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Biomedical subjects

S Hofmann

Publications and source records attributed to S Hofmann.

At least 19 recordsLinked to original sources
PubMed2002

The tumour necrosis factor-alpha induced vascular permeability is associated with a reduction of VE-cadherin expression.

BACKGROUND: Vascular permeability is controlled by endothelial cell-to-cell junctions. Vascular endothelial (VE)-cadherin, the major component of adherence junctions (AJ) in the endothelium, is the target of the permeability-increasing agent tumour necrosis factor-a (TNF-alpha). We investigated whether TNF-alpha regulates the synthesis of VE-cadherin on the transcriptional level. MATERIALS AND METHODS: Human endothelial cells, isolated from aorta (aEC) and umbilical cord (HUVEC), were exposed to TNF-alpha (200 U/ml) for 6 h or 12 h, with and without subsequent incubation with TNF-alpha for 24 h. VE-cadherin mRNA was evaluated by semi-quantitative RT-PCR. The VE-Cadherin protein expression was analyzed by flow cytometry (FACS). RESULTS: The VE-cadherin amplification curve of TNF-alpha treated cells was shifted to the right compared to controls, indicating a lower mRNA amount. The number of cycles at which half-maximal amplification (N50) was achieved, was lower for control aEC (30.7) than for TNF-alpha treated aEC (33.0). The N50 of HUVEC treated with TNF-alpha for 12 h and 12 h + 24 h medium (N50 = 32.1), was higher compared to controls (N50 = 29.7) and cells treated with TNF-alpha for 6 h (N50 = 30.8). As determined by FACS analysis, incubation with TNF-alpha caused a small decrease of VE-cadherin protein expression from 7.44 to 6.05 mean channel intensity. CONCLUSION: Our results indicate that TNF-alpha affects VE-cadherin gene expression on the transcriptional level, inducing a downregulation of the VE-cadherin expression.

Antigens, CD↗
PubMed2002

[MR arthrography of the hip joint].

MR arthrography of the hip joint is usually performed after a conventional MRI has been obtained to rule out other pathologies of the hip joint as for instance bone marrow edema or osteonecrosis of the hip. MR arthrography is mainly performed as a very special investigation, and it is executed in most cases if the clinician asks for the diagnosis of a labral lesion. In very rare cases, MR arthrography of the hip is performed to image cartilage disease or osteochondrosis dissecans or free intraarticular bodies. In this paper, the indications, the technique, and the most important pathology of the hip joint--labral lesions--will be described as well as variants of the normal acetabular labrum. After a conventional MRI of the hip joint has been performed, a MR arthrography of the hip will be obtained to search for labral pathology or cartilage disease. MR arthrography is obtained after the intraarticular injection of 10-20 ml of a 0.1 mmol solution of gadopentate-dimeglumine has been performed. The intraarticular injection can either be fluoroscopic-guided or CT-guided or directly MR-guided. After the intraarticular injection, MR arthrography will be performed by the use of paracoronal and parasagittal T1-weighted spin echo or gradient echo sequences. In cases of labral lesions (degeneration, labral tear, labral detachment) or cartilage disease MR arthrography proved to be more sensitive as conventional MRI as shown in the literature. The sensitivity of MRI to detect labral pathology was reported to be about 65%, and that of MR arthrography was reported to be about 92-95% compared to surgical results. According to the current literature, MR arthrography is the most sensitive method to delineate these kind of pathologies. Therefore, the invasive technique of MR arthrography may be justified for the correct diagnosis of these kind of pathologies after other pathologic entities have been ruled out by conventional MRI.

Acetabulum↗
PubMed2002

[Rotational abnormalities of the hip joint].

Changes or limitations of the rotational range of motion of the hip are a non-specific clinical sign. There is a big variety of underlying morphological pathologies resulting in a symptomatic alteration of hip rotation. They need to be assessed by imaging techniques: based on plain radiographs (including specialized projections), often CT or MRI are necessary to visualize the underlying changes of shape, rotation and offset of the articulating surfaces, which might result in a painful "femoroacetabular impingement" as a trigger of secondary osteoarthritis. Highly sophisticated MR-arthrography-protocols are able to visualize conventionally "obscure" but biomechanically relevant morphological changes, that might be individually normalized by joint-preserving corrective surgery.

