A Community-based Study of Prolonged Fatigue and Chronic Fatigue

Previous estimates of the prevalence of fatigue and chronic fatigue have derived largely from treated populations and have been biased by differential access to health-care treatment linked with gender, racial/ethnic and social class status. This study involves a community-based prevalence study of prolonged fatigue and chronic fatigue. It addresses: (1) the rate of prolonged fatigue and chronic fatigue in a socioeconomically and ethnically diverse sample of 28,673 adults in Chicago; and (2) establishes the relative prevalence of prolonged fatigue and chronic fatigue across race/ethnicity, socio-economic status and gender. Univariate and multivariate statistical techniques were utilized to delineate the overall rate of prolonged fatigue and chronic fatigue in the Chicago population and its relative prevalence by gender, race/ethnicity, and social class. Findings indicated that fatigue is common in urban populations, but that prolonged fatigue and chronic fatigue occur in about 5.00 to 7.68 percent and 2.72 to 4.17 percent, respectively, of the sample of the population. Highest levels of fatigue were consistently found among women and those with lower levels of education and occupational status.     

Purification and properties of a glycoprotein acid phosphatase from the yeast form of Yarrowia lipolytica

An acid phosphatase from derepressed cells of the yeast form of Yarrowia lipolytica was purified 176-fold by ammonium sulfate precipitation, chromatography on DEAE-Sephacel and gel filtration in Biogel A 5-M. The enzyme is a glycoprotein with a sugar content of 60%. The MICHAELIS constant of the enzyme is 5.5 × 10^?4 M for p-nitrophenyl phosphate as substrate; the isoelectric point estimated by electrofocusing is around 4.6 and the optimum pH is 6.2. Phosphatase activity was destroyed by exposure of the enzyme to 40 °C for 30 min or at pH 3 for 30 min. The purified enzyme shows size heterogeneity within a linear concentration gradient of polyacrylamide (4–20%) which indicates an apparent molecular weight in the range of 90,000–200,000 in the presence of sodium dodecyl sulfate. The heterogeneity of the enzyme is due to its carbohydrate content, as can be demonstrated by gel filtration and by treatment with endoglycosidase H. The carbohydrate-depleted protein has a molecular weight of 60,000. Aminoacid analysis revealed a high content of aspartic acid, serine, threonine, glycine and alanine. Antibodies against the protein moiety show cross reactivity with the acid phosphatase of Saccharomyces cerevisiae.     

Changes in the human immunodeficiency virus p7-p1-p6 gag gene in drug-naive and pretreated patients

Resistance to antiretroviral agents often results from mutations within the human immunodeficiency virus (HIV) pol gene. Moreover, insertions within the p6 gag-pol region have recently been found to be involved with resistance to nucleoside analogs. Overall, we found that 21% of 156 specimens collected from HIV-infected individuals (17.6% from 74 drug-naive patients and 24.4% from 82 pretreated patients) harbored these insertions. Insertions around the KQE (Lys-Gln-Glu) motif were found in 12.2% of the pretreated patients but in none of the drug-naive subjects (P = 0.002). In contrast, insertions around the PTAP (Prol-Thre-Ala-Prol) motif were seen at similar rates ( approximately 15%) among drug-naive and pretreated patients, which supports the idea that they may be natural polymorphisms.     

Cloning,isolation, and IgE-binding properties of Helix aspersa (brown garden snail) tropomyosin

BACKGROUND: Gastropod consumption is quite frequent in the Mediterranean countries and cross-reactivities with crustaceans have been described, but the mechanism of this allergenic cross-reactivity has not been studied in detail. This study aimed to produce recombinant Helix aspersa (brown garden snail) tropomyosin and investigate its implication for cross-reactivity among invertebrates. METHODS: A tropomyosin-specific cDNA encoding H. aspersa tropomyosin was synthetized, and recombinant allergen was overexpressed in Escherichia coli as nonfusion protein. IgE-binding reactivity was studied by immunoblotting and immunoblot inhibition experiments with sera from snail-allergic patients. RESULTS: Cloned brown garden snail tropomyosin shares high homology with other edible mollusk tropomyosins (84-69% identity) as well as with those from arthropods (65-62%), and less homology with vertebrate ones (56% identity). Tropomyosin reacted with 18% of the sera from patients with snail allergy. Inhibition experiments, using natural and recombinant tropomyosins, showed different degrees of cross-reactivity between invertebrate tropomyosins. Sera from snail-allergic subjects recognized tropomyosins in both mollusks and crustacean extracts. CONCLUSIONS: Tropomyosin represents a minor allergen in snail extracts, but it is clearly involved in invertebrate cross-reactivity.     

