Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 163 records · Page 9Linked to original sources

PubMed1996

[Questionnaire on psychosexual development of children--development of a guideline for diagnosis of sexual abuse].

The purpose of this paper is to present a questionnaire which can collate data on the psychosexual development of children. There are as yet few contributions from the field of empirical research dealing with the question of "normal" psychosexual development patterns. There is also a lack of standardised procedures by which this aspect of child development can be assessed. For this reason we have developed a questionnaire relating to the theme of child sexuality which can be used in the framework of history and which was examined as part of a clinical study supported by a grant from the Deutsche Forschungsgemeinschaft. The questionnaire contents questions put to parents relating to the sexual development of children, on how sexuality is talked about and dealt with in the family, and on precisely-defined and described experiences of the child and other members of the family. At the time we present a method of judging normative sexual development of the child and of disturbances such a sexual abuse. In order to deal with this question the collation of information from four different areas is required: physical development and symptoms, behaviour of the child, family context including psychosocial adversities and parent-child interaction. Case studies will illustrate how data from the four areas are related and can accordingly be assessed in order to be able to make judgments on the psychosexual development of children. We see this method as helpful in order to determine whether or not a child was sexual abused. Thus, consideration of each individual case in context is necessary if a balanced judgment is to be arrived at.

Adolescent↗

PubMed1995

The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B.

The t(8;21) translocation, commonly found in acute myelogenous leukemia (AML), generates a fusion protein containing N-terminal AML1 and C-terminal ETO amino acids. The human AML1 gene encodes several related proteins that specifically bind to the sequence TGT/cGGT, located in the promoter regions of a variety of hematopoietic growth factor genes. To examine the abilities of the AML1B protein (which contains 479 amino acids), a shorter AML1A isoform (which contains amino acids 1-250), and the AML1/ETO fusion protein (which contains AML1A amino acids 1-177) to stimulate transcription from the GM-CSF promoter, we performed co-transfection experiments in T cells using a human GM-CSF promoter-CAT reporter gene plasmid and expression vectors that contain the cDNAs for one of the above proteins. Our data demonstrate that AML1B, but not AML1A or AML1/ETO transactivates the GM-CSF promoter, requiring the TGTGGT sequence contained between base pairs -68 and -53. Furthermore, we show that AML1/ETO, but not AML1A, inhibits the ability of AML1B to stimulate CAT expression. Electrophoretic mobility shift assays demonstrated the specific binding of AML1 proteins to the GM-CSF promoter TGTGGT sequence, which does not require GM-CSF sequences immediately upstream of this binding site. Our data support a role for AML1B as a transcriptional activator and establish that the AML1/ETO fusion protein can act as a dominant negative protein on the human GM-CSF promoter. Although AML1/ETO does not stimulate the transcription of GM-CSF, it may function by inhibiting the normal activity of AML1B in AML cells with the t(8;21) translocation.

Base Sequence↗

PubMed1995

Inhibition of dipeptidyl peptidase IV (DP IV) by anti-DP IV antibodies and non-substrate X-X-Pro- oligopeptides ascertained by capillary electrophoresis.

Dipeptidyl peptidase IV (DP IV)-catalyzed hydrolysis of the NH2-X-Pro-containing N-terminal dodecapeptide of IL-2 was studied using free zone capillary electrophoresis as an alternative peptidase assay. In contrast to the conventional DP IV substrate glycyl-prolyl-p-nitroanilide (Gly-Pro-pNA), the hydrolysis of this peptide by DP IV was found to be significantly inhibited by anti-DP IV antibodies. Inhibition of DP IV was also observed with a number of non-substrate oligopeptides containing an N-terminal X-X-Pro- structure, including the HIV Tat protein. For Met-IL-2(1-6), we determined a competitive inhibition with an inhibition constant of ca. 100 microM.

