Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 91 records · Page 5Linked to original sources

PubMed2000

Catheter ablation of atrial flutter guided by electroanatomic mapping (CARTO): a randomized comparison to the conventional approach.

INTRODUCTION: Three-dimensional electroanatomic (CARTO) activation mapping of the cavotricuspid isthmus can be helpful to guide atrial flutter ablation, but to date has not been investigated in comparison to conventional strategies. The aim of the present study was to assess the efficacy of the CARTO navigation system, especially with respect to the fluoroscopy time required for successful atrial flutter ablation. METHODS AND RESULTS: Eighty patients with recurrent common-type atrial flutter were randomly assigned to temperature-controlled radiofrequency (RF) catheter ablation, either guided by conventional criteria (group 1) or additionally oriented on electroanatomic mapping (group 2). In all patients, similar multipolar catheters were inserted into the coronary sinus and placed at the tricuspid annulus, respectively. In group 2, positioning of the mapping electrode and delivery of RF pulses within the cavotricuspid isthmus was mainly oriented on the CARTO map to achieve the most linear and continuous RF lesions. Abolition of intra-atrial conduction verified by conventional criteria (group 1) and electroanatomic mapping (group 2) could be verified in all patients. The overall number of RF pulses (group 1: 16.7+/-6.5; group 2: 13.2+/-5.3) and mean procedure duration (group 1: 172.5+/-47.4 min; group 2: 169.3+/-47.3 min) were not different between the two groups, but mean fluoroscopy time was significantly shorter when the CARTO technology was used (group 1: 29.2+/-9.4 min; group 2: 7.7+/-2.8 min; P = 0.0001). Recurrence of atrial flutter was observed in 3 (9%) patients in each group after a mean follow-up of 8.5+/-2.8 months. CONCLUSION: Atrial flutter can be abolished effectively using the conventional technique as well as oriented on electroanatomic mapping. However, overall X-ray exposure can be significantly reduced by the CARTO-guided approach without prolongation of procedure duration.

Aged↗

PubMed2000

Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas.

Tangier disease (TD) fibroblasts have defective cholesterol release in the presence of lipid-free apolipoproteins. We compared normolipidemic probands and patients with apolipoprotein A-I (apoA-I) deficiency, apoE deficiency, or TD in terms of the plasma capacity to induce the efflux of [3H]-cholesterol from normal and TD fibroblasts and to esterify this cell-derived cholesterol. Compared with normal fibroblasts, TD fibroblasts released a significantly smaller fraction of [3H]-cholesterol into normal, high-density lipoprotein (HDL)-deficient, and apoE-deficient plasmas. Supplementation of apoE-deficient plasma with exogenous apoE normalized the cholesterol efflux from normal cells but did not fully restore the reduced cholesterol efflux from TD fibroblasts. Compared with control plasma, HDL- and apoE-deficient plasmas had a significantly reduced activity to esterify cell-derived cholesterol. Cholesterol derived from TD fibroblasts was less available for esterification in either patient or normal plasmas than cholesterol derived from normal cells. The esterification defect of TD cell-derived cholesterol was more pronounced in patient plasmas than in control plasma. We conclude that (1) apoA-I and, to a lesser degree, apoE are important determinants of the cholesterol efflux and esterification capacity of plasma, (2) TD fibroblasts have a reduced capacity to release cholesterol into the plasma, and (3) TD cell-derived cholesterol is less available for esterification in plasma than cholesterol from normal fibroblasts. The absence of distinct apoA-I- or apoE-containing subclasses aggravates the defective efflux and esterification of cholesterol derived from TD cells.

Adult↗

PubMed2000

[Analysis of the p53 gene status of lymph node metastasis in the head and neck region in occult primary cancer].

