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Biomedical subjects

E Hoffmann

Publications and source records attributed to E Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed2000

Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking.

In humans, 80% of nicotine is metabolized to the inactive metabolite cotinine by the enzyme CYP2A6, which can also activate tobacco smoke procarcinogens (e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). Previously, we demonstrated that individuals who are nicotine-dependent and have defective CYP2A6 alleles (*2, *3) smoked fewer cigarettes; however, we recognize that the genotyping method used for the CYP2A6*3 allele gave a high false-positive rate. In the current study we used improved genotyping methods to examine the effects of the defective CYP2A6*2 and CYP2A6*4 alleles on smoking behavior. We found that those with the defective alleles (N = 14) smoked fewer cigarettes per day than those homozygous (N = 277) for wild-type alleles (19 versus 28 cigarettes per day, P <.001). In addition, we identified a duplicated form of the CYP2A6 gene, corresponding to the gene deletion CYP2A6*4 allele, developed a genotyping assay, assessed the gene copy number, and examined its prevalence in Caucasian smokers (N = 296). We observed an ascending rank order for plasma cotinine and breath carbon monoxide levels (an index of smoke inhalation) in individuals with null (CYP2A6*2 and CYP2A6*4) alleles (N = 14), those homozygous for wild-type (CYP2A6*1/*1) alleles (N = 277), and those with our newly identified CYP2A6 gene duplication (N = 5). The phenotype, as determined by plasma nicotine/cotinine ratios, had a descending rank order for these three genotype groups that did not reach significance. Although further characterization is required for the duplication gene variant, these results extend our previous findings and suggest a substantial influence of CYP2A6 genotype and phenotype on smoking behavior.

Adolescent↗
PubMed2000

Characterization of the influenza A virus gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1?

In 1997, an H5N1 influenza virus outbreak occurred in chickens in Hong Kong, and the virus was transmitted directly to humans. Because there is limited information about the avian influenza virus reservoir in that region, we genetically characterized virus strains isolated in Hong Kong during the 1997 outbreak. We sequenced the gene segments of a heterogeneous group of viruses of seven different serotypes (H3N8, H4N8, H6N1, H6N9, H11N1, H11N9, and H11N8) isolated from various bird species. The phylogenetic relationships divided these viruses into several subgroups. An H6N1 virus isolated from teal (A/teal/Hong Kong/W312/97 [H6N1]) showed very high (>98%) nucleotide homology to the human influenza virus A/Hong Kong/156/97 (H5N1) in the six internal genes. The N1 neuraminidase sequence showed 97% nucleotide homology to that of the human H5N1 virus, and the N1 protein of both viruses had the same 19-amino-acid deletion in the stalk region. The deduced hemagglutinin amino acid sequence of the H6N1 virus was most similar to that of A/shearwater/Australia/1/72 (H6N5). The H6N1 virus is the first known isolate with seven H5N1-like segments and may have been the donor of the neuraminidase and the internal genes of the H5N1 viruses. The high homology between the internal genes of H9N2, H6N1, and the H5N1 isolates indicates that these subtypes are able to exchange their internal genes and are therefore a potential source of new pathogenic influenza virus strains. Our analysis suggests that surveillance for influenza A viruses should be conducted for wild aquatic birds as well as for poultry, pigs, and humans and that H6 isolates should be further characterized.

Animals↗
PubMed2000

[Mental disorders in prisons--view of prison governors].

This article reports on experiences with prisoners with mental diseases. Due to the multitude of drug supply of all kind in Frankfurt, several addicted humans are living in this area. Their way of life is frequently accompanied by arrest and imprisonment. It is demonstrated what we experienced with these prisoners and what kind of problems has occurred. The employees of a penal institution are not prepared enough to deal with such problems. Such demands are demonstrated.

Human Rights↗
PubMed2000

[The coronary circulation and myocardial ischemia].

In this review concerning the relationship between coronary circulation and myocardial ischemia, the authors focus on the factors influencing myocardial oxygen demand and supply, through the evaluation of the determinants of myocardial oxygen consumption and coronary flow regulation. The concepts of coronary flow reserve and endothelial control, the latter being probably a link among vasoconstriction, thrombosis and inflammation in the genesis of acute ischemic syndromes, have been particularly investigated. Moreover, the hemodynamic effects of coronary artery stenoses have been shortly mentioned. The complex mechanisms involved in the regulation of coronary artery tone and flow and the evolution of atherosclerotic plaques are clinically expressed in the so-called "ischemic cascade" leading from local ischemia to chest pain.

Coronary Circulation↗
PubMed1999

Generation of influenza A viruses entirely from cloned cDNAs.

