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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 19 recordsLinked to original sources

Identification of human TFIID components and direct interaction between a 250-kDa polypeptide and the TATA box-binding protein (TFIID tau).

Previous studies have indicated that human transcription initiation factor TFIID is a large complex that contains a TATA-binding polypeptide (TFIID tau or TBP) and other components that qualitatively alter promoter interactions and are uniquely required for activator-dependent (versus basal) transcription. TFIID tau-specific antibody columns have been employed to identify a number of human TFIID polypeptides that are tightly associated with TFIID tau. These differ in size from polypeptides in known general initiation factors, including the initiator-binding factor (TFII-I) which shares some promoter binding characteristics with TFIID. The largest component (p250) identified in TFIID was shown to interact directly and tightly with TFIID tau, suggesting that it may play a major role in the assembly of the TFIID complex.

DNA-Binding Proteins

[Heart valve substitution: the effect of preoperative findings on long-term outcome].

BACKGROUND: In a retrospective analysis of 653 consecutive patients who underwent heart valve replacement by one single type of mechanical prosthesis (St. Jude Medical) at three Swiss university medical centers (Basel, Bern, Lausanne), the outcome was judged on the basis of preoperative variables. These variables should facilitate the timing of heart valve replacement. METHODS: Preoperative evaluation includes NYHA classification of symptoms, chest X-ray, ECG, and LVEF on angiography. Postoperative outcome was assessed clinically at yearly intervals by NYHA classification, documentation of complications and mortality. RESULTS: Five-year-survival rates were 96 and 88%, and complication-free rates were 82 and 76% respectively in patients after isolated aortic and mitral valve replacement. An unsatisfactory outcome with death or persistent severe symptoms was more frequent when preoperative symptoms at rest and atrial fibrillation were present. CONCLUSION: Heart valve replacement should not be postponed until severe symptoms and functional impairment occur. Clinical criteria are at least as important for the timing of operation as the findings of more complex investigations.

Adolescent

Crystal structure of TFIID TATA-box binding protein.

The structure of a central component of the eukaryotic transcriptional apparatus, a TATA-box binding protein (TBP or TFIID tau) from Arabidopsis thaliana, has been determined by X-ray crystallography at 2.6 A resolution. This highly symmetric alpha/beta structure contains a new DNA-binding fold, resembling a molecular 'saddle' that sits astride the DNA. The DNA-binding surface is a curved, antiparallel beta-sheet. When bound to DNA, the convex surface of the saddle would be presented for interaction with other transcription initiation factors and regulatory proteins.

Amino Acid Sequence

Fourier transform resonance Raman spectroscopy of phytochrome.

The Pr and Pfr forms of phytochrome in H2O and D2O have been studied by Fourier transform resonance Raman spectroscopy with near-infrared excitation (1064 nm). It is demonstrated that this technique is a powerful method for analyzing the chromophore structures of photosensitive pigments. The high spectral quality allows discussion of vibrational assignments based on an empirical approach using previously published data obtained from model compounds. The reduction in intensity of a high-frequency band assigned to the ring-C/D methine bridge vibration is an indication for the non-coplanarity of the ring D in Pfr. The high intensity of a C-H out-of-plane vibration also supports this hypothesis. In Pr, a broad peak at approximately 1100 cm-1 is assigned to an out-of-plane vibration of a strongly hydrogen-bonded pyrrole C=NH+ group. It is missing in Pfr, suggesting deprotonation of the corresponding ring during the transformation from Pr to Pfr.

Chemical Phenomena

[Therapy of arrhythmias in clinical practice].

The primary care physician should be cautious and restrictive in the treatment of cardiac arrhythmias and adhere to the well established modalities only. For supraventricular arrhythmias digitalis, verapamil, quinidine and betablocking agents are the drugs of choice. In atrial fibrillation oral anticoagulants and in some cases aspirin seem to be beneficial for the prevention of stroke in selected subgroups of patients. Criteria for their use are outlined in Tables 1 and 2. Ventricular arrhythmias in healthy persons generally should not be treated. In patients with coronary artery disease and severely compromised left ventricular function amiodarone is very effective for the treatment of complex ventricular arrhythmias. If other antiarrhythmics are to be used, the advice of a cardiologist is strongly recommended, as proarrhythmic effects are particularly common in severe cardiac conditions. Severely symptomatic patients with recurrent ventricular tachycardia and syncope should be offered invasive evaluation in order to determine effective medical or surgical treatment.