Acetabulum↗
PubMed2002

[Perthes disease].

The Legg-Calve-Perthes disease is an idiopathic avascular necrosis of the hip during early childhood. It is characterized by different stages with the main risk of persisting hip deformation, dysfunction of the joint movement, and the potential for early osteoarthritis. For the evaluation of prognosis and therapy planning patients age and extent of the necrotic area of the epiphysis are important factors. For an early diagnosis and sufficient therapy all radiological efforts have to be performed. MR imaging is an ideal method for the assessment of osteonecrotic changes of the Morbus Perthes. Compared to plain radiography by MR imaging pathologic alterations can be detected earlier and with higher specificity. However, conventional radiograms have to be still used as basic imaging modality. Nowadays x-rays and MR imaging should be the main methods for the evaluation of children suffering from Perthes disease.

Arthrography↗
PubMed2002

[Osteonecrosis of the hip joint in adulthood].

Osteonecrosis (ON) of the hip joint remains an unsolved therapeutical problem. Diagnosis of ON of the hip has been improved by the technical progress of imaging modalities and better understanding pathomorphology. Over a long period only plain radiographs have been available. Scintigraphy and computed tomography contributed to differential diagnosis and early detection of bone necrosis. Diagnosis in an early reversible stage is of importance. Understanding of pathophysiology, early diagnosis and therapeutical approach has been significantly improved by MR imaging. Using the ARCO system all imaging modalities and their diagnostic viability are described in the five ARCO stages. At the end a diagnostic algorithm will be proposed.

Diagnostic Imaging↗
PubMed2002

Screening for carnitine palmitoyltransferase II deficiency by tandem mass spectrometry.

Mitochondrial carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of lipid metabolism in adults. Currently the routine diagnosis is based on the determination of CPT enzyme activity in muscle tissue. We have analysed the tandem mass spectra of serum acylcarnitines of nine CPT II-deficient patients. These spectra were compared to those of a cohort of 99 patients with other neuromuscular disorders and metabolic conditions supposed to cause alterations of the long-chain acylcarnitines. The spectra in CPT II deficiency showed characteristic elevations of C16:0 and C18:1 acylcarnitines while acetylcarnitine C2 was not elevated. In the present study, the ratio (C16:0+C18:1)/C2 has detected all CPT II deficiencies and discriminated them from unspecific alterations of serum acylcarnitines. The ratios of CPT II-deficient patients showed virtually no overlap with those observed in patients with other neuromuscular disorders. We suggest mass spectrometry of serum acylcarnitines as a rapid screening test that should be included early in the diagnostic work-up of patients with recurrent myoglobinuria, recurrent muscular weakness and myalgia.

Adolescent↗
PubMed2001

Clinical experiences with low-molecular weight heparins in pediatric patients.

The courses of 79 children (2 weeks to 19 years old) treated with two different low-molecular weight heparins (LMWHs)--nadroparin (n=66) and enoxaparin (n=13)--were retrospectively analysed. In 62 patients, LMWHs were given for short-term prophylaxis (1-2 weeks) during immobilization after surgery or trauma. Thirteen children with thromboembolic events received long-term prophylaxis with LMWHs for 2-18 months--six after thrombolytic therapy and seven after therapy with unfractionated heparin (UFH). Because of thromboembolic events, four patients were initially treated with LMWHs. In all patients with short-term prophylaxis, no thrombosis occurred. After thrombolytic therapy, three children had no reocclusion, two had no thrombus apposition and one had complete recanalization. In the seven patients treated with LMWHs after UFH, four had no reocclusion, two had recanalization and one had reocclusion. In all patients receiving LMWHs for initial treatment of thrombosis, no thrombus apposition, but also no recanalization, occurred. For short-term prophylaxis, nadroparin was used independent of the body weight and without determination of anti-factor Xa (anti-FXa) activity. Long-term prophylaxis was given mainly as doses of 45-100 anti-FXa U/kg resulting in anti-FXa activities between 0.2 and 0.4 U/ml. For treatment of thrombosis, doses of 200-300 anti-FXa U/kg corresponded to 0.5-1.0 anti-FXa U/ml. Side effects--slight gastrointestinal bleeding and temporary reversible hair loss--were seen in two patients. In conclusion, LMWHs proved to be efficacious and safe especially in prophylaxis of thromboembolic events in children.