We describe a new reverse-genetics system that allows one to efficiently generate influenza A viruses entirely from cloned cDNAs. Human embryonic kidney cells (293T) were transfected with eight plasmids, each encoding a viral RNA of the A/WSN/33 (H1N1) or A/PR/8/34 (H1N1) virus, flanked by the human RNA polymerase I promoter and the mouse RNA polymerase I terminator-together with plasmids encoding viral nucleoprotein and the PB2, PB1, and PA viral polymerases. This strategy yielded >1 x 10(3) plaque-forming units (pfu) of virus per ml of supernatant at 48 hr posttransfection. The addition of plasmids expressing all of the remaining viral structural proteins led to a substantial increase in virus production, 3 x 10(4)-5 x 10(7) pfu/ml. We also used reverse genetics to generate a reassortant virus containing the PB1 gene of the A/PR/8/34 virus, with all other genes representing A/WSN/33. Additional viruses produced by this method had mutations in the PA gene or possessed a foreign epitope in the head of the neuraminidase protein. This efficient system, which does not require helper virus infection, should be useful in viral mutagenesis studies and in the production of vaccines and gene therapy vectors.

Animals↗
PubMed1999

The structure of human parathyroid hormone-related protein(1-34) in near-physiological solution.

Parathyroid hormone-related protein plays a major role in the pathogenesis of humoral hypercalcemia of malignancy. Under normal physiological conditions, parathyroid hormone-related protein is produced in a wide variety of tissues and acts in an autocrine or paracrine fashion. Parathyroid hormone-related protein and parathyroid hormone bind to and activate the same G-protein-coupled receptor. Here we present the structure of the biologically active NH2-terminal domain of human parathyroid hormone-related protein(1-34) in near-physiological solution in the absence of crowding reagents as determined by two-dimensional proton magnetic resonance spectroscopy. An improved strategy for structure calculation revealed the presence of two helices, His-5-Leu-8 and Gln-16-Leu-27, connected by a flexible linker. The parathyroid hormone-related protein(1-34) structure and the structure of human parathyroid hormone(1-37) as well as human parathyroid hormone(1-34) are highly similar, except for the well defined turn, His-14-Ser-17, present in parathyroid hormone. Thus, the similarity of the binding affinities of parathyroid hormone and parathyroid hormone-related protein to their common receptor may be based on their structural similarity.

Amino Acid Sequence↗
PubMed1999

[Documentation of the effects of child cap pistols].

The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor permanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family life, but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40,000 Euro).

Audiometry, Pure-Tone↗
PubMed1999

[Long-term efficacy of antitachycardia pacing for treatment of ventricular tachycardia in patients with implantable cardioverter/defibrillator].

UNLABELLED: Antitachycardia pacing techniques (ATP) have proved useful for termination of ventricular tachycardia (VT). However, little is known about the efficacy and safety off ATP during long-term follow-up in a larger study population. We analyzed the data of 80 ICD patients (pts) with spontaneous monormorphic VT, mean age 59 +/- 12 years, the mean follow-up was 26 +/- 17 months. 50 pts (62.5%) had coronary artery disease, 18 (22.5%) dilative cardiomyopathy (DCM), the remaining 12 pts (15%) had no or other cardiac diseases. 2926 episodes of ventricular tachycardia (cycle length 349 +/- 51 ms, 240-520 ms) occurred in 64/80 pts (80%), overall efficacy of ATP was 89.9%, acceleration occurred in 4.1% of VTs. Success of ATP did not correlate with positive ATP testing on induced arrhythmias, LVEF, NYHA class or aneurysm. Neither underlying heart disease nor antiarrhythmic medication had an impact on the ATP success rate. ATP efficacy was linked significantly to short VT cycle length (VTCL, 240-300 ms, p < 0.01) and long coupling intervals (91-97%), p < 0. 01). Acceleration occurred in 32% of pts and in 4.1% of VT episodes; it was also dependent on short VT cycle length (< 300 ms vs > 300 ms, p < 0.04) and short coupling intervals (< 81% vs >/= 81%, p </= 0. 01). CONCLUSIONS: First, ATP is a highly effective therapy, independent of patients characteristics. Second, short VT cycle length and long ATP coupling intervals were identified as predictors for successful ATP. Best conversation rates were obtained with coupling intervals between 90 and 97% of VTCL in tachycardias with a cycle length < 300 ms. Third, testing ATP on induced VTs before hospital discharge did not improve efficacy, empiric modes showed equal success rates. Fourth, acceleration rate of ATP depends on VT cycle length and coupling interval; therefore, aggressive ATP modes should be carefully applied in patients with VTs faster than 300 ms.

Adult↗
PubMed1999

Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods.

