Biomedical subjects

C Grond-Ginsbach

Publications and source records attributed to C Grond-Ginsbach.

17 recordsLinked to original sources

PubMed2002

Sequence analysis of the COL5A2 gene in patients with spontaneous cervical artery dissections.

The authors searched for mutations in the gene that codes for the alpha2 chain of type V procollagen in 10 patients with spontaneous cervical artery dissections (sCAD). Two patients carried a missense mutation affecting the predicted C-propeptide (T1227S; D1429V). A third patient carried two mutations (V509A and P830L) in the same alpha2(V) chain. The T1227S mutation and the V509A/P830L haplotype also were detected among 50 healthy subjects. The D1429V substitution was detected neither in a series of 150 healthy control subjects nor among 50 additional patients with sCAD.

Amino Acid Sequence↗

PubMed2002

Lipopolysaccharide receptor CD14 polymorphism and risk of stroke in a South-German population.

BACKGROUND: The monocyte receptor for bacterial lipopolysaccharide CD14 is an important mediator of the inflammatory response. Recently, a polymorphism in the promotor of the CD14 gene, C (-260) T, was detected as a risk factor for coronary heart disease. OBJECTIVE: We tested the hypotheses that this polymorphism is a risk factor 1. for cerebral ischemia in general and 2. for cerebral ischemia due to large artery atherosclerosis or microangiopathy in particular. PATIENTS AND METHODS: We performed a case control study including 151 consecutive patients with acute cerebral ischemia treated at our university hospital and 149 control subjects. All control subjects were randomly selected from the general population of the same region in South-West Germany. Genotype frequencies of the C(-260) T polymorphism in the promotor of the CD14 gene were examined by restriction length analysis. RESULTS: The TT-genotype was not associated with cerebral ischemia in general either in univariate or in multivariate analysis together with classical vascular risk factors (odds ratio in multivariate analysis: 1.11; 95 %CI, 0.63 to 1.95). In 70 patients with cerebral ischemia due to atherosclerosis of large arteries or microangiopathy, there was a significantly higher prevalence of the TT-genotype than into control subjects (38.6 % vs. 23.5 %; odds ratio in multivariate analysis 2.26; 95 %CI, 1.13 to 4.54). CONCLUSIONS: We demonstrated that the TT-genotype of the CD14 C(-260) T polymorphism in a South-German population is not associated with an increased risk of cerebral ischemia in general. However, we found that the TT-genotype is associated with a risk of atherosclerotic or microangiopathic stroke. This finding requires confirmation by future studies in larger populations.

Aged↗

PubMed2001

Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke.

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.

Acute Disease↗

PubMed2001

Pathogenesis of cervical artery dissections: association with connective tissue abnormalities.

BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. OBJECTIVE: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. METHODS: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers-Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. CONCLUSION: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Adult↗

PubMed2001

Increased cytokine release by leucocytes in survivors of stroke at young age.

BACKGROUND: Enhanced stimulus-induced release of pro-inflammatory cytokines by leucocytes may contribute to the pathogenesis of ischaemic stroke. DESIGN: We investigated the lipopolysaccharide-induced release of interleukin-1beta (IL-1beta), IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) in whole blood from 20 patients with a history of ischaemic stroke under the age of 50, 20 patients with a history of cervical artery dissection (CAD) and 21 age- and sex-matched healthy control subjects. RESULTS: Release of IL-8 was higher (P = 0.006) and release of TNF-alpha and IL-6 tended to be higher (P < 0.1) in young stroke patients than in control subjects. No increased release existed in CAD patients. Vascular risk factors or history of infection before stroke did not modify IL-8 production. A common T(250) --> A polymorphism in the IL-8 gene promotor was newly identified but did not correlate with the variability of IL-8 release. The C(260) --> T polymorphism in the gene of the monocytic LPS-receptor CD14--a risk factor for myocardial infarction--was not associated with increased cytokine release. CONCLUSIONS: We conclude that high inducible release of IL-8--and possibly of TNF-alpha and IL-6--may contribute to the odds of ischaemic stroke in young adults.

Adult↗

PubMed2000

[Not Available].