Adolescent↗
PubMed2001

Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria.

Tim8 and Tim13 of yeast belong to a family of evolutionary conserved zinc finger proteins that are organized in hetero-oligomeric complexes in the mitochondrial intermembrane space. Mutations in DDP1 (deafness dystonia peptide 1), the human homolog of Tim8, are associated with the Mohr-Tranebjaerg syndrome, a progressive neurodegenerative disorder. We show that DDP1 acts with human Tim13 in a complex in the intermembrane space. The DDP1.hTim13 complex is in direct contact with translocation intermediates of human Tim23 in mammalian mitochondria. The human DDP1.hTim13 complex complements the function of the TIM8.13 complex in yeast and facilitates import of yeast and human Tim23. Thus, the pathomechanism underlying the Mohr-Tranebjaerg syndrome may involve an impaired biogenesis of the human TIM23 complex causing severe pleiotropic mitochondrial dysfunction.

Animals↗
PubMed2001

Expression of cytochrome P450 2E1 in normal human bronchial epithelial cells and activation by ethanol in culture.

Serum-free primary cultures of human bronchial epithelial cells and freshly isolated samples of human bronchial epithelium were used to investigate basal expression of the cytochrome P450 enzyme CYP2E1 and its activation or induction by ethanol in bronchial epithelial cells. The cultures consisted of > or =95% cells of epithelial characteristics as determined by transmission electron microscopy and immunohistochemical staining. Monolayers were obtained from explants over a period of several months via transfer of tissue into new dishes ('generations'1-5). Using RT-PCR analysis, basal expression of mRNAs coding for CYP2B7, CYP2F1 and CYP2E1 were detected in cultures from several donors. The basal expression of CYP2E1 protein and mRNA showed differences between the donors. The mRNA was detected even in cultures from higher generations and increased in some cultures over time. The CYP2E1 protein content was low and in most cultures of generations 2-5 could not be detected by immunoblot analysis of native protein extracts. Nevertheless, in some cases immunoreactive CYP2E1 protein was present in monolayers obtained from the fourth and fifth transfer (18-week 'generation'). CYP2E1 activity was measured via 6-hydroxylation of chlorzoxazone either by a destructive assay using cell lysate or by a non-invasive assay using the medium of cell cultures. In short-term cultured isolated bronchial epithelium, ethanol treatment increased CYP2E1 activity by up to 5-fold within 4 days but with inter-individual differences. In cells up to 4 weeks in culture, CYP2E1 activity remained inducible by a single dose of ethanol. Differentiated primary human cells in culture may be useful tools as model systems for the evaluation of CYP2E1-driven processes in man.

Aged↗
PubMed2001

Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry.

Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is an inborn error of the urea cycle. The leading symptom is progressive hyperammonaemia, which is a life-threatening condition, particularly in patients with a neonatal onset. Early diagnosis and treatment of the hyperammonaemia are necessary to improve survival and the long-term outcome of ASL-deficient patients. Currently, the diagnosis of ASL deficiency is based on the measurement of urea cycle intermediates and amino acids by automated quantitative ion exchange chromatography in plasma and urine. Here, we report a newborn presenting with coma and severe hyperammonaemia. ASL deficiency was suspected on the basis of an adapted tandem mass spectrometric (MS-MS) procedure which allows determination of argininosuccinate in addition to the amino acids in serum samples. MS-MS measurements revealed a characteristic increase of argininosuccinate, a moderate increase of citrulline, and lowered levels of arginine and ornithine in the serum of the patient. The diagnosis was confirmed by the detection of a novel homozygous frameshift mutation in exon 14 of the argininosuccinate lyase gene. We propose MS-MS as a diagnostic tool suitable for the rapid detection of specific alterations in the amino acid spectra caused by ASL deficiency.

