'Progression' in typical arrhythmogenic right ventricular dysplasia cardiomyopathy could be mainly demonstrated in case reports and generally implies decreasing left ventricular function; systematic follow-up data are only available on clinical features such as recurrent arrhythmias, late potentials or left ventricular ejection fraction. Due to methodological problems, continuous data on structural and functional right ventricular performance are not available. In order to get some more information about basic mechanisms of possible progression in arrhythmogenic right ventricular dysplasia-cardiomyopathy, the age-dependency of right ventricular enddiastolic volume, right ventricular ejection fraction, number of bulges, left ventricular involvement and the form of tachycardias was analysed at a single examination after having made the diagnosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy. In the whole cohort of patients (n = 66), age-dependency of right ventricular volume could be demonstrated using linear regression analysis, chi-square-test and paired t-test (P < 0.01); global right ventricular ejection fraction and the number of right ventricular bulges did not differ significantly in younger and older patients. The same was true for mild left ventricular impairment and sustained or non-sustained ventricular tachycardias, respectively. In a follow-up, two older patients developed dramatic left ventricular dilatation and reduction of left ventricular function requiring heart transplantation. A third older patient died from isolated right heart failure. Increasing age-related right ventricular dilatation is possibly a marker of disease progression as a basis for right heart failure. Dramatic left heart involvement seems to be an event with abrupt onset in most cases due to acute or chronic myocarditis.

Adolescent↗

PubMed1996

T cell recognition of Tn-glycosylated peptide antigens.

The mouse hemoglobin-derived decapeptide Hb (67-76), VITAFNEGLK, which binds well to Ek and is non-immunogenic in CBA/J mice, was O-glycosylated with the tumor-associated carbohydrate Tn (alpha-D-N-acetylgalactosamine, or alpha-D-GalNAc). Each of the ten positions in the peptide was substituted with serine or threonine having the Tn antigen attached. The complete set of Tn-glycosylated peptides were then studied for binding to Ek and for immunogenicity in CBA/J mice. All of those glycopeptides which had the Tn attached to serine or threonine at a position in the peptide where, according to the crystal structure determinations, the amino acid side chain was oriented downwards into the binding site of the major histocompatibility complex (MHC) molecule, completely lost their capacity for binding to Ek. This was the case for the glycopeptides with Tn attached at position 68 and 76, which are the major anchor residues and for those with Tn attached at position 71 and 73, which function as secondary anchor residues. Those glycopeptides which had Tn attached to serine or threonine at positions where the side chain pointed away from the binding site maintained their capacity for binding to Ek, except for those with Tn attached at position 70 and 74. Furthermore, some of the MHC-binding glycopeptides were immunogenic. In particular, this was the case for the glycopeptide with Tn attached to the central position 72 in the decapeptide. From previous studies, this is known to be the dominant T cell receptor contact residue of Hb (67-76). The results suggest that T cells may be capable of recognizing epitopes which are partially defined by a small glycan group.

Amino Acid Sequence↗

PubMed1996

Specificity of O-glycosylation by bovine colostrum UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase using synthetic glycopeptide substrates.

The factors determining glycosylation of mucin type glycoproteins are not well understood. In the present work, we investigated the role of the peptide moiety and of the presence of O-glycan chains on O-glycosylation by UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyl-transferase (ppGalNAc-T). We used purified ppGalNAc-T from bovine colostrum and a series of synthetic glycopeptide and peptide substrates most of which contained sequences derived from the tandem repeat region of MUC2 mucin. The rate of incorporation of GalNAc into Thr was significantly greater than toward Ser residues. The presence of one or two GalNAc-Thr moieties in the substrate significantly reduced enzyme activity, and this effect was more pronounced when the disaccharide Gal beta 1-3GalNAc was present. Thus the sequential attachment of a second GalNAc residue in the vicinity of a pre-existing GalNAc-Thr or Gal beta 1-3GalNAc-Thr occurs at a slower rate than primary glycosylation of carbohydrate-free peptide. Analysis of products by HPLC showed that the enzyme was selective in glycosylating peptides or glycopeptides with the PTTTPIST sequence in that the preferred primary glycosylation site was the third Thr from the amino-terminal end; secondary glycosylation depended on the site of the primary glycosylation. Negatively but not positively charged amino acids on the carboxy-terminal side of the putative secondary glycosylation site resulted in high activity suggesting charge-charge interactions of substrates with the enzyme. These studies indicate that O-glycosylation by bovine colostrum ppGalNAc-T is a selective process dependent on both the amino acid sequence and prior glycosylation of peptide substrates.