Amino Acid Sequence↗

PubMed1995

Evaluation of radionuclide angiography in diagnosis of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The accuracy of Fourier analysis of radionuclide angiography for the diagnosis of arrhythmogenic right ventricular cardiomyopathy was assessed versus X-ray right ventricular angiography. BACKGROUND: In patients with recurrent right ventricular tachycardia, the diagnosis of arrhythmogenic right ventricular cardiomyopathy is based on the presence of right ventricular wall motion abnormalities on conventional X-ray angiography without evidence of other heart disease. METHODS: X-ray and radionuclide angiography were prospectively compared in 73 patients with ventricular tachycardia. We analyzed the presence of a right ventricular enlargement, global hypokinesia and segmental wall motion abnormalities, using visual analysis for both techniques and Fourier analysis for radionuclide angiography. Disease was noted as absent or present and as diffuse or localized. The interobserver reproducibility of both techniques for the diagnosis of right ventricular wall motion abnormalities was tested in 27 randomly selected patients. RESULTS: According to X-ray angiography, 53 patients were considered to have arrhythmogenic right ventricular cardiomyopathy (22 diffuse, 31 localized forms) and 20 patients a normal right ventricle. The sensitivity of radionuclide angiography was 94.3%, specificity 90% and positive and negative predictive values 96% and 85.7%, respectively. Agreement for the location of the wall motion abnormalities was 60% for the apex, 76% for the outflow tract, 82% for the inferior wall and 74% for the free wall. The diagnostic interobserver reproducibility of X-ray and radionuclide angiography was 74% and 96.2%, respectively. CONCLUSIONS: In a selected cohort, Fourier analysis of radionuclide angiography is an accurate and reproducible tool for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

Adult↗

PubMed1995

A role for phosphatidylinositol transfer protein in secretory vesicle formation.

Vesicular traffic in eukaryotic cells is characterized by two steps of membrane rearrangement: the formation of vesicles from donor membranes and their fusion with acceptor membranes. With respect to vesicle formation, several of the cytosolic proteins implicated in budding and fission have been identified. A feature common to all these proteins is that their targets, when known, are other proteins rather than lipids. Here we report, using a previously established cell-free system derived from a neuroendocrine cell line, the purification of cytosolic factors that stimulate the formation of constitutive secretory vesicles and immature secretory granules from the trans-Golgi network. One such factor, referred to as CAST1, was identified as the alpha and beta isoforms of the mammalian phosphatidylinositol transfer protein (PtdIns-TP) (refs 3-5). The yeast PtdIns-TP, SEC14p (ref. 6), which has no sequence homology to mammalian PtdIns-TP (refs 7,8), was able to substitute for the mammalian PtdIns-TP in secretory vesicle formation. Our results suggest a highly conserved role for phosphoinositides in vesicle formation.

Animals↗

PubMed1995

Experimental deposition of Alzheimer amyloid beta-protein in canine leptomeningeal vessels.

To study the pathogenesis of cerebral amyloid angiopathy (CAA), organ cultures of canine leptomeninges were incubated with fluorescein-conjugated amyloid beta-protein (FA beta, residues 1-40; 10 nM to 200 microM). Fluorescence microscopy showed focal and dose-dependent FA beta binding to blood vessels affected by CAA at FA beta-concentrations as low as 10 nM. The new A beta deposits appeared to be extracellular and were localized to the middle and outer layers of leptomeningeal arterioles. FA beta partially co-localized with apolipoprotein E (ApoE) as revealed by confocal microscopy, suggesting that A beta in situ binds to ApoE. Young dogs or old dogs without CAA showed no deposition of FA beta. Our results indicate that after initiation of CAA pathology, physiological concentrations of soluble A beta are sufficient to sustain its further deposition and therefore the progression of CAA.

Alzheimer Disease↗

PubMed1995

Identification of the active-site nucleophile in 6-phospho-beta-galactosidase from Staphylococcus aureus by labelling with synthetic inhibitors.

Kinetic parameters for the inactivation of the 6-phospho-beta-galactosidase of Staphylococcus aureus by a series (fluoro, chloro, bromo) of 2,4-dinitrophenyl-2-deoxy-2-halogeno- galactoside-6-phosphates have been determined. These inhibitors function by the formation of a stabilised glycosyl-enzyme intermediate. Inactivation and reactivation studies indicate that the fluoro derivative is formed most rapidly, but is also hydrolysed fastest. The chloro derivative forms the most stable covalent intermediate. HPLC profiles of V8-protease digestion of native and inhibited protein show significant differences, whereas the inhibited 6-phospho-beta-galactosidase and a point mutant of 6-phospho-beta- galactosidase (E375Q) yield the same proteolytic fragments. The suggestion that E375 is derivatised is strengthened by matrix-assisted laser-desorption ionisation mass spectrometry experiments which show that the two peptides, residues 336-375 and 376-383, are not produced, due to the absence of the expected cleavage at residues 375 and 376. The reason for the altered proteolysis pattern of the inhibited protein is blocking of the respective V8 cleavage site due to the chemical reaction of the inhibitor at position 375. Specific modification of the glycosyl bond between the inhibitor and E375 by aminolysis with benzylamine generated a glutamatic-acid-5-benzylamide complex at that position in the peptide. The Edman derivative of the modified E375 appears to be stable and was isolated by Edman degradation of trypsin-digested V8-peptide. It was shown to be identical to an authentic, synthetic sample. From this, it is evident that E375 is the active-site nucleophile of 6-phospho-galactosidase, consistent with previous findings for enzymes in this family.

