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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 253 records · Page 14Linked to original sources

Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase.

beta-Trace protein from pooled human CSF was purified to homogeneity. An apparent molecular mass of 23-29 kDa was determined for the polypeptide on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino-terminal sequencing of the polypeptide yielded the unique amino acid sequence APEAQVSVQPNFQQDKFLGRWFSA. Alignment of amino acid sequences obtained from tryptic peptides with the sequence previously deduced from a cDNA clone isolated by other investigators allowed the identification of beta-trace protein as prostaglandin D synthase [prostaglandin-H2 D-isomerase; (5Z, 13E)-(15S)-9 alpha, 11 alpha-epidioxy-15-hydroxyprosta-5,13-dienoate D-isomerase; EC 5.3.99.2]. A conservative amino acid exchange (Thr instead of Ser) was detected at amino acid position 154 of the beta-trace polypeptide chain in the corresponding tryptic peptide. The two N-glycosylation sites of the polypeptide were shown to be almost quantitatively occupied by carbohydrate. Carbohydrate compositional as well as methylation analysis indicated that Asn29 and Asn56 bear exclusively complex-type oligosaccharide structures (partially sialylated with alpha 2-3- and/or alpha 2-6-linked N-acetylneuraminic acid) that are almost quantitatively alpha 1-6 fucosylated at the proximal N-acetylglucosamine; approximately 70% of these molecules contain a bisecting N-acetylglucosamine. Agalacto structures as well as those with a peripheral fucose are also present.

Amino Acid Sequence↗

Agonistic behavior and its cardiovascular components elicited by microinjection of L-glutamic acid into the basal midbrain of the toad Bufo paracnemis.

Microinjection of L-glutamic acid into the basal midbrain of the toad Bufo paracnemis induced a series of responses linked to antipredator behavior such as flight, backward locomotion and defensive postures. Furthermore, alerting/orientation occurred in 20% of the animals, a behavior which is probably important for the animal to achieve the above responses. Locomotion occurred in 18% of the toads. The existence of a mesencephalic premotor control for locomotion in these animals is discussed comparatively. All responses were accompanied by changes in arterial pressure, heart rate and intrabuccal pressure. In some animals which exhibited backward locomotion responses, defensive postures and alerting/orientation, bradycardia or cardiac arrest occurred, with no appreciable changes in arterial pressure. This fact is discussed on the basis of studies which have shown the occurrence of similar alterations in situations of fear in other vertebrates. Autonomic changes without other responses occurred in 16% of the animals. Flight behavior was usually observed as a consequence of stimulation of sites located in the anterodorsal tegmental nucleus and lateral portions of the midbrain tegmentum. In contrast, locomotion was obtained by stimulating basal sites of the tegmentum located in the anteroventral nucleus and in the reticular formation lateral to it. Sites related to the remaining behaviors were located more diffusely in the basal midbrain.

Agonistic Behavior↗

Progression of aortic stenosis. Role of age and concomitant coronary artery disease.

To determine the spontaneous progression of valvular aortic stenosis and to delineate clinical factors related to progression, a longitudinal study, including 49 patients (aged 16 to 81 years), was performed. All patients had auscultatory findings of aortic stenosis and multiple Doppler echocardiograms separated by at least 11 months. Rapid progression of aortic stenosis was defined as an increase of maximal instantaneous pressure gradient by > or = 10 mm Hg per year. During a mean follow-up period of 32 months (11 to 66 months), maximal pressure gradient rose from 38 +/- 15 to 60 +/- 20 mm Hg in the entire study population, resulting in a median increase of 7.2 mm Hg per year. In 21 patients (43 percent), an increase of > or = 10 mm Hg per year was found; in this subgroup with rapid progression, patients were older (64 vs 53 years, p < 0.01) and coronary artery disease was more prevalent (38 percent vs 7 percent, p = 0.01). We conclude that nearly half the patients with initially mild to moderate valvular aortic stenosis reveal a progression of > or = 10 mm Hg per year.

Adolescent↗

[Esophageal duplication in a former bronchogenic cyst. Case report and review of the literature].

