A dinucleotide repeat and a Hae III polymorphism in the human nicotinic acetylcholine receptor alpha-subunit gene (CHRNA1).
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Deoxyribonucleases, Type II Site-Specific↗
Biomedical subjects
L Gomez
Publications and source records attributed to L Gomez.
Hypersensitivity pneumonitis related to a covered and heated swimming pool environment.
Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis is a lung disease caused by a large group of inhaled antigens of various sources. The most common HP occurring in the farm environment is classically caused by exposure to various thermophilic actinomycetes and fungi that can grow in the farm environment. Pullularia species and thermophilic actinomycetes have been involved in HP related to humidifier water and saunas. Our case illustrates the value of a site visit in the diagnosis of HP. During a visit to the covered and heated swimming-pool where our patient used to swim we could see that favourable conditions to fungal growth existed. To determine the possible aetiological agents of a suspected HP, cultures from several parts of the swimming-pool were taken. These cultures showed an intense growth of thermophilic actinomycetes, Neurospora and Aspergillus species. Precipitating antibodies against Neurospora species and Mycropolyspora faeni were detected. A case of HP related to a covered and heated swimming-pool environment is reported. Thermophilic actinomycetes and Neurospora species may be the causing agents.
Actinomycetales↗
Specific oncological contribution of cathepsin D and pS2 in human breast cancer: their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification.
The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
Adult↗
Age-dependent penetrance and mapping of the locus for juvenile and early-onset open-angle glaucoma on chromosome 1q (GLC1A) in a French family.
The GLC1A locus for autosomal dominant primary open-angle glaucoma (POAG) with juvenile onset (before 20 years) has been mapped to chromosome 1q21-q31. Recently, a French-Canadian family was described in which both juvenile-onset and middle-age or early-onset POAG were observed and linked to GLC1A. We now describe a second POAG family with variable age of onset (range 11-51, median 36 years of age). Linkage to GLC1A was established with a maximum lod score of 6.21 at the D1S452 locus. A recombination event in a severely glaucomatous patient restricted the distal boundary of the GLC1A interval proximal to the AFM154xc9 marker. This study strengthens the idea that early-onset POAG may also be determined by the GLC1A genetic region.
Adolescent↗
CD40lbase: a database of CD40L gene mutations causing X-linked hyper-IgM syndrome.
X-linked hyper-IgM syndrome (X-HIM) is an immunodeficiency caused by mutations in the gene encoding the CD40 ligand (CD40L). A database (CD40Lbase) of CD40L mutations has now been established, and the resultant information, together with other mutations reported elsewhere in the literature, is presented here.
CD40 Antigens↗
Bone marrow transplantation in 26 patients with Wiskott-Aldrich syndrome from a single center.
We retrospectively analyzed the outcome of bone marrow transplantation (BMT) performed in 26 patients with Wiskott-Aldrich syndrome (WAS) in one center. Twenty-eight transplantation procedures were performed. Ten unselected patients received unmanipulated marrow from a donor with genetically identical human leukocyte antigen (HLA). Eight patients were cured and survive 1.5 to 16.5 years after BMT. One patient successfully received a T-cell-depleted marrow from a matched unrelated donor. Sixteen patients were selected to receive a related HLA partially incompatible BMT because of the occurrence of life-threatening complications from the WAS (i.e., refractory thrombocytopenia, autoimmunity including vasculitis and sepsis). All but one received T-cell-depleted marrow after a conditioning regimen of busulfan and cyclophosphamide. One patient had two BMTs. Engraftment occurred in 12 of 17 attempts. The addition of monoclonal antibodies to lymphocyte function-associated antigen-1 and CD2 molecules appeared to improve engraftment. Six patients were long-term survivors, whereas others died of viral infections (n = 7), among which Epstein-Barr virus-induced B-lymphocyte proliferative disorder was predominant. Delay in development of full T- and B-cell functions accounted for severe infectious complications. These results confirm the excellent outcome of HLA genetically identical BMT in WAS, whereas BMT from HLA partially incompatible donors should be strictly restricted to patients with severe complications of WAS.
Adolescent↗
Role of complex asparagine-linked glycans in the allergenicity of plant glycoproteins.
