Fluorescence of (+)-anti-benzo(a)pyrene diol epoxide [(+)-anti-BPDE] covalently bound to poly(dG-dC) has been studied with steady-state and time-resolved techniques. Extensive formation of excimers is found, even at small (0.008) BPDE/nucleotide ratios. This indicates favored covalent binding to bases close to already modified guanines. Both fluorescence excitation spectra and lifetime measurements reveal two populations of (+)-anti-BPDE adducts: one that can form excimers and one that cannot. Three excimer lifetimes (4.5, 29, and 83 ns) are observed. Differently shifted monomer and excimer excitation spectra are discussed in terms of pyrene-pyrene exciton interactions, consistent with a distance shorter than 7 A between the excimer-forming BPDE chromophores.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMedDate not supplied

Familial benign chronic intrahepatic cholestasis.

Three of four adult siblings in a family which was studied for three generations had clinical and/or laboratory signs of slowly progressive intrahepatic cholestasis. Slight hyperpigmentation, facial hypertrichosis, and hypothyroidism were seen in affected individuals who also had prolonged increase in serum transaminase, gamma-glutamyltranspeptidase, and alkaline phosphatase activities. Asymptomatic intervals were characterized by abnormal bromosulfophthalein retention, reduced N-demethylation capacity, elevated fasting total serum bile acid levels, and normal light microscopic findings. A high serum alpha-lipoprotein level was found in individuals affected with this hitherto unknown entity which appears to have an autosomal recessive mode of inheritance.

Adult↗

PubMedDate not supplied

Complement components and activation in primary biliary cirrhosis.

Total complement activity was normal in 18 patients with primary biliary cirrhosis using two hemolytic assays capable of distinguishing between defects in classical and alternative pathways. Activation of the classical pathway was demonstrated in all patients by formation of complexes between C1r, C1s, and C1 inactivator. Large amounts of free C1q, not in complex with C1r and C1s, were demonstrated in the majority of patient sera. Furthermore, C4 levels were within the normal range or slightly subnormal. No evidence for alternative pathway activation was found. Increased mean levels of several complement components, in particular C1 inactivator, C2, C3, factor B, factor H, were noted. A significant correlation between these complement factors, derived mainly from the liver, and ceruloplasmin suggests that this elevation might be secondary to cholestasis. In contrast, no significant correlation with levels of early reacting acute phase reactants, immunoglobulins, or circulating immune complex-like material were observed. It is concluded that activation of the complement system by the classical pathway is common in patients with primary biliary cirrhosis.

Antigen-Antibody Complex↗

PubMedDate not supplied

Biosynthesis of abnormally glycosylated alpha 1-antitrypsin by a human hepatoma cell line.

The human hepatoma cell line PLC/PRF/5 synthesized and secreted a functional alpha 1-antitrypsin (alpha 1-AT) glycoprotein with normal molecular size but retarded electrophoretic mobility. The total process of translation, glycosylation and export required about 40 min and followed the same synthetic pattern as seen in rat hepatocytes, i.e., a signal peptide is cleaved cotranslationally; a core-glycosylated protein in the high-mannose form is formed in the rough endoplasmic reticulum, trimmed, and a stable complex-glycosylated alpha 1-AT is found intracellularly prior to export. alpha 1-AT export to medium was delayed by tunicamycin, inhibited by cycloheximide but unaffected by colchicine. After addition of exogenous alpha 1-AT to culture medium, neither negative nor positive feedback induction of synthesis could be demonstrated. Electrophoretic techniques indicated the presence of atypical, highly branched but incompletely sialylated carbohydrate chains in the hepatoma cell-derived alpha 1-AT. The accumulation of intracellular alpha 1-AT inclusions seen in the endoplasmic reticulum may reflect an imbalance between a high rate of polypeptide synthesis and terminal glycosylation.

Biological Transport↗

PubMedDate not supplied

Low levels of coagulation inhibitors in patients with Clostridium difficile infection.

To investigate levels of coagulation inhibitors in sera from patients with Clostridium difficile-associated diarrhoea and colitis, commercially available antigen assays were used for immunochemical determination of antithrombin III, protein C and free protein S. Sera from patients with Clostridium difficile-associated diarrhoea and colitis showed significantly lowered levels of all measured inhibitors as compared to controls (Student's t test). Protein C (mean +/- SD): 0.70 +/- 0.30 vs. 1.28 +/- 0.23, t = 6.61, p less than 0.001; antithrombin: 0.70 +/- 0.21 vs. 0.90 +/- 0.17, t = 3.12, p less than 0.01; free protein S: 0.27 +/- 0.06 vs. 0.37 +/- 0.08, t = 3.7, p less than 0.001. Infection with C. difficile may lead to loss of coagulation inhibitors and constitutes a risk for thromboembolic complications.

Aged↗

PubMedDate not supplied

Concentration and purification of feline leukaemia virus (FeLV) and its outer envelope protein gp70 by aqueous two-phase systems.

The major protective antigens of retroviruses are considered to be their glycosylated envelope proteins. However, the methods commonly employed to enrich and purify virus from culture media such as pelleting and density-gradient centrifugation result in a low recovery of the viral external glycoproteins. This is an obvious drawback when the virus is intended for use in a vaccine. In search for alternative methods to concentrate and purify FeLV, we have attempted extraction in two-phase systems based on water-soluble polymers (Albertsson PA., Biochem Biophys Acta 1958; 27: 378-395). A variety of polymer systems was tested. Some of them seem attractive for a large-scale concentration of the virus and/or its glycoprotein. The distribution between the phases of two FeLV proteins, the outer envelope protein, gp70, and the gag protein, p27, was determined. With a system composed of dextran sulfate and polyvinyl alcohol both the glycoprotein and the gag protein were almost completely recovered in the lower phase which constitutes about 3% of the total system in weight. The two proteins were more than 40-fold purified as calculated on protein basis. The proteins can be extracted readily.

Animals↗

PubMedDate not supplied

Retrospective analysis of the efficacy of cefotaxime sodium dosed twice daily. The Swedish experience.

In a Swedish multicenter, comparative, retrospective study, patients with different types of infections--bacteremia-septicemia, genitourinary, intra-abdominal, central nervous system, and lower respiratory tract infections--were randomly selected from the hospital records. Patients treated with cefotaxime twice or three times a day as monotherapy (excluding metronidazole) for at least 1 day (240 cases) were analyzed in terms of clinical and bacteriologic outcome, these results were correlated with the dosing regimen. Similarly high success rates (cure and improvement) at hospital discharge were observed in both group initially treated with cefotaxime 1 g twice daily and 2 g twice daily (97 and 96%, respectively). A total of 73% of patients were initially treated with cefotaxime for only 3 days at most before changing to a lower dose regimen, an alternate intravenous treatment, or oral drug follow-up. Clinical evaluation at hospital discharge revealed a clinical success rate between 87 and 100%, depending on the type of infection.

Adolescent↗