We report a case of a cystic esophageal duplication with primary cardiac symptoms and bronchogenic cyst in an adult. Duplications of the esophagus are often operated on the diagnosis of mediastinal tumor. With new imaging techniques the diagnosis can be guessed before operation. Nuclear magnetic resonance and endoluminal ultrasound are two newer techniques which are valuable in assessing "mediastinal" tumors.

Adult↗

[The pharmacokinetics of a new anti-arrhythmic substance, Z-2-amino-5-chlorobenzophenoneamidinohydrazone (AWD-G256)].

In 4 studies blood levels and metabolites of Z-2-amino-5-chlorobenzophenoneamidinohydrazoneacetate (AWD-G256) after different dosages and forms of application on patients and healthy volunteers were investigated. In addition the pharmacokinetic parameters were calculated. The determination of pharmacokinetic parameters was possible only after i.v. application of dosages higher than 0.30 mg.kg-1 b.m. as well as p.o. administration of dosages higher than 100 mg. The blood level curve after i.v. application demonstrated a 2-compartment model and after p.o. application a 1-compartment model. Exact pharmacokinetic data can't be clear estimated with this studies.

Administration, Oral↗

[Clinical-electrophysiologic studies on the actions of the anti-arrhythmic substance AWD-G256 in man].

The effects of the new antiarrhythmic drug AWD-G256 (1) were investigated by clinical electrophysiology (His bundle electrography, programmed electrical stimulation) in 19 patients with supraventricular tachycardias but without structural heart disease. In a maximal dosage of 0.45 mg/kg body mass 1 only minimally affects electrophysiological parameters of the impulse formation and conduction. At this time the therapeutic value of 1 is not clear.

Adult↗

[Hemodynamic effects and adverse effects of the anti-arrhythmic substance AWD-G256 in man].

In 19 patients with different supraventricular tachycardias the antiarrhythmic drug AWD-G256 was studied to investigate the effects on hemodynamic parameters. Over all, stroke volume, pulmonary pressure and systemic blood pressure were not significantly altered. The only main adverse effect was a transient rise of serum transaminases in two patients. We conclude that AWD-G256 is usually hemodynamically tolerated, but the antiarrhythmically effective dosage is not reached yet.

Adult↗

The Omnicarbon tilting-disc heart valve prosthesis. A clinical and Doppler echocardiographic follow-up.

From 1986 to 1990, 172 patients with a median age of 60.5 years (range 20 to 79 years) received 187 Omnicarbon valves (109 aortic valve replacements, 48 mitral valve replacements, and 15 double valve replacements). Patients were followed-up for a median observation period of 2.5 years (range 4 months to 5.2 years) by clinical and Doppler echocardiographic examination. Follow-up was complete in 98%. Operative mortality (death within 30 days) was 1.7%, and linearized late mortality was 2.6% per patient-year, corresponding to an actuarial survival rate for operative survivors of 89% after 4 years. The overall 4-year postoperative survival was 87% (93% for aortic valve replacement, 77% for mitral valve replacement). Compared with age- and sex-adjusted Swiss death rates, there was an excess mortality of 5% after 4 years. Percentages for freedom from valve-related complications at 4 years are as follows: thromboembolism, 98% (aortic valve replacement, 98%, and mitral valve replacement, 96%); anticoagulant-related hemorrhage, 95%; valve endocarditis, 96%; reoperation, 96%; and permanent valve-related impairment, 99%. The overall 4-year event-free survival was 76% (80% for aortic valve replacement and 69% for mitral valve replacement). New York Heart Association class improved in 88% of the patients by 1 to 3 grades, and only 3% remained in class III after operation. For the most commonly used aortic valve (23 mm), Doppler echocardiography revealed a peak pressure gradient of 29 +/- 10 mm Hg, a fractional shortening/peak pressure gradient ratio of 1.34 +/- 0.61, and a performance index of 0.35 +/- 0.08. In the most commonly used mitral valve (27 mm), the mean pressure gradient was 4.0 +/- 2.1 mm Hg. We conclude that excellent clinical and hemodynamic results can be obtained with the Omnicarbon prosthesis, in both the aortic and mitral positions.

Adult↗

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↗