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1.
Clin Genet ; 92(3): 332-337, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28139825

ABSTRACT

Costello syndrome (CS) is caused by heterozygous germline HRAS mutations. Most patients share the HRAS mutation c.34G>A (p.Gly12Ser) associated with the typical, relatively homogeneous phenotype. Rarer mutations occurred in individuals with an attenuated phenotype. Although many disease-associated HRAS alterations trigger constitutive activation of HRAS-dependent signalling pathways, additional pathological consequences exist. An infant with failure-to-thrive and hypertrophic cardiomyopathy had a novel de novo HRAS mutation (c.179G>T; p.Gly60Val). He showed subtle dysmorphic findings consistent with attenuated CS and died from presumed cardiac cause. Functional studies revealed that amino acid change p.Gly60Val impairs HRAS binding to effectors PIK3CA, phospholipase C1, and RAL guanine nucleotide dissociation stimulator. In contrast, interaction with effector rapidly accelerated fibrosarcoma (RAF) and regulator NF1 GTPase-activating protein was enhanced. Importantly, expression of HRAS p.Gly60Val in HEK293 cells reduced growth factor sensitivity leading to damped RAF-MAPK and phosphoinositide 3-kinases-AKT signalling response. Our data support the idea that a variable range of dysregulated HRAS-dependent signalling dynamics, rather than static activation of HRAS-dependent signal flow, may underlie the phenotypic variability in CS.


Subject(s)
Costello Syndrome/diagnosis , Costello Syndrome/genetics , Mutation , Phenotype , Proto-Oncogene Proteins p21(ras)/genetics , Alleles , Amino Acid Substitution , Autopsy , Cell Line , Costello Syndrome/metabolism , Fatal Outcome , Genetic Association Studies , Genotype , Humans , Infant , Male , Proto-Oncogene Proteins p21(ras)/metabolism , Signal Transduction
2.
Schizophr Res ; 156(2-3): 157-60, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24837684

ABSTRACT

BACKGROUND: The fornix is a compact bundle of white matter fibers that project from the hippocampus to the mamillary bodies and septal nuclei. Its association with memory, as well as with symptoms in schizophrenia, has been reported in chronic schizophrenia. The purpose of this study is to determine whether or not fornix abnormalities are evident at the onset of schizophrenia. METHODS: Diffusion tensor imaging (DTI) and DT tractography were used to evaluate the fornix in 21 patients with first episode schizophrenia (16 males/5 females) and 22 healthy controls (13 males/9 females). Groups were matched on age, gender, parental socioeconomic status, education and handedness. Fractional anisotropy (FA), a measure of white matter integrity, radial diffusivity (RD), thought to reflect myelin integrity, trace, a possible marker of atrophy or cell loss, and axial diffusivity (AD), thought to reflect axonal integrity, were averaged over the entire tract extracted by means of DT tractography, and used to investigate fornix abnormalities in first episode schizophrenia compared with healthy controls. RESULTS: Significant group differences were found between first episode patients and controls for FA (p=0.0001), RD (p=0.001) and trace (p=0.006). CONCLUSION: These findings suggest abnormalities in the fornix in the early stages of schizophrenia, and further suggest that white matter abnormalities, which are apparent in the early course of the disease, may reflect myelin disturbances.


Subject(s)
Fornix, Brain/pathology , Schizophrenia/pathology , Anisotropy , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Female , Humans , Male , Myelin Sheath/pathology , Nerve Fibers, Myelinated/pathology , White Matter/pathology , Young Adult
3.
Clin Genet ; 84(6): 560-5, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23350639

ABSTRACT

Synaptopathies constitute a group of neurological diseases including autism spectrum disorders (ASD) and intellectual disability (ID). They have been associated with mutations in genes encoding proteins important for the formation and stabilization of synapses, such as SHANK1-3. Loss-of-function mutations in the SHANK genes have been identified in individuals with ASD and ID suggesting that other factors modify the neurological phenotype. We report a boy with severe ID, behavioral anomalies, and language impairment who carries a balanced de novo triple translocation 46,XY,t(11;17;19)(q13.3;q25.1;q13.42). The 11q13.3 breakpoint was found to disrupt the SHANK2 gene. The patient also carries copy number variations at 15q13.3 and 10q22.11 encompassing ARHGAP11B and two synaptic genes. The CHRNA7 gene encoding α7-nicotinic acetylcholine receptor subunit and the GPRIN2 gene encoding G-protein-regulated inducer of neurite growth 2 were duplicated. Co-occurrence of a de novo SHANK2 mutation and a CHRNA7 duplication in two reported patients with ASD and ID as well as in the patient with t(11;17;19), severe ID and behavior problems suggests convergence of these genes on a common synaptic pathway. Our results strengthen the oligogenic inheritance model and highlight the presence of a large effect mutation and modifier genes collectively determining phenotypic expression of the synaptopathy.


