Biomedical subjects
A Hoffmann
Publications and source records attributed to A Hoffmann.
Arabidopsis thaliana contains two genes for TFIID.
The general transcription initiation factor TFIID plays a primary part in the activation of eukaryotic genes transcribed by RNA polymerase II. Binding of TFIID to the TATA box initiates the assembly of other general transcription factors as well as RNA polymerase II at the promoter resulting in a preinitiation complex capable of accurate transcription initiation in vitro. Human TFIID has been shown to interact with various regulatory factors. The observation that stimulation of transcription by different trans-acting factors is mediated through distinct TATA elements led to the suggestion that different types of TFIID may exist in yeast, humans and plants. Here we report the cloning and characterization of two distinct TFIID complementary DNA clones from Arabidopsis thaliana. Furthermore, we have found that TFIID from Arabidopsis and other organisms shows homology to helix-loop-helix proteins.
[A case from practice (171). Pseudohyperaldosteronism in licorice abuse].
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Fe3+ as near-infrared luminescence center in ZnS.
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[Clinical presentation and diagnosis of coronary heart disease].
Coronary artery disease may present as silent ischemia, chronic typical angina pectoris, unstable angina, Prinzmetal angina, acute myocardial infarction, and sudden cardiac death. These manifestations can usually be differentiated by the clinical history. Each of them has its own pathophysiology and, accordingly, therapy and prognosis are different. Myocardial ischemia is common to all of the manifestations and this can be assessed by history taking, ECG stress-testing, ambulatory monitoring, myocardial perfusion scanning, or radionuclide angiography (RNA). The diagnostic accuracy of these diagnostic procedures varies from 70% (history) to 81% (RNA).
Patients at risk for cardiac death late after aortic valve replacement.
A total of 100 patients aged 24 to 78 years were screened prospectively a mean of 71 months after aortic valve replacement for the presence of left ventricular hypertrophy (LVH) on the ECG (Estes scores greater than or equal to 5.0) and for repetitive ventricular premature beats VPBs greater than or equal to 2 couplets/24 hr) during 24-hour Holter monitoring. During the subsequent 41-month follow-up (range 10 to 50 months), the yearly cardiac mortality rate was 1.3% in patients with LVH, 2.9% in patients with VPBs, and 8.0% in patients with LVH plus VPBs but only 0.6% when none of these factors was present (p less than 0.05 chi 2 test). The patient groups did not differ with regard to age, time elapsed since operation, underlying valve lesion, and coronary artery disease. Both LVH and VPBs occurred more frequently in patients with left ventricular dysfunction. We conclude that after aortic valve replacement cardiac mortality is markedly increased in patients with LVH and repetitive VPBs, since they are noninvasive markers of left ventricular dysfunction.
Changes in electric activity (EEG) of the telencephalon of conscious toads (Bufo paracnemis) caused by cholinergic stimulation of the mesencephalic tegmentum.
Studies were carried out to investigate the effect of microinjection of cholinergic agonist carbamylcholine (carbachol) into the mesencephalic tegmentum of conscious toads (Bufo paracnemis), subjected or not to section of the olfactory nerves, on the electrical activity (EEG) of the telencephalon. The response depended on the type of preexisting EEG activity. Marked desynchronization was observed both in animals with intact nerves and in animals with sectioned nerves, whose previous basal activity was already desynchronized (high frequency and low amplitude). In toads with synchronized basal activity and with intact nerves, an increase, a fall or even abolition of preexisting spindle-like activity occurred, whereas in animals with sectioned nerves the effect was reduction or abolition of spindle-like activity. The data show that stimulation of the mesencephalic tegmentum can alter the electrical activity of the telencephalon and that this effect is not only secondary to a change in nasal air flow alterations since it occurs in toads with sectioned olfactory nerves.
Long-term follow-up of patients with silent ischemia during exercise radionuclide angiography.
A retrospective 5 year follow-up study was performed in 140 patients with unequivocal ischemia during exercise radionuclide angiography (greater than or equal to 10% decrease in left ventricular ejection fraction or greater than or equal to 5% decrease in ejection fraction together with a distinct regional wall motion abnormality). In 84 patients (60%), ischemia during radionuclide angiography was silent (silent ischemia group), whereas 56 patients experienced angina during the test (symptomatic group). Work load and antianginal medication were similar in both groups. Critical cardiac events (unstable angina, myocardial infarction, cardiac death) occurred in 27% of patients in the silent ischemia group and 16% of those in the symptomatic group (p = NS); however, myocardial infarction or death was more frequent in patients with silent ischemia (22% versus 9%; p less than 0.05). If there was additional exercise-induced ST segment depression, the rate of critical events was further increased (p less than 0.05). The difference in critical cardiac events seemed to be influenced by the higher incidence of revascularization procedures in symptomatic patients, whereas medical therapy had no similar effect. Thus, these findings suggest that patients with documented severe ischemia should undergo left heart catheterization and revascularization irrespective of symptoms to improve their prognosis.
