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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 91 records · Page 5Linked to original sources
PubMed2000

ACE-gene polymorphism is associated with the development of allograft vascular disease in heart transplant recipients.

BACKGROUND: Cardiac allograft vascular disease is (CAVD) the most important cause of death following heart transplantation (HTX). Although in the past, researchers focused predominantly on mechanisms of endothelial injury, the possible role of recipient-related and genetically determined factors has not been studied in detail. METHODS: Stimulated by recent observations in native coronary artery disease, we analyzed the potential impact of angiotensin-converting enzyme (ACE) polymorphism (insertion/deletion [I/D], intron 16) on development and progression of CAVD. We characterized genotype in 146 patients 1 to 12 years after HTX (121 men; mean age, 46.2+/-11.3 years; observation period, 6.1+/-3.8 years) and correlated genotype to the onset and progression of CAVD, defined as luminal obstruction > 50%. RESULTS: We found allelic frequencies to be 28.8% (n = 42) for ACE-DD, 49.3% (n = 72) for ACE-DI, and 21.9% (n = 32) for ACE-II. Differences in actuarial freedom from vasculopathy were significant 6 years after transplantation, with 84.6% for ACE-II compared with 54.4% for ACE-DD. We observed intermediate results for ACE-DI genotype (77.3%, p = 0.015). CONCLUSIONS: In this large cohort study, we demonstrated a close relationship between the recipient-related ACE-D genotype and development of advanced CAVD. These observations suggest that gene-environment interactions might be clinically important in coronary vasculopathy after HTX.

Actuarial Analysis↗
PubMed2000

Differential role of angiotensin II receptor subtypes on endothelial superoxide formation.

The physiological role of the angiotensin II AT2 receptor subtype is not fully characterized. We studied whether AT2 receptor could antagonize AT1 mediated superoxide formation in endothelial cells. In quiescent human umbilical vein endothelial cells (HUVEC) superoxide formation was measured after long-term incubation (6 h) with angiotensin II in the presence or absence of its receptor blocker candesartan (AT1) or PD123319 (AT2) using the cytochrome c assay. In separate experiments, the effects of AT2 mediated effects on activities of cellular phosphates including the src homology 2 domain containing phosphatases (SHP-1) was studied. The basal superoxide formation (0.19+/-0.03 nmol superoxide mg protein(-1) min(-1)) in HUVEC was increased by 37.1% after exposure to angiotensin II (100 nM,) which was due to an activation of a NAD(P)H oxidase. This was abolished by candesartan (1 microM) as well as the tyrosine kinase inhibitor genistein. In contrast, blockade of AT2 receptors by PD123319 enhanced the superoxide formation by 73.7% in intact cells. Stimulation of AT2 went along with an increased activity of tyrosine phosphatases in total cell lysates (29.8%) and, in particular, a marked stimulation of src homology 2 domain containing phosphatases (SHP-1, by 293.4%). The tyrosine phosphatase inhibitor vanadate, in turn, prevented the AT2 mediated effects on superoxide formation. The expression of both angiotensin II receptor subtypes AT1 and AT2 was confirmed by RT - PCR analysis. It is concluded that AT2 functionally antagonizes the AT1 induced endothelial superoxide formation by a pathway involving tyrosine phosphatases.

Cells, Cultured↗
PubMed2000

Micromanipulation by laser microbeam and optical tweezers: from plant cells to single molecules.

Complete manipulation by laser light allows precise and gentle treatment of plant cells, subcellular structures, and even individual DNA molecules. Recently, affordable lasers have become available for the construction of microbeams as well as for optical tweezers. This may generate new interest in these tools for plant biologists. Early experiments, reviewed in this journal, showed that laser supported microinjection of material into plant cells or tissues circumvents mechanical problems encountered in microinjection by fragile glass capillaries. Plant protoplasts could be fused with each other when under microscopical observation, and it was no major problem to generate a triple or quadruple fusion product. In the present paper we review experiments where membrane material was prepared from root hair tips and microgravity was simulated in algae. As many plant cells are transparent, it is possible to work inside living, intact cells. New experiments show that it is possible to release by optical micromanipulation, with high spatial resolutions, intracellular calcium from caged compounds and to study calcium oscillations. An example for avian cardiac tissue is given, but the technique is also suitable for plant cell research. As a more technical tool, optical tweezers can be used to spatially fix subcellular structures otherwise moving inside a cell and thus make them available for investigation with a confocal microscope even when the time for image formation is extended (for example at low fluorescence emission). A molecular biological example is the handling of chromosomes and isolated individual DNA molecules by laser microtools. For example, chromosomes can be cut along complex trajectories, not only perpendicular to their long axis. Single DNA molecules are cut by the laser microbeam and, after coupling such a molecule to a polystrene microbead, are handled in complex geometries. Here, the individual DNA molecules are made visible with a conventional fluorescence microscope by fluorescent dyes such as SYBRGreen. The cutting of a single DNA molecule by molecules of the restriction endonuclease EcoRI can be observed directly, i.e. a type of single molecule restriction analysis is possible. Finally, mechanical properties of individual DNA molecules can be observed directly.

