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M Lluch

Publications and source records attributed to M Lluch.

At least 19 recordsLinked to original sources
PubMed2005

Double-blind study of tolerability and antibody production of unmodified and chemically modified allergen vaccines of Phleum pratense.

BACKGROUND: The physicochemical modification of allergen extracts provides a chance for administering higher doses of allergen vaccines. OBJECTIVE: To evaluate the safety of a chemically modified (depigmented-glutaraldehyde polymerized) therapeutic vaccine of Phleum pratense administered at doses that are 10 times higher than those used in clinical practice, in comparison with conventional doses of the corresponding non-modified alum-adsorbed vaccine. MATERIALS AND METHODS: The design of the study was randomized, double-blind, parallel and included two groups of patients. Twenty-three patients were treated weekly during nine visits for the build-up phase, followed by two weekly maintenance doses (a total of 11 injections per patient). Twelve patients received a vaccine containing the standardized unmodified extract, at a maximum concentration of 308.5 mcg of freeze dried material/mL (Group A). Eleven patients received a standardized modified allergen extract (Group B). The maximum dose used was 2400 mcg/mL. Safety was evaluated recording all adverse events. Skin test results and specific antibody levels were evaluated at the beginning and at the end of the study. RESULTS: Group A patients experienced three local immediate (two clinically irrelevant and one with a diameter>5 cm) and 18 delayed reactions (15 irrelevant and three with a diameter>10 cm), while Group B experienced six local immediate and 12 delayed reactions (all clinically irrelevant). Nine Group A patients experienced 12 systemic reactions (one immediate of grade 1, one of grade 2; and one delayed of grade 1; four of grade 2 and three of grade 3), while Group B patients experienced one immediate systemic reaction of grades 1, and 1 delayed reaction of grade 1. CONCLUSIONS: The modified extract of P. pratense is safe to treat sensitive patients, even at concentrations that are 10 times higher than those regularly administered in clinical practice. The majority of the local reactions were clinically irrelevant. No systemic reactions of grade 2, 3 or 4 were reported using the modified extract.

Adult↗
PubMed2005

Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations.

To better characterize Niemann-Pick type C (NPC) in Spain and improve genetic counselling, molecular analyses were carried out in 40 unrelated Spanish patients. The search identified 70/80 alleles (88%) involving 38 different NPC1 mutations, 26 of which are described for the first time. No patient with NPC2 mutations was identified. The novel NPC1 mutations include 14 amino acid substitutions [R372W (c.1114C>T), P434L (c.1301C>T), C479Y (c.1436G>A), K576R (c.1727G>A), V727F (c.2179G>T), M754K (c.2261T>A), S865L (c.2594C>T), A926T (c.2776G>A), D948H (c.2842G>C), V959E (c.2876T>A), T1036K (c.3107C>A), T1066N (c.3197C>A), N1156I (c.3467A>T) and F1224L (c.3672C>G)], four stop codon [W260X (c.780G>A), S425X (c.1274C>A), C645X (c.1935T>A) and R1059X (c.3175C>T)], two donor splice-site mutations [IVS7+1G>A (g.31432G>A) and IVS21+2insG (g.51871insG)], one in-frame mutation [N961_F966delinsS (c.2882del16bpins1bp)] and five frameshift mutations [V299fsX8 (c.895insT), A558fsX11 (c.1673insG), C778fsX10 (c.2334insT), G993fsX3 (c.2973_78delG) and F1221fsX20 (c.3662delT)]. We also identified three novel changes [V562V (c.1686G>A), A580A (c.1740C>G) and A1187A (c.3561G>T)] in three independent NPC patients and five polymorphisms that have been described previously. The combination of these polymorphisms gave rise to the establishment of different haplotypes. Linkage disequilibrium was detected between mutations C177Y and G993fsX3 and specific haplotypes, suggesting a unique origin for these mutations. In contrast, I1061T mutation showed at least two different origins. The most prevalent mutations in Spanish patients were I1061T, Q775P, C177Y and P1007A (10, 7, 7 and 5% of alleles, respectively). Our data in homozygous patients indicate that the Q775P mutation correlates with a severe infantile neurological form and the C177Y mutation with a late infantile clinical phenotype.

Adolescent↗
PubMed2003

Analysis of organic acids after incubation with (16-2H3)palmitic acid in fibroblasts from patients with mitochondrial beta-oxidation defects.

The analysis of acylcarnitines as products of incubation of intact fibroblasts with isotope-labelled precursors, usually (16-(2)H(3))hexadecanoic acid, is an advanced in vitro method for the study of mitochondrial beta-oxidation defects. We propose a technique for the measurement of the organic acid intermediates after hydrolysis of the acylcarnitines using electron-impact gas chromatography-mass spectrometry. For some mitochondrial beta-oxidation deficiencies, the characteristic profile enables us to approach the diagnosis with clear differentiation.

