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T Hofmann

Publications and source records attributed to T Hofmann.

At least 163 records · Page 9Linked to original sources
PubMed1986

The RPO31 gene of Saccharomyces cerevisiae encodes the largest subunit of RNA polymerase III.

The 5' end of the RNA transcript of the Saccharomyces cerevisiae RNA polymerase related gene, RPO31, was localized on the RPO31 locus using Northern analyses and primer extension experiments. The amino terminal protein sequence was determined for the largest (relative mass approximately 160,000) subunit polypeptide of S. cerevisiae RNA polymerase III. The N-terminal amino acid sequence of this polypeptide was shown to be identical to that predicted for a putative RPO31 polypeptide initiated at the first ATG codon located 208-216 base pairs 3' to the major RPO31 mRNA start sites. The RPO31 locus thus encodes the largest subunit of S. cerevisiae RNA polymerase III.

Amino Acid Sequence↗
PubMed1986

[Diagnosis of thoracic aortic aneurysms and dissections using transesophageal echocardiography].

Transesophageal echocardiography was performed in 25 patients with the clinical suspicion of an aneurysm or dissection of the thoracic aorta. The results obtained were compared to those of conventional transthoracic echocardiography. An aortic dissection was found in 11 patients, an aortic aneurysm in 9 patients, and an aneurysm of the left subclavian artery, an abscess of the aortic ring and a perforated aortic sinus in one patient each. In 2 patients no abnormalities of the thoracic aorta could be found. The intimal flap was detected in 11 patients with transesophageal imaging and in 9 patients with the transthoracic approach. Aortic dissection was suspected in another 5 patients with transthoracic echocardiography which could be excluded by transesophageal echocardiography. In 13 patients (52%) imaging of the descending thoracic aorta was not possible with transthoracic echocardiography but in all patients it was possible from the transesophageal approach. Transesophageal echocardiography seems to be a useful diagnostic approach when diseases of the thoracic aorta were clinically suspected.

Abscess↗
PubMed1985

Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation.

The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Structural differences in the two calcium binding sites of the porcine intestinal calcium binding protein: a multinuclear NMR study.

Cadmium-113 and calcium-43 NMR spectra of Cd2+ and Ca2+ bound to the porcine intestinal calcium binding protein (ICaBP; Mr 9000) contain two resonances. The first resonance is characterized by NMR parameters resembling those found for these cations bound to proteins containing the typical helix-loop-helix calcium binding domains of parvalbumin, calmodulin, and troponin C, which are defined as EF-hands by Kretsinger [Kretsinger, R. H. (1976) Annu. Rev. Biochem. 45, 239]. The second resonance in both spectra has a unique chemical shift and is consequently assigned to the metal ion bound in the N-terminal site of ICaBP. This site is characterized by an insertion of a proline in the loop of the helix-loop-helix domain and will be called the pseudo-EF-hand site. The binding of Cd2+ to the apo form of ICaBP is sequential. The EF-hand site is filled first. Both binding sites have similar, but not identical, affinities for Ca2+: at a Ca2+ to protein ratio of 1:1, 65% of the ion is bound in the EF-hand site and 35% in the pseudo-EF-hand site. The two sites do not appear to act independently; thus, replacement of Ca2+ or Cd2+ by La3+ in the EF-hand site causes changes in the environment of the ions in the pseudo-EF-hand site. In addition, the chemical shift of Cd2+ bound to the EF-hand site is dependent on the presence or absence of Ca2+ or Cd2+ in the pseudo-EF-hand site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Echocardiographic aortic to mitral valve opening area ratio for determining the presence and severity of mitral regurgitation.

A simple and accurate noninvasive method to quantify the degree of mitral regurgitation (MR) is lacking. Therefore, the ratio of the aortic (AVO) to mitral valve opening area (MVO) from 2-dimensionally guided M-mode echocardiographic tracings was examined as an estimate for the presence and severity of MR. Seventy-two patients who had undergone catheterization were studied: 49 with idiopathic dilated cardiomyopathy, 7 with coronary artery disease and 16 with organic MR. Twenty-eight patients had no MR (group I), 23 had mild/moderate MR (group II) and 21 had severe MR (group III). The AVO/MVO ratio was 0.86 +/- 0.2 in group I, 0.53 +/- 0.1 in group II and 0.31 +/- 0.1 in group III (p less than 0.001). An AVO/MVO ratio of 0.65 or less predicted MR with a sensitivity of 98% and a specificity of 86%. Furthermore, a strong relation was found between the ratio and the angiographic severity of MR. Thus, the AVO/MVO ratio is a simple echocardiographic parameter for detecting the presence and severity of MR.