Animals↗
PubMed2000

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease.

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype.

Aged↗
PubMed2000

Combined assessment of obstructive sleep apnea syndrome with dynamic MRI and parallel EEG registration: initial results.

RATIONALE AND OBJECTIVES: To detect obstructive pharyngeal changes in sleeping patients with obstructive sleep apnea syndrome by dynamic MRI and concurrent EEG monitoring during true apneic episodes. METHODS: Five volunteers and eight patients with clinically diagnosed obstructive sleep apnea were polysomnographically monitored inside the scanner before, during, and after sleep discontinuation. After sleep interruption, the Mueller maneuver was performed to compare induced pharyngeal collapse with real collapse during sleep. RESULTS: In all patients, on-line EEG registration was achieved in the static magnetic field. Sleep was proved in four of the eight patients who showed typical EEG findings. A complete pharyngeal collapse was shown in two of the four sleeping patients. The other patients predominately showed local epi- and oropharyngeal obstructions in the apneic state. Compared with the apneic episodes, the Mueller maneuver did not reveal the same extent of pharyngeal narrowing, nor a complete collapse. CONCLUSIONS: Polysomnographically monitored MRI can directly assess findings induced by the pathophysiology of sleep apnea and shows promise for use in sleep investigation and therapy planning and monitoring.

Adult↗
PubMed2000

The bone morphogenetic protein 2 signaling mediator Smad1 participates predominantly in osteogenic and not in chondrogenic differentiation in mesenchymal progenitors C3H10T1/2.

The role of the bone morphogenetic protein (BMP)-signaling mediator Smad1 in osteogenic or chondrogenic differentiation was investigated in murine parental mesenchymal progenitors C3H10T1/2 and its derivatives constitutively expressing BMP-2 (C3H10T1/2-BMP-2) and, therefore, undergo BMP-mediated osteogenic/ chondrogenic development. The functions of the three Smad1 domains, that is, the N-terminal (MH1) domain, the C-terminal (MH2) domain, and the midregional proline-rich linker domain, were documented and compared with full-length Smadl. We showed that expression of the MH2 domain in parental C3H10T1/2 cells was sufficient to initiate osteogenic differentiation. Interestingly, MH1 was sufficient to initiate transcription of osteogenic marker genes like the osteocalcin or parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor. However, MH1 interfered with the histologically distinct formation of osteoblast-like cells. A dominant-negative effect on MH2-mediated osteogenic development in C3H10T1/2 cells was observed by the dose-dependent trans-expression of the midregional linker domain. Importantly, in contrast to osteogenic differentiation, Smad1 and its domains do not mimic or interfere with BMP-2-dependent chondrogenic development as monitored by the inability of MH2 to give rise to histologically distinct chondrocytes in parental C3H10T1/2 cells and by the inefficiency of the MH1 or linker domain to interfere with BMP-2-mediated chondrogenic differentiation.

Alkaline Phosphatase↗
PubMed2000

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis.

OBJECTIVES: We retrospectively reviewed 5 patients with neurosarcoidosis, who all presented with central diabetes insipidus and hypogonadism. DESIGN: This was a single-centre, retrospective analysis of 5 cases with a minimum follow-up of 2 years. METHODS: Case analysis included clinical, biochemical, and endocrinological evaluation and frequent CT/MRI scans of involved organs as primary evaluation and in response to immunosuppressive therapy. RESULT: Neurosarcoidosis was diagnosed in all patients. Two patients had no proven extracerebral manifestation and had a stable disease over 3 and 5 years. One patient showed deterioration with corticosteroids alone but partial remission after additional cyclophosphamide. Pituitary dysfunction remained unchanged in all patients, despite total clinical and radiological remission in two patients. However, one of these patients died of acute granulomatous meningoencephalitis after two years of follow-up. CONCLUSION: Although the presenting symptoms of neurosarcoidosis may vary, the occurrence of central diabetes insipidus associated with typical radiological features is suggestive of neurosarcoidosis. However, there is an increasing number of case reports on lymphocytic hypophysitis. Without the bioptic diagnosis, the differentiation between potentially lethal isolated neurosarcoidosis and lymphocytic hypophysitis is difficult. These cases demonstrate the difficulties in diagnosing neurosarcoidosis and reflect experiences with follow-up parameters.

