Structural effects of the slow/b-cardiac myosin heavy chain R453C mutation in cardiac and skeletal muscle

Objectives. Hypertrophic cardiomyopathy (HCM) represents an important cause of sudden cardiac death particularly in otherwise healthy young individuals. In some families, HCM is caused by distinct mutations of the cardiac beta myosin heavy chain gene (MYH7). Design. We have analyzed the expression of the malignant MYH7Arg453Cys mutation, in cardiac and skeletal muscle, and related it to morphological alterations. Results. Morphological investigation revealed hypertrophic cardiomyocytes but regularly arranged myofibrils. Skeletal muscle showed no sign of structural alterations. Conclusions. Our results indicate that cardiomyocyte hypertrophy is secondary, due to impaired function, and that the mutation causes no structural alteration in myofibrillar structure in cardiac or skeletal muscle.     

Detecting viruses by using salivary diagnostics

BackgroundDiagnostics that involve the use of oral fluids have become increasingly available commercially in recent years and are of particular interest because of their relative ease of use, low cost and noninvasive collection of oral fluid for testing.Types of Studies ReviewedThe authors discuss the use of salivary diagnostics for virus detection with an emphasis on rapid detection of infection by using point-of-care devices. In particular, they review salivary diagnostics for human immunodeficiency virus, hepatitis C virus and human papillomavirus. Oral mucosal transudate contains secretory immunoglobulin (Ig) A, as well as IgM and IgG, which makes it a good source for immunodiagnostic-based devices.Clinical ImplicationsBecause patients often visit a dentist more regularly than they do a physician, there is increased discussion in the dental community regarding the need for practitioners to be aware of salivary diagnostics and to be willing and able to administer these tests to their patients.     

Expression of MMPs and TIMP-1 in smoker and nonsmoker chronic periodontitis patients before and after periodontal treatment

Mouzakiti E, Pepelassi E, Fanourakis G, Markopoulou C, Tseleni‐Balafouta S, Vrotsos I. Expression of MMPs and TIMP‐1 in smoker and nonsmoker chronic periodontitis patients before and after periodontal treatment. J Periodont Res 2012; 47: 532–542. © 2012 John Wiley & Sons A/S Background and Objective: Nonsurgical periodontal treatment controls periodontal inflammation. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are implicated both in the destruction and in the healing of periodontal tissues. The aim of the present study was to compare the mRNA expression of MMP‐1, ‐3, ‐8, ‐9 and ‐13 and TIMP‐1 in chronic periodontitis before and after initial periodontal treatment. Material and Methods: Ninety gingival samples were harvested from 30 patients with chronic periodontitis (15 nonsmokers and 15 smokers) before and after nonsurgical treatment and from 30 periodontally healthy control subjects (15 nonsmokers and 15 smokers). Clinical parameters were assessed before and after treatment. Total RNA was isolated, and mRNA expression of MMPs and TIMP‐1 was assessed by RT‐PCR. Results: Periodontal treatment significantly increased TIMP‐1 expression and decreased the ratios of MMPs/TIMP‐1. Post‐treatment, nonsmokers with periodontitis had significantly higher MMP‐8 and TIMP‐1 expression than healthy nonsmokers, and smokers with periodontitis had significantly higher MMP‐13 and TIMP‐1 expressions than healthy smokers. Post‐treatment, smokers had significantly higher TIMP‐1 expression and lower MMP‐8/TIMP‐1 ratio than nonsmokers. Post‐treatment, there was no correlation among MMPs, and the expression of MMPs and TIMP‐1 was not correlated with clinical measurements. Conclusion: Periodontal treatment increased TIMP‐1 expression and decreased the ratios of MMPs/TIMP‐1 in chronic periodontitis. The post‐treatment increase in TIMP‐1 expression was higher for smokers. The TIMP‐1 expression was higher post‐treatment than in health. Post‐treatment, MMP‐8 expression was higher in nonsmokers with periodontitis than in healthy nonsmokers, whereas MMP‐13 expression was higher in smokers with periodontitis than in healthy smokers.     

Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system

Abstract

Point mutations in the transmembrane domain of c-erbB-2 gene in human brain tumours were studied by DNA amplification with the polymerase chain reaction method. Amplified gene fragments in M13 phage vector were cloned, and subsequent nucleotide sequences were determined. Studied specimens were 10 human malignant and 3 human benign tumours of the central nervous system, and a normal human placenta. In malignant tissues, Val-to-Glu mutation that induces transforming activity of c-erbB-2 did not appear at codon 659 of c-erbB-2. In malignant tissues, many other types of mutations appeared in low frequency, either at codon 659 or other positions of the transmembrane domain of c-erbB-2. The ratio of mutated genes to normal genes was very low in all specimens of malignant tumours. The point mutations were not observed in benign brain tumour or normal human placental tissues. The transmembrane domain of c-erbB-2 may have several highly mutable hot spotswhere brain tumour tissues show a predilection for point mutation.     

Mitochondrial disease and epilepsy

Mitochondrial diseases are a group of diseases caused by dysfunctional mitochondria, organelles that generate energy for the cell. Mitochondrial diseases are often caused by mutations, acquired, or inherited in the mitochondrial DNA or nuclear genes that code for respiratory chain complexes in the mitochondrion. Mitochondrial diseases involve multiple organs and show heterogeneous and unpredictable progression. The most common clinical presentation of mitochondrial diseases is encephalomyopathy, and epileptic seizures can frequently occur as a presenting sign of mitochondrial encephalopathy. While whether mitochondrial dysfunction or epilepsy is the cause or consequence is still debatable, they may be interrelated to create a vicious cycle. Epileptic phenotypes vary in different mitochondrial diseases. At present, there are no curative treatments for mitochondrial diseases, and the efficacy of many anticonvulsants, vitamins, nutritional supplements, and the ketogenic diet remain to be proven. Understanding the pathophysiology of mitochondrial diseases may further facilitate effective diagnostic and therapeutic approaches to these diseases.     

Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.     

中药外源性污染物检测技术的现代研究

中药外源性污染物残留现已成为引起中药不良反应的重要原因之一,按照其来源不同主要包括农/兽药残留、重金属污染、真菌毒素残留、病原微生物污染及其他有机污染物残留。对中药的主要外源性污染物的检查对象及检测方法的现代研究进行综述,为补充、完善、提升中药质量安全体系提供参考和依据。