Amino Acid Sequence↗
PubMed2001

New mutations in the neuronal ceroid lipofuscinosis genes.

Thirty-eight mutations and seven polymorphisms have recently been reported in the genes underlying the neuronal ceroid lipofuscinoses (NCLs) including 11 new mutations described here. A total of 114 mutations and 28 polymorphisms have now been described in the five human genes identified which cause NCL. Thirty-eight mutations are recorded for CLN1/PPT; 40 for CLN2/TTP-1, 31 for CLN3, four for CLN5, one for CLN8. Two mutations have been described in animal genes (cln8/mnd, CTSD). All mutations in NCL genes are contained in the NCL Mutation Database (http://www.ucl.ac.uk/NCL).

Child↗
PubMed2001

[Magnetic resonance imaging and magnetic resonance arthrography of the acetabular labrum: comparison with surgical findings].

AIM OF THE STUDY: To evaluate the accuracy of magnetic resonance imaging (MRI) and magnetic resonance (MR) arthrography in detecting acetabular labral lesions in correlation to surgical findings. PATIENTS AND METHODS: Forty patients (40 hips) with chronic hip pain and a strong clinical suspicion of labral lesions were examined with MRI in the coronal and axial plane by obtaining T1 weighted and proton density-weighted spin echo sequences. Additionally, MR arthrography of the hip joint in the coronal oblique and sagittal oblique plane was performed by obtaining T1-weighted three-dimensional gradientecho sequences after the intraarticular injection of gadopentate dimeglumine. The labra were prospectively evaluated on the basis of morphology, signal intensity, the presence or absence of a tear, and their attachment to the acetabulum. All patients underwent surgery, and the MRI findings and MR arthrography findings were compared with the surgical results. RESULTS: Surgically, 34 labral lesions, and 6 normal labra were detected. MRI correctly depicted labral lesions in 24 patients and two normal labra, and MR arthrography correctly depicted labral lesions in 30 patients and 5 normal labra compared with the surgical results. The sensitivity of MRI was 80%, the accuracy of MRI was 65%, the sensitivity of MR arthrography was 95%, and the accuracy of MR arthrography was 88%. CONCLUSIONS: MR arthrography enables considerably more accurate detection of acetabular labral lesions than MRI. MR arthrography should be the method of choice for the diagnosis of the presence or absence of acetabular labral lesions in patients with chronic hip pain and a strong clinical suspicion of labral lesions.

Acetabulum↗
PubMed2001

Magnetic resonance imaging and histology of repair in femoral head osteonecrosis.

Different repair processes affect the clinical course of nontraumatic avascular femoral head osteonecrosis, not just necrotic lesion size and location. Fourteen femoral heads were retrieved at total hip arthroplasty after core decompression treatment, or after conservative treatment was done on 13 male patients diagnosed with different stages of femoral head osteonecrosis. To determine repair types, features of coronal magnetic resonance images were correlated with light microscopy findings on corresponding coronal undecalcified sections and microradiographs of the retrieved femoral heads. In five femoral heads, repair of necrotic bone and marrow remained restricted to the reactive interface for as many as 63 months, producing the diagnostic osteosclerotic rim with adjacent hypervascularity (limited repair). Nine femoral heads showed extension of the repair process into the necrosis. In five femoral heads, predominant resorption of necrotic bone led to femoral head breakdown within 2 to 50 months (destructive repair). In four femoral heads, reparative bone formation had started from subchondral fractures and/or the reactive interface, definitely reducing the size of the necrotic area (reconstructive repair). In the latter, the disease progressed slowly or stopped for as many as 45 months, irrespective of treatments, but elimination of risk factors seemed beneficial. Although core decompression did not always reach the necrotic area and improve repair, it reduced accompanying bone marrow edema and could delay the disease progress. Osteonecrosis with limited repair can be identified on magnetic resonance images obtained at followup, but the similar signal changes of destructive and reconstructive repair cannot be distinguished on magnetic resonance images alone. The evidence of reconstructive repair in nontraumatic osteonecrosis, however, gives hope for treatments that can improve repair to a sufficient creeping substitution of the affected femoral head.