Adult↗
PubMed2000

Analysis of point mutation in exon 2 of CYP2E1 gene in renal cell/urothelial cancer patients in comparison with control population.

OBJECTIVE: Genetic polymorphisms of human cytochrome P450s have been implicated to be of importance for susceptibility to different cancers. Recently, a point mutation was found in the exon 2 of the CYP2E1 gene (CYP2E1*2) [Hu et al. 1997]. In order to evaluate a possible link between the point mutation in exon 2 of the CYP2E1 gene and the susceptibility to renal cell/urothelial cancer, we developed a screening method based on the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). MATERIAL: DNA of peripheral white blood cells was isolated from 158 renal cell/urothelial cancer patients as well as from 150 controls. METHOD: Primers for PCR were designed by the Primer 3 release 0.1 program. The PCR yield a product of 215 base pairs (bp), which was digested with the restriction enzyme Hha I. The DNA fragments were separated on a 3% agarose gel stained with ethidium bromide. Restriction enzyme digestion of the PCR product obtained from the wild-type DNA resulted in the appearance of a 66 bp, a 43 bp, a 40 bp, a 39 bp and a 28 bp DNA fragment. In contrast to the wild-type, the digestion of the PCR product from DNA carrying the point mutation resulted in the loss of the 39 bp and 40 bp fragments and the appearance of an additional 79 bp fragment. Therefore, the loss of one Hha I restriction site caused by a single nucleotide exchange is suitable for the identification of the point mutation in exon 2 of CYP2E1 gene. RESULTS: However, we could not detect any point mutation in any of the 158 renal cell/urothelial cancer patients or the 150 controls. The distribution of the point mutation in exon 2 of CYP2E1 gene did not show any difference in renal cell/urothelial cancer patients and controls. CONCLUSION: This might indicate a lack of association between this CYP2E polymorphism (CYP2E1*2) and renal cell/urothelial cancer.

Base Sequence↗
PubMed2000

Bioavailability of a new effervescent tablet of diclofenac.

OBJECTIVE: The bioavailability of a newly developed effervescent tablet containing 50 mg diclofenac Na (DIC-effervesc) was investigated and compared with an enteric-coated dragée (DIC-enteric). SUBJECTS AND METHOD: 24 healthy, male and informed volunteers (mean body weight 78.8 kg, mean age 31.9 years) received in a randomized cross-over design a single dose of 50 mg diclofenac as DIC-effervesc and DIC-enteric. A total of 19 blood samples were obtained before and up to 12 h after administration according to the different properties of the galenic formulation. Diclofenac was analyzed by a sensitive HPLC method with a lower limit of quantification of 20 ng/ml. The bioavailability was compared as ratios of the geometric means of AUC0-infinity and Cmax. RESULTS: DIC-effervesc shows no lag time, a tmax within 30 min and a double peak of Cmax in 15/24 subjects. The mean Cmax (arithm. mean +/- SD) for DIC-effervesc is 950+/-341 ng/ml (first Cmax) and for DIC-enteric 1364+/-335 ng/ml. The mean AUC0-infinity, (arithm. mean +/- SD) amounts to 1097+/-210 ng/ml x h for DIC-effervesc and 1262+/-220 ng/ml x h for DIC-enteric. Based on the point estimator and the 90% interval DIC-effervesc is bioequivalent in respect to amount absorbed (86.4%; 81.8 - 91.3%). DIC-effervesc was well tolerated. CONCLUSION: The new effervescent tablet of diclofenac Na shows a rapid absorption without lag time, the same amount of absorption and a slightly lower Cmax (caused by a double peak phenomenon) in comparison to the enteric-coated dragee. A rapid onset of therapeutic effect is postulated in acute pain disorders.