Aged↗
PubMed1985

Immunochemical characterization of P pili from invasive Escherichia coli.

P pili (or fimbriae) are present on most pyelonephritogenic Escherichia coli strains, and they mediate binding to erythrocytes and epithelial cells. To determine the antigenic diversity of P pili, we purified the pili from 14 bacteremic E. coli strains which caused mannose-resistant hemagglutination. Pilus preparations consisted of one to three bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ranged in molecular weight from 14,000 to 19,500. There was no single band common to all the strains. An enzyme-linked immunosorbent inhibition assay detected 20 ng of pilus antigen. When four different rabbit antisera were used, only two or fewer heterologous strains could inhibit the enzyme-linked immunosorbent assay. Immunoblots yielded the same results. Protein sequences of four P pili had identical N termini. These results show that despite having identical amino-terminal sequences, P pili are antigenically heterogeneous. The receptor-binding domains which are likely to be identical in all strains must be immunorecessive.

Amino Acid Sequence↗
PubMed1985

1H nuclear magnetic resonance studies of ytterbium-substituted porcine intestinal calcium-binding protein.

The addition of ytterbium to calcium-saturated porcine intestinal calcium-binding protein resulted in the appearance of broad lanthanide-shifted resonances well outside the normally observed region of the 1H nuclear magnetic resonance spectrum of the calcium form of the protein. Variation of the salt concentration and temperature have led us to conclude that aggregation and chemical exchange do not contribute to the line widths of these resonances. Assuming that the line broadening of these lanthanide-shifted resonances arises from the contribution of the susceptibility line-broadening mechanism for protein residues proximal to the bound Yb3+ ion, we have calculated Yb3+-proton distances for nuclei in the metal-binding site. These lanthanide-shifted resonances provide very sensitive probes of the structure of the protein in solution.

Animals↗
PubMed1985

[Determinants of the prognosis in dilated cardiomyopathy: significance of ventricular cardiac arrhythmias].

The prognostic value of ventricular arrhythmias on the natural history of idiopathic dilated cardiomyopathy remains controversial. Our findings in 105 patients suggest that those with reduced left ventricular ejection fraction (less than 40%) in whom frequent episodes of ventricular tachycardia or ventricular pairs (greater than 10 to 20/24 hours) were detected by 24 hour Holter monitoring are at risk of sudden death.

Arrhythmias, Cardiac↗
PubMed1984

Cryoenzymology of penicillopepsin; with an appendix: mechanism of action of aspartyl proteinases.

Intrinsic spectral and kinetic properties of penicillopepsin and its action on N-acetylalanylalanyllysyl-p-nitrophenylalanylalanylalanine amide have been investigated at subzero temperatures in aqueous methanol and dimethyl sulfoxide solutions in an attempt to find evidence for or against a covalent mechanism in the catalyzed hydrolysis of peptide bonds. The study of fluorescence and circular dichroism spectra as a function of solvent concentrations gave no evidence for any solvent-induced structural effects at temperatures below the thermal denaturation transition. The effect of temperature on the intrinsic fluorescence of penicillopepsin in either 60% (v/v) methanol or 50% (v/v) dimethyl sulfoxide did not indicate any temperature-induced structural changes. On the other hand, Arrhenius plots for the hydrolysis reaction over the range 0 to -50 degrees C showed downward curvature. A probable explanation for this phenomenon is that the reduction in flexibility of the enzyme due to thermal and viscosity factors leads to the stabilization of a nonproductive conformation. The pH optima of kcat/Km are shifted from 5.1 in aqueous solvents to 5.6 in 60% methanol and to 6.6 in 50% dimethyl sulfoxide. Aqueous methanol caused small decreases of Km and of Kcat; the decrease in the latter was greater than that brought about by the decrease in the water concentration. In aqueous dimethyl sulfoxide, there was no detectable change in kcat up to 15%, but Km increased by more than an order of magnitude. Above 15%, only kcat/Km could be measured. No evidence for the accumulation of either covalent amino or covalent acyl intermediates was obtained when penicillopepsin was incubated at -70 degrees C in 67% methanol with several substrates. Although negative, these experiments do not rule out conclusively the involvement of covalent intermediates in penicillopepsin-catalyzed reactions.

Aspartic Acid Endopeptidases↗
PubMed1984

Long-term antiarrhythmic therapy with flecainide.