Acyl-CoA Dehydrogenase↗
PubMed2001

Phenotype and genotype heterogeneity in Mediterranean citrullinemia.

We summarize the diagnosis, outcome, and molecular studies of five Mediterranean patients with citrullinemia: four neonatal classical forms and one subacute form, who also suffers from Down syndrome and presented with severe hepatic encephalopathy at age 7. Mutational analysis revealed three alleles with a common mutation and five new mutations: two Moroccan siblings are homozygous for G390R, the subacute form is compound heterozygous for G390R/G117D (new mutation), and the two other neonatal forms are compound heterozygous for four new mutations: V69A/E270Q and T119I(R108L)/?.

Argininosuccinate Synthase↗
PubMed2000

Polyamine uptake in cultured astrocytes: characterization and modulation by protein kinases.

The properties and regulation of the polyamine transport system in brain are still poorly understood. The present study shows, for the first time, the existence of a polyamine transport system in cerebellar astrocytes and suggests that polyamine uptake is mediated by a single and saturable high-affinity transport system for putrescine, spermine, and spermidine (K:(m) = 3.2, 1.2, and 1.8 microM:, respectively). Although substitution of NaCl by choline chloride produced a decrease in the putrescine, spermine, and spermidine uptake, it seems that polyamine transport in cerebellar astrocytes is not mediated by an Na(+) cotransport as in the presence of Na(+) and cholinium, polyamine uptake was much lower than when measured in a sucrose-based medium. On the other hand, ouabain, gramicidin (a Na(+) ionophore), and ionomycin (a Ca(2+) ionophore) produced a strong inhibition of polyamine uptake, suggesting that membrane potential could have an important role in the functioning of the astroglial polyamine uptake system. Moreover, protein kinase C inhibition produced an enhancement of polyamine uptake, whereas stimulation of protein kinase C with phorbol esters inhibited polyamine uptake. Alternatively, the tyrosine kinase inhibitor genistein caused a marked reduction in the uptake. No effects on polyamine uptake were observed with inhibitors and activators of cyclic AMP-dependent protein kinase or when Ca(2+)/calmodulin-dependent protein kinase II was inhibited with KN-62. These results suggest that the polyamine uptake system in cerebellar astrocytes could be modulated by protein kinase C and tyrosine kinase activities.

Animals↗
PubMed1998

Extracellular acidification modifies Ca2+ fluxes in rat brain synaptosomes.

We examined the influence of external acidification on Ca2+ fluxes (45Ca2+ influx and 45Ca2+ efflux) in rat brain synaptosomes. A change on external pH (pHe) from 7.5 to 6.5 linearly decreased the 45Ca2+ uptake (5nmoles/mg protein/pHunit) and increased the 45Ca2+ efflux (1.5 fold/pH unit). These changes were both Na+ dependent and amiloride sensitive suggesting that the Na+/Ca2+ exchanger could be involved. The addition of the Ca2+ channel blockers (diltiazem, verapamil, nifedipine) did not prevent the decrease of the 45Ca2+ uptake evoked by acid pHe and so the involvement of the voltage-sensitive Ca2+ channels could be discarded. In order to determine whether the Na+/Ca2+ exchanger was directly activated by H+ or was indirectly activated by an internal mobilization of Ca2+ from intrasynaptosomal stores we examined the effect of pHe variation on phophoinositide hydrolisis. An increase on phosphoinositide hydrolisis was observed at acid pHe values (7 and 6.5). The hydrolisis was amiloride insensitive. On the other hand 1mM neomycin did inhibit the effect of acidic pHe on Ca2+ fluxes. Taken together, the results of our study provide evidence that external acidification stimulates phospholipase C leading to an increase in phosphoinositide hydrolisis and Ca2+ mobilization. The increase in intracellular Ca2+ would stimulate the Na+/Ca2+ exchanger, increasing Ca2+ efflux and reducing the global Ca2+ influx.

Animals↗
PubMed1998

Peach allergy pattern: experience in 70 patients.

We report the clinical characteristics of peach allergy encountered in a population of peach-allergic patients. We evaluated 165 patients. The 70 peach-allergic patients were diagnosed through clinical history, the skin prick-prick test, and open oral challenge and rub tests to peach. As a pollinic control group, 95 pollen-allergic patients were also evaluated. Some 49% of the patients were male and 51% female. The mean age was 20 +/- 8 years. Oral allergy syndrome (86%) was the most common symptom, followed by contact urticaria (61%) and systemic symptoms (26%). Some 67% of the patients were allergic to peach pulp and 36% reported symptoms related to canned peach. Canned peach and pulp symptoms were statistically associated (P < 0.01), and symptoms to canned peach were more frequently reported by patients with systemic symptoms (P < 0.05). On evaluation of the peach-allergic patients' characteristics, three risk factors--allergy to peach pulp, allergy to canned peach, and peach allergy in non-pollen-allergic patients--were found, indicating development of systemic symptoms on eating peach. Most of the peach-allergic patients (81%) also had pollen allergy, which was linked to a higher prevalence of asthma (73%) than in the pollen-allergic patients of the control group (48%); this difference was statistically significant (P < 0.01). Finally, two groups were clearly defined by the seriousness of the peach allergy--the non-pollen-allergic patients were more predisposed to the occurrence of systemic symptoms (> 50%), and the pollen-allergic patients to asthma (> 70%).