Anti-Arrhythmia Agents

Central chemoreceptor drive to breathing in unanesthetized toads, Bufo paracnemis.

Central chemoreceptor drive to breathing was studied in unanesthetized toads, equipped with face masks to measure pulmonary ventilation and arterial catheters to analyze blood gases. Two series of experiments were performed. Expt. 1: The fourth cerebral ventricle was perfused with solutions of mock CSF, adjusted to stepwise decreasing pH values. Concomitant perfusion-induced increases of pulmonary ventilation, pHa and PaO2 were measured. Expt. 2: Inspiration of hypercapnic gas mixtures was applied to stimulate both central and peripheral chemoreceptors. Subsequently, only peripheral chemoreceptors were stimulated. This was accomplished by repeating the hypercapnic conditions while the fourth ventricle was perfused with mock CSF at pH 7.7. This procedure reduced the slope of the ventilatory response curve by about 80%. Taken together, the experiments suggest a highly dominant role of central chemoreceptors in the ventilatory acid-base regulation of the toad.

Animals

Prolonged clinically asymptomatic evolution after HIV-1 infection is marked by the absence of complement C4 null alleles at the MHC.

The length of time after which persons infected with HIV-1 progress to AIDS is variable. Certain alleles at the MHC have been shown to influence negatively the clinical outcome of HIV-1-infected persons and to be associated with special clinical manifestations. We investigated the MHC class I, class II and class III antigens in 54 Caucasian HIV-1-infected persons. The MHC profile of individuals with a prolonged period before AIDS is marked by a lower frequency of C4 null alleles.

Acquired Immunodeficiency Syndrome

Doppler sonographic evaluation of mechanical and bioprosthetic mitral valve prostheses during exercise with a rate corrected pressure half time.

OBJECTIVE: To compare the effect of exercise on pressure half time in patients with mechanical or bioprosthetic mitral valves. A relative pressure half time (pressure half time as a percentage of RR interval) was used in an attempt to correct for the shortening of the diastolic time interval caused by the increase in heart rate during exercise and thus to uncover the effects of valve design on pressure half time during exercise. PATIENTS: Twenty clinically stable (New York Heart Association grade I-II) patients with mechanical (n = 12) or bioprosthetic (n = 8) mitral valves (median age 51) years. The median time since valve replacement was 42 months. METHODS: Continuous wave Doppler echocardiography from the apical view at rest and during moderate supine bicycle exercise (50 W). RESULTS: During exercise the mean (SD) heart rate increased from 79 (12) to 101 (12) beats per minute (95% confidence interval (95% CI) of difference, 15 to 29/min) and the peak pressure gradient from 11 (5) to 18 (6) mm Hg (95% CI of difference 5 to 9 mm Hg). The pressure half time decreased from 114 (30) to 78 (26) ms (95% CI of difference (30-42 ms). There was no difference between the valve types. The relative pressure half time remained unchanged in patients with mechanical valves during exercise (13 (4) rest and 13 (5)% exercise, respectively) and decreased in patients with bioprostheses (17 (3) and 12 (3)%, respectively (95% CI of difference 2 to 8%, p = 0.025). CONCLUSIONS: In patients with mechanical mitral valves the decrease in the pressure half time during exercise is probably mostly the result of the shortening of the diastolic time interval with increasing heart rate whereas in patients with bioprosthetic valves an increase in functional valve area may contribute to the shortening of pressure half time during exercise.

Adult

Influence of different pressure gradients on late clinical outcome after aortic valve replacement.

