HLA class II antigens in endogenous psychoses.
Explore the source record for details and available documents.
Alleles↗
Biomedical subjects
A Lorenz
Publications and source records attributed to A Lorenz.
Protein-protein interactions in high molecular weight forms of the transformation-related phosphoprotein p53.
The transformation-related cellular phosphoprotein p53 interacts with a variety of viral and cellular proteins and with itself to form high molecular weight complexes. The formation of high molecular weight complexes correlates with the transformed morphology of the cells whereas in non-transformed cells low molecular weight forms are predominant. Thus, aggregation seems to be involved in the regulation of biological functions of p53. Analyzing wild-type and mutant p53 in the same cellular environment i.e. after an in vitro transcription/translation reaction in rabbit reticulocytes we found high molecular weight forms for wild-type and mutant p53. The sedimentation profile resembled the profile obtained for mutant p53 from transformed cells. As shown by dilution experiments, aggregation of p53 was not due to high p53 protein concentrations. Although p53 is known to bind RNA, treatment with RNAse did not change the aggregation state of p53 suggesting that RNA may not contribute to the quaternary structure of p53. High molecular weight aggregates of p53 were resistant to treatment with 1 M NaCl and also stable in weak acidic conditions. Alkaline pH as well as treatment with 3.5 M NaCl led to a disaggregation of high molecular weight complexes of p53. This treatment resulted in low molecular weight forms consisting probably of dimers to tetramers whereas monomers of p53 are hardly detectable. A nearly complete disaggregation was obtained only with the ionic denaturing detergent sodium dodecyl sulfate. Therefore, one has to assume different types of protein-protein interactions leading to the various quaternary structures of p53.
Animals↗
Antisense effect of oligodeoxynucleotides with inverted terminal internucleotidic linkages: a minimal modification protecting against nucleolytic degradation.
The synthesis of a new class of antisense oligonucleotide compounds with 3'-3' and 5'-5' end inversion (INV-oligonucleotides) is described. Besides the advantage of simplicity of synthesis, physico-chemical studies show that these compounds do not disturb Watson-Crick base-pairing. INV-oligonucleotides have a half-life of 30 h in human serum. We show that they are capable of inhibiting SV40 large T-antigen expression in COS-1 cells, both in vitro and in vivo, and by modulation of the expression of cellular oncoprotein p53 in vitro.
Animals↗
Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses.
Healthy volunteers received intravenous and/or oral doses of sodium dichloroacetate (DCA) in various single and multiple dose regimens. A crossover bioavailability study proved abortive because second and subsequent doses showed significantly longer terminal elimination half-lives (means 3.64 h and 9.9 h, respectively) than was the case for initial doses (1.58 h). A parallel bioavailability comparison failed to show that oral doses were significantly different from 100 per cent bioavailability (AUCoral, 604 micrograms h-1 ml-1; AUCi.v., 489 micrograms h-1 ml-1). The time required to elapse between individual doses, in order to prevent second doses having relatively long half-life values, varied in different individuals from 1 week to greater than 3 months. No cardiac or central nervous system effects were recorded by echocardiography and digit symbol substitution tests, respectively. The mean renal clearance of DCA was 42.9 ml h-1. No differences were observed in DCA kinetics between male and female subjects.
Administration, Oral↗
Computerized ultrasound B-scan texture analysis of experimental diffuse parenchymal liver disease: correlation with histopathology and tissue composition.
By means of statistical pattern recognition procedures, a quantitative description of the ultrasound B-scan images of experimental diffuse liver disease has been carried out. Fatty livers, fatty fibrosis/cirrhosis, and cirrhosis without fatty infiltration of the liver were studied in female Wistar rats. Separation accuracies of more than 80% between the tissue classes "normal" vs "fatty infiltration," or "normal" vs "fatty cirrhosis," using only two statistical image parameters were found. A subclassification of the diffuse parenchymal liver disease was not possible. It is shown by multiple linear regression analysis that the image parameter "mean grey level" correlates better with total lipid content than with the amount of connective tissue. Furthermore it is demonstrated that connective tissue leads only to a weak increase in "mean grey level," whereas the addition of connective tissue to a given tissue lipid can lead to a reduction in image brightness.