The antiarrhythmic efficacy and safety of oral flecainide were assessed during a controlled 2-week and a subsequent 48-week long-term trial. Fifteen patients with frequent (more than 30 per hour) and complex ventricular arrhythmias (Lown grade IVA or IVB) who had been resistant or intolerant to 2 or more antiarrhythmic agents, were included in the study. Antiarrhythmic efficacy was controlled by 24-hour Holter monitoring at 2, 12, 24 and 48 weeks. The administration of 100 to 200 mg flecainide twice daily resulted in more than 90% suppression of VPCs and of complex ventricular arrhythmias in 14 of 15 patients. The minimum effective therapeutic dose could be titrated in 9 of 14 patients to 100 mg twice daily, in 3 of 14 patients to 150 mg twice daily and in 2 of 14 patients to 200 mg twice daily. During this therapy and a mean plasma concentration of 886 +/- 103 ng/ml, PQ and QRS duration, as well as QTc time and JTc interval were not significantly changed. Side effects (gastrointestinal complaints, nausea, obstipation, dizziness, visual disturbances, headache and impaired potency) were seen in 5 of 14 patients after 12 weeks, in 3 of 4 patients after 24 weeks and in only 2 of 14 patients after 48 weeks. Side effects were described as mild and tolerable and did not limit flecainide therapy except in 1 patient, who had discontinued therapy with flecainide after 3 days because of intense gastrointestinal symptoms. In conclusion, flecainide is highly effective and well tolerated in the long-term treatment of serious ventricular arrhythmias.

Adult↗
PubMed1984

Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy.

The incidence and prognostic significance of ventricular arrhythmias identified by 24-hour ambulatory electrocardiography (Holter) was prospectively assessed in 74 patients with idiopathic dilated cardiomyopathy (IDC). The criteria for diagnosis of IDC were based on clinical and cardiac catheterization findings. Holter monitoring was performed at the time of entry into the study. Patients were followed for 2 to 21 months (mean 11 +/- 3). Frequent ventricular premature complexes (VPCs) (greater than 1,000/24 hours) were seen in 35%, and complex VPCs (Lown grade III and IV) in 87% of the patients. Forty-nine percent of the patients had nonsustained ventricular tachycardia (VT) consisting of 3 to 32 beats with rates from 110 to 230 beats/min, and 20% had ventricular pairs. No correlation was found between clinical symptoms or the degree of left ventricular (LV) impairment and the number of ventricular pairs or episodes of VT. During follow-up, 19 patients died, 7 from congestive heart failure (CHF) and 12 suddenly. Patients who died suddenly had significantly more episodes of VT, ventricular pairs or total VPCs (p less than 0.01 each) compared with survivors and those who died from CHF. No significant differences were found between patients who died from CHF or suddenly with respect to LV end-diastolic pressure, LV end-diastolic volume index, LV ejection fraction (EF) and cardiac index. A linear stepwise discriminant function analysis using hemodynamic (LVEF and cardiac index) and arrhythmic (number of VT episodes and ventricular pairs) variables resulted in a meaningful separation between survivors and patients who died from CHF or suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1984

Effect of pH on the activities of penicillopepsin and Rhizopus pepsin and a proposal for the productive substrate binding mode in penicillopepsin.

The pH dependence of kinetic parameters for penicillopepsin and Rhizopus pepsin acting on acetylalanyl-alanyllysyl-p-nitrophenylalanylalanylalanine amide has been determined. The velocity constants, Kcat, show optima between pH 4 and pH 4.5. The Michaelis-Menten constants, Km, show a strong pH dependence for both enzymes and rise from low values at pH 6.0 (0.08 mM for penicillopepsin and 0.23 mM for Rhizopus pepsin) to approximately 8 mM and 1.1 mM, respectively, at pH 2.0. This dependence strongly suggests that for this substrate, with lysine in the P1 position, binding is controlled by negatively charged carboxyl group(s) on the enzyme. These groups have been tentatively identified in penicillopepsin as aspartic acid-115(114) and glutamic acid-16(13) on the basis of model building and by comparison with the binding of a pepstatin analogue. The S1 binding site also has hydrophobic character which shows itself in the low Km (0.004 mM) for the substrate leucylseryl-p-nitrophenylalanylnorleucylalanylleucine methyl ester. Tyrosine-75(75), phenylalanine-112(111), and leucine-121(120) are the most likely residues involved in the hydrophobic binding. The binding site for P1' residues is also hydrophobic and probably involves phenylalanine-190(189), isoleucine-211(213), phenylalanine-295(299), and isoleucine-297(301). In light of the structure of penicillopepsin, now refined at 1.8-A resolution, the detailed binding mode of a pepstatin analogue also studied at 1.8-A resolution, and model-building studies, a productive binding mode for the scissile bond to aspartyl proteinases is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid Endopeptidases↗