Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 37 records · Page 2Linked to original sources

PubMed2003

Serious perinatal complications of non-proteinuric hypertension: an international, multicentre, retrospective cohort study.

OBJECTIVE: To determine the proportion of births complicated by either a pre-existing or a gestational non-proteinuric hypertension, presenting at <34 weeks' gestation, and the associated incidence with 1 or more serious perinatal complications or birth weight <3rd centile for gestational age. METHODS: A retrospective chart review was conducted in 5 international centres, from 1998 to 2002, where "tight" control (normalization) of blood pressure (BP) is the norm. International Classification of Diseases (ICD) codes were used to identify women who delivered at > or =20 weeks' gestation, with any hypertensive disorder of pregnancy. Women were included if they had a diastolic blood pressure (dBP) of 90 to 109 mm Hg, due to either a pre-existing or a gestational non-proteinuric hypertension, presenting at <34 weeks' gestation. Women were excluded if they had ongoing severe hypertension, or if at presentation with dBP of 90 to 109 mm Hg, they had 1 or more of the following: proteinuria, an indication for "tight" control of BP or imminent delivery, or a known intrauterine fetal death or lethal fetal anomaly. Data were collected on paper forms, scanned into an electronic database, and summarized descriptively by type of hypertension. RESULTS: There were 305 eligible women (0.7% deliveries, 12.8% hypertensive deliveries) identified with non-proteinuric hypertension that was either pre-existing (133 [43.6%]) or gestational (172 [56.4%]). Regardless of hypertension type, 16.4% (n = 50) of pregnancies were complicated by birth weight <3rd centile or 1 or more serious perinatal complications, 34.3% (n = 100) by preterm birth, 30.8% (n = 94) by preeclampsia, and 2.0% (n = 6) by serious maternal complications. CONCLUSION: Non-proteinuric pre-existing or gestational hypertension, presenting before 34 weeks' gestation, identifies a subpopulation of hypertensive pregnant women at both substantial perinatal risk and maternal risk. The CHIPS (Control of Hypertension In Pregnancy Study) trial is designed to determine how best to manage the hypertension of such women in order to optimize perinatal outcome.

Adult↗

PubMed2003

Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human.

AIMS: To characterize the in vitro and in vivo inhibitory effect of stiripentol, a new anticonvulsant, on the metabolism of carbamazepine and saquinavir, which are substrates of CYP3A4. METHODS: Human liver microsomes and cDNA-expressed CYP enzymes were used for the in vitro experiments. Pharmacokinetic data from epileptic children and healthy adults were used for the carbamazepine and saquinavir in vivo studies, respectively. RESULTS: Carbamazepine biotransformation to its 10,11-epoxide by human liver microsomes (Vmax = 10.3 nmol min(-1) nmol(-1) P450, apparent Km = 362 microm), cDNA-expressed CYP3A4 (Vmax = 1.17 nmol min(-1) nmol(-1) P450, apparent Km = 119 microm) and CYP2C8 (Vmax = 0.669 nmol min(-1) nmol(-1) P450, apparent Km = 757 microm) was inhibited by stiripentol (IC50 14, 5.1, 37 microM and apparent Ki 3.7, 2.5, 35 microm, respectively). Saquinavir biotransformation to its major metabolite M7 by human liver microsomes (Vmax = 5.7 nmol min(-1) nmol(-1) P450, apparent Km = 0.79 microm) was inhibited by stiripentol (IC50 163 microM, apparent Ki 86 microm). In epileptic children treated with carbamazepine and stiripentol, the plasma concentration ratio of carbamazepine epoxide/carbamazepine was decreased by 65%. The in vivo apparent Ki for stiripentol ranged from 10.5 to 41.4 microm. The pharmacokinetics of saquinavir was not modified by stiripentol in healthy adults. The 95% confidence intervals for the difference for Cmax and AUC of saquinavir between the placebo and stiripentol phase were (-39.8, 39.8) and (-33.2, 112), respectively. CONCLUSIONS: These results showed that stiripentol was a weak inhibitor of saquinavir metabolism both in vitro and in vivo. In contrast, stiripentol is a potent inhibitor of carbamazepine 10,11-epoxide formation in vitro and in vivo in epileptic patients.