A review of "Lexikon der Zauberpflanzen" by Christian Rätsch.
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[The behavior of collaterals during percutaneous transluminal angioplasty].
The fate of 106 collaterals was investigated following percutaneous transluminal dilatation of 113 stenoses and occlusions. Following dilatation, 78% of collaterals were unchanged and 22% could no longer be demonstrated. The success of the dilatation had no bearing on the fate of the collaterals. Collaterals beginning or ending in a dilated portion of vessel disappeared more frequently (30%) than the others (11%). Following five dilatations, some vessels were demonstrated in the area of stenosis, which had not been demonstrated previously. Evidently local events, such as displacement of arteriosclerotic plaques may lead to occlusion or reopening of vessels. Remaining collaterals may be of great importance in saving a limb if there is an acute occlusion complicating a dilatation.
Heart valve replacement with the Björk-Shiley and St Jude Medical prostheses: a randomized comparison in 178 patients.
In 178 patients, a randomized prospective comparison between the 60 degrees spherical disc Björk-Shiley (BS) and the St Jude Medical (SJM) heart valve prostheses was performed. Four-week perioperative mortality was zero in the BS (n = 84) and 4.3% in the SJM group (n = 94). During a mean (+/- SD) follow-up of 52 +/- 20 months or 778 patient-years, late cardiac mortality per year was 2.4% in the BS and 2.2% in the SJM group. The yearly thromboembolic rates were 1.4% in the BS and 2.0% in the SJM group. There was no mechanical valve failure or haemolytic anaemia. Paravalvular leaks and major bleeding complications occurred at low rates in both groups (1.1% and 2.2% per year in BS; 0.7% and 1.7% per year in SJM). Functional results were similarly good with 96% of patients with BS valves and 95% of patients with SJM prostheses being in NYHA classes I and II, respectively. We conclude that heart valve replacement with mechanical prostheses can be performed with equally good results using either the Björk-Shiley spherical disc valve or the St Jude Medical bileaflet prosthesis.
Cloning of the Schizosaccharomyces pombe TFIID gene reveals a strong conservation of functional domains present in Saccharomyces cerevisiae TFIID.
The gene encoding the Schizosaccharomyces pombe TATA box-binding factor (TFIID) was cloned and sequenced. The gene contains three introns and codes for a polypeptide of 231 amino acids. The cDNA-expressed protein showed both TATA box-binding and basal transcription activities. The carboxy-terminal three-quarters of S. pombe TFIID shares an extraordinary degree of amino acid sequence homology with a corresponding region of Saccharomyces cerevisiae TFIID that has been shown to be necessary and sufficient for TATA box-binding and basal transcription activities. In contrast, the amino-terminal regions of the S. pombe and S. cerevisiae TFIIDs differ markedly in amino acid sequence and composition. Structure and function relationships of TFIID are discussed in light of these data.
Progressive functional deterioration of bioprostheses assessed by Doppler ultrasonography.
Doppler echocardiography was used to study the function of bioprosthetic heart valves by noninvasive means in 32 patients aged 29 to 72 years at various postoperative intervals. There were 24 Ionescu-Shiley, four Hancock, and four Carpentier-Edwards prostheses, 19 in the aortic and 13 in the mitral position. Initial studies were performed at a mean of 2.3 years after implantation and were repeated one, two, and three years thereafter. Flow velocities in the mitral orifice, left ventricular outflow tract, and ascending aorta, as well as mitral pressure half-time, were measured from pulsed-wave or continuous-wave Doppler recordings. Mitral and aortic valve areas and aortic pressure gradients were calculated. In aortic prostheses the valve area decreased and pressure gradient increased progressively in relation to the time from implantation. The mean value (+/- SD) of the aortic valve area was 67 +/- 17 percent of the manufacturer's nominal value at the first examination and 57 +/- 20 percent one year later, 51 +/- 14 percent two years later, and 46 +/- 11 percent three years later (overall differences, p less than 0.01). In mitral prostheses, reduction of the valve area was not related to the time from implantation. The mean mitral valve area was 45 +/- 12 percent of the nominal value at rest and increased to 68 +/- 18 percent during exercise at a mean of 45 months after implantation. There was no change in these values at the one-year repeat study. It is concluded that in a population with predominantly pericardial bioprostheses, (1) aortic tissue prostheses showed a progressive functional deterioration demonstrable by Doppler echocardiography, most probably due to degenerative changes; and (2) in mitral tissue prostheses, there was no significant reduction of orifice area in relation to time from implantation. Reduction of mitral valve areas may, to some extent, reflect a less than full opening at rest.
