Validity of a postal questionnaire with regard to the prevalence of myocardial infarction in a general population sample

In order to evaluate the possibility of finding persons whohave suffered a myocardial infarction (MI) by postal questionnaire,a self-administered questionnaire was sent to a random sampleof 4400 men aged 45–64 years, drawn from the general population.The response rate was 95%. 176 men indicated that they had beenhospitalized for MI, out of which 124 cases could be verifiedfrom medical records. Of the remaining men, 33 had evidenceof cardiovascular disease (CVD) in their records but no MI,and 19 men had no evidence of CVD. The sensitivity (estimatedfrom a subsample) was 100% and the specificity 98.7%. The predictivevalue was 100% for a negative response and 70.5% for a positiveresponse. The 33 positive responders whose MI could not be verified butwho had evidence of CVD had characteristics fairly similar tothe responders with verified Mis. However, the 19 positive responderswhose MI could not be verified and who had no evidence of CVDhad characteristics that were dissimilar from the MI group aswell as from the negative responders. The questionnaire thus identified all the MI cases. The needfor validation can be limited to the relatively small groupof positive responders.     

Large rod-like photopic signals in a possible new form of congenital night blindness

A 10-year-old Persian girl has symptoms of congenital stationary night blindness and some drusen-like lesions in the region of the vascular arcades. Her electroretinogram shows no rod response to a weak stimulus, but a large (475 V) slow scotopic response to a strong stimulus that is unchanged by photopic conditions (15 F1 background illumination). However, the response to flicker had the typical (smaller) amplitude of a cone signal. This may represent a new form of night blindness in which rod sensitivity is reduced so that there is no vision under dim conditions but rod function still persists under photopic conditions.     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.     

Detecting danger--or just another odorant? Olfactory sensitivity for the fox odor component 2,4,5-trimethylthiazoline in four species of mammals

2,4,5-trimethylthiazoline (TMT) is a volatile component of the anal gland secretion of the red fox and elicits behavioral and physiological fear responses in the rat. Using instrumental conditioning paradigms, we determined olfactory detection thresholds for TMT in three rats, a natural prey species of the red fox, and compared their performance to that of three squirrel monkeys, three spider monkeys and four pigtail macaques, all non-prey species of the red fox. We found that the rats were able to discriminate concentrations between 0.04 and 0.10 ppt (parts per trillion) of TMT from the odorless solvent which is by far the lowest olfactory detection threshold for an odorant reported in rats so far. In contrast, the spider monkeys needed 0.14-1.38 ppb (parts per billion), the pigtail macaques 0.41-4.07 ppb, and the squirrel monkeys 4.07-13.80 ppb to detect TMT which does not rank among the lowest olfactory thresholds reported for these three primate species. Thus, these results support the assumption that the behavioral relevance of an odorant may be an important determinant of a species' olfactory sensitivity.     

Identification of a Thymidylate Synthase Gene within the Genome of Chilo Iridescent Virus

The thymidylate synthase (TS, EC 2.1.1.45) is essential for the de novo synthesis of dTMP in pro- and eucaryotic organisms. Consequently it plays a major role in the replication of the DNA genome of a cell or a DNA virus. The gene encoding the TS of Chilo iridescent virus (CIV) was identified by nucleotide sequence analysis of the viral genome and was mapped within the EcoRI CIV DNA fragments G and R. Computer assisted analysis of the DNA nucleotide sequence between the genome coordinates 0.482 and 0.489 revealed an open reading frame (ORF) of 885 nucleotides. This ORF was found to encode a polypeptide of 295 amino acid residues (33.9 kDa) that showed significant homologies to known TS of different species including mammals, plants, fungi, protozoa, bacteria, and DNA viruses. The highest amino acid homologies were found between the CIV-TS and the TS of herpesvirus ateles (54.0%), Saccharomyces cerevisiae (51.8%), herpesvirus saimiri (51.0%), rhesus monkey rhadinovirus (50.7%), mouse (50.5%), rat (50.2%), varicella-zoster virus (50.2%), equine herpesvirus 2 (50.0%), and the human TS (48.4%). The CIV-TS contains six amino acid domains that are highly conserved in the TS of other species. Within these domains the major amino acid residues are present for which a functional role has been reported. The CIV-TS was found to be more closely related to the TS of eucaryotes than to the TS of procaryotes indicating the phylogenetic origin of the CIV-TS gene. The identification of a TS gene in the genome of CIV is the first report of a viral TS that is not encoded by a herpesvirus or a bacteriophage.     