Adolescent↗

PubMed2003

Oxidative metabolism of amprenavir in the human liver. Effect of the CYP3A maturation.

Amprenavir is a human immunodeficiency virus-1 (HIV-1) protease inhibitor intended to be used to treat HIV-infected children. Although a pediatric dosage is proposed by the manufacturer, no data are currently available on the pharmacokinetics of amprenavir in neonates and infants. Amprenavir being primarily eliminated after oxidative biotransformation, we explored its in vitro metabolism by cytochrome P450 (P450)-dependent monooxygenases. In our conditions, five metabolites were formed in vitro and subsequently analyzed by liquid chromatography-mass spectrometry; P450-dependent oxidations occurred either on the tetrahydrofuran ring (M3 and M4), the aniline ring (M5), and the aliphatic chain (M2) or resulted from the N-dealkylation and loss of the tetrahydrofuran ring (M1). The two major metabolites, respectively M3 and M2 were formed by human liver microsomes with K(m) between 10 and 70 microM. CYP3A4 and to a lesser extent CYP3A5 were major contributors for the formation of M2, M3, and M5 metabolites, whereas CYP3A7 had no or little activity. This assumption was confirmed by inhibition with ketoconazole and ritonavir (two potent inhibitors of CYP3A) whereas sulfaphenazole (2C9 inhibitor) and quinidine (2D6 inhibitor) were inefficient. The metabolism of amprenavir was negligible in microsomes from either fetuses or neonates and steadily increased after the first weeks of life in relation with the maturation of CYP3A4/5. In conclusion, results demonstrated that the capacity of the human liver to oxidize amprenavir is low during the first weeks after birth and that dosage could be substantially reduced during the early neonatal period.

Adult↗

PubMed2002

Exhaled NH3 and excreted Nh4+ in children in unpolluted or urban environments.

Exhaled ammonia (NH3ex) was measured by chemiluminescence in a group of healthy children (n = 20) and in two groups of asthmatic children, one (Group 1) residing in a National Park in the mountains (n = 68) and other (Group 2) in an urban area (n = 52). We also determined urinary ammonia, nitrates, urea, sodium and potassium normalized to osmolarity. Unlike exhaled nitric oxide (NOex), NH3ex was not specific to asthma as the children in Group 2 and the controls exhaled more ammonia that did the children in Group 1 (14.3 +/- 10.2 and 14.8 +/- 10.3 vs. 5.6 +/- 4.7 ppb; P < .001, respectively). In the urban environment, all children, including the healthy controls, excreted more ammonia (P < .001) and potassium (P < .001) but less urea (P < .02) than did the children residing in the National Park. These manifestations of moderate metabolic acidosis would favor excretion of ammonia at the expense of urea. In the children residing in the National Park, positive correlations were observed between NH3ex and urinary ammonia, and nitrates, age and morphological parameters. The relationship with the morphological parameters is a reflection of the normal physiological formation of NH3ex. In the children residing in the urban area, the other endogenous source of NH3ex was attributed to a slight disturbance in acid-base balance. In conclusion, the measurement of NH3ex appeared of limited interest, although the higher urinary urea/NH4+ ratio in Group 1 (P < .0001), especially in the treated children, appeared to be linked to the lack of atmospheric pollutants in the National Park. Further experimentation is in progress to confirm these findings.

Air Pollutants↗

PubMed2002

[Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome)].

OBJECTIVE: To describe the long term efficacy and tolerance of stiripentol associated with valproate and clobazam in an exhaustive cohort of patients with severe myoclonic epilepsy of infancy (Dravet's syndrome), in which short term efficacy of such a treatment has recently been demonstrated in a placebo-controlled trial. RESULTS: In 46 patients the frequency and the duration of seizures was significantly reduced (p < 0.001) as well as the number of convulsive status at a median of three-year follow-up. Ten patients were dramatically improved (seizures significantly decreased in number [p = 0.002] and duration [p = 0.002] and status epilepticus disappeared), 20 were moderately improved (seizures significantly decreased in duration [p = 0.001] and status were less numerous), four had no response and efficacy was non evaluable in 12 mainly because of adverse events. Efficacy was better in the youngest patients. The most frequent adverse events were loss of appetite and loss of weight. They could be so severe in patients over 12 years of age that the stiripentol dosage could not be increased to 50 mg kg-1 j-1. CONCLUSION: This follow-up study shows that stiripentol added to valproate and clobazam maintains its efficacy at long term in children with severe myoclonic epilepsy of infancy and suggests that the tritherapy should be introduced as early as possible in these patients in order to suppress the convulsive status epilepticus.