Animals↗
Haemodialysis studies with dichloroacetate.
Seven patients undergoing routine thrice weekly haemodialysis for endstage renal failure participated in 12 investigations of dichloroacetate (DCA) pharmacokinetics and pharmacodynamics. DCA doses were 50 mg/kg by i.v. infusion over 30 min. In each investigation single doses were administered to each subject on two consecutive days, one being a day during which the patient was dialyzed. The timing of drug administration, relative to dialysis, was varied to assess the effect of dialysis on the apparent volume of distribution and elimination rate constants of DCA and on its effect on blood glucose and lactate. Dialysis increased the clearance of DCA by approximately 60%, but had no effect on its apparent volume of distribution. Dialysis did not reduce the maximal lactate-lowering effect of DCA, but slightly decreased the duration of this effect. Blood glucose levels were not significantly altered by DCA and no adverse drug effects were observed. We conclude that dialysis increases plasma clearance of DCA, but has little influence on the metabolic effects of the drug when given at 50 mg/kg doses. DCA can safely and effectively be given to hemodialysis patients who may require the drug for treatment of lactic acidosis.
Adult↗
Bone morphogenetic protein 4 (BMP-4), a member of the TGF-beta family, in early embryos of Xenopus laevis: analysis of mesoderm inducing activity.
We have screened a Xenopus ovary cDNA library using a synthetic oligonucleotide derived from that part of the inhibin beta A sequence, which is highly conserved within the TGF-beta family. Out of several clones yielding autoradiographic signals four turned out to represent Xenopus counterparts to the human bone morphogenetic protein 4 (BMP-4). Each two of the four sequences are nearly identical and probably account for different alleles whereas the two pairs showing 5% divergence may have arisen by genome duplication in this tetraploid species. The amino acid sequence of the Xenopus protein is 80% homologous to the human sequence showing no single exchange within the last 100 amino acids at the C-terminus. This region, which constitutes the main part of the mature, biologically active protein, also exhibits substantial homologies to other representatives of the TGF-beta family, especially to the Drosophila DPPC protein. Transfection of COS-1 cells with the Xenopus BMP-4 sequence under control of the CMV-promoter leads to the secretion of a protein which exhibits mesoderm inducing activity when tested with animal cap explants from Xenopus blastula stage embryos.
Amino Acid Sequence↗
Treatment of the Dunning prostate rat tumor R3327-AT1 with pulsed high energy ultrasound shock waves (PHEUS): growth delay and histomorphologic changes.
We are interested in the interaction of pulsed high energy shock waves (PHEUS) on soft tissues treated in situ to evaluate its potential for therapeutic use. The experimental apparatus built by us was adapted from a lithotripter designed for clinical use. For the present studies we used the R3327-AT1 Dunning prostate tumor growing s.c. in the thigh of Copenhagen rats. The treatments consisted of four groups of eight animals each who received 500 or 2000 pulses at 1 or 5 Hz. Sham-treated tumor bearing animals served as controls (n = 11). During each PHEUS treatment, petechial bleeding of the skin at the point of entry and exit of sound appeared. Sonication at a repetition rate of five Hz seemed to induce more macroscopic damage in terms of hematomas and skin effects. The cytotoxic effects of PHEUS to tumor tissue were sufficient to induce a significant delay (p less than 0.05) in tumor growth but no clear-cut dose relationship was established. Histological studies revealed widespread early rupture of the fine vasculature with extravasation of erythrocytes. By 72 hr., in PHEUS treated tumors, a large necrosis was seen within the central zone which was never observed in sham-treated tumors. Our results clearly indicate that PHEUS has a cytotoxic potential. The observation of a rapid onset of hemostasis, stark hemorrhage and necrosis in the treatment field would suggest that vascular damage is an important contributing factor.
