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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 19 recordsLinked to original sources
PubMed2000

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head-and-neck squamous-cell carcinoma.

Human papillomaviruses (HPVs) have been recognized as an essential pathogenic factor in anogenital cancer. HPV DNA has also been found in a subgroup of head-and-neck squamous-cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the concomitant inactivation of the tumor-suppressor protein pRb. Using 4 second-generation ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high-risk HPV types 16 and 18 in 11 of 92 sera (12%) taken from HNSCC patients at or near diagnosis, in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3. 5%) taken from sex- and age-matched healthy control individuals of the normal population. In 11 of the 12 seropositive HNSCC cases, antibodies were directed against HPV16 proteins. In patients, the HPV16 antibodies were mostly of high titer, and in 6 cases, antibodies against both HPV16 oncoproteins were present. Seven of the 8 HPV16 antibody-positive sera from the control group were of low titer, and none of the 10 antibody-positive sera reacted with both oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV DNA found in the tumor. Of 19 patients known to have HPV16 DNA-positive tumors, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests that the antibodies were formed in an immune response against HPV E6 and E7 proteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC.

Adult↗
PubMed2000

Does (99m)Tc-Sestamibi in high-grade malignant brain tumors reflect blood-brain barrier damage only?

(99m)Tc-Sestamibi (MIBI) has been successfully applied in recurrent glioblastoma. The aim of this study was to evaluate the incremental diagnostic information of MIBI as a tumor-avid radiopharmaceutical compared with (99m)Tc-pertechnetate ((99m)Tc) as sole indicator of the integrity of the blood-brain barrier. Twenty-five patients with confirmed recurrent brain tumors were included. MIBI SPET was performed 10 min after injection of 555 MBq MIBI intravenously with a triple-headed gamma camera equipped with LE-UHR-PAR collimators over 360 degrees (3 degrees /step) and stored in a 128(2) matrix. Identical acquisition parameters were used for (99m)Tc SPET, which was acquired 3 h after injection of 740 MBq (99m)Tc. Normalized tumor uptake (NU) was calculated from attenuation-corrected transaxial slices. In addition, tumor/plexus, tumor/nasopharynx, and tumor/parotid gland ratios were assessed in both studies. No statistically significant differences were detected for the mean NU of tumor tissue with MIBI (0.26 +/- 0.10) and (99m)Tc (0.39 +/- 0. 33) and for the tumor/nasopharynx and tumor/parotid gland ratios; only the tumor/plexus ratio was significantly higher for (99m)Tc than for MIBI (p < 0.05). In conclusion, our data indicate that MIBI scintigraphy in brain tumors at 10 min postinjection reveals no additional visual information over that provided by the conventional (99m)Tc-pertechnetate brain scan, and in addition, tracer retention reflects primarily blood-brain barrier damage.

Adult↗
PubMed2000

Change of sternal perfusion following preparation of the internal thoracic artery--a scintigraphical study.

BACKGROUND: Today the internal thoracic artery (ITA) is the bypass graft of choice due to its superior long-term patency rate. It was the aim of this present prospective study to investigate possible perfusion disturbances and consecutive impaired wound healing induced by the ITA preparation. The sternal perfusion was assessed by bone scintigraphy. METHODS: Forty-four patients were included in the study. There were three groups: group I (control, no ITA preparation; n = 12); group II (preparation of the left ITA; n = 21); group III (preparation of both ITAs; n = 11). In all patients a median sternotomy was performed. A bone scintigraphy was performed 4 days before and 12 days after the bypass procedure. Scintigraphical pictures of all patients were assessed visually (one specialized investigator) and the impulse rate was counted by the aid of a computer program. RESULTS: Results of both evaluation methods showed congruently that neither the use of the left nor of both ITAs causes a statistically significant impairment of sternal perfusion. The percentage of postoperative increase of the rate of impulses was in group I: total sternum 55%; right side 56%; left side 55%. The respective numbers for group II were 58, 63 and 53%, and for group III 54, 52 and 56%. Surprisingly, perfusion scans in group II revealed an increase in the right sternal half after left ITA preparation. This may be due to the additional blood flow demand of collaterals branching between the right ITA and contralateral intercostal arteries representing a compensatory mechanism of the loss of the left ITA. During the observed postoperative time frame (mean 15 days) no healing disturbance of the sternal wound occurred in any patient. CONCLUSION: According to the present data the use of one or both ITAs does not cause an increase of healing disturbances, consecutive to a postoperatively decreased sternal blood perfusion.