Anti-Anxiety Agents↗

PubMed2002

Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants, and children.

The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine and urea concentrations on pharmacokinetic parameters. There is no specific formulation of amikacin for neonates and infants. We therefore used an error model to account for errors due to dilution during preparation of the infusion. The covariates that reduced the variance of clearance from plasma and the volume of distribution by more than 10% were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%, respectively). The expected reduction of clearance was about 10% for the plasma creatinine concentration. The other covariates studied (Apgar scores, plasma urea concentration, gestational age, sex) were found to have little effect. Simulations showed that a smaller percentage of patients had a maximum concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1 to 8 mg/liter.

Age Factors↗

PubMed2002

Long-term outcome of patients with non-cardiac chest pain.

OBJECTIVE: To assess long-term outcome for patients with chest pain in our environment, to estimate direct resource use, and to evaluate the influence of patient views regarding pain origin on outcome. PATIENTS AND METHODS: All patients referred to our Department between 1994 and 1998 to undergo pH-metry as a result of chest pain were identified. Those detected were subjected to a structured direct interview on the telephone. RESULTS: 104 patients with a follow-up period (since pH-metry) of 3.76 years were evaluated. Thirty nine percent of patients were free from pain (37.5%), and one had died from a seemingly unrelated cause (1%), whereas the rest still suffered from pain. The mean number of visits per patient during the last year was 2.83 to their general practitioner, 1.04 to an specialist, and 0.99 to an Emergency Unit; hospitalisations were 0.26, and ICU admissions 0.09. Patients who trusted medical diagnoses showed better outcomes than those who did not trust or understand them, in association with lower resource use, particularly Emergency Unit use. CONCLUSION: Patients with chest pain had a favourable life prognosis, but 60% still suffer from pain after nearly 4 years of follow-up, which entails a relevant use of health-care resources. Trust in medical diagnosis seemingly influences outcome, and the use of diagnostic procedures to determine pain origin is thus likely beneficial for patient.

Adult↗

PubMed2002

Which is the best distension protocol to study rectal sensitivity in the irritable bowel syndrome?

OBJECTIVE: To evaluate any differences in rectal distension perception between healthy subjects and patients with irritable bowel syndrome (IBS) according to an isobaric distension protocol (progressive or phasic). MATERIAL AND METHODS: 10 healthy subjects and 41 patients with IBS (Rome II criteria). Rectal distension was performed using a barostat connected to a 500 mL bag, and a progressive distension protocol (continuous distension at a rate of 0.36 mmHg/sec) was compared to phasic distension protocol (distensions for 60 sec with 4 mmHg increases separated by 0 mmHg pressures during 60 sec). Perception was evaluated using three descriptive scales of 7 categories each for perception type, intensity, and affectivity. Perception thresholds were assessed. RESULTS: No significant differences in any perception thresholds were found between control subjects and IBS patients using a progressive distension protocol. Differences in the perception of inconvenient distension and maximum tolerable distension were encountered with the phasic distension protocol. Uncomfortable distension thresholds below those of controls were found in 48.8% of patients with IBS when a phasic distension protocol was used, versus only 9.7% with a progressive protocol. CONCLUSION: Hypersensitivity in patients with IBS is mainly seen with the use of phasic distension isobaric protocols for affective negative perceptions.

Adult↗

PubMed2002

Prevalence of rectal hypersensitivity in patients with irritable bowel syndrome and its clinical subgroups.