Adolescent↗
PubMed1997

Histamine modulation of glutamate release from hippocampal synaptosomes.

Histamine is widely believed to act as a neuromodulator in the central nervous system. Histaminergic fibers arriving at the hippocampus could be involved in the modulation of glutamatergic neurotransmission. Therefore, we have investigated the effect of histamine on [3H]glutamate release from hippocampal synaptosomes by using a superfusion system. Calcium-dependent [3H]glutamate release was stimulated by KCI or 4-aminopyridine. When submaximal concentrations of the depolarizing agents were used (15 mM KCI or 50 microM 4-aminopyridine), histamine, acting via histamine H1 and H2 receptors, produced a concentration-dependent increase in the evoked release of glutamate. Maximal effect was obtained with 500 microM histamine. Histamine (up to 1 mM) did not modify basal release. These data suggest that histaminergic afferents may modulate activity-dependent glutamatergic presynaptic terminals in the hippocampus.

Animals↗
PubMed1997

A new case of multiple mitochondrial enzyme deficiencies with decreased amount of heat shock protein 60.

Heat shock protein 60 (hsp60) is a mitochondrial matrix protein involved in the folding and correct assembly of polypeptides into complex mitochondrial enzymes. Its deficiency has recently been described as the most likely primary cause of congenital lactic acidaemia with multiple mitochondrial enzyme deficiencies in a female patient. We describe a new case of a girl with a substantially decreased amount of hsp60 in cultured fibroblasts. She presented from birth with hypotonia, unusual facial features, feeding difficulties and failure to thrive. Death occurred at age 4.5 years. Biochemical findings included metabolic acidosis with lactic acidaemia, hyperammonaemia and intermittent ketosis. In contrast to the previously reported case, organic acid analysis showed an altered profile throughout her life. In agreement with this profile, various mitochondrial enzyme activities were deficient in cultured fibroblasts, including enzymes of the respiratory chain and the Krebs cycle, the pyruvate dehydrogenase complex and the mitochondrial biotindependent carboxylases. Fibroblast mitochondria showed ultrastructural abnormalities, were swollen, and were mainly localized around the nucleus. The description of a second case of multiple mitochondrial enzyme deficiencies with reduced amount of hsp60 supports the idea that hsp60 deficiency might be a more common cause of mitochondrial disease. This opens new possibilities for the diagnosis and understanding of congenital lactic acidaemia.

Amino Acids↗
PubMed1996

Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to amoxicillin and with good tolerance of penicillin.

In recent years, patients allergic to amoxicillin (AX) but with good tolerance of penicillin G (PG) have been described. It has been suggested that the epitope implicated in this type of sensitization might be located on the side-chain of the AX molecule. Thus, cross-reactivity between AX and cephadroxil (CEPH), a cephalosporin which shares an identical side-chain with AX, is suspected. This study aimed to demonstrate clinical cross-reactivity between AX and CEPH in patients allergic to AX and showing good tolerance of PG. In 76 of 576 subjects with suspected allergic reaction to PG and/or AX, the diagnosis of allergy was confirmed. All of these had specific IgE to PG, penicillin V, or AX, and/or positive skin tests to PPL (penicilloyl-polylysine), or MDM (minor determinant mixture), or PG, or AX, and/or positive challenge tests with PG and/or AX. Sixteen subjects (21%) allergic to AX (11 with positive skin test and five with positive challenge test to AX) and good tolerance of PG (all with negative parenteral challenge test) were selected. These 16 patients were subsequently challenged with CEPH (up to 500 mg). Fourteen patients tolerated CEPH, and two (12%) had an immediate allergic reaction. Our study indicates that allergy to the side-chain of aminopenicillins seems to have little clinical relevance in patients with allergic reactions to aminopenicillins but with good tolerance of PG, as 88% of patients with this clinical characteristic tolerate a cephalosporin which shares an identical side-chain. It seems that IgE from most of these patients recognizes an epitope different from the side-chain and the beta-lactam ring.

Adolescent↗
PubMed1993

Hypersensitivity to mustard seed.

Two patients were studied. Both underwent a thorough clinical evaluation, including a comprehensive physical examination. Both were also prick tested for inhalants, pollens, and food (including fruit). A nasal provocation test, serum immunoglobulins, total IgE serum, specific IgE serum, and a histamine release test were also carried out. The results of all these tests were positive to mustard seed.

Adult↗