BACKGROUND: Lymph node metastasis in the head and neck region with occult primary cancer are a fairly rare tumor entity in head and neck cancer. Tumor biological parameters as well as mechanism and cause for the development of this so called "cancer of unknown primary" (CUP) are not well investigated in head and neck cancer. Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration of human malignancies and show an incidence of up to 50% in head and neck cancer. For a further tumor biological definition of CUP the p53 status was determined. METHODS: Twenty-three archival formalin fixed paraffined CUP of an occult squamous cell carcinoma of the head and neck region were examined. In all cases a primary cancer was never diagnosed. The DNA extracted from the tumor material was amplified with specific primers for exon 4-9 of the p53 gene and subsequently sequenced. RESULTS: None of the 23 CUP cases showed a mutation or polymorphism in exon 4-9 of the p53 gene. CONCLUSIONS: The total absence of p53 mutations in the so called mutational "hot spots" shows a significant difference to the frequency of primary tumors of the head and neck region. May be this tumor biological characterisation helps to further elucidate the growth behaviour of CUP in the head and neck region and the reason for their development.

Antisense Elements (Genetics)↗

PubMed2000

Pharmacokinetics of nicotine in kidney failure.

BACKGROUND: Smoking is an important risk factor for cardiovascular and cerebrovascular complications in patients with chronic kidney failure. Very high plasma nicotine concentrations have been reported in patients with severe kidney failure, indicating that the disposition of nicotine in these patients may be different. The purpose of this study was to assess the pharmacokinetics of intravenously administered nicotine in healthy subjects and in patients with kidney failure. METHODS: Nine healthy subjects (glomerular filtration rate [GFR], 84 to 143 mL/min/1.73 m2), four patients with mild kidney failure (GFR, 63 to 73 mL/min/1.73 m2), five patients with moderate kidney failure (GFR, 18 to 36 mL/min/1.73 m2), and six patients with severe kidney failure (GFR, 1 to 10 mL/min/1.73 m2) were recruited. Three patients were treated with continuous ambulatory peritoneal dialysis. An intravenous infusion of nicotine (0.028 mg/kg) was given for 10 minutes. Nicotine and cotinine concentrations were measured in plasma, urine, and peritoneal dialysate from 0 to 24 hours after start of infusion RESULTS: There were significant correlations between GFR and total clearance, nonrenal and renal clearance of nicotine, area under the plasma concentration-time curve extrapolated to infinity, terminal elimination half-life, and mean residence time. Nonrenal clearance was 1303 mL/min and 661 mL/min in healthy subjects and patients with severe kidney failure, respectively. Only 1% to 2% of the nicotine dose was excreted unchanged in a 24-hour collection of peritoneal dialysate. The elimination of cotinine was also decreased in patients with kidney failure. CONCLUSION: Progressive kidney failure is associated with a gradual decrease of renal and nonrenal elimination of nicotine.

Adult↗

PubMed2000

Tracing human papillomavirus DNA in nasal polyps by polymerase chain reaction.

Human papillomavirus (HPV) infections are related to the genesis of various benign and malignant human neoplasias. The HPV types 16 and 18 seem to be causally related to the development of most squamous cell carcinoma of the anogenital tract and a proportion of carcinomas of the upper aerodigestive tract. The near 100% positivity of the HPV types 6 and 11 in laryngeal papillomatosis is well established. We investigated whether HPV also plays a role in non-neoplastic mucosal entities such as sinunasal polyposis, the genesis of which has been discussed as being triggered by viral infections. On DNA from 39 sinunasal polyps (33 patients), polymerase chain reaction (PCR) was performed using beta-globin primers for demonstration of amplifiable DNA in the tissue extracts. Consensus primers for the detection of several different HPV types were applied to the beta-globin-positive samples. The results were confirmed by Southern blot hybridization using consensus probes. Cycle sequencing was performed on the positive cases. All 39 samples showed positive signals for beta-globin. HPV-DNA investigations showed a slight positive signal in only 1 of the 39 investigated cases (2.6%). Further molecular investigations of this sample, including cycle sequencing, could not confirm this result. All the other tissue samples remained HPV-DNA-negative. Therefore, those HPV types readily detectable with the PCR primers and probes used are not frequently associated with sinunasal polyposis. The data confirm the hypothesis that HPV is correlated to a lesser extent to infectious mucosal lesions than to proliferative lesions. Furthermore, the results emphasize that the presence of HPV in specific lesions does not occur by chance, but represents a specific infection of the mucosa leading to proliferation and even to malignancy.

DNA, Viral↗

PubMed2000

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device.