AIM: To evaluate the prevalence of rectal hypersensitivity in our irritable bowel syndrome (IBS) patients, the relationship of hypersensitivity to rectal distensibility and the differences in sensitivity among clinical subgroups of IBS. MATERIAL AND METHODS: 18 healthy subjects and 56 IBS patients (Rome-II criteria; 22 diarrhea-predominant, 15 constipation-predominant and 19 alternating). Rectal sensitivity and distensibility were studied by isobaric phasic distension of a poliethilene bag with a barostat. RESULTS: IBS patients showed a lower threshold for discomfort, pain and maximum tolerate distension, without any differences in rectal distensibility. 64% of IBS patients were hypersensitive. 89% of patients with alternating IBS were hypersensitive while only 68% and 26% of patients with diarrhea-predominant IBS and constipation-predominant IBS, respectively, were. There were no differences in rectal distensibility between hypersensitive and normosensitive patients. CONCLUSION: 64% of our IBS patients show rectal hypersensitivity, apparently not related to rectal distensibility. Hypersensitivity is mostly found in alternating IBS patients, and rare in constipation-predominant IBS.

Adult↗

PubMed2002

Adaptation and validation of a gastroesophageal reflux questionnaire for use on a Spanish population.

OBJECTIVE: To produce and validate for telephone use in Spain a cross-cultural adaptation of the gastroesophageal reflux questionnaire (GERQ) developed by Locke et al. MATERIAL AND METHOD: The Spanish version of the questionnaire was developed through translation, assessment of comprehensibility, back translation, and appraisal of applicability. Subsequently, reproducibility was measured by a test-retest procedure in 125 patients, and concurrent validity was evaluated by comparing self-reported questionnaire data against a gastroenterologist's findings from clinical interviews with 50 patients. RESULTS: The Spanish version showed itself to be easily understandable and widely applicable. Reproducibility for the two cardinal symptoms of gastroesophageal reflux disease (heartburn and acid regurgitation) as measured by the kappa index (95% confidence interval), was 0.85 (0.73-0.97) and 0.81 (0.70-0.92), respectively. With respect to the process of concurrent validation, kappa values (95% confidence interval) for heartburn and acid regurgitation were 0.85 (0.68-1) and 0.91 (0.79-1), respectively. Median kappa for all questions on the questionnaire was 0.75 (range: 0.42 a 1) in the reproducibility analysis and 0.83 (range: 0.44 a 1) in the concurrent validity analysis. CONCLUSIONS: The reproducibility and concurrent validity of the Spanish version of the GERQ is excellent and comparable to that of the original English version.

Cross-Cultural Comparison↗

PubMed2001

Dopamine induces intracellular Ca2+ signals mediated by alpha1B-adrenoceptors in rat pineal cells.

We have studied the functional interaction of dopamine with alpha1-adrenoceptor subtypes by measuring intracellular Ca2+ levels in pineal cells, a cell type where adrenoceptors are well characterized. We show that dopamine induces transient intracellular Ca2+ signals in only 70% of cells responding to phenylephrine. Dopamine-induced Ca2+ signals desensitise faster than Ca2+ transients elicited with phenylephrine and are selectively blocked by desipramine, imipramine, and alpha1B-adrenoceptor antagonists. These results suggest that dopamine induced Ca2+ signals are mainly due to the activation of one subtype of alpha-adrenoceptor, the alpha1B.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2001

Protective effect of stiripentol on acetaminophen-induced hepatotoxicity in rat.