Adult↗
PubMed2001

Periodic fever (TRAPS) caused by mutations in the TNFalpha receptor 1 (TNFRSF1A) gene of three German patients.

TNF-receptor-associated periodic syndrome (TRAPS) is a recently recognized disorder characterized by prolonged attacks of high fever and severe localized inflammation. TRAPS is caused by dominant mutations in the 55 kDa TNF receptor gene (TNFRSF1A). We here describe three German TRAPS patients of two families with Cys30-->Arg and Thr50-->Met mutations, respectively. Both mutations have already been observed before in other nonrelated families. The Thr50-->Met amino acid exchange, caused by an ACG-->ATG transition, has been reported in two other families of different ethnic background. The possibility that the ACG-->ATG sequence alteration is a mutational hot spot causing TRAPS is discussed. Furthermore, we describe and discuss the symptoms of our patients, possible inducers of febrile attacks, and treatments which the patients had received when their diagnoses were still unknown.

Adult↗
PubMed2000

Interaction of the G protein beta 3 subunit T825 allele and the IRS-1 Arg972 variant in type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus is a common late-onset disease with a strong genetic component. It is characterized by insulin resistance which results from alterations in insulin signal transduction. The G protein beta 3 subunit 825T allele was recently found to be associated with hypertension and obesity which makes it a sensible candidate gene for type 2 diabetes. METHODS: In a case-control study on 320 male patients and 962 male healthy controls we investigated the association of two candidate genes with diabetes, i.e. (i) the GNB3 825T allele, associated with a G protein beta 3 subunit splice variant and enhanced intracellular signal transduction, and (ii) the insulin receptor substrate-1 (IRS-1) 972Arg variant, which encodes a protein variant associated with cellular insulin resistance. RESULTS: The GNB3 825T allele and the IRS-1 972Arg variant were significantly associated with diabetes (odds ratios for either variant 1.4 1.8). Odds ratios were 3 4 in males carrying both alleles. CONCLUSIONS: The results document an association of a hypertension susceptibility gene with type 2 diabetes which may partially explain the frequent coexistence of both disorders.

Adult↗
PubMed2000

A triplet of differently shaped spin-zero states in the atomic nucleus 186Pb

Understanding the fundamental excitations of many-fermion systems is of significant current interest. In atomic nuclei with even numbers of neutrons and protons, the low-lying excitation spectrum is generally formed by nucleon pair breaking and nuclear vibrations or rotations. However, for certain numbers of protons and neutrons, a subtle rearrangement of only a few nucleons among the orbitals at the Fermi surface can result in a different elementary mode: a macroscopic shape change. The first experimental evidence for this phenomenon came from the observation of shape coexistence in 16O (ref. 4). Other unexpected examples came with the discovery of fission isomers and super-deformed nuclei. Here we find experimentally that the lowest three states in the energy spectrum of the neutron deficient nucleus 186Pb are spherical, oblate and prolate. The states are populated by the alpha-decay of a parent nucleus; to identify them, we combine knowledge of the particular features of this decay with sensitive measurement techniques (a highly efficient velocity filters with strong background reduction, and an extremely selective recoil-alpha-electron coincidence tagging methods). The existence of this apparently unique shape triplet is permitted only by the specific conditions that are met around this particular nucleus.

Journal Article↗
PubMed2000

[Heart rate variability--physiology, methods of registration and application in pediatric sleep laboratory].

Heart rate variability (HRV) has become the focus of interest of a multitude of investigations being a parameter that can easily be recorded. Accepted clinical indications in adults include evaluation of diabetic neuropathy and prediction of prognosis after myocardial infarction in adults. In children, HRV is regularly being registered in the pediatric sleep laboratory in sleep related breathing disorders, after apparent life threatening events, or in infants with assumed increased risk for sudden infant death syndrome. However, uniform interpretation criteria have not been established in these situations, at least partially due to insufficient understanding of physiology and pathophysiology of HRV in this age group. In this overview, current knowledge on HRV in infants and children is summarized and its clinical relevance discussed. In addition, technical requirements and methods of analysis which have a major impact on calculated parameters are being presented.

Austria↗