Subject(s)
Epistasis, Genetic , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Nerve Tissue Proteins/genetics , Phenotype , alpha7 Nicotinic Acetylcholine Receptor/genetics , Comparative Genomic Hybridization , DNA Copy Number Variations , Facies , Genetic Association Studies , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Translocation, Genetic
4.
Environ Technol ; 33(13-15): 1511-6, 2012.
Article in English | MEDLINE | ID: mdl-22988609

ABSTRACT

The ethanol industry has grown rapidly during the past ten years, mainly due to increasing oil prices. However, efficient and cost-effective solutions for treating thin stillage wastewater have still to be developed. The anaerobic membrane bioreactor (AnMBR) technology combines classical anaerobic treatment in a completely-stirred tank reactor (CSTR) with membrane separation. The combination of these two technologies can achieve a superior effluent quality and also increase biogas production compared to conventional anaerobic solutions. A pilot-scale AnMBR treating thin stillage achieved very high treatment efficiencies in terms of chemical oxygen demand (COD) and total suspended solids (TSS) removal (>98%). An average permeate flux of 4.3 L/m2 x h was achieved at relatively low transmembrane pressure (TMP) values (0.1-0.2 bars) with flat-sheet membranes. Experience gained during the pilot-scale studies provides valuable information for scaling up of AnMBRs treating complex and high-strength wastewaters.


Subject(s)
Bioreactors , Ethanol , Industrial Waste , Waste Disposal, Fluid/instrumentation , Waste Disposal, Fluid/methods , Anaerobiosis , Biological Oxygen Demand Analysis , Equipment Design , Filtration
5.
Mol Syndromol ; 2(1): 27-34, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22570643

ABSTRACT

Hallermann-Streiff syndrome (HSS) is a rare inherited disorder characterized by malformations of the cranium and facial bones, congenital cataracts, microphthalmia, skin atrophy, hypotrichosis, proportionate short stature, teeth abnormalities, and a typical facial appearance with prominent forehead, small pointed nose, and micrognathia. The genetic cause of this developmental disorder is presently unknown. Here we describe 8 new patients with a phenotype of HSS. Individuals with HSS present with clinical features overlapping with some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia (MAD). HGPS is caused by de novo point mutations in the LMNA gene, coding for the nuclear lamina proteins lamin A and C. MAD with type A and B lipodystrophy are recessive disorders resulting from mutations in LMNA and ZMPSTE24, respectively. ZMPSTE24 in addition to ICMT encode proteins involved in posttranslational processing of lamin A. We hypothesized that HSS is an allelic disorder to HGPS and MAD. As the nuclear shape is often irregular in patients with LMNA mutations, we first analyzed the nuclear morphology in skin fibroblasts of patients with HSS, but could not identify any abnormality. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in the 8 patients with HSS revealed the heterozygous missense mutation c.1930C>T (p.R644C) in LMNA in 1 female. Extreme phenotypic diversity and low penetrance have been associated with the p.R644C mutation. In ZMPSTE24 and ICMT, no pathogenic sequence change was detected in patients with HSS. Together, we found no evidence that HSS is another laminopathy.

6.
Cell Death Differ ; 11(1): 80-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-12970676

ABSTRACT

Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKB-protein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.