Several devices for selection of CD34+ peripheral blood stem cells (PBSC) have been used during the last years for reducing tumor cell contamination of the graft. The new CliniMACS system (magnetic-activated cell separation system by Miltenyi Biotech GmbH, Bergisch-Gladbach, Germany) was recently approved for clinical use in Europe. To evaluate its purging efficiency and engraftment data in the autologous transplant, PBSC from 28 adult patients with various malignant diseases (non-Hodgkin's lymphoma, n = 17; chronic lymphocytic leukemia, n = 5; multiple myeloma, n = 4; acute lymphocytic leukemia, n = 1; medulloblastoma, n = 1) were mobilized by chemotherapy and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg per day). Thirty leukapheresis products from 28 patients with a median of 4.4 x 10(8) nucleated cells/kg body weight (bw)(range 0.6-10.8 x 10(8)/kg bw) and a median of 7.1 x 10(6) CD34+ cells/kg bw (range 2.8 to 18.8 x 10(6)/kg bw) were selected using the Cobe spectra cell separator (Cobe BCT Inc., Lakewood, CO). After the CliniMACS procedure, the median yield of CD34+ selected cells was 4.5 x 10(6)/kg (range 2.2-11.1 X 10(6)/kg bw) with a median recovery of 69.5% (range 46.9-87.3%) and a median purity of 97.7% (range 89.4-99.8%). The procedure did not alter viability of selected cells, which was tested by propidium iodide staining. So far, purified PBSC were used for autologous transplantation in 15 out of 28 patients after total body irradiation and/or high-dose chemotherapy. Median time to reach an absolute neutrophil count > 500/microl was 12 days (range 10-18 days), platelet recovery >50,000/microl occurred at day + 16 (range 11-22). With a median follow-up time of 12 months (range 3-19), 5 patients died of relapse. We confirmed the feasibility and safety of the CliniMACS CD34+ cell enrichment procedure in adult patients with autologous PBSC transplantation.

Adult↗

PubMed2000

RNA degradation buffers asymmetries of transcription in Arabidopsis mitochondria.

To understand better the relative contributions of transcriptional and post-transcriptional processes towards the regulation of gene expression in plant mitochondria, we compared the steady state levels of RNAs with the respective transcriptional activities. All of the protein and rRNA coding genes of the Arabidopsis mitochondrial genome and several orfs were analyzed by run-on and northern experiments. rRNAs constitute the bulk of the steady state RNA in Arabidopsis mitochondria, but are (different from maize mitochondria) not equally prominent among the run-on transcripts. Their relatively low rate of active transcription is apparently compensated by their high stability. Run-on transcription values differ significantly between genes coding for different subunits of the same protein complex. The steady state RNA levels are considerably more homogeneous, indicating that high variations of transcription rates are counterbalanced by post-transcriptional processes. The relative amounts of the steady state transcripts for the different subunits in a given protein complex reflect the relative stoichiometries of the protein subunits much more closely than the respective transcriptional activities. Post-transcriptional RNA processing and stability thus contribute significantly to the regulation of gene expression in Arabidopsis mitochondria.

Arabidopsis↗

PubMed2000

Influence of albumin and collagen on the cell mortality evoked by zinc oxide-eugenol in vitro.

Zinc oxide-eugenol (ZOE) is cytotoxic in vitro but does not cause pulp damage. Various dentin proteins may play a protective role in vivo. We investigated the influence of bovine serum albumin (BSA) and collagen on ZOE cytotoxicity in the Millipore filter test and a dentin barrier test. Agar or agarose with 1% or 5% BSA or calf collagen (1% and 2%) were introduced between L-929 fibroblasts and test specimens. ZOE was severely toxic in the absence of BSA. However BSA (1% and 3%) reduced cell damage to 50% and 35%. In contrast, collagen did not provide protection from ZOE cytotoxicity. When dentin was loaded with 3% BSA and the "pulpal" side of a dentin barrier test chamber was perfused with cell culture medium containing 3% BSA, cytotoxicity of ZOE was completely inhibited. Therefore we conclude that albumin may be one factor responsible for the absence of ZOE toxicity in pulp studies.

