Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease

Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl ester storage disease (CESD). Direct sequencing of genomic DNA revealed that: patient 1 was a compound heterozygote for a P181L mutation and an A to G3' splice site substitution that causes skipping of exon 7, with a loss of 49 amino acids from LAL (delta 205-253); patient 2 was a compound heterozygote for a G66V mutation and a 5' splice site mutation (G to A) that leads to skipping of exon 8 (delta 254-277); and patient 3 was a compound heterozygote for a L273S mutation and an unidentified null allele. Furthermore, patients 2 and 3 showed a novel G-2A polymorphism that could be detected by an Xbal restriction fragment length polymorphism. All these mutants and a previously reported H274Y allele were expressed in vitro in HeLa cells using the vaccinia T7 expression system. The resulting recombinant proteins were inactive towards cholesteryl oleate and trioleylglycerol, demonstrating the direct involvement of these mutations in the pathogenesis of CESD. Immunoblotting of normal LAL expressed in HeLa cells revealed four major molecular forms, at least two of high molecular mass (54 and 50-51 kDa) and two of low molecular mass (42 and 43 kDa). L273S and P181L substitutions and delta 254-277 were shown to result in altered LAL molecular forms, some of which suggest that post-translational processing may interfere with the catalytic activity of LAL.      

Predictors of maternal mortality in institutional deliveries in Nigeria

Background

Maternal mortality in poor countries reflects the under-development in these societies. Global recognition of the burden of maternal mortality and the urgency for a reversal of the trend underpin the Millenium Development Goals (MDGs).

Objective

To determine risk factors for maternal mortality in institutional births in Nigeria.

Method

Twenty one health facilities in three states were selected using stratified multi-stage cluster sampling strategy. Information on all delivered mothers and their newborn infants within a three-month period was culled from medical records.

Results

A total of 9 208 deliveries were recorded. About one-fifth (20.5%) of women had no antenatal care while 79.5% had at least one antenatal visit during pregnancy. Four-fifths (80.5%) of all deliveries were normal deliveries. Elective and emergency caesarean section rates were 3.1% and 11.5% respectively. There were 79 maternal deaths and 8 526 live births, giving a maternal mortality ratio of 927 maternal deaths per 100 000 live births. No antenatal care, parity, level of education, and mode of delivery were significantly associated with maternal mortality. Low maternal education, high parity, emergency caesarean delivery, and high risk patients risk independently predicted maternal mortality.

Conclusion

Meeting goal five of the MDGs remains a major challenge in Nigeria. Multi-sectoral approaches and focused political will are needed to revert the high maternal mortality.     

The polymorphism of heat shock protein 70 genes in Chinese Han population in Fujian province

Heat shock protein 70 (HSP70) genes are themost important and conserve gene members intheheat shock protein family,and locate in an areaadjacent tothe TNFgenesinthe classⅢregionofmajor histocompatibilitycomplex(MHC) .Its geneproductsHSP70proteins are encoded by 3 differ-ent genes ,HSP70-1,HSP70-2andHSP70-hom.Previous studies showed that three kinds ofpolymorphisms existin3loci of thesethree genes ,i .e .+190 G/CBsrBⅠrestrictionsite onHSP70-1, +1267 A/GPstⅠrestriction site onHSP…     

Saliva as a source of HCMV DNA in allogeneic stem cell transplantation patients

Oral Diseases (2010) 16 , 210–216 Objective: The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood. Materials and methods: Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole‐blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value ≤0.05 was considered statistically significant. Results: Human cytomegalovirus DNA load in saliva showed a high correlation with viral DNA in the blood ( R = 0.858; P < 0.0001). Blood DNA levels also correlated with HCMV antigenemia ( R = 0.773; P < 0.0001). The HCMV levels in saliva ( P = 0.015) and blood ( P = 0.008) showed higher levels at the beginning of antiviral treatment, with clear reduction after this period. Saliva showed earlier HCMV reactivation than blood detected by real time PCR and antigenemia assay in 11 out of 22 subjects. Conclusions: This study shows that the real time PCR test could be useful to identify HCMV DNA in saliva and to monitor patients at risk of cytomegalovirus disease after allogeneic hematopoietic stem cell transplant. However, further studies are necessary to confirm this data.     

Molecular mechanisms involved in receptor editing at the Ig heavy chain locus

In receptor editing, a phenomenon that has recently come to light and into favor, a rearranged VDJ or VJ gene segment encoding a variable region of an Ig chain is replaced by another. In this commentary, the molecular mechanisms involved in the editing process are examined in some detail. Editing is most likely mediated by the same V(D)J recombinase activity responsible for the formation of the original VDJ or VJ segment. An embedded heptamer, which is present near the 3' end of many VH elements, is used as the recombination signal sequence at the Ig heavy chain locus. It has been postulated that the mediation of receptor editing is the evolutionary force maintaining the embedded heptamer. Some of the evidence for and against this hypothesis is discussed.      

Think before you prescribe: how dentistry contributes to antibiotic resistance

Antibiotic resistance presents a daunting challenge to health professionals worldwide and has the potential to create major problems for modern health care, resulting in more medical expenditure, extended hospital stays and increased morbidity and mortality. Advanced genome sequencing technologies present a complex picture of resistance, extending our understanding beyond the pharmacotherapeutic interface between pathogens and antibiotics. This review discusses the global scope and scale of antibiotic resistance and contextualizes it for the dental practitioner, emphasizing the role we must play in limiting the progression of resistance through antibiotic stewardship and disease prevention.     

Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.     

Exploring doctor and patient views about risk communication and shared decision-making in the consultation

Background There have been significant conceptual developments regarding shared decision‐making (SDM) and assessments of people's hypothetical preferences for involvement in treatment or care decisions. There are few data on the perceptions of patients and professionals about SDM in actual practice. Objective To explore, from paired doctor–patient interviews, participants’ perceptions of SDM in the consultation and the level of consensus between the participants in the consultation process. Design Qualitative analysis of semi‐structured interview data. Setting and participants Twenty general practitioners received training packages in ‘risk communication’ (RC) and ‘SDM’ to use as tools within the consultation. Forty patients with one of four conditions, for which a range of treatment options is available, were selected. Patient/doctor pairs were interviewed separately following consultations at four stages –‘baseline’ [general practitioner's (GP) usual consultation style], SDM training, RC alone, and both RC and SDM training. Interviews were transcribed and analysed using NVivo software. Results Risk communication interventions by doctors appeared to result in a greater perception of decisions being made in the consultation. High levels of satisfaction with consultations were evident before application of the interventions and did not change after the interventions. Doctors’ and patients’ perceptions of the consultations were highly congruent at all phases of the study. Conclusion Shared decision‐making and RC approaches were helpful in selected consultations and showed no detrimental effects to patients. However, the use of RC and SDM made only small differences to decision‐making in consultations within the population studied. Increasing patient participation may be seen as more ethically justifiable than the traditional paternalistic approach but this needs to be set against the additional training costs incurred.