Amino Acid Sequence↗

PubMed1995

Determination of cyclic nucleotide-dependent protein kinase substrate specificity by the use of peptide libraries on cellulose paper.

An iterative approach to the a priori determination of the substrate specificity of cAMP- and cGMP-dependent protein kinases (PKA and PKG) by the use of peptide libraries on cellulose paper is described. The starting point of the investigation was an octamer library with the general structure Ac-XXX12XXX, where X represents mixtures of all 20 natural amino acids and 1 and 2 represent individual amino acid residues. The library thus contained all possible 2.56 x 10(10) octamers, divided into 400 sublibraries with defined amino acids 1 and 2 each consisting of 6.4 x 10(7) sequences. After phosphorylation with the kinases in the presence of [gamma-32P]ATP, the sublibrarys Ac-XXXRRXXX and Ac-XXXRKXXX were identified as the best substrates for PKA and PKG, respectively. The second-generation libraries had the structures Ac-XXXRR12X and Ac-XXXRK12X for PKA and PKG and resulted in the most active sequence pools Ac-XXXRRASX and Ac-XXXRKKSX. After delineation of every position in the octameric sequence and extension of the investigation to decameric peptides, the best sequences, Ac-KRAERKASIY and Ac-TQKARKKSNA, were obtained for PKA and PKG, respectively. Promising octameric and decameric peptides were assembled 5 or 10 times each and assayed in order to determine the experimental scatter inherent in the approach. The kinetic data of several octameric and decameric sequences were determined in solution and compared to data for known substrates. The recognition motif of PKA was confirmed by this approach, and a novel substrate sequence for PKG was identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1995

Simultaneous and combinatorial chemical synthesis techniques for the generation and screening of molecular diversity.

By skillful 'mixing and sorting', thousand millions of different compounds, so-called molecular repertoires or molecular libraries, can be produced and screened for biological activity in a very short time. Today, both sophisticated as well as surprisingly simple procedures for simultaneous and combinatorial chemical synthesis open fascinating new perspectives for basic research, biotechnology and drug development. This contribution will give a brief survey of current strategies in the chemical synthesis of oligonucleotide and peptide repertoires with special emphasis on techniques employing membrane-type solid supports developed in this laboratory.

Amino Acid Sequence↗

PubMed1995

Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120.

The depletion of CD4+ T cells in AIDS is correlated with high turnover of the human immunodeficiency virus HIV-1 and associated with apoptosis. The molecular mechanism of apoptosis in HIV infection, however, is largely unknown. T-cell apoptosis might be affected by viral proteins such as HIV-1 Tat and gp120 (refs 10, 11). T-cell-receptor (TCR)-induced apoptosis was recently shown to involve the CD95 (APO-1/Fas) receptor. We show here that HIV-1 Tat strongly sensitizes TCR- and CD4(gp120)-induced apoptosis by upregulation of CD95 ligand expression. Concentrations of Tat found to be effective in cultures of HIV-1-infected cells were also observed in sera from HIV-1-infected individuals. Taken together, our results indicate that HIV-1 Tat and gp120 accelerate CD95-mediated, activation-induced T-cell apoptosis, a mechanism that may contribute to CD4+ T-cell depletion in AIDS.

Antigens, Surface↗

PubMed1995

Structural studies of HIV-1 Tat protein.

Tat (trans-activator) proteins are early RNA binding proteins regulating lentiviral transcription. These proteins are necessary components in the life cycle of all known lentiviruses, such as the human immunodeficiency viruses (HIV) or the equine infectious anemia virus (EIAV). Tat proteins are thus ideal targets for drugs intervening with lentiviral growth. The consensus RNA binding motif (TAR, trans-activation responsive element) of HIV-1 is well characterized. Structural features of the 86 amino acid HIV-1, Zaire 2 isolate (HV1Z2) Tat protein in solution were determined by two dimensional (2D) nuclear magnetic resonance (NMR) methods and molecular dynamics (MD) calculations. In general, sequence regions corresponded to structural domains of the protein. It exhibited a hydrophobic core of 16 amino acids and a glutamine-rich domain of 17 amino acids. Part of the NH2 terminus, Val4 to Pro14, was sandwiched between these domains. Two highly flexible domains corresponded to a cysteine-rich and a basic sequence region. The 16 amino acid sequence of the core region is strictly conserved among the known Tat proteins, and the three-dimensional fold of these amino acids of HV1Z2 Tat protein was highly similar to the structure of the corresponding EIAV Tat domain. HV1Z2 Tat protein contained a well defined COOH-terminal Arg-Gly-Asp (RGD) loop similar to the recently determined decorsin RGD loop.

