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Biomedical subjects

H Kraft

Publications and source records attributed to H Kraft.

At least 19 recordsLinked to original sources
PubMed1999

New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites.

SIP1, a Smad-interacting protein, and deltaEF1, a transcriptional repressor involved in skeletal and T-cell development, belong to the same family of DNA binding proteins. SIP1 and deltaEF1 contain two separated clusters of zinc fingers, one N-terminal and one C-terminal. These clusters show high sequence homology and are highly conserved between SIP1 and deltaEF1. Each zinc finger cluster binds independently to a 5'-CACCT sequence. However, high-affinity binding sites for full-length SIP1 and deltaEF1 in the promoter regions of candidate target genes like Xenopus Xbra2, and human alpha4-integrin and E-cadherin, are bipartite elements composed of one CACCT and one CACCTG sequence, the orientation and spacing of which can vary. Using transgenic Xenopus embryos, we demonstrate that the integrity of these two sequences is necessary for correct spatial expression of a Xbra2 promoter-driven reporter gene. Both zinc finger clusters must be intact for the high-affinity binding of SIP1 to DNA and for its optimal repressor activity. Our results show that SIP1 binds as monomer and contacts one target sequence with the first zinc finger cluster, and the other with the second cluster. Our work redefines the optimal binding site and, consequently, candidate target genes for vertebrate members of the deltaEF1 family.

Animals↗
PubMed1999

SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes.

Activation of transforming growth factor beta receptors causes the phosphorylation and nuclear translocation of Smad proteins, which then participate in the regulation of expression of target genes. We describe a novel Smad-interacting protein, SIP1, which was identified using the yeast two-hybrid system. Although SIP1 interacts with the MH2 domain of receptor-regulated Smads in yeast and in vitro, its interaction with full-length Smads in mammalian cells requires receptor-mediated Smad activation. SIP1 is a new member of the deltaEF1/Zfh-1 family of two-handed zinc finger/homeodomain proteins. Like deltaEF1, SIP1 binds to 5'-CACCT sequences in different promoters, including the Xenopus brachyury promoter. Overexpression of either full-length SIP1 or its C-terminal zinc finger cluster, which bind to the Xbra2 promoter in vitro, prevented expression of the endogenous Xbra gene in early Xenopus embryos. Therefore, SIP1, like deltaEF1, is likely to be a transcriptional repressor, which may be involved in the regulation of at least one immediate response gene for activin-dependent signal transduction pathways. The identification of this Smad-interacting protein opens new routes to investigate the mechanisms by which transforming growth factor beta members exert their effects on expression of target genes in responsive cells and in the vertebrate embryo.

Amino Acid Sequence↗
PubMed1997

The C-terminal domain of Mad-like signal transducers is sufficient for biological activity in the Xenopus embryo and transcriptional activation.

We report the characterization of two vertebrate homologs of Drosophila mothers against dpp (Mad) isolated from the mouse and the Xenopus embryo, named MusMLP (mad-like protein) and XenMLP, respectively, together with a summary of their expression patterns in the embryo. Overexpression of XenMLP causes ventralization of Xenopus embryos and we demonstrate that the C-terminal domain is necessary and sufficient to confer this biological effect. This domain also has the potential for transcriptional activation, as shown in one-hybrid assays in mammalian cells. We further demonstrate that MLPs are multidomain proteins by showing a cis-negative effect of the N-terminal domain on the transactivation by the C-terminal domain and that the proline-rich, middle domain maximizes the activity of the C-terminal domain. We also mapped the MusMLP gene to a region on mouse chromosome 13 that corresponds to a region on human chromosome 5q that contains cancer-related genes.

Amino Acid Sequence↗
PubMed1997

Suicidality among HIV-positive psychiatric in-patients.

Rates of suicidality with HIV-infected, seriously mentally ill individuals were investigated. Fifty asymptomatic HIV-positive psychiatric in-patients were compared to a demographically-matched HIV-negative cohort. The groups were similar, except that seropositive subjects were less likely to be diagnosed with schizophrenia. Both groups had high rates of suicidality, with higher rates associated with non-schizophrenic diagnoses. HIV-positive subjects had higher rates of suicidality, with those diagnosed with schizophrenia showing the greatest difference from their HIV-negative counterparts. HIV-positive patients required less in-patient treatment. These data expand previous reports showing an association between HIV and increased suicidality, even among individuals with already elevated suicidal rates.

Adult↗
PubMed1997

Survey among physicians by means of dynamic access to an Internet information server database.

