Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion

BACKGROUND: In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma. OBJECTIVE: Using 15-year follow-up data from the Copenhagen City Heart Study, we now further explore this relationship. METHODS: As part of 3 surveys in 1976 to 1978, 1981 to 1983, and 1991 to 1994, we measured pulmonary function and asked all participants about asthma and pulmonary risk factors. RESULTS: There was no difference in annual decline in lung function between DeltaF508 heterozygotes and noncarriers overall; however, among individuals with familial asthma, the annual declines in FEV(1) and forced vital capacity (FVC) were 49 and 36 mL in DeltaF508 heterozygotes versus 24 and 17 mL in noncarriers (P =.01 and P =.12, respectively). Cross-sectionally based on triple measurements, FEV(1) and FVC in individuals aged 20 to 70 years were lower in heterozygous participants versus noncarriers (P =.02 and P =.004, respectively). The average reduction of FEV(1) and FVC in DeltaF508 heterozygotes versus noncarriers was 70 mL (P =.06) and 136 mL (P =.008). Finally, 10% of carriers reported asthma versus 7% of noncarriers (P =.02), resulting in an odds ratio of 2.0 (1.3-3.2) for asthma in DeltaF508 heterozygotes. CONCLUSION: Cystic fibrosis DeltaF508 heterozygotes may be overrepresented among individuals with asthma and may have poorer lung function than noncarriers. Furthermore, DeltaF508 heterozygosity in context with familial predisposition to asthma may be associated with a greater annual FEV(1) decline.     

Congenital anomalies and genetic disorders in families of children with central nervous system tumours.

Medical genetic histories of 165 children with primary central nervous system (CNS) tumours and 4599 relatives of these probands were examined to identify birth defects or genetic disorders that may be associated with the aetiology of CNS tumours. Twelve primary malignancies were found in 329 (4%) of the parents of probands. Two of 99 half sibs but no full sibs had malignancies. Twenty-four percent of families had histories warranting consultation for an inherited disorder or birth defect. Single instances of malformations or genetic disorders were reported in 36 families and several disorders were reported in more than one family, including familial hypercholesterolaemia (4), olivopontocerebellar atrophy (2), and familial abdominal aortic aneurysm (2). Although recurring abnormalities were not identified in probands, it is possible that one or more of the birth defects or genetic disorders observed in probands or relatives may be associated with CNS tumourigenesis.     

Reactions of Musca domestica L. (Diptera: Muscidae) to parasitism by Aphaereta pallipes (Say) (Hymenoptera: Braconidae), with special reference to host diet and parasitoid toxin

Summary Varying host reaction of the house fly, Musca domestica L., to parasitism by the braconid Aphaereta pallipes (Say) was chiefly correlated with the diet of the host. Some evidence was found that implicated the strain of the host, the rearing temperatures, the ages of the parasitoid and the host, and the site of oviposition. Though development of A. pallipes embryos was inhibited before they became encapsulated with melanin within the host, the presence of the parasitoid and (or) the effect of its paralyzing toxin that was injected into the host just before oviposition prevented normal larval, pupal, or adult development of the six house fly strains tested. A considerable increase of parasitoid survival occurred when M. domestica larvae were reared on a chemically defined diet.

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Zusammenfassung Musca domestica L. reagierte unterschiedlich auf die Parasitierung durch die Braconide Aphaereta pallipes (Say). Die verschiedenen Reaktionen waren im wesentlichen mit der Art der Wirtsnahrung korreliert. Daneben finden sich Hinweise, daß auch der Wirtsstamm, dessen Zuchttemperatur, das Alter von Parasit und Wirt und der Eiablageort des Parasiten die Reaktionen beeinflussen. Obgleich die Entwicklung von Parasitenembryonen bereits gehemmt war, ehe sie innerhalb des Wirtes von Melanin eingeschlossen wurden, so verhinderten doch die Parasiten-embryonen und/oder die Wirkung der vor der Eiablage abgegebenen Paralysierungstoxine die normale Entwicklung der Wirte aus sechs Fliegenstämmen. Eine beträchtliche Steigerung der Überlebensrate der Parasiten trat ein, wenn M. domestica-Larven in einem Gemisch chemisch genau definierter Nahrung gezogen wurden.