Animals↗

PubMed1996

[Dangers and risks of thoracic drainage at the accident site].

For several years it has been argued that a chest tube should be placed at the scene of an accident if thoracic trauma is suspected. However, during emergency treatment in hospital it has been observed that a high number of such tubes have been placed incorrectly. To validate this impression, we conducted a retrospective analysis of the clinical course of 33 trauma victims who had chest tubes placed at the scene of accident. It was found that 39.4% of the chest tubes were placed completely incorrectly and 21.2% required some correction; 39.4% were placed correctly. In two cases (6.1%) life-threatening complications developed because of the chest tube, necessitating a thoracotomy in 1 patient and repeated pericardial punction in the other. Based on the results of our study we believe that a more critical attitude should be adopted to the placement of chest tubes at the scene of the accident.

Chest Tubes↗

PubMed1996

A dissociation between the ability to print and write cursively in lower-case letters.

This paper reports the case of a patient with a peripheral spelling impairment who is much more severely impaired at writing in lower-case letters than in upper-case letters. This pattern can be observed when writing both words and single letters of the alphabet. Despite this, his problems in writing lower-case letters are no longer present when he is writing cursively. This case therefore indicates that the ability to print letters in lower-case can be selectively impaired in the absence of similar problems in printing upper-case letters or in writing lower-case letters cursively. In terms of the model of writing put forward by Ellis (1982, 1988), this suggests that allographic level representations for print handwriting styles can be functionally dissociated from allographic representations for cursive styles.

Aged↗

PubMed1996

Comparison of intrathecal synthesis of Treponema pallidum-specific IgG antibodies and polymerase chain reaction for the diagnosis of neurosyphilis.

An indirect Treponema pallidum-IgG enzyme-linked immunosorbent assay (Tp-IgG-ELISA) was used for the estimation of intrathecal synthesis of specific IgG antibodies in patients with syphilis. Detection of T. pallidum DNA in cerebrospinal fluid (CSF) samples of syphilitic patients was performed by amplification of treponemal DNA, using the polymerase chain reaction (PCR). Both methods were compared as to their suitability for diagnosis of neurosyphilis in 37 patients with syphilis. Intrathecal synthesis of T. pallidum-specific IgG and PCR was negative in 16 patients with treated syphilis or untreated secondary syphilis. In contrast, an intrathecal IgG antibody production was found in all 21 patients with treated or untreated neurosyphilis. PCR was only positive in CSF samples from six out of ten patients with untreated neurosyphilis. The findings suggest that the intrathecal production of T. pallidum-specific IgG antibodies is an important indicator for the diagnosis of neurosyphilis. In addition, a positive result by PCR performed in CSF establishes a diagnosis of active neurosyphilis.

Antibodies, Bacterial↗

PubMed1996

Expression and function of receptors for extracellular matrix proteins in human ductal adenocarcinomas of the pancreas.

Extracellular matrix proteins (ECM) may influence cellular differentiation via their receptors, the integrins. We recently presented evidence that ductal adenocarcinomas of the pancreas are able to produce ECM in vitro and in vivo (Br J Cancer 1994;49:144-51). This study examines whether pancreatic carcinoma cells are able to interact with ECM by expressing functionally active integrins. In eight human pancreatic tumor cell lines (AsPC-1, BxPC-3, CAPAN-1 and -2, PANC, PaTu-2, -3, and -44) and six xenografted tumors RNA and protein expression of integrin subunits alpha 5 (fibronectin receptor), alpha 6 (laminin receptor), and alpha V (vitronectin receptor) was investigated. In addition, alpha 1-alpha 6 and alpha V as well as beta 1-beta 4 were studied by fluorescence-activated cell sorter analysis. Integrin function was tested by attachment assays. alpha 2, alpha 3, alpha 5, alpha 6, and alpha V as well as beta 1, beta 3, and beta 4 were expressed, at both the RNA and the protein level, by all pancreatic tumors in vitro and in vivo. The tumor cell lines showed dose dependent adhesion to collagen, fibronectin, and laminin. Integrin expression could be modulated in part by serum depletion. None of the tumors showed alpha 1, alpha 4, and beta 2. Tumor cell differentiation or production of ECM was not correlated with integrin expression. Pancreatic ductal adenocarcinomas express a certain pattern of functionally active integrins that enable interaction with most matrix proteins, e.g., collagen, fibronectin, and laminin. Pancreatic adenocarcinomas possess both the ligands and the receptors of the extracellular matrix network. We speculate that through both classes of molecules, the tumor cells may bind to fibroblasts and probably stimulate their growth. However, it remains unclear whether and how integrin-ECM interaction exerts an influence on tumor cell differentiation.

