Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia

Background G protein‐coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings. Objective To analyze the association of G protein‐coupled receptor 154 with asthma and total and mite‐specific IgE levels in a population of the Caribbean Coast of Colombia. Methods We genotyped seven single nucleotide proteins (SNPs) in GPR154 in 475 asthmatics, 394 controls and 116 families from Cartagena, Colombia using either SnaPshot or TaqMan. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Hardy–Weinberg equilibrium was assessed and case–control and family‐based analyses were performed to evaluate the association between the SNPs and their haplotypes and asthma and IgE. Association analyses in the case–control dataset were corrected by population stratification using 52 ancestry informative markers. Results Allelic distribution was similar to that described in other populations. Two SNPs were associated with the same direction of the effect in both datasets. Allele A of Hopo546333 was protective for asthma (case–control OR: 0.42; 95% CI: 0.17–0.99, P=0.042; P=0.043; families Z score=?2,236; P=0.025). Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28–0.70, P=0.00017; P_c=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09–0.88, P=0.015; P_c=0.030) in the case–control study and families (Z score=?3.207, P=0.0013; Z score=?3.182, P=0.0014, respectively). Haplotype CCAGGT was associated with total IgE (OR: 1.76; 95% CI: 1.14–2.71, P=0.006, P_c=0.007) in the case–controls group and CGCGGT with both phenotypes (P=0.044 and P=0.032, respectively) in families. Neither SNPs nor haplotypes were associated with levels of mite‐specific IgE. Conclusions Our findings in a sample of asthmatics from Colombia suggest a relevant role of G protein‐coupled receptor 154 in the pathogenesis of asthma and allergy.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

A spectrum of monoclonal antibodies reactive with human mammary tumor cells.

Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a "pancarcinoma" reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.     

Hormone profiling in a novel enteroendocrine cell line pGIP/neo: STC-1

Objective.GIP is a peptide hormone of therapeutic interest in type 2 diabetes and obesity. This study evaluated pGIP/neo STC-1 as a potential K-cell model for studying GIP secretion.Methods.We evaluated cellular storage and medium accumulation of GIP along with other gastrointestinal peptides cholecystokinin (CCK), peptide YY (PYY), obestatin and ghrelin over 72 h and probed possible intracellular signals (PKA, PKC, Ca^2 + and GPCR) involved in peptide hormone synthesis/secretion.Results.Results demonstrate for the first time that pGIP/Neo STC-1 cells produce and secrete 3 to 6 times more GIP than STC-1. The cells clearly retain the ability to synthesize and secrete CCK and PYY but reduced levels indicate a shift towards a predominantly K-cell phenotype. Furthermore, gastric peptides such as obestatin and ghrelin are not produced in either STC-1 or pGIP/Neo STC-1 cells.Discussion.This study demonstrates the potential usefulness of pGIP/Neo cells for studying GIP secretion and further investigations will establish its suitability for investigating hormone release in vitro.     

Informativeness of the spoken narratives of younger and older adolescents with specific language impairment and their counterparts with normal language

A large body of literature describing the narrative skills of young children with and without language impairments exists. However, there has been only limited study of the informativeness of narratives of adolescents with normally developing language (NL) and those of adolescents with specific language impairment (SLI), even though narratives play an important role in adolescents' complex social and academic lives and there is emerging evidence that narrative abilities in young children portend their later language proficiency. This study examined the informativeness of oral narratives produced by four groups of adolescents: younger adolescents with NL (mean age = 13years:2 months), older adolescents with NL (15:10), younger adolescents with SLI (13:2) and older adolescents with SLI (15:9). The results indicated that the narratives produced by the SLI adolescents consisted of fewer informative and more irrelevant/inaccurate responses than the narratives of their peers with NL. The SLI adolescents also tended to give more vague responses in their narratives than their NL counterparts, as well tending not to provide any responses to the pictures representing the story. Taken together, these results painted a picture of SLI adolescents producing less satisfying, complete, and cohesive narratives, findings consistent with those of the research on children with SLI. Language status more than age appeared to be the factor that affected the likelihood of the adolescents providing or not providing informative responses. These results suggested that the performance of adolescents with SLI may not catch up to the level of performance of their NL counterparts during adolescence.     

Interdisciplinary management in the paediatric patient: restoration of a complicated crown-root fracture

Complicated crown-root fractures in permanent teeth present both patient-centred and restorative problems when treating the adolescent. This case highlights an alternative and conservative technique for the management of a traumatically involved maxillary left central incisor in a 12-year-old boy. The injury was successfully managed through an interdisciplinary approach using a combination of endodontics, minor oral surgery and orthodontics. The approach resulted in utilizing the patient's own tooth fragment to facilitate restoration back into successful function and aesthetics with the absence of any pathological changes.