Current database management systems, client-server architecture and the internet infrastructure are simplifying the exchange of information. Large and widespread electronic medical record systems are accessible via platform-independent browsing applications. The following brief summary shows one of the manifold conceivable applications of these technologies in medicine. It describes a survey among physicians with the scope of quality assurance in medicine. The dynamic, platform-independent, world-wide access to databases offers interesting aspects in medical informatics.

Computer Communication Networks↗
PubMed1991

Effect of the calcium antagonists nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal motility in man.

Nifedipine has been proven to be effective and safe in the treatment of primary oesophageal motility disorders which can cause angina-like chest pain and/or dysphagia. The effects of the calcium channel blockers nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal smooth muscle function in healthy male volunteers were studied by oesophageal manometry using the rapid pull-through-technique, in two randomized, double-blind crossover studies. Lower oesophageal sphincter pressure, oesophageal contraction amplitude and duration after a wet swallow (measured 5 cm and 10 cm above the lower oesophageal sphincter) were determined 30 min before and at 10 minute intervals up to 90 min after the administration of nimodipine and up to 120 min after nifedipine, nitrendipine and nisoldipine. The plasma drug concentration was measured at baseline (-15 min) and in parallel with the manometric measurements. Compared to placebo, lower oesophageal sphincter pressure was significantly decreased by 24% by nifedipine and 17% by nimodipine, whereas the effects of nitrendipine (decrease of 15%) and nisoldipine (9%) were not significant. Nifedipine significantly decreased by 17% the oral contraction amplitude compared to placebo and nimodipine by 11%. The duration of the contraction amplitudes was not altered. The decrease in sphincter pressure was correlated with the corresponding plasma drug levels of nifedipine r = 0.92, nitrendipine r = 0.80 and nisoldipine r = 0.79. Nimodipine showed no such correlation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

[Ultrasound controlled aspiration cytology of liver, bile ducts and pancreas].

Aspiration cytology is an effective and safe method for diagnosis of intraabdominal malignancies. In a prospective study we analysed the cytology in 84 patients. The results showed a sensitivity of 95% with an accuracy of 96%. No false positive diagnosis was found where open biopsy was possible. The aspiration cytology is a good method to decide whether endoscopic stents or embolization of the liver can be used without explorative laparotomy.

Biopsy, Needle↗
PubMed1989

Pharmacokinetics of rioprostil in human plasma as assayed by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry.

To investigate the pharmacokinetics of rioprostil in man an assay is developed to analyse levels of rioprostil in plasma. After extraction and purification by solid-phase cartridges rioprostil is measured by negative ion chemical ionization mass spectrometry using a deuterated internal standard. The method is validated by a recovery experiment. Levels of rioprostil in the plasma of four volunteers following a single oral dose of 600 micrograms rioprostil are found as always below 100 pg/ml. The data presented here suggest that rioprostil is transformed rapidly in man to its more polar metabolites.

Adult↗
PubMed1989

[CO2-stunning of swine for slaughter from the anesthesiological viewpoint].

For investigations of CO2-stunning of feeder- and slaughter-pigs parameters of behaviour, blood-gas-analyses and electroencephalograms were chosen. The following results were obtained: 1. Blood-gas-analyses proved that the CO2-stunning does not produce unconsciousness due to a lack of oxygen. 2. The criterias of general anaesthesia: unconsciousness, muscle-relaxation and analgesia with total reversibility could be confirmed. 3. The violent convulsive symptoms were evaluated as reactions identical with the stage II of GUEDEL's scheme of anaesthesia. 4. Muscular agitation, which sometimes appeared a few seconds before the stage of excitation, was judged to belong either to the start of the excitation phase or to the end of Guedel's stage of analgesia, during which the sensitivity is decreased. Neither study of behavior nor objective measurements showed, during the first 10 to 20 seconds of exposure to the CO2, any sign of pain or suffering related to the Act for Prevention of Cruelty to Animals, and accordingly such suffering should not be ascribed to the CO2 stunning method.

Abattoirs↗
PubMed1989

[Performance testing of mules and Haflinger horses used as pack animals].

During 20 weeks blood constituents in peripheral blood (Erythrocyte count, Packed cell volume, Hemoglobin, Sedimentation rate, activities of Aspartate aminotransferase, Alanine aminotransferase, Creatine phosphokinase, Lactate dehydrogenase, Lactate dehydrogenase-1-isoenzyme, Glucose, Lactate, Total bilirubin), pulse and respiration rate were determined at rest and after exercise. Significant increase of blood values after exercise could be noted in relation to the intensity of exercise and the performance of the animals. The well trained horses had an increase of their performance according the tendency of the blood values, some horses had a high activity of enzymes as a result of muscle cell damage. Differences between Mules and Haflinger horses according their performances could be noted.