Kant's discussion of the ethical implications of smallpox inoculation is presented here. In four fragments Kant analyzes the moral legitimacy of endangering other people in medical practice and especially endangering people who are incapable of giving consent. In addition, we re-evaluate the alleged "success story" of the development of smallpox prevention and review the technical and theoretical difficulties of smallpox inoculation at the time of Kant.

Ethics, Medical↗

PubMed2000

Mutations in the tropoelastin gene (ELN) were not found in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The majority of patients with spontaneous cerebral artery dissection show ultrastructural alterations in dermal collagen and elastic fibers. METHODS: We studied the gene encoding tropoelastin (ELN) by reverse transcription-polymerase chain reaction and subsequent sequence analysis in 10 patients with abnormalities in their elastic fibers. RESULTS: No mutations were found in the whole coding region of the ELN gene. The simultaneous visualization and quantification of ELN splice variants by gene scanning enabled the analysis of the regulation of alternative splicing of ELN mRNA. No differences could be detected between fibroblast cultures of the patients and a control subject. CONCLUSIONS: Neither mutations in the ELN gene nor dysregulation of its activity appears to be the cause of the connective tissue disorder that is found in most patients with spontaneous dissections.

Adult↗

PubMed2000

Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis.

In a pilot study, we identified Chlamydia pneumoniae in the cerebrospinal fluid by polymerase chain reaction in 5 of 10 patients with definite multiple sclerosis (MS). In a second series, 2 of 20 patients with definite MS and 3 of 17 patients with possible/probable MS or MS variants, but none of 56 patients with other neurological, diseases were polymerase chain reaction-positive. We confirm that C. pneumoniae can be found in the cerebrospinal fluid of MS patients, but our rate of positive results is lower than in a recent report.

Adolescent↗

PubMed1999

[Leptomeningeal dissemination of chronic lymphatic leukemia. Molecular genetic detection in cerebrospinal fluid].

The diagnosis of leptomeningeal dissemination of chronic lymphatic leukemia (CLL) by conventional cytology is unreliable because cytomorphologic criteria of malignancy are often lacking. Immunophenotyping of leukocyte differentiation antigens may also be of limited diagnostic value due to the small number of cells in cerebrospinal fluid (CSF) samples. Molecular methods may support the specific diagnosis of leptomeningeal infiltration of CLL. We present an 54 old patient who was diagnosed with CLL five years ago. Despite clinical signs of leptomeningeal involvement neither magnetic resonance imaging (MRI) nor conventional CSF analysis were suggestive of lymphomatous meningitis. Using PCR we selectively amplified the highly variable and clone-specific CDR3 region of the locus encoding the immunoglobulin heavy chain (IgH) in DNA obtained from both CSF and peripheral blood cells. Analysis of PCR products by high resolution gel electrophoresis revealed a single DNA fragment respectively indicating the presence of a monoclonal cell population in both compartments. DNA sequence analysis of the amplified CDR3 segments confirmed the clonal identity of cells and the leptomeningeal dissemination of CLL.

B-Lymphocytes↗

PubMed1999

Mutations in the COL5A1 coding sequence are not common in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (COL5A1) as a candidate gene for sCAD. METHODS: We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction-amplified fragments of the whole COL5A1 coding sequence. RESULTS: We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular COL5A1 sequences with some silent polymorphisms. CONCLUSIONS: Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD.

Adult↗

PubMed1998

Complex chromosomal rearrangements associated with congenital erythrophagocytotic histiocytosis.

We describe a patient with a congenital malignant blood disorder and a constitutional de novo chromosomal rearrangement that includes four breakpoints. By conventional cytogenetic analysis an obviously reciprocal balanced translocation with the breakpoints 1p36 and 5q11.2 was diagnosed. Due to a suspicious dark band in the breakpoint area of 1p a more detailed analysis of the breakpoints was performed using microdissection and reverse chromosome painting. This revealed a small inversion at 1p36 that must have occurred prior to the reciprocal translocation. The three breakpoints in chromosome 1 (1p36.11, 1p36.21 and 1p36.31) are within or close by regions known to contain tumor suppressor genes. The chromosomal rearrangement might have resulted either in a submicroscopic deletion, in loss of heterozygosity of one or more imprinted genes, or in gene position effects as possible explanations for the clinical course of our patient.