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With 8 Figures in the Text

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Formerly National Research Council Postdoctorate Fellow, Research Institute, Belleville, Ontario.     

Radioimmunoscintigraphy and radioimmunotherapy of renal cell carcinoma xenografts

From a panel of monoclonal antibodies (MAb) reactive with human renal cell carcinoma generated by this laboratory, three (designated A6H, C5H, and D5D) were selected for in vivo studies with a nude mouse xenograft model. These studies included 131I- and 111In-labeled MAb radioimmunoscintigraphy and 131I-labeled MAb radioimmunotherapy. In the imaging studies, these radiolabeled MAb allowed visualization of subcutaneous xenografts larger than 40 mg and subrenal capsule xenografts smaller than 20 mg. Comparisons of tumor to non-tumor tissue radiolabel distribution yielded unusually high ratios and depended on the MAb-xenograft combination. The 111In-radiolabeled A6H showed increased accumulation in the liver compared with 131I-A6H, but this still did not necessitate background subtraction for good visualization of small, subrenal capsule renal cell carcinoma xenografts. Radioimmunotherapy studies with 131I-A6H in BALB/c nu/nu mice bearing established renal cell carcinoma xenografts showed a prolonged (greater than 90 days) regression in tumor burden and possible "cures," whereas three sets of control mice showed progressive and rapid increases in tumor size. These studies indicated that MAb, which show good tissue biodistribution and high imaging sensitivity, could also be capable of delivering effective radiotherapy to the tumor when "human equivalent" radiolabeled-MAb doses are used.     

218. Prostaglandin E I verhindert die Aspirin-bedingte Ischämie der Magenmucosa; ein Mechanismus der Cytoprotektion?

Zusammenfassung Der Mechanismus der Cytoprotektion von Prostaglandin (PG) auf die Magenmucosa ist unbekannt. Anaesthesierte Kaninchen erhielten in der Gruppe (GR) I (n=8) im. Aspirin (ASA) (100 mg/kg als Bolus, 66 mg/kg/h kontinuierlich) in der GR 11 (n=10) NaCI und in der GR III (n=7) zusätzlich zum ASA, PGE I (0,1 g/kg/min) als Infusion über 120 min. Der Mucosa-Blutfluß (MBF) wurde mit radioaktiven Mikrosphären gemessen. In der GR I fiel der MBF nach 15 min um 72,3+3,8% (+ SEM) und nach 120 min um 73,1+3,8% (p 0,05 gegen % Änderung in GR II und III). Nach 120 min zeigte sich in der GR I 19,8 + 7,6% der Fundusmucosa hämorrhagisch, in der GR 11 6,1 +5,2% und in der GR 1112,0+ 1,4% (p 0,05 gegen GR II und III). Wir schließen, daß der cytoprotektive Effekt des PGE I auf einer Aufhebung der ASA bedingten Mucosaischämie beruht.     

Clinical utility of PTSD,resilience, sleep,and blast as risk factors to predict poor neurobehavioral functioning following traumatic brain injury: A longitudinal study in U.S. military service members

Quality of Life Research - This study examined the clinical utility of post-traumatic stress disorder (PTSD), low resilience, poor sleep, and lifetime blast exposure as risk factors for predicting...     

Plasma B Vitamers: Population Epidemiology and Parent-Child Concordance in Children and Adults

Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent–child dyads are scarce. Profiling B vitamers in parent–child dyads enables an insightful determination of gene–environment contributions to their circulating concentrations. We aimed to characterise: (a) parent–child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28–71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia’s Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent–child pairs (10–31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.     

Comparative Effects of the Branched-Chain Amino Acids,Leucine, Isoleucine and Valine,on Gastric Emptying,Plasma Glucose,C-Peptide and Glucagon in Healthy Men

(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using ¹³C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0–30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.