Amino Acid Sequence↗

PubMed1995

Lactose-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. Purification of the histidine-tagged transmembrane component IICBLac and its hydrophilic IIB domain by metal-affinity chromatography, and functional characterization.

The lactose-specific integral-membrane-protein enzyme II (IICBLac) of the bacterial phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus catalyses the uptake and phosphorylation of lactose. It consists of an N-terminal membrane-spanning IIC domain and a C-terminal hydrophilic IIB domain. IICBLac was fused with a C-terminal tag of six histidine residues using recombinant DNA technology. The resulting protein, IICBLac-His, was produced in Escherichia coli and purified under nondenaturing conditions to homogenity. The purification procedure consists of a NaOH extraction step followed by solubilisation with Triton X-100, and metal-affinity chromatography using Ni(2+)-nitrilotriacetic acid resin. The purified recombinant His-tagged protein possessed substrate specificity identical to that of the wild-type protein. To investigate the hydrophilic IIB domain, the DNA sequence coding for IIB and the His tag were fused in-frame to a DNA sequence specific for an initiation signal. The overproduced recombinant IIBLac-His was obtained by metal-affinity chromatography in pure form. Bacterial phosphotransferase-system-dependent phosphorylation of IIB-His was demonstrated in a photometric assay and by urea/polyacrylamide gel electrophoresis. The phosphorylation activity of the mutant protein [C476S]-IICBLac, containing the mutagenized phosphorylation site, was restored in the presence of IIBLac-His in a phosphorylation assay.

Base Sequence↗

PubMed1995

Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope.

Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo.

Amino Acid Sequence↗

PubMed1995

HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state.

This study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1995

Time- and frequency-domain analyses of the signal-averaged ECG in patients with arrhythmogenic right ventricular dysplasia.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by recurrent ventricular tachycardia of right ventricular origin and a cardiomyopathy with hypokinetic areas involving the free wall of the right ventricle. Subjects have a risk of sudden cardiac death, particularly during sports and strenuous exercise. Routine clinical examinations may be normal, but fragmented or delayed electrograms are usually recorded in the right ventricle of these patients. However, the frequency with which late potentials are detected by conventional time-domain analysis of the signal-averaged ECG (SAECG) is not high. This study evaluated the usefulness of the frequency-domain analysis of the SAECG in addition to the conventional time-domain analysis for a screening test to detect patients with ARVD. METHODS AND RESULTS: SAECG was recorded by using a bipolar X, Y, and Z lead system in 28 patients with ARVD (mean age, 38 +/- 13 years) and 35 age-matched normal subjects (mean age, 35 +/- 11 years). The conventional time-domain analysis of the SAECG was performed at two different high-pass filter settings, 25 and 40 Hz, and the low-pass cutoff frequency was fixed at 250 Hz. The fast-Fourier transform analysis of SAECG was performed using a Blackman-Harris window. Area ratio 1 (area of 20 to 50 Hz)/(area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz)/(area of 0 to 40 Hz) were calculated. In the conventional time-domain analysis, 20 (71%) and 18 (64%) patients had positive criteria at filter settings of 25 and 40 Hz, respectively. In the frequency-domain analysis, 18 (64%) and 20 (71%) patients had abnormal values in area ratios 1 and 2, respectively. Combining the time- and frequency-domain analyses, all patients were judged positive, with a sensitivity of 100% and a specificity of 94%. CONCLUSIONS: Each result of the time- and frequency-domain analyses revealed that both methods had equivalent value. Combining the two domain analyses improved the sensitivity without reducing the specificity. These findings suggest that combining the time- and frequency-domain analyses of the SAECG may be useful as a screening test to detect patients with ARVD.

Adult↗

PubMed1995

Protein reverse staining: high-efficiency microanalysis of unmodified proteins detected on electrophoresis gels.