Agar↗

PubMed2000

Cerebrovascular findings in Takayasu disease.

The authors define the frequency, nature, and extent of cerebrovascular sequelae of Takayasu arteritis using functional imaging. Retrospective analysis of the cases derived from the Durban Stroke Data Bank (n = 1100) and Durban Metropolitan Vascular Surgery Database (n = 5300) consisted of evaluation by contemporary neuroimaging modalities including single positron emission computed tomography (SPECT), magnetic resonance imaging (MRI) diffusion scanning, and transcranial Doppler (TCD). Of all the patients identified with Takayasu disease (n = 142), 29 (20%) patients were identified with a primarily cerebrovascular presentation. The recent advent of modern functional imaging techniques allowed only the 10 most recent patients with a cerebrovascular presentation to be evaluated. Of these 10, 8 (80%) had normal neurologic deficit scores (Canadian neurologic score) and 9 (90%) were not disabled as determined by handicap scores (Rankin). The anatomic brain scans (9 MRI, 1 CT) were normal in 5 patients (50%). In 7 patients, transcranial Doppler sonography revealed increased velocities mainly in the anterior circulation with turbulence that was not circumscribed. Single positron emission computed tomography scanning revealed areas of hypoperfusion, mostly multiple, in all of the 7 cases investigated. The cerebral perfusion index was determined in 7 patients, with a good prognosis in 2 patients and a moderate prognosis in 5. Cerebral effects of Takayasu disease are best monitored by a combination of clinical and functional imaging such as TCD and SPECT scanning.

Adult↗

PubMed2000

Gastric emptying: a contributory factor in gastro-oesophageal reflux activity?

AIMS: To evaluate the impact of total and proximal stomach emptying on 24 hour and postprandial reflux as well as the number of reflux episodes per hour in relation to the impact of lower oesophageal sphincter (LOS) pressure, and oesophageal contractile and clearance function. METHODS: Seventy one outpatients (37 female, 34 male; age 23-82 years) with symptoms suggestive of both delayed gastric emptying and reflux referred for further investigations participated in the study. Gastric emptying of a semisolid 1168 kJ meal and oesophageal clearance of a water bolus (supine) were recorded scintigraphically, reflux by 24 hour pH monitoring, and oesophageal motility manometrically. RESULTS: Slow proximal but not slow distal or total stomach emptying correlated with increased 24 hour and postprandial acid exposure and increased number of reflux episodes/hour. No relationship was found between total or proximal emptying and LOS resting pressure, oesophageal contraction amplitude, percentage of failed contractions, or clearance. Multiple linear regression analyses showed that slow proximal emptying and low LOS pressure contributed significantly to both 24 hour (p=0.0007 and p=0. 0001) and two hour postprandial acid exposure (p=0.007 and p=0.0001). In contrast, the rate of total emptying contributed to neither 24 hour nor postprandial acid exposure. CONCLUSION: Our data suggest that in contrast with total stomach emptying, the rate of proximal stomach emptying contributes to the extent of 24 hour as well as postprandial acid exposure and the number of reflux episodes/hour.

Adult↗

PubMed2000

Serum p53 autoantibodies in the follow-up of head and neck cancer patients.

p53 autoantibodies (AAB) are a fairly new serological parameter in patients with malignancies. Although the actual mechanism of how they develop is still unclear, it seems that these AAB could be of prognostic relevance. Very few studies demonstrated the usefulness of p53 AAB in the follow-up of cancer patients. In this study, 109 patients with head and neck cancer were investigated using an ELISA for the presence of p53 AAB in their serum and were followed-up for at least 36 months. In 21 of the cancer patients, p53 serum AAB were detected. In 5/21 p53-seropositive AAB patients, a correlation with the clinical course was observed. Sixteen of the p53-positive patients did not show any significant AAB titer changes during the follow-up, and no significant correlation with the clinical course was seen. According to these results, the clinical value of p53 AAB in the follow-up of patients with head and neck cancer seems to be limited.

Adult↗

PubMed2000

Cerebrovascular disease in young, HIV-infected, black Africans in the KwaZulu Natal province of South Africa.

