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Biomedical subjects

K Richter

Publications and source records attributed to K Richter.

At least 163 records · Page 9Linked to original sources
PubMed1995

DNA binding site of the yeast heteromeric Ino2p/Ino4p basic helix-loop-helix transcription factor: structural requirements as defined by saturation mutagenesis.

The inositol/choline-responsive element (ICRE) is an 11 bp cis-activating sequence motif with central importance for the regulated expression of phospholipid biosynthetic genes in the yeast Saccharomyces cerevisiae. The ICRE containing the CANNTG core binding sequence (E-box) of basic helix-loop-helix (bHLH) regulatory proteins is recognized by the heteromeric bHLH transcription factor Ino2p/Ino4p. In this study, we define the Ino2p/Ino4p consensus binding sequence (5'-WYTTCAYR-TGS-3') based on the characterization of all possible single nucleotide substitutions. Interestingly, this analysis also identified a single functional deviation (CACATTC) from the CANNTG core recognition element of bHLH proteins. The DNA binding specificities of different yeast bHLH proteins may now be explained by distinct nucleotide preferences especially at two positions immediately preceding the CANNTG core motif.

Base Sequence↗
PubMed1995

Isolation of two interleukin-6 response element binding proteins from acute phase rat livers.

Proteins binding at the IL-6 response element of the rat alpha 2 macroglobulin gene were purified by a combination of conventional chromatographic procedures and binding-site specific DNA affinity chromatography. The proteins were purified from the nuclei of rat livers, excised at the peak of an experimentally induced acute phase response. By this procedure three polypeptides of 92, 91 and 86 kD were enriched more than 6,000-fold. Partial proteolysis with lysyl endopeptidase and aminoacid sequence analysis of proteolytic peptides identified the 86 and 91 kD species as the transcription factor Stat3 and the 92 kD species as a Stat factor distinct from Stats 1 and 3. cDNA clones for Stats 1, 3 and this 92 kD factor were isolated from a cDNA library prepared with mRNA from acute phase rat livers. Parts of their DNA sequences were determined and the sequences of the purified peptides were found in these cDNA sequences. Thus, the identity of the factors as Stat3 and a Stat factor different from Stats 1 and 3 was confirmed. These results suggest, that APRF/Stat3 and p91/Stat1 are not the only factors mediating the effects of IL-6 on class 2 acute phase genes. The 92 kD Stat factor binding at the IL-6 RE probably also functions as a transcription factor in the cytokine-induced activation of the alpha 2M gene.

Acute-Phase Reaction↗
PubMed1995

Sequence of the porcine full-length cDNA encoding ribosomal protein rpS12.

The full-length cDNA encoding the porcine ribosomal protein rpS12 was shown to be differentially expressed in endothelial and smooth muscle cells. A cDNA clone containing the entire rpS12 sequence was isolated from growth-stimulated capillary endothelial cells by use of subtractive hybridization and differential screening. The porcine rpS12 cDNA coding region exhibits 94% identity to the rat rpS12 and 92% to the human rpS12 cDNAs.

Amino Acid Sequence↗
PubMed1995

Disposition and bioavailability of the beta 1-adrenoceptor antagonist talinolol in man.

In an open randomized crossover study, the pharmacokinetics and bioavailability of the selective beta 1-adrenoceptor antagonist talinolol (Cordanum--Arzneimittelwerk Dresden GmbH, Germany) were investigated in twelve healthy volunteers (five female, seven male; three poor and nine extensive metabolizers of the debrisoquine hydroxylation phenotype) after intravenous infusion (30 mg) and oral administration (50 mg), respectively. Concentrations of talinolol and its metabolites were measured in serum and urine by HPLC or GC-MS. At the end of infusion a peak serum concentration (Cmax) of 631 +/- 95 ng mL-1 (mean +/- SD) was observed. The area under the serum concentration-time curve from zero to infinity (AUC0-infinity) was 1433 +/- 153 ng h mL-1. The following parameters were estimated: terminal elimination half life (t 1/2), 10.6 +/- 3.3 h; mean residence time, 11.6 +/- 3.1 h; volume of distribution, 3.3 +/- 0.5 L kg-1; and total body clearance, 4.9 +/- 0.6 mL min-1 kg-1. Within 36 h 52.8 +/- 10.6% of the administered dose was recovered as unchanged talinolol and 0.33 +/- 0.18% as hydroxylated talinolol metabolites in urine. After oral administration a Cmax of 168 +/- 67 ng mL-1 was reached after 3.2 +/- 0.8 h. The AUC0-infinity was 1321 +/- 382 ng h mL-1. The t 1/2 was 11.9 +/- 2.4 h. 28.1 +/- 6.8% of the dose or 55.0 +/- 11.0% of the bioavailable talinolol was eliminated as unchanged talinolol and 0.26 +/- 0.17% of the dose as hydroxylated metabolites by kidney. The absolute bioavailability of talinolol was 55 +/- 15% (95% confidence interval, 36-69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in comparison with single-dose kinetics.

Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine-induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, Cmax,ss = 391.8 ng mL-1 against Cmax,sd = 132.8 ng mL-1; M2, Cmax,ss = 143.2 ng mL-1 against Cmax,sd = 25.8 ng mL-1). However, significant increases of AUC (AUC tau = 261.9 ng h mL-1 against AUC0-infinity,sd = 182.9 ng h mL-1), Cmax (Cmax,ss = 75.9 ng mL-1 against Cmax,sd = 56.9 ng mL-1) and t 1/2 beta (t 1/2 beta,ss = 4.0 h against t 1/2 beta,sd = 2.4 h) of the parent compound indicate non-linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non-renal tiracizine clearance with repeated dosing led to the assumption that non-linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at the tmax of the parent compound, whereas there was no change in any ECG parameter after a single-dose administration of 50 mg tiracizine.

Administration, Oral↗
PubMed1995

Investigation of the thermal stability of Ni/C multilayers by X-ray methods.

Microstructural properties of Ni/C multilayers prepared by PLD (pulsed laser deposition) have been investigated after heat treatment in vacuum at temperatures in the range of 50 degrees C to 500 degrees C. X-ray diffractometry, X-ray reflectometry, fluorescence EXAFS (extended X-ray absorption fine structure) and HREM (high resolution transmission electron microscopy) have been applied to characterize samples in the initial state and after annealing. The multilayer reflectivity remained unchanged or increased at temperatures below 400 degrees C due to sharpening of the interfaces caused by the formation of alpha-nickel and nickel carbide. The reflectivity decreased at temperatures above 400 degrees C because of the fragmentation of the nickel layers. It can be shown, that both chemical and mechanical driving forces are responsible for the observed modifications of the initial specimen state.

Journal Article↗
PubMed1995

Quantitative parameters measured by a new sonographic method for differentiation of benign and malignant breast disease.

RATIONALE AND OBJECTIVES: To differentiate lesions on sonography by clinical amplitude/velocity reference imaging (CARI). METHODS: Diameters of 144 breast lesions were measured preoperatively with a new sonographic method (CARI). This method uses mammography-identical positioning of the breast for examination and a reference structure for detection of changes of sound amplitude and velocity by through transmission of lesions. Ratios of diameters were calculated after correction for abridgement by increased velocity within some lesions. Tables were made for each ratio class containing the uncorrected craniocaudal diameter of all measurable lesions and, if present, its corresponding change of velocity (measure of elevation of the reference structure). RESULTS: By retrospective analysis of the distribution of data and use of a limit to guarantee that all cancers should be detected, only 18% of the benign lesions were not distinguishable from malignant lesions. CONCLUSIONS: After further technical development, CARI could be used synchronously with mammography to improve the detection and differentiation of benign and malignant breast lesions.

Biopsy↗
PubMed1995

Clinical amplitude/velocity reconstructive imaging (CARI)--a new sonographic method for detecting breast lesions.