Acetaminophen (APAP) is mainly eliminated at a therapeutic dose through glucuronidation and sulfatation and a small fraction is oxidized by cytochromes P450 (CYP) 2E1, 3A4, and 1A2 to N-acetyl-p-benzoquinone-imine (NAPQI), a highly reactive metabolite further conjugated with glutathione into APAP-GSH, and then metabolized to APAP-cystein and APAP-mercapturate excreted in urine. After APAP overdose, the glucuronidation and sulfatation pathways are saturated and the production of NAPQI increases, causing hepatic injury. Stiripentol (STP); (200 mg/kg), an anticonvulsant drug inhibitor of CYP1A2 and CYP3A4 in vivo in humans was tested against APAP-induced toxicity in rat in comparison with N-acetylcysteine (NAC; 100 mg/kg). The mortality rates 24 h after APAP overdose (2 x 500 mg/kg) were 63% (control), 38% (NAC), 0% (STP), and 4% (STP + NAC). The mean plasma transaminase concentrations 5 and 24 h after overdose were significantly higher in control than in STP and NAC groups. The percentage of rats without microscopic liver necrosis 5 h after APAP overdose was significantly higher in rats receiving STP (100%), NAC (83%), or STP + NAC (83%) than controls (42%). In another experiment, four similar groups were administered 50 mg/kg APAP. Plasma AUC(0-5 h) for APAP-GSH, APAP-cystein, and APAP-mercapturate as well as urine APAP-mercapturate mean amounts were significantly lower in STP animals than in the other groups. STP (200 mg/kg) inhibited NAPQI synthesis through CYP inhibition, thus preventing both liver necrosis and mortality in rats.

Acetaminophen↗

PubMed2001

Evidence of impaired cisapride metabolism in neonates.

AIMS: Cisapride has been shown to cause QTc prolongation in neonates in the absence of any of the known risk factors ascribed to children or adults (excessive dosage, drug-drug interactions). Our hypothesis was that the early neonatal liver may show defective elimination of cisapride resulting in its accumulation in the immature child. Owing to the difficulties associated with in vivo pharmacokinetic studies in a paediatric population, we explored the in vitro metabolism of cisapride by human cytochrome P450. METHODS: Experiments were conducted with recombinant CYPs stably expressed in mammalian cells and with liver microsomes obtained from human foetuses, neonates, infants and adults. Cisapride metabolites were measured by high performance liquid chromatography. RESULTS: The rate of biotransformation of cisapride was greater by recombinant CYP3A4 than by CYP3A7 (0.77 +/- 0.5 and 0.01 +/- 0.01 nmol metabolites formed in 24 h, respectively), whereas CYP1A1, 1A2, 2C8, 2C9 and 3A5 showed no activity. Norcisapride formation was significantly correlated with testosterone 6beta-hydroxylation, a CYP3A4 catalysed reaction (r = 0.71, P = 0.03) but not with the 16-hydroxylation of dehydroepiandrosterone, catalysed by CYP3A7 (r = 0.30, P = 0.29) by microsomes from a panel of livers from foetuses, neonates and infants. No or negligible cisapride metabolic activity was observed in microsomes from either foetuses or neonates aged less than 7 days, which contained mostly CYP3A7 and no CYP3A4. The metabolism of cisapride steadily increased after the first week of life in parallel with CYP3A4 activity to reach levels exceeding adult values. CONCLUSIONS: The low content of CYP3A4 in the human neonatal liver appears to be responsible for its inability to oxidize cisapride and could explain its accumulation in plasma leading to the cases of QTc prolongation reported in this paediatric population.

Adult↗

PubMed2001

Pharmacokinetics of alizapride in children receiving chemotherapy for solid tumour.

The purpose of the present study was to determine the pharmacokinetics of alizapride to optimize its use in children aged 1 month to 15 years old who were receiving chemotherapy. Seventeen children were given a single 4 mg/kg alizapride infusion prior to the administration of cytostatic drugs. Blood and urine samples were collected within 10 h after onset of the infusion. Kinetic parameters were calculated and showed a decrease in plasma clearance expressed per unit of body weight with age. The current data suggest that dosage expressed per unit of body weight should be higher in children than in adults and higher in infants than in children.

Adolescent↗

PubMed2001

Isoniazid pharmacokinetics in children according to acetylator phenotype.

The pharmacokinetics of isoniazid (INH) was studied in children (0-196 months old) according to their acetylator phenotype, estimated from the metabolic acetyl INH/INH molar plasma concentration ratio (MR) measured 3 h after INH oral administration. There were 17 slow (MR < 0.48) and 17 fast acetylators (MR > or = 0.48). The mean apparent plasma clearance was significantly lower, the mean apparent volume of distribution higher and the half-life longer in the slow acetylator group (C1, 0.298 +/- 0.099 L/h/kg; Vd, 1.56 +/- 0.65 L/kg; t1/2, 3.88 +/- 01.89 h) than in the fast acetylator group (Cl, 0.528 +/- 0.234 L/h/kg; Vd, 1.06 +/- 0.45; t1/2, 1.64 +/- 1.1 h). The half-life decreased with age. An impaired isoniazid elimination was suggested in children less than three months old, which may be in favour of an individual dose adjustment in this population.