Adult↗
PubMed2000

A common variant of the angiotensinogen gene and the risk of coronary artery disease in a German population.

The thymidine to cytosine transition at position 704 in exon 2 of the angiotensinogen gene leads to the amino acid substitution of threonine for methionine (T235 variant) and is responsible for elevated plasma levels of angiotensinogen. To examine the influence of T235 on the risk of coronary artery disease (CAD) we genotyped 184 CAD patients, 77 controls in whom CAD was excluded angiographically, and 155 healthy controls without signs of CAD by polymerase chain amplification and restriction enzyme digestion. Allele frequencies for A (wildtype) and a (mutant allele) in the total study population were 0.538 and 0.462, 0.536 and 0.464 in the healthy controls, and 0.481 and 0.519 in patients with excluded CAD, respectively. The allele frequencies and the genotype distribution in these groups did not show a significant difference. In conclusion, we did not observe an association between the T235 variant of the angiotensinogen gene and the risk of CAD.

Amino Acid Substitution↗
PubMed2000

Stringent endocrinological testing reveals subnormal growth hormone secretion in some patients with fibromyalgia syndrome but rarely severe growth hormone deficiency.

OBJECTIVE: Several reports suggest that growth hormone (GH) deficiency may be a pathogenic factor in fibromyalgia syndrome (FM). This hypothesis has never been adequately examined. METHODS: We measured serum GH concentration after insulin induced hypoglycemia in subjects with FM. GH secretion in subjects with a maximal GH increase < 10 ng/ml after hypoglycemia was assessed by additional arginine stimulation. RESULTS: In one of 56 subjects tested, GH remained below 3 ng/ml in both tests, satisfying the criteria for adult GH deficiency. Thirty-two subjects (67%) had a maximal GH > 10 ng/ml. We retrospectively found an inverse correlation between low density lipoprotein levels and maximal GH concentration in a subgroup of patients. CONCLUSION: Severe GH deficiency is not a significant pathogenic factor in most patients with FM. We observed an impaired reactivity of the somatotropic axis in one-third of patients with FM, in keeping with a functional alteration of the hypothalamus.

Adult↗
PubMed2000

Late conduction defects following aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the incidence and clinical significance of late cardiac conduction defects (CD) after aortic valve replacement (AVR). METHODS: An analysis was made of 100 consecutive cases after AVR in a prospective outpatient evaluation program. RESULTS: The perioperative (30-day) mortality rate was 5%, and incidence of perioperative pacemaker implantation 3%. Among patients, 19% had CDs before surgery; a normal ECG was present during all periods in 45% of patients. The most frequent perioperative CD was left anterior hemiblock (LAHB; n = 8), and the most frequent late CD was left bundle branch block (LBBB; n = 8). Overall, 13.7% of operative survivors with normal preoperative and perioperative ECGs developed late CDs; one patient (1%) required pacemaker implantation 82 months after AVR. A further three patients (3%) had worsening of pre-existent CDs. Late CDs occurred over a wide time range (3 to 102 months) after surgery. CONCLUSION: There is an important incidence of CDs that occur late after AVR, even if the perioperative ECGs are normal; however, a need for late pacemaker implantation is rare. As CDs may occur at any time after surgery, regular follow up with precise evaluation of ECGs is called for.

Adult↗
PubMed2000

Complications and neurosurgical interventions during early rehabilitation in head injured patients.

Guidelines for the treatment of traumatic brain injury (TBI) are subject of actual efforts in neurosurgery, anaesthesiology and traumatology as well as in the basic sciences. International collaborations such as European Brain Injury Consortium (EBIC), Pan-European-Advisory Board (PAB) and Euroacademy of Multidisciplinary Neurotraumatology (EMN) are working on pathophysiological understanding and evaluation of clinical outcomes to establish standards for a holistic concept from resuscitation to rehabilitation. We reviewed the courses of 252 brain injured patients, treated over a four year period in our department including surgery, intensive care and early rehabilitation. Our special interest was focussed on complications during the early rehabilitation period and the neurological outcomes to define quantity and quality of monitoring as well as the need for invasive interventions at the interface between acute and rehabilitative medicine.

Brain Diseases↗
PubMed1999

Fate of plasmid-bearing, luciferase marker gene tagged bacteria after feeding to the soil microarthropod Onychiurus fimatus (Collembola).

