The necessary role of the autopsy in cardiovascular epidemiology

The autopsy rate in the United States today is remarkably low, with proportionally fewer autopsies for natural causes of death. Consequently, most cardiovascular epidemiology studies do not use autopsy data and rely on death certificates, medical records, questionnaires, and family interviews as sources of mortality information. These practices introduce a high degree of variability and uncertainty regarding cause of death. This review illustrates the necessity for increased use of autopsies in cardiovascular epidemiology by critically evaluating other measures of cardiovascular disease (CVD) incidence. We evaluated the literature regarding CVD as cause of death and conducted discussions with cardiologists, pathologists, and epidemiologists. No attempt was made for meta-analysis. This review shows the limited reliability of death certificates, medical records, and interviews as sources of mortality statistics. In addition, the autopsy's role in clearly indicating the presence of CVD is illustrated. The autopsy used in conjunction with medical records is the only reliable means for establishing cause of death from CVD. There is an urgent need to reassess the current dependence of statistical mortality data on death certificates and other inadequate sources of CVD incidence. Death certificates, in general, are inadequately monitored for quality control and appropriate administrative oversight. With an increase in the number of hospitals performing no autopsies to investigate cause of death, a uniform national autopsy database is needed.     

Plateletapheresis with a next generation blood cell separator

Baeyer-Villiger monooxygenases (BVMOs) are enzymes able to perform highly regio-plus steroselective nucleophilic and electrophilic biooxygenations on various substrates. The resultant chiral products (lactones and sulfoxides) can be valuable for the chemoenzymatic synthesis of a wide range of useful compounds. Recent studies have provided a number of alternative active-site models that attempt to explain the exquisite and unusual selectivity of BVMOs. This article reviews some of the established applications, and considers the merits of the various predictive models.     

Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe

Sinus pericranii is an anomalous extracranial vascular malformation that is in continuity with the intracranial dural venous sinuses. Five case reports, three congenital and two traumatic, are described. Clinical management, including evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by plastic surgeons will allow for earlier diagnosis and appropriate surgical management, resulting in decreased risk of complications.     

Brain glyceraldehyde-3-phosphate dehydrogenase activity in human trinucleotide repeat disorders

BACKGROUND: Although the abnormal gene products responsible for several hereditary neurodegenerative disorders caused by repeat CAG trinucleotides have been identified, the mechanism by which the proteins containing the expanded polyglutamine domains cause cell death is unknown. The observation that several of the mutant proteins interact in vitro with the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) suggests that interaction between the different gene products and GAPDH might damage brain neurons. OBJECTIVE: To measure the activity of GAPDH in postmortem brain of patients with CAG repeat disorders. PATIENTS AND METHODS: Activity of GAPDH was measured in morphologically affected and unaffected brain areas of patients with 4 different CAG repeat disorders (Huntington disease, spinocerebellar ataxia 1 [SCA1], SCA2, and SCA3-Machado-Joseph disease), in brains of patients with Friedreich ataxia (a GAA repeat disorder) and Alzheimer disease, and in brains of matched control subjects. RESULTS: Brain GAPDH activity was normal in all groups with the exception of a slight but statistically significant region-specific reduction in the patients with Huntington disease (caudate nucleus, -12%) and Alzheimer disease (temporal cortex, -19%). CONCLUSION: The presence of the polyglutamine-containing proteins in CAG repeat disorders does not result in substantial irreversible inactivation or in increased activity of GAPDH in human brain.     

Magnito-, electro- and echocardiography in detecting symptoms of the "hypertensive heart"

The study compared diagnostic potential of magnetocardiography (MCG), electrocardiography (ECG) and echocardiography (echo-CG) in 18 patients with arterial hypertension (AH). 32 healthy males served as control. Elements of MCG from normal subjects have been analyzed morphologically in 36 points of precordial leads. Left ventricular hypertrophy was registered at echo-CG, MCG, ECG in 11 (61%), 16 (84%) and 7 (34%) of the AH patients, respectively. Left atrial hypertrophy was discovered primarily by echo-CG and MCG. Defects in ventricular repolarization were recorded by MCg in 7 (39%) patients basing on MCG, echo-CG and rarely ECG signs of left ventricular hypertrophy. MCG is recommended as an effective tool in diagnosis of "hypertensive heart".     