Adult↗
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

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

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↗
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↗
PubMed1999

[Direct coronary stent implantation without predilatation--a new therapeutic approach with a special balloon catheter design].

Stent implantation serves as the gold standard for proximal lesions of the coronary arteries with a diameter between 2.75-3.5 mm. Our new concept aims at a reduced procedure duration and fluoro-time as well as a decreased ischemic period during stent implantation. A new therapeutic concept of a direct stent implantation without predilatation was tested using a specially developed balloon catheter on which various 14-16 mm long "slotted-tube" stents are mounted between two conical, radiopaque markers. In 105 consecutive patients, who were scheduled for angioplasty, this method of direct stent implantation was performed. Six of the procedures were performed for acute myocardial infarction and 8 in so-called high-risk procedures. The direct stent implantation was successful in 88%. In 6%, predilatation of the lesion site was necessary before stent placement. In the remaining 6%, a stent could not be successfully implanted despite the availability of various other systems. Comparison of the direct stent implantation with conventional stent placement with predilatation revealed that 1) The fluoro-time for direct stent implantation, compared to the conventional method, was 8.4 +/- 4.9 min vs. 13.7 +/- 8.0 min; p < 0.05, respectively. Furthermore, there were less balloons used per lesion for direct stent implantation (1.4 +/- 0.4) compared to the conventional method (1.7 +/- 0.7), but there was not a significant difference. 2) If we compare those patients with successful direct stent implantation with those with the unsuccessful procedures, the latter group had a higher percent of angiographically visible calcification at the site of the lesion (80% vs. 18%; p < 0.01). In addition, these patients had an increased average age (72 +/- 7 vs. 61 +/- 11 yrs; p < 0.01). The success rate of direct stent implantation did not depend on lesion diameter stenosis before PTCA. Stent dislocation was observed in 3.8% of the procedures, and a single case of stent embolism was seen. In conclusion, the direct stent implantation offers the advantages of a shortened fluoro-time, the use of fewer balloons, and has the potential of less ischemic stress compared to the conventional method of stent implantation with predilatation, if old patients with calcified lesions are excluded. This should be proved on a large scale in future studies also considering a learning curve with regard to the new method. Whether this new approach also reduces the restenosis rate, warrants further studies.

Adult↗
PubMed1999

Cotranscription of the rpl5-rps14-cob gene cluster in pea mitochondria.

In pea mitochondria the rpl5, rpsl4 and cob ORFs are clustered in a unique genomic environment and are cotranscribed into a 4.7-kb primary transcript and several other polycistronic RNAs with sizes between 4.0 and 2.3 kb. All of the larger RNAs terminate at a common 3' end, 52 nucleotides downstream of the cob gene. Transcription is initiated at a promoter about 1.3 kb upstream of the rpl5 start codon. The promoter sequence 5'-AATAAGAGA-3' corresponds to the highly conserved 5'-CRTAAGAGA-3' motif often found in promoters in dicot plants. Functional analysis in a homologous in vitro transcription system showed the pea rpl5 promoter to be active, despite the presence of an altered base in first position of the promoter motif. In Oenothera, in contrast to pea, transcription of the rpl5 gene is driven by a promoter motif that conforms perfectly to the consensus sequence. Double inverted repeats located in the 3' flanking regions of the rpsl4 and cob ORFs in pea were investigated with respect to their possible role in defining transcript termini and their potential function in controlling exo- and endonucleolytic processing or transcript stabilization.

Base Sequence↗
PubMed1999

Time course of motion adaptation: motion-onset visual evoked potentials and subjective estimates.

