Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male

Factor VII (FVII) is the plasma serine protease zymogen which, on binding to its cellular receptor tissue factor (TF), initiates blood coagulation. A 47-year-old man with no clinical bleeding tendency was found to have undetectable plasma FVII activity when tested in a one- stage assay using rabbit brain TF, but 0.3 U/mL using recombinant human TF and 1.04 U/mL FVII antigen. Variant FVII purified from his plasma showed an identical migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to wild-type zymogen. By enzyme kinetic analysis the Km of the variant using FX as a substrate was 12-fold higher than that of normal FVII. Also, the variant FVII was unable to compete with wild-type FVII for limited rabbit TF binding sites. A ligand blot procedure was used to directly demonstrate reduced binding of recombinant human TF to the variant FVII compared with normal FVII. Genetic analysis of leukocyte DNA showed a G to A mutation in the propositus' gene at codon 304 that results in the substitution of a glutamine for an arginine residue in the catalytic domain of the protease. We conclude that this region of the FVII molecule is important for its function.     

Four new recurring translocations in non-Hodgkin lymphoma

The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy- chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.     

Activation of factor VII during alimentary lipemia occurs in healthy adults and patients with congenital factor XII or factor XI deficiency, but not in patients with factor IX deficiency

Factor VII activity (FVIIc), a risk marker for coronary heart disease, is increased during postprandial lipemia. Factor VII activation accompanies lipolysis of triglyceride-rich lipoproteins, but the nature of this association and whether it is causal remain uncertain. To explore this issue, four patients with homozygous factor XII deficiency, four with complete factor XI deficiency, six with factor IX deficiency, and their respective age- and sex-matched controls were given two isocaloric dietary regimens, one providing on average 136 g fat and the other 19 g fat. Blood was taken before breakfast, immediately before lunch at 195 minutes, and at completion of the study at 390 minutes. All samples for each subject and matched control were assayed as one batch for FVIIc, activated factor VII, and factor VII antigen (FVIIag). Activation of factor VII was observed with the high- fat regimen but not with the low-fat regimen in all controls, factor XII-deficient patients, and factor XI-deficient patients. No factor VII activation was observed during either regimen in factor IX-deficient patients, but a normal postprandial responsiveness of factor VII to dietary fat was restored in one patient who replicated the study after factor IX therapy. Plasma FVIIag was not altered postprandially in either regimen in any group of patients or controls. Factor IX apparently plays an obligatory role in the postprandial activation of factor VII, although the mechanism remains to be determined.     

A population based time series analysis of asthma hospitalisations in Ontario, Canada: 1988 to 2000

Background  

Asthma is a common yet incompletely understood health problem associated with a high morbidity burden. A wide variety of seasonally variable environmental stimuli such as viruses and air pollution are believed to influence asthma morbidity. This study set out to examine the seasonal patterns of asthma hospitalisations in relation to age and gender for the province of Ontario over a period of 12 years.     

On pandemics and the duty to care: whose duty? who cares?

Background  

Studying the contribution of individual countries to leading journals in a specific discipline can highlight which countries have the most impact on that discipline and whether a geographic bias exists. This article aims to examine the international distribution of publications in the field of bioethics.     

Possible association between genetic variability at the apolipoprotein(a) locus and Alzheimer's disease in apolipoprotein E2 carriers

Apolipoprotein(a) (Apo(a)) is a glycoprotein that is linked by a disulfide bond to apolipoprotein B on low density lipoprotein particles to form lipoprotein(a) (Lp(a)). High plasma levels of Lp(a) are thought to contribute directly to the development of atherosclerosis. We tested a variant (T3888P) located in the Kringle-IV region of Apo(a) in a case-control series. Overall, there were no differences between case and controls. However, in the apoE2 positive subgroup, we noticed that the mutant allele is over-represented in the cases (P=0.005). We suggest that this polymorphism and others at the Apo(a) locus be further studied in relation to Alzheimer's disease.     

Seasonality of primary care utilization for respiratory diseases in Ontario: A time-series analysis

Background  

Respiratory diseases represent a significant burden in primary care. Determining the temporal variation of the overall burden of respiratory diseases on the health care system and their potential causes are keys to understanding disease dynamics in populations and can contribute to the rational management of health care resources.     

Light activated disinfection: an alternative endodontic disinfection strategy

Background:  An improved light activated disinfection technique utilizing a specific photosensitizer formulation, liquid optical-conduit, oxygen-carrier and light energy of appropriate wavelength has been introduced recently. This study tested the efficacy of this improved light activated disinfection on ex vivo biofilms of Enterococcus faecalis at two different stages of maturation.
Methods:  Eighty-five tooth sections were prepared and endodontic biofilm of E. faecalis were grown within the root canal. In stage 1, conventional light activated disinfection (LAD), chemical disinfectant (sodium hypochlorite) and improved LAD were tested on four-day-old (immature) biofilms. In stage 2, conventional LAD, improved LAD and chemomechanical disinfection (alone and in combination with improved LAD) were tested on four-week-old (mature) biofilms.
Results:  Sodium hypochlorite and improved LAD showed the ability to significantly inactivate bacteria in four-day-old biofilms when compared to the control and LAD (p < 0.05). Inactivation of bacteria from deeper dentine was higher in improved LAD than sodium hypochlorite. In four-week-old biofilms, a combination of chemomechanical disinfection and improved LAD produced significant bacterial killing compared to either chemomechanical disinfection or improved LAD alone.
Conclusions:  This study highlighted the potential of improved LAD to kill bacteria within dentinal tubules. In combination with chemomechanical preparation, the improved LAD significantly inactivated four-week-old biofilm bacteria.