Evaluation of formalin-inactivated Clostridium difficile vaccines administered by parenteral and mucosal routes of immunization in hamsters.

Clostridium difficile produces toxins that cause inflammation, necrosis, and fluid in the intestine and is the most important cause of nosocomial antibiotic-associated diarrhea and colitis. We evaluated C. difficile antigens as vaccines to protect against systemic and intestinal disease in a hamster model of clindamycin colitis. Formalin-inactivated culture filtrates from a highly toxigenic strain were administered by mucosal routes (intranasal, intragastric, and rectal) with cholera toxin as a mucosal adjuvant. A preparation of culture filtrate and killed whole cells was also tested rectally. The toxoid was also tested parenterally (subcutaneously and intraperitoneally) and by a combination of three intranasal immunizations followed by a combined intranasal-intraperitoneal boost. Serum antibodies against toxins A and B and whole-cell antigen were measured by enzyme-linked immunosorbent assay, neutralization of cytotoxic activity, and bacterial agglutination. The two rectal immunization regimens induced low antibody responses and protected only 20% of hamsters against death and 0% against diarrhea. The intragastric regimen induced high antibody responses but low protection, 40% against death and 0% against diarrhea. Hamsters immunized by the intranasal, intraperitoneal, and subcutaneous routes were 100% protected against death and partially protected (40, 40, and 20%, respectively) against diarrhea. Among the latter groups, intraperitoneally immunized animals had the highest serum anticytotoxic activity and the highest agglutinating antibody responses. Hamsters immunized intranasally and revaccinated intraperitoneally were 100% protected against both death and diarrhea. Protection against death and diarrhea correlated with antibody responses to all antigens tested. The results indicate that optimal protection against C. difficile disease can be achieved with combined parenteral and mucosal immunization.     

Histidinuria: A renal and intestinal histidine transport deficiency found in two mentally retarded children

Two siblings presenting slight mental retardation showed an abnormal elimination of histidine, their blood levels for the same amino acid being normal. The percentage of tubular resorption of histidine was calculated in both boys, and the values were 40.1 per cent (case 1) and 52.8 per cent (case 2). All other amino acids essayed were normal. After an oral overload test with histidine, a low intestinal absorption was found in the two boys, the values of this test in the parents being intermediate between those of the children and of the three normal controls and corresponding to heterozygosity. In view of the studies carried out on the two boys, it is possible to conclude that they are suffering from an impairment in their histidine membrane transport system which affects the kidney and intestines. Since they are siblings a genetically determined trait may be suspected.     

Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells

Autosomal-dominant polycystic kidney disease is a multiorgan disease and its vascular manifestations are common and life-threatening. Despite this, little is known about their pathogenesis. Somatic mutations to the normal PKD allele in cystic epithelia and cyst development associated with the unstable Pkd2(WS25) allele suggest a two-hit model of cystogenesis. However, it is unclear if this model can account for the cardiovascular pathology or if haploinsufficiency alone is disease-associated. In the present study, we found a decreased polycystin-2 (PC2, protein encoded by Pkd2 gene) expression in Pkd2( +/-) vessels, roughly half the wild-type level, and an enhanced level of intracranial vascular abnormalities in Pkd2 (+/-) mice when induced to develop hypertension. Consistent with these observations, freshly dissociated Pkd2 (+/-) vascular smooth muscle cells have significantly altered intracellular Ca(2+) homeostasis. The resting [Ca(2+)](i) is 17.1% lower in Pkd2 (+/-) compared with wild-type cells (P=0.0003) and the total sarcoplasmic reticulum Ca(2+) store (emptied by caffeine plus thapsigargin) is decreased (P<0.0001). The store operated Ca(2+) (SOC) channel activity is also decreased in Pkd2 (+/-) cells (P=0.008). These results indicate that inactivation of just one Pkd2 allele is sufficient to significantly alter intracellular Ca(2+) homeostasis, and that PC2 is necessary to maintain normal SOC activity and the SR Ca(2+) store in VSMCs. Based on these findings, and the fact that [Ca(2+)](i) signaling is essential to the regulation of contraction, production and secretion of extracellular matrix, cellular proliferation and apoptosis, we propose that the abnormal intracellular Ca(2+) regulation associated with Pkd2 haploinsufficiency is directly related to the vascular phenotype.