The aim of this study was to quantitatively describe the dynamics of adaptation to visual motion with electrophysiological and psychophysical methods in man. We recorded visual evoked potentials (VEPs) to motion onset of random dot patterns from occipital and occipito-temporal electrodes during a succession of adaptation-recovery sequences. In these sequences the test stimulus was used to set the adaptation level: seven trials with 70% motion duty cycle (adaptation) followed by seven trials of 7% motion duty cycle (recovery). In a similar paradigm we determined the length of the perceptual motion after-effect to obtain a psychophysical measure of the time course of motion adaptation. Our results show a highly significant reduction of the N2 amplitude in the maximally compared to the minimally adapted condition (P < 0.001). Electrophysiological and psychophysical results both indicate that adaptation to visual motion is faster than recovery: The data were fit with an exponential model yielding adaptation and recovery time constants, respectively, of 2.5 and 10.2 s for the N2 amplitude (occipito temporal derivation) and of 7.7 and 16.7 s for the perceptual motion after-effect. Implications for the design of motion stimuli are discussed, e.g. a motion stimulus moving 10% of the time may lead to about 30% motion adaptation.

Adaptation, Ocular↗
PubMed1999

Guidelines for anti-emetic therapy: acute emesis.

Anti-emetic therapy has become integral to the management of patients with cancer. Goals related to complete emesis control include providing treatment that reduces hospitalisation and time in the ambulatory setting, care that is convenient for the patient and therapy that enhances patients' quality of life. A panel of clinical, health economic and basic scientists with expertise in various oncology disciplines reviewed published literature to develop evidence-based consensus guidelines for the prevention and treatment of chemotherapy-induced emesis. Currently, serotonin receptor antagonists and corticosteroids are the two categories of anti-emetics that are most effective, have the fewest side-effects and are convenient to use. These agents are recommended in combination for highly emetogenic chemotherapy regimens and as single agents or in combination for moderately to highly emetogenic chemotherapy. When possible, these agents may be given orally in single doses; current evidence does not support dose escalation for either category of anti-emetics. In special situations, such as the use of high-dose chemotherapy combination regimens, the most emetogenic component of the regimen should dictate the choice of anti-emetic. Appropriate anti-emetic use described in these guidelines represents both good medical practice and a sensible economic approach to care.

Acute Disease↗
PubMed1999

Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type.

BACKGROUND: On the basis of promising data on the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) whole body positron emission tomography (WB-FDG-PET) in the staging of patients with lymphoma, we initiated a pilot series to evaluate the role of WB-FDG-PET in the staging of extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. PATIENTS AND METHODS: We examined ten consecutive patients with histologically-verified MALT-type lymphomas of various origin before initiation of therapy. Nine patients had low-grade lymphomas (five cases of gastric lymphoma, two patients with lymphoma arising in the lung, one parotid and one lacrimal gland lymphoma), while one patient had a high-grade gastric lymphoma arising from a low-grade background. Two patients had stage EI, seven had stage EII disease, and one presented with stage EIII. WB-FDG-PET scans were performed 40 min following the injection of 300-380 MBq of F18-FDG. The PET scans were correlated with extensive conventional staging including ophthalmologic investigation, otolaryngologic examination, gastroscopy, endosonography, enteroclysis, colonoscopy, CT of thorax and abdomen, and bone marrow biopsy. RESULTS: WB-FDG-PET documented no lymphoma in any of the 10 patients studied, as no focal tracer uptake was demonstrated in either gastric or extragastric lesions or in involved lymph nodes, irrespective of histologic grading. In three patients the scan showed a false negative result with respect to the MALT lesions but showed focal tracer uptake indicating tumor spread, which, however, was ruled out by further follow-up and biopsy, respectively, and was thus rated false positive. Due to these results, the study was discontinued prematurely after the first ten patients. CONCLUSIONS: These discouraging results indicated that WB-FDG-PET is not useful for staging and follow-up of MALT-type lymphoma, and should therefore not be included in the clinical decision making process.

Aged↗
PubMed1999

Surveillance of antibiotic resistance in ICUs in southeastern Sweden. ICU Study Group of the South East of Sweden.

BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

APACHE↗