Animals↗
[Influence of abdominal wall composition and thickness on ultrasound B scan].
Using a tissue-mimicking phantom and a computerised sonography system an ultrasound b scan analysis was performed. The images were acquired with different fat-muscle combinations as ultrasound wave path. These are simulations of a different composition or thickness of the abdominal wall. The analysis of the ultrasound images was performed using mathematical statistical parameters for ultrasound tissue characterisation. We examined the influence of the thickness or composition of the abdominal wall on ultrasound image brightness, microtexture and macrotexture. A dependence of ultrasound image brightness and microtexture on the thickness of the fat path was observed. Muscle tissue shows only a weak influence on the microtexture of the ultrasound image. These data demonstrate that a thick fat layer leads to a darker and diffuse image. This disturbs the evaluation e.g. of the liver parenchyma by analysis of the echo structure and may lead to false diagnoses especially in adiposity.
Abdominal Muscles↗
Expression of p53 during mouse embryogenesis.
By in situ hybridisation we have examined the expression of p53 during mouse embryogenesis from day 8.5 to day 18.5 post coitum (p.c.). High levels of p53 mRNA were detected in all cells of the day 8.5 p.c. and 10.5 p.c. mouse embryo. However, at later stages of development, expression became more pronounced during differentiation of specific tissues e.g. of the brain, liver, lung, thymus, intestine, salivary gland and kidney. In cells undergoing terminal differentiation, the level of p53 mRNA declined strongly. In the brain, hybridisation signals were also observed in postmitotic but not yet terminally differentiated cells. Therefore, gene expression of p53 does not appear to be linked with cellular proliferation in this organ. A proposed role for p53 in cellular differentiation is discussed.
Animals↗
Species-dependent differences of high affinity [3H]PAF-binding to platelets from humans and pigs and its inhibition by selected antagonists.
The sensitivity of blood platelets towards PAF (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) strongly varies with species and is primarily responsible for different pathophysiological effects after its administration to experimental animals. Platelets from domestic pigs were shown to possess one single class of high-affinity PAF-binding sites. Receptor density and sensitivity of pig platelets towards PAF were distinctly higher than those from humans. Preincubation of platelets from both species with PAF-specific antagonists diminished the high affinity [3H]PAF-binding concentration-dependently. Eight PAF-related antagonists, the ginkgolide BN 52021, as well as the hetrazepine WEB 2086 were included and mean inhibitory concentrations (IC50) between 0.09 and 124 mumol/l ascertained. Comparing the rank order of inhibitory potency considerable differences became evident between both species. The quotients of the IC50 values obtained with human and pig platelets differed for about two orders of magnitude. Moreover, the inhibitory profile of the PAF-related antagonists was found to be highly sensitive to small structural changes. Based on these findings a species-dependent difference at the PAF receptor level of platelets from pigs and humans is suggested.
Animals↗
Echographic tissue characterization in diffuse parenchymal liver disease: correlation of image structure with histology.
Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization.
Fatty Liver↗
Computerized ultrasound B-scan texture analysis of experimental fatty liver disease: influence of total lipid content and fat deposit distribution.
Statistical pattern recognition procedures allow a quantitative description of ultrasound-B-scan image texture. According to well-established animal models, different types of fatty liver disease were induced in female Wistar rats. For the correlation of the computerized ultrasound image with its underlying histology a variable tissue model based on histomorphological data, texture analysis of the histological image and biochemical measurements of total lipid, water and hydroxyproline content was created. Whereas a regional arrangement of large fat deposits leads to a significant increase in the "mean grey level" (measure of image brightness) of the ultrasound-B-scan image, there is no difference in image brightness between normal liver tissue and liver steatosis for the tissue model with diffuse homogeneous fatty infiltration. It is demonstrated by multiple linear regression analysis that the "mean grey level" of the ultrasound-B-scan image depends not only on total lipid content but even more on the histomorphological fat deposit distribution.