Animals↗

PubMed1996

Structure and stability of the plasma crystal.

Explore the source record for details and available documents.

Journal Article↗

PubMed1996

Diagnostic value of endomyocardial biopsies of the right ventricular septum in arrhythmias originating from the right ventricle.

The aim of the study was to classify the value of endomyocardial biopsies taken from the right ventricular septum in patients with ventricular tachyarrhythmias originating from the right ventricle. In a cohort of 62 young patients (mean age 35.6 years) 4-5 endomyocardial biopsies were taken from the right ventricular septum and myocardial atrophy, fibrosis and lipomatosis were analysed qualitatively and semi-quantitatively. Much interest was focused on the arrangement and type of fibrosis. Lipomatosis, myocardial atrophy and a finer form of fibrosis surrounding individual myocytes or groups of myocytes were judged as the typical histopathological findings of arrhythmogenic right ventricular dysplasia. The cohort of patients was subdivided clinically into idiopathic right ventricular outflow tract tachycardia (n = 50) and arrhythmogenic right ventricular dysplasia (n = 12). In the group of arrhythmogenic right ventricular dysplasia pathological findings were found in 92% with typical fibrolipomatosis in two cases, severe fibrosis ( > 40% per biopsy) in 5 cases, a finer form of fibrosis surrounding individual myocytes without lipomatosis in two cases and a slight interstitial or subendocardial fibrosis in two cases. In only one patient the endomyocardial biopsy was normal. In right ventricular outflow tract tachycardia normal endomyocardial biopsy findings predominated (80%). In two cases lipomatosis without fibrosis was a more or less normal finding, and in two other cases a slight interstitial or subendocardial fibrosis was found. Fibrosis was judged to be moderate or severe with discrete signs of inflammation in only two cases; in a long-term follow-up these two patients developed typical features of idiopathic dilated cardiomyopathy. Endomyocardial biopsies taken exclusively from the right ventricular septum were able to distinguish between right ventricular outflow tract tachycardia and arrhythmogenic right ventricular dysplasia, although the typical finding of fibrolipomatosis in cases with arrhythmogenic right ventricular dysplasia was rare. Characteristics of fibrosis are the key to the correct diagnosis provided that histopathological analysis is based on experienced qualitative criteria (type and arrangement of fibrosis). In conclusion, qualitative and semi-quantitative analyses of endomyocardial biopsies are far better than computerized quantitative methods. Biopsies from the free right ventricular wall cannot be generally recommended if a correct definition of arrhythmogenic right ventricular dysplasia in endomyocardial biopsies from the right ventricular septum is used.

Adult↗

PubMed1996

RJR-2403: a nicotinic agonist with CNS selectivity II. In vivo characterization.

We have evaluated the physiological and behavioral effects of the CNS-selective nicotinic agonist (E)-N-methyl-4-(3-pyridinyl) -3-butene-1-amine (RJR-2403) using a number of different methods, including 1) reversal of pharmacologically induced amnesia in a step-through passive avoidance paradigm, 2) radial arm maze performance in rats with chemically induced brain lesions, 3) changes in HR and blood pressure in rats and 4) changes in body temperature, Y-maze activity, acoustic startle response and respiration in mice. Our results indicate that RJR-2403 is equal to or better than nicotine on measures of CNS function and cognitive enhancement. Specifically, RJR-2403 significantly improved passive avoidance retention after scopolamine-induced amnesia and enhanced both working and reference memory in rats with ibotenic acid lesions of the forebrain cholinergic projection system in an 8-arm radial maze paradigm. By comparison, RJR-2403 was 15 to 30-fold less potent than nicotine in decreasing body temperature, respiration, Y-maze rears and crosses and acoustic startle response. RJR-2403 also demonstrated greatly reduced cardiovascular effects. RJR-2403 was approximately 10-fold less potent than nicotine in increasing HR and 20-fold less potent in increasing blood pressure. These results are consistent with in vitro data indicating this compound's high selectivity for CNS nicotinic ACh receptor subtypes relative to peripheral ganglionic and muscle-type nicotinic ACh receptors. Therefore, RJR-2403 may be a valuable tool for understanding the central and peripheral pharmacology of nicotinic cholinergic systems as well as a potential lead compound for the development of nicotinic therapeutics to treat neurological diseases where cholinergic neurotransmission has been compromised.

Animals↗