Subject(s)
Apoptosis/physiology , Cell Nucleus/metabolism , DNA-Binding Proteins/metabolism , Recombinant Proteins/metabolism , Transcription Factors/metabolism , cdc25 Phosphatases/metabolism , Animals , Apoptosis/drug effects , Artificial Gene Fusion , Cell Compartmentation , Cell Cycle Proteins , Cell Line, Tumor , Forkhead Box Protein O1 , Forkhead Box Protein O3 , Forkhead Transcription Factors , Genetic Vectors , Humans , Nerve Tissue Proteins , Rats , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Recombinant Proteins/genetics , Transformation, Genetic , Tumor Necrosis Factor-alpha/pharmacology , cdc25 Phosphatases/genetics
7.
Oncogene ; 20(33): 4542-53, 2001 Jul 27.
Article in English | MEDLINE | ID: mdl-11494150

ABSTRACT

The phosphatase Cdc25A was shown to be a target of the transcription factor c-Myc. Myc-induced apoptosis appeared dependent on Cdc25A expression and Cdc25A over-expression could substitute for Myc-triggered apoptosis. These findings suggested that an important downstream component of Myc-mediated apoptosis was identified. However and in contrast, we recently reported that during TNFalpha-induced apoptosis, which required c-Myc function, Cdc25A was down-regulated in a human carcinoma cell line. We now provide evidence that Cdc25A rendered the non-transformed rat embryonic cell line 423 refractory to apoptosis, which was induced by serum deprivation and in absence of detectable c-myc levels. The survival promoting activity of cdc25A was abolished upon infection of cells with a full-length cdc25A antisense construct. To identify the signaling proteins mediating the survival function of the phosphatase, cdc25A- and akt- over-expressing pooled clones were exposed to selected chemicals, which inhibit or activate key proteins in signaling pathways. Inhibition of apoptosis by SU4984, NF023 and Rapamycin placed Cdc25A and Akt function downstream of FGF.R, PDGF.R, and compensated G-protein- and PP2A- activity. Interestingly, upon treatment with LY-294002, cdc25A- and akt- over-expressing clones exhibited similar apoptotic patterns as control cells, which indicates that neither Akt- nor Cdc25A-mediated survival functions are dependent on PI.3 kinase activity in rat 423 cells. In cdc25A-overexpressing cells increased levels of serine 473 phosphorylated Akt were found, which co-precipitated with Cdc25A and Raf1. Since activation of proteins requires dephosphorylation of particular residues in addition to site-specific phosphorylation, the anti-apoptotic effect of Cdc25A might derive from its participation in a multimeric protein complex with phosphoAkt and Raf1, two prominent components of survival pathways.


Subject(s)
Apoptosis/drug effects , Arabidopsis Proteins , Culture Media, Serum-Free/pharmacology , cdc25 Phosphatases/physiology , Animals , Cell Line/drug effects , Chromones/pharmacology , Cytokines/pharmacology , Depression, Chemical , Doxycycline/pharmacology , Embryo, Mammalian/cytology , Fibroblast Growth Factor 2/pharmacology , Gene Expression Regulation , Genes, myc , Growth Substances/pharmacology , Intercellular Signaling Peptides and Proteins , Macromolecular Substances , Morpholines/pharmacology , Peptides/pharmacology , Phosphorylation , Piperazines/pharmacology , Plant Proteins/physiology , Platelet-Derived Growth Factor/pharmacology , Potassium Channels/physiology , Protein Processing, Post-Translational , Proto-Oncogene Proteins c-myc/physiology , Proto-Oncogene Proteins c-raf/physiology , Rats , Recombinant Fusion Proteins/physiology , Sirolimus/pharmacology , Suramin/analogs & derivatives , Suramin/pharmacology , Transfection
8.
Exp Hematol ; 29(5): 623-32, 2001 May.
Article in English | MEDLINE | ID: mdl-11376876