Differential Fear of Cardiopulmonary Sensations in Emergency Room Noncardiac Chest Pain Patients

Fear of bodily sensations has received extensive attention in relation to panic disorder, and more recently, other types of anxiety pathology and chronic pain problems. Extending this work, the present study examined fear of bodily sensations and its underlying dimensions in emergency room patients with Noncardiac Chest Pain (NCCP; n = 63). We posited a differential specificity hypothesis, expecting that specific cardiopulmonary fears would be more strongly associated with NCCP symptoms relative to other bodily fears. As hypothesized, participants reported cardiopulmonary sensations as significantly more fear-provoking than numbness, dissociation, and gastrointestinal sensations. Additionally, regression analysis indicated that after accounting for theoretically relevant demographic variables and health status, cardiopulmonary fear was the best predictor of a composite index of cardiac complaints intensity, even after removing variance related to the absolute number of cardiac complaints. We discuss these findings in relation to the specific role for the fear of cardiopulmonary sensations in chest pain complaints, with implications for better understanding the underlying psychological processes involved in NCCP.     

DHPLC screening of cystic fibrosis gene mutations

Denaturing high performance liquid chromatography (DHPLC) using ion-pairing reverse phase chromatography (IPRPC) columns is a technique for the screening of gene mutations. In order to evaluate the potential utility of this assay method in a clinical laboratory setting, we subjected the PCR products of 73 CF patients known to bear CFTR mutations to this analytic technique. We used thermal denaturation profile parameters specified by the MELT program tool, made available by Stanford University. Using this strategy, we determined an initial analytic sensitivity of 90.4% for any of 73 known CFTR mutations. Most of the mutations not detected by DHPLC under these conditions are alpha-substitutions. This information may eventually help to improve the MELT algorithm. Increasing column denaturation temperatures for one or two degrees above those recommended by the MELT program allowed 100% detection of CFTR mutations tested. By comparing DHPLC methodology used in this study with the recently reported study based on Wavemaker 3.4.4 software (Transgenomic, Omaha, NE) [Le Marechal et al., 2001) and with previous SSCP analysis of CFTR mutations [Ravnik-Glavac et al., 1994] we emphasized differences and similarities in order to refine the DHPLC system and discuss the relationship to the alternative approaches. We conclude that the DHPLC method, under optimized conditions, is highly accurate, rapid, and efficient in detecting mutations in the CFTR gene and may find high utility in screening individuals for CFTR mutations. Hum Mutat 19:374-383, 2002. Published 2002 Wiley-Liss, Inc.     

Vascular smooth muscle sensitivity to noradrenaline is reduced during an infection with trypanosoma brucei in rats and rabbits

α₁-adrenoceptor sensitivity to noradrenaline has been studied in some arterial smooth muscles of rats and rabbits infected with T. brucei. In rabbits, a decrease in sensitivity of the arterial smooth muscles to noradrenaline was observed in the thoracic aorta, central ear but not renal arteries. No change in the sensitivity of the smooth muscles to histamine was observed. In rats, noradrenaline potency was reduced in the aorta, renal but not tail arteries. In both species, affinity of noradrenaline for a,-adrenoceptors was significantly (P < 0.05) reduced in arteries where the potency of noradrenaline was reduced. Prazosin K_B values in infected animals were significantly (P < 0.05) lower than controls. These results are interpreted to suggest either an alteration in the structure of a,-adrenoceptors during an infection, or accumulation of some factor(s) in the receptor microenvironment that modulated binding of agonists and antagonists to the receptors during an infection with T. brucei. The possible role of reduced α₁-adrenoceptor affinity in the hypotension observed during an infection with T. brucei is discussed.