Acetylation↗

PubMed2000

Delineation of the human systemic lupus erythematosus anti-Smith antibody response using phage-display combinatorial libraries.

The anti-Smith (Sm) autoantibody response is highly specific for systemic lupus erythematosus and is predominantly targeted to the Sm-B/B' and -D1 polypeptides. In all animal species thus far studied, anti-Sm Abs initially recognize proline-rich epitopes in the carboxyl terminus of the Sm-B/B' protein and subsequently to multiple other epitopes in B/B' and D. The absence of appropriate mAbs has limited our understanding of the genetic and structural basis of this autoimmune response. Using phage-display technology and lymphocytes from a systemic lupus erythematosus patient we have generated the first and only panel of human IgG anti-Sm mAbs thus far available. These Abs reproduced to a remarkable extent the serological reactivity of the patient. Epitope mapping and genetic studies revealed that the anti-Sm response is produced by distinct B cell clones with restricted epitope reactivity. All of the Abs in our study were exclusively encoded by different members of the V(H)4 gene family. On the aggregate, our results demonstrate that combinatorial libraries can recapitulate the immune repertoire of peripheral blood B memory cells and that epitope spreading appears to occur through the sequential recruitment of nonclonally related autoreactive B cell clones.

Amino Acid Sequence↗

PubMed2000

Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group.

BACKGROUND: Stiripentol is an inhibitor of cytochrome P450 that showed antiepileptic efficacy in severe myoclonic epilepsy in infancy (SMEI) in association with clobazam and valproate in an open study. To confirm these results, 41 children with SMEI were included in a randomised, placebo-controlled, add-on trial. METHODS: After a baseline period of 1 month, placebo (n=20) or stiripentol (n=21) was added to valproate and clobazam during a double-blind period of 2 months. Patients then received stiripentol in an open fashion. Responders were defined as having more than 50% reduction in the frequency of clonic (or tonic-clonic) seizures during the second month of the double-blind period compared with baseline. FINDINGS: 15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none were seizure free; stiripentol 95% CI 52.1-90.7 vs placebo 0-14.6). The 95% CI of the difference was 42.2-85.7. Percentage of change from baseline was higher on stiripentol (-69%) than on placebo (+7%), p<0.0001. 21 patients on stiripentol had moderate side-effects (drowsiness, loss of appetite) compared with eight on placebo, but side-effects disappeared when the dose of comedication was decreased in 12 of the 21 cases. INTERPRETATION: This controlled trial shows the antiepileptic efficacy, of add-on stiripentol in children with SMEI. The results also provide good reason to focus studies on a specific epilepsy syndrome-a small sample of patients is sufficient to show the efficacy that might have been missed in a heterogeneous population.

Anti-Anxiety Agents↗

PubMed2000

Characterization of human anti-acetylcholine receptor monoclonal autoantibodies from the peripheral blood of a myasthenia gravis patient using combinatorial libraries.

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the nicotinic acetylcholine receptor (AChR). Using phage-display technology we have characterized the largest panel of anti-AChR monoclonal antibodies thus far isolated from a single patient. Despite having been isolated with either Torpedo AChR or a human peptide, the recombinant antibodies shared with the donor's serum the ability to recognize human AChR expressed in its native configuration on the surface of TE671 cells. Their specificity for the main immunogenic region (MIR) of the AChR was demonstrated using a synthetic peptide corresponding to the region 67-76 of the human AChR alpha subunit and by inhibition of a highly pathogenic rat anti-MIR monoclonal antibody (mAb35). This work demonstrates the value of combinatorial libraries in isolating pathogenic autoantibodies from peripheral blood lymphocytes. Future genetic, structural, and functional analyses of the monoclonal antibodies reported herein should enhance our understanding of the pathogenesis of MG.

Animals↗