[Early diagnostic criteria of ankylosing spondylitis in patients with acute anterior uveitis].
A group of 59 patients with acute anterior uveitis (AAU) were examined for ankylosing spondylitis (AS) according to the New York criteria und criteria for early diagnosis of AS: 17/59 (29%) presented AS according to the New York criteria: a further 13/59 (22%) were classified as having incipient AS according to the early diagnosis criteria. These findings indicate that in a group of AAU patients there are, in addition to patients with definite AS, patients with initial AS though X-rays of the sacroiliac joints are still negative or equivocal. Early diagnosis criteria seem to be useful for identification of these patients at an early stage and can be used as a major selection criterion for monitoring programs.
[Simultaneous administration of various model substances for characterizing in vivo biotransformation in chronic liver diseases].
16 patients with different chronic liver diseases were given single doses of the model substances caffeine, metamizol, sufamethacine and debrisoquine. This was followed by the simultaneous administration of all these substances as a "cocktail". A comparison between the single and the "cocktail" dosage did not reveal any significant differences in the pharmacokinetic parameters. So the "cocktail" administration is even possible in chronic liver diseases. Requiring relatively little time, it makes statements possible concerning various cytochrome P450 enzymes including the types of hydroxylation and acetylation. Intraindividual variations can be ruled out.
[Effect of 3 months of thioacetamide treatment on liver biotransformation in vivo and in vitro (various times after discontinuation)].
Female Uje: WIST rats received thioacetamide (TAA) in the tap water (0.3 g/l) from the 4th to 6th months of life to produce experimental liver cirrhosis. Immediately, 2 and 7 days after TAA cessation it was investigated by means of in vivo (caffeine and metamizol elimination) and vitro methods (cytochrome P-450, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation), whether this animal model represents the restricted cytochrome P-450-dependent biotransformation comparable to human liver cirrhosis. The total capacity of the liver was diminished immediately and 2 days after TAA cessation. After 7 days the capacity was unchanged compared to the controls or partly even enhanced. Therefore, this animal model reflects rather a short time than a stable alteration of biotransformation after TAA cessation comparable to human liver cirrhosis.
Disruptive effect of the mesencephalic reticular formation on tonic immobility in guinea pigs.
Cholinergic stimulation of the mesencephalic reticular formation with carbachol impairs the induction of tonic immobility (TI) by restraining maneuvers and reduces the duration of immobility episodes in guinea pigs. This finding apparently disagrees with the hypothesis that environmental monitoring occurs during TI which permits the animal to evaluate the best time for escape. It is possible that this monitoring involves circuits and neurotransmitters other than the ascending cholinergic system originating in the mesencephalic reticular formation.
[Biotransformation in liver damage].
Xenobiotics may produce liver damages. Vice versa primary liver diseases influence metabolism and elimination of drugs. The activity of the isoenzymes of the monooxygenase system which catalyze biotransformation reactions in the liver can be tested by model substances (Cyt P-450Pb: Metamizol, Cyt P-450MC: Caffeine, Cyt P-450db1: Debrisoquine). It can be influenced by estrogens, gestagens, smoking, alcohol. Only severe stages of liver diseases reduce the biotransformation of drugs. Thus in liver cirrhosis the excretion of unchanged furosemide is increased. The bioavailability of propranolol is changed by a reduced first pass effect in liver cirrhosis. In patients with drug hepatitis after dihydralazine 15 out of 17 patients are genetically slow acetylators and they show also a lower activity of phase I cytochrom P-450 catalyzed biotransformation reactions. The same holds true for patients with haemochromatosis. Determination of the 7-ethoxycoumarin-O-deethylase (ECOD) in liver biopsy samples allows the correlation of the decrease in biotransformation with the increase of liver cell necrosis, intraacinous fibrosis and structural changes. Possibly the changes in biotransformation caused by liver diseases are connected with a disturbed regeneration of the liver corresponding to the concept of the "streaming liver".