In order to study the potential impact of the soil microarthropod Onychiurus fimatus (Collembola) on the microbial community, we analysed the fate of luciferase marker gene tagged bacterial strains fed to young adult specimens in petri dish microcosm experiments. In faeces collected from O. fimatus, Escherichia coli S17-1/pRP4luc and Sinorhizobium meliloti L33 were only detectable for 2 days after feeding whereas strain HR2/pRP4luc, a close relative of Stenotrophomonas maltophilia, isolated from another collembolan species, could be detected for 16 days. The amount of shed cells of strain HR2 increased during the frequent releases of the cast-off skins (exuvia). In order to analyse whether gut associated bacteria could serve as recipients for mobile genetic elements, plasmid-bearing E. coli donor strains were incubated with faeces in filter mating-like experiments and, in other experiments, directly fed to O. fimatus specimens. Transconjugants were obtained with both the conjugative self-transferable broad host range plasmid pRP4luc and the mobilisable (Mob(+)) broad host range plasmid pSUP104luc, the latter, however, only with a mobilising donor strain. No transfer was detected with the narrow host range plasmids pSUP202luc (Mob(+)), pUC18luc (Mob(-)), or with the broad host range transposon delivery plasmid pUTluxCDABE (Mob(+)). Transconjugants of pRP4luc were detected within one day of the beginning of a feeding experiment and then throughout the incubation period of two weeks, with gaps of no detection after 5, 12 and 14 days, probably caused by moulting. The results of this study indicate that feeding activities of collembola can modify the structure of soil-inhabiting microbial communities and enhance the spread of plasmids from non-indigenous to indigenous soil bacteria.

Journal Article↗
PubMed1999

Analysis of volatile organic compounds in human urine by headspace gas chromatography-mass spectrometry with a multipurpose sampler.

A multipurpose sampler (Gerstel MPS), designed for liquid large volume, gaseous and headspace samples was used for the GC-MS analysis of organic volatiles in human urine. Headspace sampling with a volume-, temperature- and speed-controlled gas-tight syringe was combined with a temperature-controlled cold injection system (CIS) for cold trapping, enrichment and focusing of analytes. Regular 2-ml GC vials filled with 1 ml acidified urine were used as headspace sampling vials. A 100-vial autosampler tray was equipped with an additional temperature and heating time controlled "preheating station" for five vials. Profiles of organic volatiles in human urine were determined and 34 components identified. Trimethylamine (TMA) and 4-heptanone as two metabolites of medical interest were quantified. Calibration curves and intra assay imprecision for 4-heptanone concentrations in the range of 40 to 800 ng/ml showed a correlation coefficient of r = 0.9980 and a relative standard deviation (RSD) between 3.0 and 3.4%. Calibration curves and intra-assay imprecision for TMA concentrations in the range of medical interest from 0.5 to 20 micrograms/ml showed a correlation coefficient of r = 0.9968 and a RSD between 4.1 and 6.8%. The high practicability of the multipurpose sampler for both gaseous and liquid samples together with the here shown good reproducibility and sensitivity make this single CIS-GC-MS system very attractive for routine clinical use in metabolic profiling of organic volatiles (headspace) and non-volatiles (liquid).

Gas Chromatography-Mass Spectrometry↗
PubMed1999

Identification of plasticizers in medical products by a combined direct thermodesorption--cooled injection system and gas chromatography--mass spectrometry.

The combination of a new thermodesorption module with a cooled injection system now provides a powerful system for direct analysis of volatile trace compounds in gaseous, liquid and solid samples by gas chromatography-mass spectrometry (GC-MS). As a cooled injection system is used for the cryofocusing of the desorbed volatiles the GC-MC system still can be used for the regular analysis of liquid samples. Although plasticizers usually are analyzed by GC-MS after solvent extraction, contaminated solvents and glassware are very well known problems. Analysis of plasticizers in plastic materials by direct thermodesorption instead saves time and avoids cross contaminations. Many medical products are made of plasticized polyvinyl chloride. Extraction of the common plasticizer di(2-ethylhexyl) phthalate (DEHP) into blood will occur, and harmful effects of DEHP in the human body have been suggested. We therefore analyzed 21 different plastic devices which are used for various invasive techniques in medicine by direct thermodesorption GC-MS. In some of the plastics up to 30 different components were identified. By far the most common plasticizer found was DEHP, followed by diethyl and dibutyl phthalates.

Diethylhexyl Phthalate↗