X-ray mammography and breast ultrasound are methods for the detection of breast lesions, especially cancers. They work in a complementary manner, but only X-ray mammography can be used for screening purposes because the recent sonographic techniques are not as cost-effective, not as fast as mammography, observer-dependent and, in some instances, not reliable enough. A new ultrasound method is described which uses an X-ray-identical examination set-up and the following two properties of breast lesions: change of echo patterns behind the lesion and increased sound velocity, especially within malignant lesions. These features can be imaged on a reference structure, a reflecting plate positioned on the side of the breast which is opposite to the transducer. Results of pre-operative examinations of 80 patients with 39 benign and 52 malignant lesions are reported. Clinical, histopathological, and especially X-ray mammography findings are compared. Five cancers were not detectable by ultrasound but had clear suspicious signs on X-ray mammography. Nine cancers were not detected by X-ray mammography but were clearly visible with the new sonographic examination. By the combination of X-ray mammographic findings and their behaviour with the new sonographic method some lesions could correctly be identified as benign. The new sonographic method works in a complementary way to X-ray mammography. By further technical development it could be automated and probably performed as easily, as fast and as reproducibly as X-ray mammography. Using this method systematically in combination with X-ray mammography the detection rate of breast cancer could possibly be increased and unnecessary biopsies of benign lesions could be prevented.

Breast Diseases↗
PubMed1995

[A new ultrasound method for examination of the breast].

In the present paper, a new sonographic method of examining the breast is described. In the form of a laboratory model, it has been used to investigate 245 preoperative patients and 146 women referred for conventional sonography of the breast. All the patients had also undergone mammography. With the new procedure the examination situation is identical to that used for mammography, with a stainless steel plate (reference reflector) placed beneath the breast, and which appears on the B scan behind healthy tissue as a straight white line. Disordered reflectivity and elevation of this line indicate the presence of a lesion. Measurement of the lesion and the elevation of the reference line permit differentiation between benign and malignant disease. The use of both X-ray and sonographic findings improved the detection of cancers and reduced false-positive benign findings. Further technical improvements to this sonographic procedure could make it as rapid and reliable as mammography.

Breast Neoplasms↗
PubMed1995

Sonographic differentiation of benign from malignant breast lesions: value of indirect measurement of ultrasound velocity.

OBJECTIVE: The purpose of this study was to test the value of indirect measurements of ultrasound velocity in the sonographic differentiation of benign from malignant breast lesions. SUBJECTS AND METHODS: One hundred six mammographically examined preoperative patients with 54 benign and 70 malignant histopathologically proven lesions were examined as follows. The compressed breast was completely penetrated by an ultrasound beam from a 7.5-MHz linear transducer. A stainless steel plate underneath the breast appeared on sonograms of normal breast tissue as a hyperechoic line. Some lesions caused changes in the attenuation and velocity of the ultrasound beam, which in turn caused the hyperechoic line representing the steel plate below those lesions on sonograms to appear elevated and changed in echogenicity. By measuring elevation, if any, and the corresponding length of lesions on the sonogram, we studied the results of this sonographic examination and compared them with mammographic findings. RESULTS: Sixty of the 70 cancers caused the hyperechoic line representing the steel plate on sonograms to appear elevated and changed in echogenicity at points below those lesions. Twenty-five of the 54 benign lesions also showed this effect, but the amount of elevation seen on sonograms was smaller with 14 of these 25 lesions than with 57 of the 60 malignant lesions. The new method complements mammographic findings by true definition of mammographically false-negative cancers and false-positive benign lesions. Accuracy was improved by use of both mammography and sonography in comparison with that obtained with mammography alone (85% versus 73%). CONCLUSION: Indirect measurement of relative ultrasound velocity can help differentiate benign from malignant breast lesions. The systematic use of mammography and this new sonographic method might improve the detection of cancers and help avoid biopsies of benign lesions.

Adult↗
PubMed1995

Day-night variations in the renal excretion of the antiarrhythmic agent tiracizine and its metabolites.