Many plant proteins, particularly those found in foods and pollen, are known to act as sensitizing agents in humans upon repeated exposure. Among the cereal flour proteins involved in asthmatic reactions, those members of the alpha-amylase inhibitor family which are glycosylated, polypeptides, BMAI-1, BTAI-CMb*, and WTAI-CM16* are particularly reactive both in vivo and in vitro. We show here that these major glycoprotein allergens carry a single asparagine-linked complex glycan that contains both beta 1-->2 xylose and alpha 1-->3 fucose. Evidence is presented that the xylosyl residue and, to a lesser extent, the fucosyl residue are key IgE-binding epitopes and largely responsible for the allergenicity of these and unrelated proteins from plants and insects. Our results suggest that the involvement of xylose- and fucose-containing complex glycans in allergenic responses may have been underestimated previously; these glycans provide a structural basis to help explain the cross-reactivities often observed between pollen, vegetable food, and insect allergens.
Allergens↗
Pathological study of experimentally induced bovine respiratory syncytial viral infection in lambs.
An experimental model was designed to characterize lesions in the lung of lambs inoculated with bovine respiratory syncytial virus (BRSV). Twenty-five Merino lambs of both sexes, with a live weight of 17 +/- 3 kg, received an intratracheal inoculation of 20 ml saline solution containing 1.26 x 10(6) TCID50 BRSV (strain NMK-7) per ml. Lambs were slaughtered 1, 3, 7, 11 and 15 days postinoculation (DPI), and samples were taken for analysis using light-microscopic and immunohistochemical techniques. The results reflected the effect of the virus on airway epithelia. The presence of BRSV in ciliated bronchial and bronchiolar epithelial cells gave rise to cytopathological changes, including loss of cilia and cell necrosis; these changes might be expected to decrease the efficiency of mucociliary clearance, favouring the development of secondary bacterial bronchopneumonia. These results suggest a reduction in BRSV tropism for alveolar epithelia compared to bronchial and bronchiolar epithelia. Light-microscopic analysis revealed a narrowing of alveolar and airway lumina and a considerable interstitial inflammatory reaction.
Animals↗
Correlation of PCNA expression with clinico-pathologic features of neuroblastoma.
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Child↗
Treatment of Omenn syndrome by bone marrow transplantation.
We report the outcome of allogeneic bone marrow transplantation (BMT) in nine consecutive patients with Omenn syndrome treated between 1980 and 1989. Five patients received unmanipulated marrow from a related matched donor, and four received T cell-depleted marrow from a haploidentical donor. The patients were conditioned with cyclophosphamide (200 mg/kg) and, except in one case, busulfan (16 mg/kg). Antithymocyte globulin and etoposide were given to three patients each; three recipients of T cell-depleted haploidentical marrow also received intravenous injections of an anti-leukocyte function-associated antigen type 1 antibody as graft rejection prophylaxis. All the patients were fed parenterally for 1 to 5 months before BMT to improve nutritional status and received topical corticosteroids (n = 8), systemic steroids (n = 2), etoposide (n = 1), or cyclosporine (n = 1) to control T-cell activation. Engraftment occurred in four of five recipients of human leukocyte antigen (HLA)-identical marrow and three of four recipients of HLA-haploidentical marrow. One patient died with cytomegalovirus infection. The other six patients are alive 4 to 11 years after BMT, with full chimerism in all but one case. Chronic graft-versus-host disease persists in one patient; the other five survivors have fully restored immune function and have no manifestations of Omenn syndrome, including failure to thrive. We conclude that both HLA-identical and haploidentical BMT can cure Omenn syndrome, provided that parenteral nutrition and immunosuppressive therapy are given before transplantation.
Bone Marrow Transplantation↗
Influence of lasalocid, cationomycin and feeding frequency on the postprandial kinetics of some plasma parameters in the rumen vein, portal vein and mesenteric artery of sheep.
Two adult sheep, A and B, received successively during three experimental periods a forage-based pelleted feed, then the same diet supplemented with 33 mg/kg of lasalocid (L) or cationomycin (C). The feed was given in either eight (sheep A) or two (sheep B) daily meals. After four weeks of adaptation, 11 blood samples were taken through catheters in the rumen vein (RVA) and the mesenteric artery (MAA) in sheep A and in the rumen vein (RVB) and portal vein (PVB) in sheep B over a 5-hour period after the morning meal. Because of a blockage in the catheter it was not possible to measure the effect of C in MAA. Food intake had no immediate effect on the plasma levels measured: the distribution of eight daily meals stabilized plasma levels and made it easier to determine the effect of the ionophores. This effect varied according to the sampling site, the animal and the antibiotic, sometimes contradictorily. All the plasma parameters monitored in RVA were significantly modified by either one of the ionophores. A decrease in plasma albumin concentration (P < 0.05) was observed with L in MAA and with C in RVA and MAA. Aceto-acetate concentration decreased (P < 0.05) with L in MAA but increased with L and C in RVB. A decrease in glycaemia and uraemia (P < 0.05) was observed with L in MAA, RVA and RVB and with C in RVA. Total amino acid concentration decreased (P < 0.05) with C in RVA or increased (P < 0.05) with L in PVB and RVB. These variations in results may be due to different mechanisms of action of L and C on digestion, particularly in the rumen. While the changes undergone by the ketone bodies in the blood suggested a decrease in hepatic ketogenesis with L, there was no evidence that the ionophores had a direct postprandial effect.