The objective of this study was to elucidate the mechanisms of an ischemic stroke in a human immunodeficiency virus, type 1 (HIV)-infected population. Several clinical and autopsy studies have suggested an increased incidence of strokes in HIV-infected persons. These studies have been performed on diverse populations with numerous confounds for strokes, including, drug abuse and coexistent opportunistic infection. Because of these confounding factors, it has been difficult to assess whether a unique stroke propensity exists among HIV-infected persons. A retrospective case-controlled study was carried out of patients registered in the Durban Stroke Data Bank (DSDB) (n=1298) located in KwaZulu Natal province of South Africa. Sixteen per cent of all strokes in young (<50 year old) black Africans living in KwaZulu Natal province on the east coast of South Africa reported to the DSDB occurred in association with HIV infection. This HIV-infected population was free of drug abuse and relatively devoid of opportunistic infections. The incidence rate of HIV in this stroke population paralleled that of the young black population at large, suggesting no significant overall increased rate of stroke in association with HIV. However, when compared to strokes occurring in an age- and sex-matched, HIV-seronegative control population, the cryptogenic stroke was more common in the HIV-infected population. Although the incidence of rate of stroke appeared to be no higher among HIV-infected young black Africans in the KwaZulu province than among HIV-seronegative controls, the increased incidence of a large vessel cryptogenic stroke in the former suggests the presence of a co-existent prothromobotic state.

Adolescent↗

PubMed2000

Stroke in the young in South Africa--an analysis of 320 patients.

BACKGROUND: Aetiology of young stroke populations varies markedly between countries. AIM: We present one of the largest prospective studies of stroke in young adults, with specific attention given to aetiology and black-white differences to assist with secondary prevention and economic planning. SETTING: Durban, KwaZulu-Natal, South Africa. METHODS: Only first occurrence of stroke by World Health Organisation definition was recorded in patients who had undergone anatomical brain imaging. A hierarchy of investigative modalities divided into three tiers was applied and a range of standardised scales was scored for each patient. This protocol allowed for quantification of clinical deficit, aetiopathogenesis, disability and handicap. Cognitive impairment was evaluated separately according to predefined criteria. RESULTS: Young stroke patients (15-49 years) comprised one-quarter of patients seen at this tertiary referral institution (320:1, 260, 25.4%). Significant black-white differences were encountered for mean age, risk factors, severity of clinical stroke, topography of stroke, severity of neurological deficit (Canadian Neurological scale), handicap (Rankin scale), aetiology (Trial of Org 10172 in Acute Stroke (TOAST) classification) and frequency and subtype of cognitive impairment. In blacks, HIV-associated stroke was highest in the otherwise unknown aetiological TOAST category. CONCLUSION: In South Africa, race and endemic disease both appear to be important determinants of stroke in young adults. Knowledge of these variations will streamline the increasingly expensive diagnostic and therapeutic approach.

Adolescent↗

PubMed1999

Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx.

Alterations of gene expression in squamous cell carcinoma (SCC) cell lines derived from the larynx and keratinocytes derived from adjacent normal mucosa of the larynx have been studied using the mRNA differential display technique. Lane-to-lane comparison of reverse transcribed mRNA showed a strong repression of a 148 bp fragment in SCC cells. The fragment was reamplified and cloned. Sequencing revealed a 99.3% homology with a region in exon 17 of the human galactocerebrosidase (GALC) gene. Northern blot analysis confirmed the differential expression of this gene in both carcinoma cell lines and laryngeal SCC biopsies in contrast with corresponding normal mucosa. To provide further evidence for the differential expression rate, both types of cells were transiently transfected with a 152 bp (-176 to -24) high regulatory promoter element of the 5' flanking region of the GALC gene. Results of 3 independent transfection experiments indicated a 16-fold repression of the GALC gene expression in SCC cells compared with benign keratinocytes. However, neither mutation nor other alterations of the promoter sequence were detected. Expression of the GALC gene is thus greatly affected in SCCs of the larynx.

Base Sequence↗

PubMed1999

Continuous primary sequence requirements in the 18-nucleotide promoter of dicot plant mitochondria.