ABSTRACT

OBJECTIVE: Amidox and didox are two polyhydroxy-substituted benzohydroxamic acid derivatives that belong to a new class of ribonucleotide reductase (RR) inhibitors. RR is the rate-limiting enzyme for de novo deoxyribonucleotide synthesis, and its activity is significantly increased in tumor cells in proportion to the proliferation rate. Therefore, RR is a target for antitumor therapy. MATERIALS AND METHODS: HL-60 and K562 leukemia cells were treated with increasing doses of amidox and didox. Thereafter, the mode of cytotoxic drug action was determined by Hoechst 33258/propidium iodide (HO/PI) double staining, annexin binding, DNA fragmentation, and caspase activation. This was correlated to the decrease in dNTP levels. Staining with HO/PI and binding of fluorescein isothiocyanate-conjugated annexin V to externalized phosphatidylserine were used to quantify apoptosis. RESULTS: Low doses of amidox or didox resulted in an increase of apoptotic HL-60 cells within 48 hours. Higher doses (50 microM amidox or 250 microM didox) led to rapid induction of apoptosis, which could be detected as early as 4 hours after treatment. After 48 hours with these concentrations, almost 100% of the HL-60 cells died by apoptosis without an increase in necrosis. K562 cells were found to be resistant to amidox but not to didox. In HL-60 cells, upstream caspase 8 is processed in response to didox, whereas caspases 8 and 9 are processed upon amidox treatment. Didox-induced apoptosis, but not amidox-induced apoptosis, can be correlated with the decrease in dNTP levels. The results suggests that amidox induces several apoptosis mechanisms in HL-60 cells. In contrast, only caspase 9 is activated by didox in K562 cells, and because amidox hardly induces apoptosis in this cell line, no caspase cleavage is observed. CONCLUSIONS: Didox triggers distinct apoptosis pathways in HL-60 and K562 cells.


Subject(s)
Apoptosis/drug effects , Caspase Inhibitors , Caspases/drug effects , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Neoplasm Proteins/antagonists & inhibitors , Oximes/pharmacology , Ribonucleotide Reductases/antagonists & inhibitors , Annexin A5/metabolism , Caspase 8 , Caspase 9 , DNA Fragmentation , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Gelsolin/metabolism , HL-60 Cells/drug effects , HL-60 Cells/enzymology , Humans , K562 Cells/drug effects , K562 Cells/enzymology , Phosphatidylserines/metabolism , Pilot Projects , Poly(ADP-ribose) Polymerases/metabolism
10.
Circulation ; 102(9): 1000-6, 2000 Aug 29.
Article in English | MEDLINE | ID: mdl-10961964

ABSTRACT

BACKGROUND: Elevated C-reactive protein (CRP) serum levels, an exquisitely sensitive objective marker of inflammation, relate to long-term prognosis in patients with coronary artery disease and in apparently healthy men. Because abnormalities of endothelial regulation of vascular function may contribute to the occurrence of coronary events, we tested the hypothesis that elevated CRP levels are associated with an abnormal systemic endothelial vascular reactivity. METHODS AND RESULTS: Endothelium-dependent (10 to 50 microg/min acetylcholine) and endothelium-independent (2 to 8 microg/min sodium nitroprusside) forearm blood flow responses were measured with venous occlusion plethysmography in 60 male patients with angiographically documented coronary artery disease. Forearm blood flow responses to acetylcholine were inversely correlated with CRP serum levels (r=-0.46, P:=0.001). With multivariate analysis that included the classic risk factors for coronary artery disease, elevated CRP serum level remained a statistically significant independent predictor of a blunted endothelial vasodilator capacity. Most important, normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months. CONCLUSIONS: Thus, elevated CRP serum levels indicative of a systemic inflammatory response are associated with a blunted systemic endothelial vasodilator function. The identification of elevated CRP levels as a transient independent risk factor for endothelial dysfunction might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.


Subject(s)
C-Reactive Protein/analysis , Coronary Disease/physiopathology , Endothelium, Vascular/physiopathology , Acetylcholine/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Aspirin/therapeutic use , Biomarkers/blood , Brachial Artery , Coronary Disease/blood , Follow-Up Studies , Forearm , Humans , Inflammation/blood , Infusions, Intra-Arterial , Male , Middle Aged , Multivariate Analysis , Nitroprusside/pharmacology , Regional Blood Flow/drug effects , Risk Factors , Vasodilation/drug effects , Vasodilator Agents/therapeutic use
11.
Life Sci ; 67(26): 3131-42, 2000 Nov 17.
Article in English | MEDLINE | ID: mdl-11191620