A methodology is presented for efficiently gaining structural information from electrophoresed proteins after on-gel detection by imidazole-sodium dodecyl sulfate-zinc reverse staining. As a consequence of reverse staining, (a) protein bands arise transparent against a deep white-stained background, limits of detection being in the femtomole range; (b) there is no loss of image when the gel is kept in distilled water (even during years); and (c) protein bands result immobilized, i.e., they do not diffuse upon gel storage. To recover reverse-stained proteins or fragments thereof from the gel, the immobilization of bands must first be abrogated by chelating the zinc ions from stain (protein mobilization). We had originally described mobilization at low pH by using citric acid. Here, we improve this procedure regarding the protein electrotransfer. We demonstrate that mobilization is efficiently done at neutral to alkaline pH by short-term (5 to 10 min) incubation of the gel in a buffer containing glycine or dithiothreitol prior to transfer. Moreover, mobilization was most simply performed by just adding the zinc chelating agent to the transfer buffer. Reverse staining and the new mobilization procedure made electrotransferring single protein bands from gel onto small-sized (13 x 5 mm2) PVDF membrane pieces in mini sandwich-like assemblies practical. Equipment is described for the protein electroblotting in such minisandwiches. Microsequence analysis of the electroblotted proteins showed initial yields in the range of those achieved when the transfer was done from unstained control gels. Protein bands kept in the reverse-stained gel for prolonged time periods (even for as long as 2 years) could be similarly analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophoresis, Polyacrylamide Gel↗

PubMed1995

Single-step electrotransfer of reverse-stained proteins from sodium dodecyl sulfate-polyacrylamide gel onto reversed-phase minicartridge and subsequent desalting and elution with a conventional high-performance liquid chromatography gradient system for analysis.

Isolation of proteins from polyacrylamide electrophoresis gels by a novel combination of techniques is described. A given protein band from a reverse stained (imidazol-sodium dodecyl sulfate--zinc salts) gel can be directly electrotransferred onto a reversed-phase chromatographic support, packed in a self-made minicartridge (2 mm in thickness, 8 mm in internal diameter, made of inert polymeric materials). The minicartridge is then connected to a high-performance liquid chromatography system and the electrotransferred protein eluted by applying an acetonitrile gradient. Proteins elute in a small volume ( < 700 microL) of high-purity volatile solvents (water, trifluoroacetic acid, acetonitrile) and are free of contaminants (gel contaminants, salts, etc). Electrotransferred proteins were efficiently retained, e.g., up to 90% for radioiodinated alpha-lactalbumin, by the octadecyl matrix, and their recovery on elution from the minicartridge was in the range typical for this type of chromatographic support, e.g., 73% for alpha-lactalbumin. The technique was successfully applied to a variety of proteins in the molecular mass range 6-68 kDa, and with amounts between 50 and 2000 pmol. The good mechanical and chemical stability of the developed minicartridges, during electrotransfer and chromatography, allowed their repeated use. This new technique permitted a single-step separation of two proteins unresolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to their different elution from the reversed-phase support. The isolated proteins were amenable to analysis by N-terminal sequencing, enzymic digestion and mass spectrometry of their proteolytic fragments. Chromatographic elution of proteins from the reversed-phase mini-cartridge was apparently independent of the specific loading mode employed, i.e., loading by conventional loop injection or by electrotransfer.

Animals↗

PubMed1995

The arrhythmogenic right ventricle. Dysplasia versus cardiomyopathy.

Twenty-four patients presenting with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ventricular tachycardia of right ventricular origin associated with structural abnormalities of the right ventricle) were divided into two groups with left ventricular ejection fraction (LVEF) above or below 45%. The distribution of LVEF in the group with LVEF below 45% was comparable with the distribution in 6 patients with idiopathic dilated cardiomyopathy who had ventricular tachycardia originating in the left ventricle (P = 0.2). They also had the same unfavorable long-term prognosis. Therefore, it is suggested that the term, arrhythmogenic right ventricular cardiomyopathy (ARVC), be restricted to patients with a LVEF below 45%. Histological data obtained in the ARVC group showed signs of acute or chronic myocarditis (in the right and left ventricles). It can be hypothesized that patients with arrhythmogenic right ventricular dysplasia (ARVD) may be prone to develop infectious myocarditis. In patients in whom an abnormal host immune response had been seen, progressive deterioration of right and left ventricular function could be observed. This pattern may be superimposed on the genetically determined background of ARVD. This could explain the wide spectrum of clinical presentation observed in patients with tachycardia originating in an abnormal right ventricle.

Adolescent↗