Late outcome vs. hemodynamic parameters were assessed and compared in a series of 44 patients followed for 10-17 years after aortic valve replacement either with a Starr-Edwards A 1260 (SE) or a Bjork-Shiley 60 degrees (BS) prosthesis. The two groups, 22 patients each, were selected by computer from the data base SG as to be matched for age, sex, underlying lesion, date of implantation, valve size, left ventricular function, and concomitant coronary artery disease. There was no significant difference in mortality and complication rates. Clinical evaluation at a mean of 12.5 +/- 2.2 years postoperatively revealed identical findings of heart size on chest X-rays (CTR 0.50 +/- 0.04 SE vs. 0.50 +/- 0.05 BS) and nearly identical incidence of left ventricular hypertrophy on the ECG (2/22 SE and 1/22 BS). There was a statistically significant difference in Doppler ultrasonic peak pressure gradients between the two valve types (SE 32 +/- 15 mmHg, BS 23 +/- 9 mmHg; p = 0.047), and of fractional shortening on M-mode echocardiograms (SE 30 +/- 9%, BS 37 +/- 8%, p = 0.038), but this was not reflected by a difference in the symptomatic status of the two groups. It is concluded, that in two groups of patients surviving 10-17 years after isolated aortic valve replacement with SE or BS valves, the statistically significant nine mmHg difference in gradient across the two valve types had no effect on long-term clinical outcome.

Aortic Valve

Drug use in pregnancy: east German data of an international collaborative study.

In an epidemiological collaborative international study under the auspices of WHO-Euro the drug use in pregnancy was investigated in 22 countries in 14,778 women and in hospitals of three different levels. The East German state Thuringia took part according to the annual birth rate with 300 women in 3 hospitals (Jena, Gera, Greiz). In the international average, 14% of the enrolled women took no drugs during pregnancy before admission to hospital for delivery. In East Germany 44% of the women taking part in the study had no drug administration during pregnancy. The critical use of iron preparations and vitamins there has to be mentioned. Under delivery, 99% of the Thuringian women received drugs. In the puerperium the administration of ergot derivatives and of laxatives exceeds the international average and has to be critically revised, but the administration of antiinfectives in only 1/5 and of analgetics 1/3 of the international average.

Drug Utilization

Investigations into a new antiarrhythmic substance Z-2-amino-5-chlor-benzophenon-amidin-hydralazin in humans.

Z-2-amino-5-chlor-benzophenon-amidin-hydralazin is a new chemical potential antiarrhythmic substance. The blood levels were investigated after different dosages and forms of administration in patients and volunteers. The determination of the substance can be performed by high-pressure liquid chromatography. In addition the pharmacokinetic parameters were calculated. The pharmacokinetic profile is similar in humans and animals.

Administration, Oral

[Drug prevention and therapy of ventricular tachycardia].

Antiarrhythmic drugs of type I to IV (Vaughan Williams) are generally used for the treatment of ventricular tachycardia, especially in patients with symptomatic and hemodynamically not tolerated arrhythmias; however, randomized controlled studies revealed a beneficial effect on sudden cardiac death only for type-II (beta-blocking agents) and type-III (Amiodarone) antiarrhythmic drugs. These drugs are, therefore, the antiarrhythmic agents of first choice; but, in addition, underlying heart disease, triggering factors and heart-rate dependency should be considered.

Anti-Arrhythmia Agents

Lack of effect of diacetyl-splenopentin (Berlopentin) on the pharmacokinetics of caffeine.

The influence of Berlopentin on caffeine clearance was measured after a 6 week i.v. treatment or a 4 week s.c. administration within a phase I trial. It was demonstrated that therapy with Berlopentin did not affect significantly caffeine elimination. Thus, clearance of drugs which are biotransformed by hepatic microsomal oxidation are unlikely to be affected by the coadministration of Berlopentin.

Adult

[Hemodynamics of various heart valve prostheses].

Modern tilting disc and bileaflet prostheses, and bio-prostheses, perform similarly regarding pressure gradients, discharge coefficient and performance index; however, only bio-prostheses increase their opening area with increasing flow. Ball valve prostheses of the Starr-Edwards type perform less satisfactorily with higher pressure gradients and lower performance indices, which may result in less favorable long-term follow-up. Bio-prostheses show degenerative changes with increasing age which, over a period of 7-10 years, can lead to clinically relevant stenoses necessitating reoperation.

Bioprosthesis