Daytime and nighttime urinary recovery as well as morning and evening trough serum levels of the antiarrhythmic agent tiracizine and three of its metabolites (M1, M2, and M3) were assessed during a 7-day multiple-dose study period (50 mg tiracizine twice daily) in eight healthy volunteers. A significantly lower mean steady-state urinary recovery was observed during the daytime as compared with during the nighttime (Ae (tot tau d)=42.0 +/- 15.7% vs. Ae (tot tau n)=51.2 +/- 19.6%). This difference is mainly due to a substantial increase of M1 and a smaller increase of M2 urinary recovery by night. Results of additional in vitro investigations showed the ratio of the nonionic/ionic forms of M1 and M2 to be highly dependent on pH in the range of pH 5-pH 7. Therefore, the observed day-night variations might be attributed to alterations of ionization, i.e., nonionic tubular reabsorption of the metabolites due to circadian differences in urinary pH. Trough serum levels of M1 and M2 tended to be higher at 7 P.M. as compared with 7 A.M. Due to the narrow therapeutic index of class I antiarrhythmics, the present results indicate the need for further investigations concerning the effect of urinary pH on the pharmacokinetics of tiracizine and its metabolites.

Adult↗
PubMed1995

The role of vertical and planar signals during the early steps of neural induction.

The classical Einsteck-test (Spemann and Mangold, Roux Arch. Dev. Biol. 100: 599-638, 1924) and data from total exogastrulae (Holtfreter, 1933) suggest that vertical signals are transmitted between the chordamesoderm (organizer) and reacting ectoderm in the early phase of neural induction. In contrast to these results with Axoloti (urodeles), several authors observed the expression of neural specific genes in Xenopus exogastrulae, isolated dorsal blastopore lip with adjacent ectoderm (open-face explants) and Keller-sandwiches. Our data with Xenopus (anurans) also show that the expression of neural specific genes takes place in exogastrulae. However, when we prepared open face explants and exogastrula-like structures by microdissection at very early gastrula stage, the signal of a class II beta-tubulin, characteristic of terminal neural differentiation, is not found in the ectoderm. These results suggest that planar signals transmitted from the chordamesoderm into the ectodermal part can fairly be excluded under these experimental conditions. In similar experiments with Triturus alpestris we could not observe either the differentiation of neural structures in the ectodermal part of exogastrulae. These results confirm earlier experiments of Holtfreter performed with Ambystoma mexicanum (Axoltl) embryos. On the basis of the published data of different authors and our results, we cannot exclude the existence of planar signals for early and/or transient expressed genes before the onset of gastrulation in Xenopus, which make the neuroectoderm susceptible for the response to vertical signals during gastrulation. On the other hand our experiments with Triturus alpestris suggest that planar neural signals are unlikely in this species. These differences between Triturus and Xenopus embryos are discussed in the context of the peculiarities in morphological structure, competence and speed of development of the two species.

Ambystoma mexicanum↗
PubMed1995

[Relative bioavailability of the antiarrhythmia agent, tiracizine and its metabolites].

Relative bioavailability of a 100 mg tablet formulation of the antiarrhythmic agent tiracizine (CAS 78816-67-8) compared to a 50 mg formulation was assessed in a simple cross over study after single administration of a 100 mg dose to 12 healthy volunteers. Tiracizine and three of its metabolites (M1, M2 and M3) were measured in serum and urine by high pressure liquid chromatography. AUC (means after administration of the test preparation and 95% nonparametric confidence interval for the ratio test preparation/reference preparation) were 391.5 ng.h/ml and 0.87-1.11 for tiracizine, 5184.5 ng.h/ml and 0.94-1.26 for M1, and 1319.9 ng.h/ml and 0.88-1.16 for M2. Mean maximum serum concentrations after the test preparation and corresponding 95% confidence interval were 111.2 ng/ml and 0.86-1.20 for tiracizine, 301.2 ng/ml and 0.98-1.22 for M1, 54.6 ng/ml and 0.86-1.17 for M2, and 35.2 ng/ml and 0.82-1.17 for M3.tmax did not differ after the two preparations for tiracizine, M2 and M3, but was significant lower for M1 after administration of the test preparation (2.2 +/- 0.7 vs 3.0 +/- 1.2 h). Total urinary recovery (sum of parent compound and metabolite recovery) up to 32 h after intake of the test preparation was 31.2% of the administered dose. The corresponding 95% confidence interval was 0.84-1.08. Statistical evaluation of all parameters revealed bioequivalence between the two preparations if a single dose of 100 mg is administered.

Adult↗