Animals↗
PubMed1988

Response-oriented therapy with CHOP and VIM-Bleo in high-grade malignant non-Hodgkin's lymphomas.

Twenty four patients with high grade malignant NHL (stage II 8, stage III 4, stage IV 12 patients respectively) were treated with a response-oriented regimen: Treatment was initiated according to the CHOP-protocol. Patients achieving at least a partial remission after 2 and a complete remission (CR) after 4 cycles were continued on CHOP to a total of 9 cycles. Patients not meeting these criteria were switched to a combination of Etoposide, Ifosfamide, Methotrexate, and Bleomycin (VIM-Bleo). With CHOP treatment, 16 patients (67%) achieved a CR. Of the remaining 8, 7 were treated with VIM-Bleo; 5 of these entered CR for a overall CR rate of 21/24 (88%). With a median follow up of 28 months 7 patients relapsed: 6 relapses occurred in patients with a rapid initial response and treated only with CHOP. We conclude, that there is a significant risk of relapse even in patients readily responding to CHOP and that consolidation therapy with a non cross-resistant regimen may improve results in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Dissociation of the natriuretic and antikaliuretic properties of triamterene derivatives by dose-response experiments.

Several derivatives of triamterene were synthesized with the aim of obtaining physicochemical properties superior to those of triamterene. Their effects on electrolyte excretion were tested with dose-response curves in rats: a dissociation of ED50 values of Na+ excretion from those of K+ retention was found; while the ED50 values of natriuresis were structure independent, the ED50 values for potassium retention depended highly on the charge of the side chain of triamterene derivatives. Acidic compounds displayed low and amines high K+-retaining potencies. Hence we postulate that there are at least two sites of action of the tested compounds in the kidney. (i) The first is the Na+ difference; this is the main driving force for K+ secretion. The affinity to the Na+ conductance is not correlated with the basic/acidic properties of the compounds. (ii) The second site is the finite K+ conductance of the luminal membrane of the distal tubule. The affinity of the drugs to this K+ conductance depends strongly on the charge of the molecule. Only pteridine derivatives with a basic side chain, i.e., with a high pKa value, block the membrane K+ conductance and are therefore potent potassium-retaining drugs.

Animals↗
PubMed1987

Improvement of myocardial function after global hypoxia by protection of the inner mitochondrial membrane.

In the present study the hypothesis is tested that hypoxia causes morphological damage to the inner mitochondrial membrane and that this damage can be reversed by modification of the reoxygenated perfusate. Using the working rat heart model, hearts in group I (n = 40) were subjected to a 30 min normothermic, normoxic phase and a 90 min hypoxic phase, followed by 60 min reoxygenation. Hearts in group II (n = 32) were also subjected to a 30 min normoxic and a 90 min hypoxic phase. However, after 30 min of reoxygenation 1.5 mmol/l 2-mercaptopropionylglycine (MPG) was injected in the reoxygenated solution in order to test its ability to improve mitochondrial function. Mitochondrial function was assessed by measuring oxygen uptake (ST3), ST4, respiratory control index (RCI), ADP/O and oxidative phosphorylation rate (OPR). In addition mechanical function (heart rate, aortic and coronary flow, cardiac output, stroke volume) was monitored along with ultrastructural parameters. 90 min of hypoxia caused a deterioration of all parameters with persistent impairment in hemodynamic, morphologic and biochemical functions after 60 min of reoxygenation (group I). The role of the ATP-synthetases in the pathogenesis of oxygen-paradox is discussed. In contrast, the MPG-enriched reoxygenated solution (group II) improved hemodynamics, ultrastructure and mitochondrial function significantly (alpha = 0.05). It is concluded from these data that the ATP-synthetases are damaged during oxygen-deficiency and that MPG may be a useful drug for protecting the inner mitochondrial membranes during reoxygenation.

Adenosine Diphosphate↗
PubMed1986

Pharmacodynamics of straight-chain and branched-chain acidic triamterene derivatives.

The diuretic, natriuretic and antikaliuretic properties of several straight-chain and branched-chain acidic triamterene derivatives were investigated in male Wistar rats. Among the straight-chain compounds the ether of hydroxytriamterene with five C atoms in the side chain (S3) revealed the maximum effects. The iso-compounds (derivatives of 4-carboxymethoxy triamterene S1) showed much better water solubility than the n-acids, but they increased the natriuresis only slightly and had no effect on kaliuresis when they were injected intravenously alone; whereas the isocompound Si4 showed potassium retaining properties when it was administered together with furosemide. From these results it can be suggested that the negative charge in the side chain has to be in a distinct distance from the pteridine ring to produce antikaliuretic effects.

Animals↗