The nucleotide requirements of mitochondrial promoters of dicot plants were studied in detail in a pea in vitro transcription system. Deletions in the 5' regions of three different transcription initiation sites from pea, soybean, and Oenothera identified a crucial AT-rich sequence element (AT-Box) comprising nucleotide positions -14 to -9 relative to the first transcribed nucleotide. Transversion of the AT-Box sequence to comple- mentary nucleotide identities results in an almost complete loss of promoter activity, suggesting that primary structure rather than a simple accumulation of adenines and thymidines in this region is essential for promoter activity. This promoter segment thus appears to be involved in sequence specific binding of a respective protein factor(s) rather than merely loosening and melting the DNA helix during or for an initiation event. Manipulation of nucleotide identities in the 3' portion of the pea atp9 promoter and the respective 3'-flanking region revealed that essential sequences extend to positions +3/+4 beyond this transcription start site. Efficient transcription initiation at an 18-base pair promoter sequence ranging from nucleotide positions -14 to +4 integrated into different sequence contexts shows this element to be sufficient for autonomous promoter function independent of surrounding sequences.

Base Sequence↗

PubMed1999

Characterization of the binding site of the histamine H3 receptor. 1. Various approaches to the synthesis of 2-(1H-imidazol-4-yl)cyclopropylamine and histaminergic activity of (1R,2R)- and (1S,2S)-2-(1H-imidazol-4-yl)-cyclopropylamine.

Various approaches to the synthesis of all four stereoisomers of 2-(1H-imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis and resolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct trans-cyclopropylhistamine enantiomers were tested for their activity and affinity on the histamine H3 receptor. (1S,2S)-Cyclopropylhistamine (VUF 5297) acts as an agonist both on the rat cortex (pD2 = 7.1; alpha = 0.75) and on guinea pig jejunum (pD2 = 6.6; alpha = 0.75). Its enantiomer, (1R, 2R)-cyclopropylhistamine (VUF 5296), is about 1 order of magnitude less active. Both enantiomers show weak activity on H1 and H2 receptors. All synthetic attempts to cis-cyclopropylhistamine were unsuccessful. Nevertheless, the results of this study provide an ideal template for molecular modeling studies of histamine H3 receptor ligands.

Animals↗

PubMed1999

Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar transcription factor UBF.

Transcription of rRNA genes by RNA polymerase I increases following serum stimulation of quiescent NIH 3T3 fibroblasts. To elucidate the mechanism underlying transcriptional activation during progression through the G1 phase of the cell cycle, we have analyzed the activity and phosphorylation pattern of the nucleolar transcription factor upstream binding factor (UBF). Using a combination of tryptic phosphopeptide mapping and site-directed mutagenesis, we have identified Ser484 as a direct target for cyclin-dependent kinase 4 (cdk4)-cyclin D1- and cdk2-cyclin E-directed phosphorylation. Mutation of Ser484 impairs rDNA transcription in vivo and in vitro. The data demonstrate that UBF is regulated in a cell cycle-dependent manner and suggest a link between G1 cdks-cyclins, UBF phosphorylation and rDNA transcription activation.

3T3 Cells↗

PubMed1999

Functional genomics in cancer research: identification of target genes of the Epstein-Barr virus nuclear antigen 2 by subtractive cDNA cloning and high-throughput differential screening using high-density agarose gels.

In the past, the identification and isolation of phenotype-associated genes was a difficult and time-consuming task. However, recent improvements of methods that are designed to isolate differentially expressed genes have remarkably speeded up the process of target gene isolation. The ultimate goal of functional genomics is to apply these technologies to clone phenotype-associated genes irrespective of the availability of probes (e.g., antibodies) and an intimate knowledge of biological background. We demonstrate the use of a novel subtractive cDNA cloning approach for the isolation and characterization of target genes of the Epstein-Barr virus nuclear antigen 2 (EBNA2). Two different subtractive cDNA libraries specific for two different time periods following activation of a conditional estrogen receptor/EBNA2 (ER/EBNA2) fusion protein were generated. Comparison of the two libraries by cross-hybridization experiments allowed the differentiation between direct and indirect target genes of EBNA2 and led to the identification of a novel direct target gene of EBNA2.

Cloning, Molecular↗