OBJECTIVES: We prospectively performed a two-step risk assessment in patients in the early phase after acute myocardial infarction (MI). BACKGROUND: Noninvasive methods like Holter electrocardiographic monitoring (HM) and determination of the left ventricular ejection fraction (EF) as well as the invasive technique of programmed ventricular stimulation (PVS) have been used to identify patients in the late phase after MI as candidates for prophylactic implantation of a cardioverter/defibrillator. However, it is unclear whether these results can be transferred to patients following acute MI. METHODS: A series of 657 patients with acute MI (< or = 75 years) underwent HM and EF. If one of the two methods yielded abnormal findings (HM > or = 20 ventricular ectopic beats/h/> or =10 ventricular pairs/day/ventricular tachycardia; EF < or = 40%), PVS was done (abnormal PVS: induction of monomorphic ventricular tachycardia, duration >10 s, cycle length > or = 230 ms). RESULTS: Of 657 patients, 304 (46%) had either an abnormal HM or EF. The PVS performed in 146 of 304 patients was abnormal in 22. During a mean follow-up of 37 months, there were 106 (16%) deaths, being sudden in 24 (3.6%), nonsudden cardiac in 45 (6.8%). The incidence of arrhythmic events (sudden cardiac death, symptomatic ventricular tachycardia, cardiac arrest) was 18% (4/22) with an abnormal PVS and only 4% (5/124) with a normal PVS (odds ratio 4.0, p=0.032). CONCLUSIONS: The rate of arrhythmic events is low in post-MI patients in the 1990s. Nevertheless, a two-step risk stratification is helpful in selecting candidates for a defibrillator trial aiming at primary prevention of sudden cardiac death after MI.

Combined Modality Therapy↗
PubMed1999

Functional changes of ventricular late potentials by provocation with increase of heart rate. Evaluation during atrial pacing.

BACKGROUND: Standard methods fail to reveal late potentials in 20 to 30% of patients with ventricular arrhythmias after myocardial infarction. However, these patients may develop transient delayed ventricular activation during increases in heart rate. METHODS AND RESULTS: Atrial pacing was performed, at the rates of 100 min-1 and 120 min-1, in 50 patients after myocardial infarction. Twenty-six patients had a history of documented, sustained ventricular tachycardia, 12 had a history of ventricular fibrillation and 12 no history of ventricular arrhythmias. The low-noise surface electrocardiogram was analysed before and during atrial pacing in the time and frequency domains. Fifteen of 26 patients with ventricular tachycardia, four of 12 with ventricular fibrillation and three of 12 without ventricular arrhythmias experienced late potentials during sinus rhythm. Atrial pacing led to a shift of 26 +/- 15 ms of preexistent late potentials into the ST segment, this being greater in patients with anterior infarctions and to an increase in magnitude in patients with inferior infarctions. In patients without late potentials during sinus rhythm, atrial pacing provoked late potentials in eight of 11 patients with ventricular tachycardia, in four of eight patients with ventricular fibrillation and in one of nine patients without ventricular arrhythmias. Low amplitude signals (LAS) were increased in patients after inferior and filtered QRS in patients after anterior infarction. In 10 patients without cardiac disease no late potentials were detectable in the time and frequency domain either at rest or during increased heart rate. CONCLUSIONS: Increase in heart rate may unmask late potentials in patients prone to malignant ventricular arrhythmias. Therefore, functional late potential analysis with non-invasive clinical stress tests, i.e. exercise tests, should be performed only with an adequate rate response. This might identify patients at risk of malignant ventricular arrhythmias otherwise not identified with conventional late potential analysis.

Arrhythmias, Cardiac↗
PubMed1999

Sampling of protein dynamics in nanosecond time scale by 15N NMR relaxation and self-diffusion measurements.

This paper presents a procedure for detection of intermediate nanosecond internal dynamics in globular proteins. The procedure uses 1H-15N relaxation measurements at several spectrometer frequencies and hydrodynamic calculations based on experimental self-diffusion coefficients. New heteronuclear experiments, using pulse field gradients, are introduced for the measurement of translation diffusion coefficients of 15N labeled proteins. An advanced interpretation of recently published (Luginbühl et al., Biochemistry, 36, 7305-7312 (1997)) backbone amide 15N relaxation data, measured at two spectrometers (400 and 750 MHz for 1H) for N-terminal DNA-binding domain (1-63) of 434 repressor, is presented. Non-applicability of commonly used fast (picosecond) dynamics model (FD) was justified by (i) poor fit of relaxation data by the FD model-free spectral density function both for isotropic and anisotropic models of the overall molecular tumbling; (ii) specific dependence of the overall rotation correlation times calculated from T1/T2 ratio on the spectrometer frequency; (iii) mismatch of the ratio of longitudinal 15N relaxation times T1, measured at different spectrometer frequencies, in comparison with that anticipated for the FD model; (iv) significantly underestimated overall rotation correlation time provided by the FD model (5.50+/-0.15 and 5.80+/-0.15 ns for 750 and 400 MHz spectrometer frequency respectively) in comparison with correlation time obtained from hydrodynamics. On the other hand, all relaxation and hydrodynamics data are in good correspondence with the model of intermediate (nanoseconds) dynamics. Overall rotation correlation time of 7.5+/-0.7 ns was calculated from experimental translation self-diffusion rate using hydrodynamics formalism (Garcia de la Torre, J. and Bloomfield, V.A. Quart. Rev. Biophys., 14, 81-139 (1981)). The statistical analysis of 15N relaxation data along with the hydrodynamic consideration clearly revealed that most of the residues in 434(1-63) repressor are involved in the nanosecond internal dynamics characterized by the the mean order parameters of 0.59+/-0.06 and the correlation times of ca. 5 ns.