ABSTRACT

Trimidox (3,4,5-trihydroxybenzohydroxamidoxime), a recently synthesized inhibitor of ribonucleotide reductase (RR), was shown to exert anti-proliferative activities in HL-60 and K562 human leukemia cell lines and to prolong the life span of mice inoculated with L1210 mouse leukemia cells. Here we test whether trimidox also exhibits anti-neoplastic properties in ovarian carcinoma cells. Since the mode of action of trimidox on cell fate has not been investigated so far, we addressed this unresolved item and find that this polyhydroxybenzoic acid derivative induces apoptosis of N.1 human ovarian carcinoma cells when tested in growth factor deprived medium. Utilizing an improved analysis, based on Hoechst 33258/propidium iodide double staining, apoptosis is quantified and discriminated from necrosis. Trimidox induces c-myc expression, which is indispensible for apoptosis of N.1 cells, and expression of plasminogen activator/urokinase type (upa), which supports the apoptotic process under more physiological conditions. Surprisingly, trimidox does not block dNTP synthesis in N.1 cells at the concentrations tested and, therefore, trimidox induces apoptosis independent of RR-inhibition. Like TNFalpha or benzamide riboside, which are also inducers of apoptosis of N.1 cells, trimidox also down-regulates the G1 cell cycle phosphatase cdc25A, whereas cyclin D1 becomes up-regulated. This report shows that trimidox destroys human ovarian carcinoma cells by inducing them to undergo apoptosis as well as corroborating previous investigations which demonstrated that apoptosis of these cells depends on c-myc over-expression when survival factors are withdrawn.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Benzamidines/pharmacology , Enzyme Inhibitors/pharmacology , Genes, myc , Ovarian Neoplasms/drug therapy , Apoptosis/genetics , Cyclin D1/biosynthesis , Deoxyribonucleotides/metabolism , Drug Screening Assays, Antitumor , Female , Gene Expression/drug effects , Genes, cdc/drug effects , HL-60 Cells , Humans , Ribonucleotide Reductases/antagonists & inhibitors , Tumor Cells, Cultured , Urokinase-Type Plasminogen Activator/biosynthesis , cdc25 Phosphatases/biosynthesis
12.
Mutat Res ; 437(3): 205-17, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10592328

ABSTRACT

Over-expression of the transcription factor c-Myc immortalizes primary cells and transforms in co-operation with activated ras. Therefore, c-myc is considered a proto-oncogene. Since its discovery c-Myc has been shown to render cells growth factor independent, accelerates passage through G1 of the cell cycle, inhibits differentiation and elicits apoptosis. Whereas the effects on immortalization, proliferation and inhibition of differentiation are in conceivable accordance with gain of function, as it is defined for a proto-oncogene, its pro-apoptotic activity disables a straight forward explanation of the physiological role of c-Myc and suggests a highly complex contribution during development. The recent accomplishments in c-Myc research shed some light on the difficile regulatory network which keeps check on c-Myc activity such as by binding to proteins some of which are transcription factors for non-c-Myc targets. Moreover, it was shown that genes are targeted by c-Myc depending on the sequence of flanking regions adjacent to the E-box or in dependence on the availability of binding partners which is most probably specific to the cellular context. Cdc25A and ornithine decarboxylase, both described to be c-Myc targets, have been brought forward as downstream effectors in the induction of proliferation under serum rich conditions, or in the induction of apoptosis when serum factors are limited. These genes seem to be regulated by c-Myc in a cell type-specific manner. H-ferritin, IRP2 and telomerase are the most recently discovered direct targets of c-Myc. The regulation of H-ferritin and IRP2 might explain the potential of c-Myc to promote proliferation and the regulation of telomerase could be responsible for the immortalizing properties of c-Myc. In the future, H-ferritin and telomerase have to be analyzed whether or not these genes are also Myc targets in other cell systems. Although the intense research efforts regarding the function of c-Myc last already two decades the role of this gene is still enigmatic.


Subject(s)
Apoptosis/genetics , Proto-Oncogene Proteins c-myc/genetics , Animals , Cell Division/genetics , Gene Expression Regulation , Humans , Proto-Oncogene Mas , RNA, Messenger/metabolism , Transcription Factors/genetics , Tumor Cells, Cultured
13.
Cell Death Differ ; 6(8): 736-44, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10467347