Acetoacetates↗
Location of the active site of the bean alpha-amylase inhibitor and involvement of a Trp, Arg, Tyr triad.
Seeds of the common bean contain three homologous proteins: phytohaemagglutinin E, phytohaemagglutinin L and the lectin-like protein alpha-amylase inhibitor (alpha AI). Whereas the active site of lectins has been studied in great detail, there is no information on the active site of the related protein alpha AI, which exerts its biological activity by making a 1:1 complex with alpha-amylase. alpha-amylase inhibitor is synthesized as a 30 kDa precursor glycoprotein that needs to be processed at Asn77 to form an active molecule. Comparison of the amino acid sequence of the bean alpha AI with that of the bacterial amylase inhibitor, tendamistat, suggested that a region around Trp188 might be involved in the inhibitory site. When a three-dimensional model of the bean alpha AI was constructed based on its homology to the legume lectins, this Trp region was alongside Asn77. To test this site hypothesis, mutants of alpha AI were created by site-directed mutagenesis of the cDNA and expressed in transgenic tobacco. The mutant proteins R74N and WSY188-190GNV, as well as the double mutant, were inactive as inhibitors. These findings suggest that the active site of alpha AI consists of W188, R74 and Y190, in analogy to the Trp-Arg-Tyr motif of tendamistat, and that the processing of the polypeptide at Asn77 may be necessary to bring these residues in close proximity.
Amino Acid Sequence↗
p53 protein expression in viral warts from patients with epidermodysplasia verruciformis.
The p53 protein is the product of a tumour suppressor gene, which is implicated in many human malignancies. p53 expression was investigated by immunohistochemistry in a series of viral warts (n = 12) from five patients with epidermodysplasia verruciformis (EV), using a monoclonal anti-p53 antibody (DO7). p53 expression was also investigated in a series of common warts (n = 8), flat warts (n = 8), and penile bowenoid papulosis (n = 6) from non-EV patients. Immunostaining was positive in 11 of 12 (92%) EV warts, whereas p53 reactivity was negative in most cases of warts from non-EV patients. Exons 5-8 of the p53 gene were screened by the polymerase chain reaction-single strand conformation polymorphism technique in four EV warts, which were strongly stained for p53, and p53 mutations were not detected. These results suggest an association between p53 accumulation (probably of wild type) and EV warts.
Epidermodysplasia Verruciformis↗
Complementation of an Arabidopsis thaliana mutant that lacks complex asparagine-linked glycans with the human cDNA encoding N-acetylglucosaminyltransferase I.
N-Acetylglucosaminyltransferase I (EC 2.4.1.101) initiates the conversion of high-mannose asparagine-linked glycans to complex asparagine-linked glycans in plant as well as in animal cells. This Golgi enzyme is missing in the cgl mutant of Arabidopsis thaliana, and the mutant cells are unable to synthesize complex glycans. Transformation of cells from the mutant plants with the cDNA encoding human N-acetylglucosaminyltransferase I restores the wild-type phenotype of the plant cells. Fractionation of the subcellular organelles on isopycnic sucrose gradients shows that the human enzyme in the complemented cells bands at the same density, 1.14 g/cm3, typical of Golgi cisternae, as the enzyme in the wild-type plant cells. These results demonstrate that complementation results from the presence of the human enzyme in the plant Golgi apparatus, where it is functionally integrated into the biosynthetic machinery of the plant cell. In addition, given the evolutionary distance between plants and mammals and the great diversity of glycoproteins that are modified in each, there is probably no specific recognition between this Golgi enzyme and the polypeptide domains of the proteins it modifies.
Arabidopsis↗
Effects of lasalocid and cationomycin on the evolution of certain parameters in the blood plasma of sheep.