Coliphages↗
PubMed1999

Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways.

A hallmark of inflammation is the burst-like formation of certain proteins, initiated by cellular stress and proinflammatory cytokines like interleukin 1 (IL-1) and tumor necrosis factor, stimuli which simultaneously activate different mitogen-activated protein (MAP) kinases and NF-kappaB. Cooperation of these signaling pathways to induce formation of IL-8, a prototype chemokine which causes leukocyte migration and activation, was investigated by expressing active and inactive forms of protein kinases. Constitutively active MAP kinase kinase 7 (MKK7), an activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathway, induced IL-8 synthesis and transcription from a minimal IL-8 promoter. Furthermore, MKK7 synergized in both effects with NF-kappaB-inducing kinase (NIK). Activation of the IL-8 promoter by either of the kinases required functional NF-kappaB and AP-1 sites. While NIK and MKK7 did not affect degradation of IL-8 mRNA, an active form of MKK6, which selectively activates p38 MAP kinase, induced marked stabilization of the transcript and further increased IL-8 protein formation induced by NIK plus MKK7. Consistently, the MAP kinase kinase kinase MEKK1, which can activate NF-kappaB, SAPK/JNK, and p38 MAP kinases, most potently induced IL-8 formation. These results provide evidence that maximal IL-8 gene expression requires the coordinate action of at least three different signal transduction pathways which cooperate to induce mRNA synthesis and suppress mRNA degradation.

Binding Sites↗
PubMed1999

Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.

Anti-Bacterial Agents↗
PubMed1998

Influenza A outbreak among adolescents in a ski hostel.

An outbreak of influenza A H3N2 with a high attack rate (49%) and abrupt onset (69% became ill within 2 days) occurred among 81 ski school participants who stayed in a crowded hostel in Austria in early 1997. Two students were hospitalized with pneumonia; one of them died. Cultures of blood and/or respiratory secretions from the hospitalized students yielded toxin-producing Staphylococcus aureus. Influenza A H3N2 was confirmed serologically in four participants, including one surviving hospitalized student, and by polymerase chain reaction of lung tissue from the deceased student. This investigation demonstrates that influenza can cause an explosive outbreak among skiers in a crowded hostel, leading to severe complications among previously healthy adolescents.

Adolescent↗
PubMed1998

[Radiofrequency catheter ablation of atrial flutter and atrial fibrillation].

Radiofrequency catheter ablation is now considered as a curative approach in patients with typical atrial flutter. Typical atrial flutter is due to a macrore-entrant circuit within the right atrium and it can be eliminated by a linear lesion in the isthmus between the tricuspid annulus and the vena cava inferior. The electrophysiological criterion of a bidirectional isthmus block has been shown to reduce the recurrence rate of atrial flutter after catheter ablation, thus achieving long-term cure of typical atrial flutter. Acute success rates of 85 to 90% and recurrence rates of 10 to 15% have been reported. The risk of paroxysmal atrial fibrillation continues to be clinically relevant in patients who underwent successful ablation of atrial flutter, in particular in patients with previously documented atrial fibrillation. The incidence of a new onset of atrial fibrillation after ablation of atrial flutter seems to be approximately 20%. Isthmus ablation has also been shown to be beneficial for the majority of patients with typical atrial flutter and atrial fibrillation: In addition to an elimination of typical atrial flutter the isthmus ablation apparently reduces the incidence of paroxysmal atrial fibrillation. At present, atrial fibrillation can only be treated by catheter ablation as a curative approach in the rare cases where an accessory pathway, an AV nodal re-entrant tachycardia, typical atrial flutter or an ectopic atrial tachycardia is the induction mechanism of the atrial fibrillation. The majority of patients with atrial fibrillation is apparently not amenable to a curative local ablation. While AV junction ablation and AV node modification can palliate some of the symptoms of atrial fibrillation by a control of ventricular rate, the arrhythmia persists with the loss of AV synchrony and continued risk of thromboembolism. The surgical MAZE procedure implies a compartimentation of the atria by surgical incisions resulting in areas to small to sustain the arrhythmia. Based on this procedure experimental and clinical studies are currently performed in order to develop catheter ablation cure of atrial fibrillation.

Atrial Fibrillation↗