Chromosomes, Human, Pair 1↗

PubMed1996

[Georges Canguilhem the medical historian].

The work of the French philosopher Georges Canguilhem is inroduced here. Medical historiography is not the ultimate aim of Canguilhems work, but rather a tool for the analysis ef epistemological questions. These questions are to be investigated, as well as the art of medical history that Canguilhem consideres to be helpful for such investigations. French "epistemology", a direction of philosophy of science to which Cangilhem belongs, is discussed first. Canguilhem's epistemology does not aim at a rational reconstruction of decontextualized scientific results, but at an historical reconstruction of science. It analyses the functioning of scientific concepts in relation of their historical context. The main themes of Canguilhems work (biological normality, scientific ideology and history of physiology) are summarized in a second part of this study. Finally we investigate the importance of Canguilhem for modern research in history of medicine.

France↗

PubMed1996

A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors.

Dominant missense mutations in the human glycine receptor (GlyR) alpha 1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1(null) allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man.

Alleles↗

PubMed1994

Molecular analysis of aniridia patients for deletions involving the Wilms' tumor gene.

A human aniridia candidate (AN) gene on chromosome 11p13 has been cloned and characterized. The AN gene is the second cloned gene of the contiguous genes syndrome WAGR (Wilms' tumor, aniridia, genitourinary malformations, mental retardation) on chromosome 11p13, WT1 being the first gene cloned. Knowledge about the position of the AN and WT1 genes on the map of 11p13 makes the risk assessment for Wilms' tumor development in AN patients possible. In this study, we analyzed familial and sporadic aniridia patients for deletions in 11p13 by cytogenetic analyses, in situ hybridization, and pulsed field gel electrophoresis (PFGE). Cytogenetically visible deletions were found in 3/11 sporadic AN cases and in one AN/WT patient, and submicroscopic deletions were identified in two sporadic AN/WT patients and in 1/9 AN families. The exact extent of the deletions was determined with PFGE and, as a result, we could delineate the risk for Wilms' tumor development. Future analyses of specific deletion endpoints in individual AN cases with the 11p13 deletion should result in a more precise risk assessment for these patients.

Adolescent↗

PubMed1994

Maternal cell contamination in amniotic fluid samples as a consequence of the sampling technique.

Maternal cell contamination in amniotic fluid samples is easily detected by in situ hybridization if the karyotype of the fetus differs from the karyotype of the mother. One out of two amniotic fluid samples appears to contain more than 20% maternal cells. Bloody samples often contain even more than 50% maternal cells. Maternal cells can also be identified on the basis of their nuclear morphology. Maternal cell contamination is regularly observed in pregnancies with an anterior placenta, whereas it is rare in posterior placenta pregnancies. The maternal cells are therefore thought to be artificially introduced into the amniotic fluid sample, as a result of placental bleeding during amniocentesis. The implications of maternal cell contamination for prenatal diagnosis using uncultured amniotic fluid samples are discussed.

Amniocentesis↗

PubMed1993

HeLa D98/aH-2 studied by chromosome painting and conventional cytogenetical techniques.

Metaphase chromosomes of HeLa D98/AH-2 cells were studied by GTG-banding, NOR-silver staining and in situ hybridization using libraries specific for each human chromosome as probes (chromosome painting). The structure and composition of all marker chromosomes could be determined, allowing a critical assessment of earlier studies. The revised HeLa D98/AH-2 karyotype should provide a reference standard in certain cancer cytogenetic studies.

Chromosome Banding↗

PubMed1991

Chromosomal in situ suppression hybridization after Giemsa banding.

We report the successive application of classical Giemsa banding and chromosomal in situ suppression hybridization in clinical cytogenetics. The use of both techniques within one protocol requires an additional fixation of the chromosome preparations and an improved suppression of the labelled repetitive sequences. The combination of these two cytological techniques allows the high resolution mapping of translocated Y-chromosomal sequences in the chromosome set of an XX-male.

Chromosome Banding↗