centre with a request to improve his poor physical condition. He was unable to walk, stand or sit because his large joints and his spine were either ankylosed or very rigid. Radiographs showed joint fusion from the third to the fifth cervical vertebrae, of both hips, of the left knee, and a bilateral osteonecrosis of the humeral head. There was no scintigraphic evidence for an active osteomyelitis (99mTc-MDP (methyldiphosphonate) bone scan, Tc monoclonal antigranulocyte scan and 99mTc sulphur colloid scan). To improve his mobility the right femoral head was resected in June 1997; 14 days later the left femoral head was resected. Four months after the resection of the right hip, a right uncemented total hip prosthesis was implanted on this side. One month later the same type of hip arthroplasty was performed on the left side. During the postoperative rehabilitation period the patient regained autonomy. We have found no previous reports of such severe and multiple joint complications in a single patient suffering from sickle cell anaemia.

Adult↗
PubMed2000

Quantitative ultrasound and dual X-ray absorptiometry measurements of the calcaneus in patients on maintenance hemodialysis.

It has been suggested that quantitative ultrasound measurements (QUS), which reflect mainly bone density, could be influenced by bone micro-architecture. The aim of the study was to assess whether the relationship of QUS to dual X-ray absorptiometry (DXA) would reflect abnormalities of bone structure observed in renal osteodystrophy. QUS and bone mineral density of the calcaneus (BMDc) were measured by DXA in 30 patients on maintenance hemodialysis and 34 age- and gender-matched controls. QUS parameters and BMDc were significantly lower in hemodialysis patients than in controls (speed of sound [SOS] and broadband ultrasound attenuation [BUA], p = 0. 030; stiffness, p = 0.003; BMDc, p = 0.006). Bone measurements were not correlated with serum parathyroid hormone (PTH). The regression lines of SOS, BUA, and stiffness to BMDc were not significantly different from that of the controls. When dividing the patients into two subgroups according to their median PTH (203 pg/mL), the slopes of the regression lines of BUA to BMDc were significantly different between these two subgroups (p = 0.052). The slope of the subgroup with PTH </= 203 pg/mL was significantly different from that of the controls (p = 0.030). In conclusion, QUS of the calcaneus can be used for bone assessment in patients on maintenance hemodialysis. The differences in the slopes of patients with a less pronounced degree of hyperparathyroidism compared with patients with a higher degree of hyperparathyroidism and to controls suggest that BUA of the calcaneus contains information on bone complementary to DXA measured at the same site. The clinical relevance of this finding is presently unclear.

Absorptiometry, Photon↗
PubMed1999

Tyrosine kinases modulate K+ channel gating in mouse Schwann cells.

1. The whole-cell configuration of the patch-clamp technique and immunoprecipitation experiments were used to investigate the effects of tyrosine kinases on voltage-dependent K+ channel gating in cultured mouse Schwann cells. 2. Genistein, a broad-spectrum tyrosine kinase inhibitor, markedly reduced the amplitude of a slowly inactivating delayed-rectifier current (IK) and, to a lesser extent, that of a transient K+ current (IA). Similar results were obtained on IK with another tyrosine kinase inhibitor, herbimycin A. Daidzein, the inactive analogue of genistein, was without effect. 3. Unlike herbimycin A, genistein produced additional effects on IA by profoundly affecting its gating properties. These changes consisted of slower activation kinetics with an increased time to peak, a positive shift in the voltage dependence of activation (by +30 mV), a decrease in the steepness of activation gating (9 mV per e-fold change) and an acceleration of channel deactivation. 4. The steepness of the steady-state inactivation was increased by genistein treatment, while the recovery from inactivation was not significantly altered. 5. The action of genistein on voltage-dependent K+ (Kv) currents was accompanied by a decrease in tyrosine phosphorylation of Kv1.4 as well as Kv1.5 and Kv2.1 encoding transient and slowly inactivating delayed-rectifier K+ channel alpha subunits, respectively. 6. In conclusion, the present study shows that tyrosine kinases markedly affect the amplitude of voltage-dependent K+ currents in Schwann cells and finely tune the gating properties of the transient K+ current component IA. These modulations may be functionally relevant in the control of K+ channel activity during Schwann cell development and peripheral myelinogenesis.

Animals↗
PubMed1999

Stilbenes and fenamates rescue the loss of I(KS) channel function induced by an LQT5 mutation and other IsK mutants.

Genetic and physiological studies have established a link between potassium channel dysfunction and a number of neurological and muscular disorders. Many 'channelopathies' are accounted for by a dominant-lethal suppression of potassium channel function. In the cardiac I(KS) channel complex comprising the alpha and beta subunits, KvLQT1 and IsK, respectively, several mutations lead to a dominant-negative loss of channel function. These defects are responsible for a human cardiovascular disease called long QT (LQT) syndrome. Here we show that binding of I(KS) channel activators, such as stilbenes and fenamates, to an extracellular domain flanking the human IsK transmembrane segment, restores normal I(KS) channel gating in otherwise inactive IsK C-terminal mutants, including the naturally occurring LQT5 mutant, D76N. Our data support a model in which allosteric interactions exist between the extracellular and intracellular boundaries of the IsK transmembrane segment as well as between domains of the alpha and beta subunits. Disruption of this allosteric interplay impedes slow activation gating, decreases current amplitude and restores channel inactivation. Owing to allosteric interactions, stilbene and fenamate compounds can rescue the dominant-negative suppression of I(KS) produced by IsK mutations and thus, may have important therapeutic relevance for LQT syndrome.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