Animals↗
Hypertension and hyperlipidaemia: garlic helps in mild cases.
Forty-seven non-hospitalised patients with mild hypertension took part in a randomised, placebo-controlled, double-blind trial conducted by 11 general practitioners. The patients who were admitted had diastolic blood pressures between 95 and 104 mmHg after a two-week acclimatization phase. The patients then took either a preparation of garlic powder (Kwai) or a placebo of identical appearance for 12 weeks. Blood pressure and plasma lipids were monitored during treatment after four, eight and 12 weeks. Significant differences between the placebo and the drug group were found during the course of therapy. For example, the supine diastolic blood pressure in the group having garlic treatment fell from 102 to 91 mmHg after eight weeks (p less than 0.05) and to 89 mmHg after 12 weeks (p less than 0.01). The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment. In the placebo group, on the other hand, no significant changes occurred.
Aged↗
Release of mycoplasmavirus L1 upon transfection of Acholeplasma laidlawii with homologous and heterologous viral DNA.
This communication reports on the release of Mycoplasmavirus L1 after infection of Acholeplasma laidlawii with purified L3 virus. Release also occurred after transfection with certain restriction fragments from MV-L3 and MV-L1 genomes. Since circular molecules are efficiently taken up in polyethylene glycol-mediated transfection, inducing fragments were applied cloned in E. coli plasmids. Release was also observed after electroporation of cells incubated with MV-L1 replicative intermediate DNA and linear MV-L3 DNA isolated from virus particles, respectively. Released MV-L1 viruses were identified after virus plaque formation on indicator lawns according to plaque morphology and hybridization with labeled viral DNA probes as well as by DNA restriction analysis. Uninfected and untransfected cells from six laboratory strains of A. laidlawii (including a MV-L1 resistant one) were examined for the presence of MV-L1 DNA. They all bear MV-L1 DNA integrated in their genomes.
Acholeplasma↗
[Quantitative studies on the influence of connective tissue and fatty structures on the ultrasonic image of the liver].
Using a computerized ultrasound system, 63 autopsied livers were examined. A quantitative description of the ultrasound image was made by using statistical parameters from pattern recognition algorithms. As a reference a chemical/morphometrical classification into normal, diffuse and regional fatty infiltration and fibrosis/cirrhosis was performed. Diagnostic accuracy varied from 77% to 92%. Ultrasound tissue characterisation showed an influence of fatty and connective tissue structures on image parameters. This supplies evidence for the fact that computerised ultrasound examination yields more information from the ultrasound image than the normal observer. This may be the cause of an increased diagnostic accuracy when using computerized ultrasound systems, especially in the case of fibrosis/cirrhosis.
Diagnosis, Computer-Assisted↗
[Computer-assisted ultrasonic B-scan texture analysis of experimental liver tumors].
Primary liver cancer has been induced experimentally in female Wistar rats by diaminoazobenzene intoxication or subcapsular liver implantation of Novikoff cell suspensions. The ultrasonic B-scan image of these malignant tumours are described via statistical texture parameters in respect of image brightness, microtexture and macrotexture. A discrimination of the tumour texture profiles is possible with an accuracy of about 80%. There are correlations between ultrasonic image parameters and histomorphological tissue components but there is no specific link between the histological tumour-type and these B-scan data.
Animals↗
[Adequate measurement of artificial mineral fibers and evaluation of the biological effect].
Epidemiological and clinical medical examinations of exposed workers to man-made mineral fibers (MMF) to fix threshold limit values are presupposed by adequate measurements of MMF-dust. As yet are used technics which are unsatisfying. In consideration of the biological conditions in the breathing system a draft to measure MMF dust is introduced and proved. This draft based on the use of two-step-gravimetrical measurements together with membranous filter devices and evaluation by an electronic microscope.
Air Pollutants, Occupational↗