Attachment relationships in infant twins: the effect of co-twin presence during separation from mother

In this study the roles of the mother and the co-twin in inhibiting emotional arousal and reducing manifest distress of a twin who had been isolated in a modified strange situation were compared. The subjects were 15 children, each a member of a twin pair. The subjects were placed in a playroom under three conditions in the following order: (a) mother and twins present; (b) twins together, mother absent; (c) subject isolated from both co-twin and mother. The episodes in which all partners were together were alternated with brief separations. The subjects' distress was minimal when they were separated from the mother with the co-twin present. Upon reunion, stable social behavior was quickly restored. However, separation from the mother and co-twin produced a high level of distress for the subjects. When reunited, the isolated twin initiated physical contact with the mother, soliciting and receiving comfort from her. Furthermore, the distress of the isolated twin was transmitted to the co-twin who had remained with the mother during the isolation period. The nonisolated twin also solicited comfort from the mother. The presence of the co-twin during the reunion following isolation had little effect in reducing the subject twin's distress.     

Gustin from human parotid saliva is carbonic anhydrase VI

It has been found that yeast mutants deficient in cytosolic superoxide dismutase CuZnSOD are hypersensitive to ferrous iron. In contrast mutants that are deficient in catalases and cytochrome c peroxidase do not differ from the standard strain in this respect. These findings suggest that iron toxicity may depend on the redox status of the cell. They also shed light on the role of superoxide dismutases in preventing the toxic effects of oxygen.     

The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family

The human gp200-MR6 molecule has previously been shown to have either an antagonistic or agonistic effect on IL-4 function, demonstrated by inhibition of IL-4-induced proliferation of T cells or mimicking of IL-4-induced maturation of epithelium, respectively. We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes. Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules. It comprises 1722 amino acids in toto (mature protein, 1695 amino acids; signal sequence, 27 amino acids) organized into 12 external domains (an N-terminal cysteine-rich domain, a fibronectin type II domain and 10 C-type carbohydrate recognition domains), a transmembrane region and a small cytoplasmic C terminus (31 amino acids) containing a single tyrosine residue (Y1679), but no obvious kinase domain. Strong amino acid sequence identity (77%) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role. We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure.     

Mosquito-Plasmodium interactions in response to immune activation of the vector

A molecular model was built for human lecithin:cholesterol acyltransferase (LCAT) based upon the structural homology between this enzyme and lipases (Peelman et al. 1998. Prot. Sci. 7: 585-597). We proposed that LCAT belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of a mixed seven-stranded beta-pleated sheet with four alpha-helices and loops linking the beta-strands. The catalytic triad of LCAT was identified as Asp345 and His377, as well as Ser181. This model is used here for the interpretation of the structural defects linked to the point mutations identified in LCAT, which cause either familial LCAT deficiency (FLD) or fish-eye disease (FED). We show that these mutations occur in separate domains of the 3D structure of the enzyme. Most mutations causing familial LCAT deficiency are either clustered in the vicinity of the catalytic triad or affect conserved structural elements in LCAT. Most mutations causing fish-eye disease are localized on the outer hydrophilic surface of the amphipathic helical segments. These mutations affect only minimally the overall structure of the enzyme, but are likely to impair the interaction of the enzyme with its co-factor and/or substrate.     

Regulation of K+ channel mRNA expression by stimulation of adenosine A2a-receptors in cultured rat microglia

Previous investigations suggest that the expression of K+ channels in cultured rat microglia is related to the activation status of these cells. Both, lipopolysaccharide (LPS) and agents that raise intracellular cyclic AMP have been shown to inhibit microglial proliferation. LPS also regulates the mRNA expression levels of K+ channels in cultured microglia, which led us to investigate possible regulatory interactions between K+ channels and adenosine A2a-receptors, which are coupled to the cAMP-signal transduction pathway. The selective adenosine A2a-receptor agonist CGS 21680 induced enhanced mRNA expression of both Kv1.3 and ROMK1, as well as an elevation of Kv1.3 protein. The selective adenosine A2a-receptor antagonist aminophenol (ZM 241385) and the nonselective antagonist 8-phenyltheophylline (8-PT) inhibited these effects. Elevations of cyclic AMP by use of dibutyryl cyclic AMP (dbcAMP), phosphodiesterase-inhibitor (RO 20-1724), forskolin, or cholera toxin (CTX), strongly enhanced Kv1.3-mRNA expression, but decreased ROMK1-mRNA levels. Results from experiments with actinomycin D suggest that K+ channel mRNA levels in cultured microglia were regulated by altered mRNA synthesis. Evidently, the CGS 21680-induced effects upon Kv1.3 were mediated via an increase in intracellular cyclic AMP, whereas ROMK1-mRNA expression appeared to be regulated by coupling of adenosine A2a-receptors to an alternative pathway, which involves activation of protein kinase C (PKC). It is concluded that the cyclic AMP second messenger system in microglia is not only involved in regulation of K+ channel activity, but also in regulation of de novo K+ channel synthesis.