ABSTRACT

One of the mechanisms of action of a new oncolytic agent, benzamide riboside (BR) is by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH) which catalyzes the formation of xanthine 5'-monophosphate from inosine 5'-monophosphate and nicotinamide adenine dinucleotide, thereby restricting the biosynthesis of guanylates. In the present study BR (10 - 20 microM) induced apoptosis in a human ovarian carcinoma N.1 cell line (a monoclonal derivative of its heterogenous parent line HOC-7). This was ascertained by DNA fragmentation, TUNEL assay, [poly(ADP)ribose polymerase]-cleavage and alteration in cell morphology. Apoptosis was accompanied by sustained c-Myc expression, concurrent down-regulation of cdc25A mRNA and protein, and by inhibition of Cdk2 activity. Both Cdk2 and cdc25A are G1 phase specific genes and Cdk2 is the target of Cdc25A. These studies demonstrate that BR exhibits dual mechanisms of action, first by inhibiting IMPDH, and second by inducing apoptosis, which is associated with repression of components of the cell cycle that are downstream of constitutive c-Myc expression.


Subject(s)
Apoptosis , Enzyme Inhibitors/metabolism , IMP Dehydrogenase/antagonists & inhibitors , Nucleosides/metabolism , cdc25 Phosphatases/biosynthesis , Adenocarcinoma , Apoptosis/drug effects , Cell Division/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Humans , Nucleosides/pharmacology , Ovarian Neoplasms , Tumor Cells, Cultured , cdc25 Phosphatases/genetics
14.
Herz ; 23(2): 130-4, 1998 Mar.
Article in German | MEDLINE | ID: mdl-9592708

ABSTRACT

The vascular endothelium plays a central role in the regulation of the arterial tone and in the control of the local hemostasis. It is also involved in the regulation of proliferation processes of the vascular wall. The presence of risk factors for coronary artery disease and/or manifest atherosclerotic lesions are associated with an impairment of endothelium-dependent vasoregulation. Since the assessment of coronary vascular reactivity requires an invasive approach, it would be desirable to non- or semi-invasively evaluate blood flow regulation and its impairment by atherosclerotic processes. Indeed, endothelial dysfunction of the coronary arteries parallels endothelium-related impairment of vasoreactivity of the brachial artery. Analysis of flow-dependent dilatation of the brachial artery by means of ultrasound represents a non-invasive diagnostic tool to assess endothelium-mediated vasomotion. By means of venous strain gauge forearm occlusion plethysmography, it is possible to measure the blood flow in a semi-invasive way. The endothelium-mediated forearm blood flow response is obtained by the infusion of acetylcholine into the brachial artery, whereas infusion of sodium-nitroprusside provides information about the endothelium-independent vasodilator capacity of the forearm resistance vasculature. Assuming that the atherosclerotic process is a generalized disease, the assessment of the forearm blood flow by venous strain gauge occlusion plethysmography may provide some information applicable to the coronary circulation. However, the proof of a positive correlation between the degree of the impaired forearm blood flow responses measured by occlusion plethysmography and the extent of coronary atherosclerosis and its disturbed vasoregulation remains to be established.


Subject(s)
Coronary Artery Disease/diagnosis , Forearm/blood supply , Acetylcholine , Brachial Artery/diagnostic imaging , Humans , Nitroprusside , Plethysmography , Regional Blood Flow , Risk Factors , Ultrasonography , Vasodilation
15.
Derm Beruf Umwelt ; 36(5): 157-62, 1988.
Article in German | MEDLINE | ID: mdl-3234268

ABSTRACT

The history of inpatients with Crohn's disease revealed several occurrences of contact dermatitis due to metal ions. Therefore, we considered the question as to whether allergic reactions to amalgam fillings or mercury, delivered in small amounts, could be a factor in the activity of regional enteritis. 23 patients with Crohn's disease (15 females, 8 males), aged from 20 to 44 years were screened by an extended standard patch test (following the rules of the ICDRG). Surprisingly, no case of hypersensitivity to amalgam and/or mercury was found. However, nickelsulfate yielded positive reactions in 39.1% of all tested patients (9/23). In comparison to the normal population this prevalence of nickelsulfate hypersensitivity is distinctly increased. It may be an epiphenomenon of Crohn's disease (sensitization via an enhanced permeability of the irritated mucous membranes for nutritive nickelsulfate) or an etiopathogenetic co-factor. In the latter case regional enteritis might be regarded as an allergic-irritative disease of the bowel.


Subject(s)
Crohn Disease/complications , Dermatitis, Contact/etiology , Nickel/adverse effects , Adolescent , Adult , Female , Humans , Hypersensitivity, Delayed/etiology , Male , Patch Tests
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