Six adult sheep were fed at maintenance level, successively over three experimental periods, 1100 g of a roughage-rich diet without supplement or containing 33 mg kg-1 of lasalocid or cationomycin. The feed was administered in eight equal meals daily, every three hours. Blood samples were taken in each animal from the jugular vein at 10.00 hours, 16.00 and 22.00 hours, one hour after the animals were fed. The ionophores did not affect the plasma concentrations of glucose, free fatty acids, total amino acids, insulin, acetate, Ca or Mg. They decreased beta-hydroxy butyrate content (P < 0.05) and increased that of albumin (P < 0.05). Lasalocid alone significantly decreased uremia, but the significant threshold was only reached at 16.00 hours (P < 0.01). With this exception, the two ionophores had similar effects. Samples taken in peripheral blood appear to be too far from nutrient absorption sites to give a clear indication of the effects of these molecules on the products absorbed or metabolised in the digestive tract.
3-Hydroxybutyric Acid↗
Acid-base status and intracellular pH regulation in lymphocytes from rats with genetic hypertension.
This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pHi) regulation in rat genetic models of hypertension. With freshly isolated thymic lymphocytes, pHi and its regulation were examined in the spontaneously hypertensive rat (SHR). In this rat model, pHi was found to be reduced as compared with that of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activity of the Na+/H+ antiporter assessed after stimulation by acute cell acidification was similar in lymphocytes from SHR and WKY rats both in the nominal absence of HCO3- and in media containing HCO3- (22 mM). The kinetic properties of the Na+/H+ antiporter, examined as a function of pHi with the Hill kinetic model, revealed no significant differences between lymphocytes from SHR and WKY rats. The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers, examined as a function of external Cl-, were also virtually identical in lymphocytes from SHR and WKY rats. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger; high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi. In Dahl/Rapp salt-sensitive rats with hypertension, the pHi of thymic lymphocytes was also reduced as compared with that of normotensive salt-resistant animals. In this model, renal net acid excretion in salt-sensitive rats was augmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titratable acid excretion and was observed while animals were placed on high, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overproduction is augmented in salt-sensitive hypertension.
Acid-Base Equilibrium↗
In vivo allergenic activities of eleven purified members of a major allergen family from wheat and barley flour.
Eleven purified members of the alpha-amylase/trypsin inhibitor family from wheat and barley that showed very different IgE-binding capacities when previously assayed in vitro, were used in double blind in vivo diagnostic tests to further evaluate their allergenic activity. These tests were carried out in 31 patients who showed allergic sensitization to wheat flour as verified by skin test, RAST and challenge test. The three members of the protein family with highest IgE binding in vitro (the glycosylated subunits of tetrameric alpha-amylase inhibitors CM16* from wheat and CMb* from barley, and the barley monomeric inhibitor BMAI-1) were found to be the strongest allergens as indicated by skin sensitivity in prick tests.
Adolescent↗
The immunologic response to experimental infection with bovine respiratory syncytial virus in lambs.
An experimental model was designed to study the humoral immune response in lambs experimentally infected with bovine respiratory syncytial virus (BRSV), 25 Merino lambs of both sexes, with a live weight of 17 +/- 3 kg, received an intratracheal inoculation of 20 ml. saline solution containing 1.26 x 10(6) TCID50 BRSV (strain NMK-7) per ml. Blood samples for serological analysis were collected from the jugular vein of the animals on days 0, 1, 3, 5, 7, 9, 11 and 15 post inoculation. Serum proteins were determined by electrophoresis, and a qualitative and quantitative analysis of immunoglobulins (Ig) was carried out using immunoelectrophoresis (IE) and light nephelometry, respectively. Serum anti-BRSV antibody levels were tested by enzyme-linked immunoabsorbent assay (ELISA). Lambs were necropsied 1, 3, 7, 11 and 15 postinoculation days (p.i.d.), and samples were taken for immunohistochemical analysis. IgA, IgG and IgM were labelled on paraffin-embedded lung sections using an avidin-biotin-peroxidase complex. Results reflected an increase in gamma fractions in experimental animals with respect to controls. IE analysis of these sera revealed a polyclonal increase in immunoglobulins. Nephelometric examination showed an increase in serum IgA, IgG an IgM levels up to 7 p.i.d., coinciding closely with high titres for humoral virus antibodies. After 9 p.i.d., titres and immunoglobulin levels both fell. Immunoglobulin labelling in formol-fixed and paraffin-embedded lung tissue samples detected IgG and IgA, mainly in bronchial, bronchiolar and alveolar epithelia. IgM, however, was not detected in the lungs of infected animals.
Animals↗