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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 163 records · Page 9Linked to original sources

Seed coat-associated invertases of fava bean control both unloading and storage functions: cloning of cDNAs and cell type-specific expression.

We have studied the molecular physiology of photosynthate unloading and partitioning during seed development of fava bean (Vicia faba). During the prestorage phase, high levels of hexoses in the cotyledons and the apoplastic endospermal space are correlated with activity of cell wall-bound invertase in the seed coat. Three cDNAs were cloned. Sequence comparison revealed genes putatively encoding one soluble and two cell wall-bound isoforms of invertase. Expression was studied in different organs and tissues of developing seeds by RNA gel analysis, in situ hybridization, enzyme assay, and enzyme activity staining. One extracellular invertase gene is expressed during the prestorage phase in the thin-walled parenchyma of the seed coat, a region known to be the site of photoassimilate unloading. We propose a model for an invertase-mediated unloading process during early seed development and the regulation of cotyledonary sucrose metabolism. After unloading from the seed coat, sucrose is hydrolyzed by cell wall-bound invertases. Thus, invertase contributes to establish sink strength in young seeds. The resultant hexoses are loaded into the cotyledons and control carbohydrate partitioning via an influence on the sucrose synthase/sucrose-phosphate synthase pathway. The developmentally regulated degradation of the thin-walled parenchyma expressing the invertase apparently initiates the storage phase. This is characterized by a switch to a low sucrose/hexoses ratio. Feeding hexoses to storage-phase cotyledons in vitro increases the sucrose-phosphate synthase/sucrose synthase ratio and changes carbohydrate partitioning in favor of sucrose. Concomitantly, the transcript level of the major storage product legumin B is downregulated.

Base Sequence↗

[15 years experience with the Ti-6Al-7Nb alloy for joint prostheses].

The Ti-6Al-7Nb alpha-beta alloy, Protasul-100 was developed between 1978 and 1982, and proved to be highly biocompatible. In 1985 the TiAlNb material was approved for clinical use. Over the last ten years, more than 200 tons of semi-finished bar material has been processed, mainly for the production of cementless femoral stem systems and elastically deformable cup shells. For uncemented femoral components of knee prostheses made of TiAlNb, a special oxygen diffusion hardening process was developed that enables a surface hardness of up to 1200 HV and 600 HV at a depth of 20 microns, as compared with 350 HV in the case of the TiAlNb base material. This ODH-treated, polished surface is extremely scratch and wear resistant, and forms a good articulating surface with UHMW polyethylene. This surface-hardened TiAlNb, Tribosul, has been in clinical use in femoral knee components since 1990, and a multicentric clinical study involving femoral heads for hip prostheses has been ongoing since 1992. These different applications in hip and knee joint prostheses may suffice to demonstrate that the custom-made Ti-6Al-7Nb alpha-beta alloy is a real alternative to the well-known Ti-6Al-4V alloy, which has been used for decades as an implant material. Both national and international standards are available, and the alloy was already approved by the FDA in 1987.

Alloys↗

[Study of myocardial viability after recent infarction by echocardiography under dobutamine. Evidence of stunned myocardium].

After myocardial infarction treated by thrombolysis, secondary improvement of contractility may be observed due to the presence of viable but stunned myocardium in a zone of ischaemia. Echocardiography with lose dose Dobutamine has been proposed as a diagnostic test of myocardial viability. The inotropic effect of the pharmacological agent improves or induces myocardial thickening in zones of ischaemia. A positive response is observed in about one out of two cases. The sensitivity ranges from 79 to 86% and the specificity from 68 to 90% in the reported series. This mode of stress echocardiography for the study of post-infarction myocardial viability is under clinical evaluation: its advantages and limitations should be compared with those of other non-invasive methods, especially thallium myocardial scintigraphy.

Cardiotonic Agents↗

[The diagnostic value of angioscopy in venous thrombectomy].

Since 1983 angioscopy was applied as a control method in 187 venous thrombectomies to improve the treatment of acute iliofemoral thrombosis. In a retrospective study we tried to show the impact of angioscopy intraoperatively and the influence on long-term results. Thrombectomy was performed in 97 patients affected at three levels, in 50 cases with pelvic-femoral, in 35 with pelvic and in 43 with femoro-tibial thrombosis. The average clinical age of the thrombosis was 5 days, 66% of the patients (age 39 years) were female. The endoscopic findings were compared with phlebological results after one year using a phleboscore between 0 points (occlusion) and 5 points (normal). The phlebographies were analyzed so that the functional status of the vein was represented. After venous thrombectomy 42.8% of the cases were endoscopically classified complete but in 57.2% residual clots were observed. It was possible to completely (24.6%) or partly (18.7%) remove these clots by further thrombectomy maneuvers, non removable remnants were found in 7.5% and a venous spur in 6.4%. The statistical analysis with Kruskal-Wallace test showed significant differences in venous morphology between the endoscopically complete thrombectomies and those with residual clots. After a follow-up period of 30 months (12-64) the clinical results were very good. In 58% we observed normal findings, a cvi grade I in 35%, grade II in 4%. Crural ulcers had developed in only 3%. From our data we conclude that endoscopy is an excellent method for intraoperative quality-control in venous thrombectomy.

Adolescent↗

Identification of recognition elements on bacteriophage Q beta minus strand RNA that are essential for template activity with Q beta replicase.

In order to identify the structural elements important for the activity of the Q beta minus strand RNA as a template for Q beta replicase, a series of minus strand RNAs with internal or external deletions were prepared by in vitro transcription from suitable expression plasmids. The template activities of the deletion mutants were determined by single-round replication assays using purified replicase holoenzyme or core enzyme (lacking subunit alpha) in vitro. Two elements of RNA structure and/or sequence important for template activity were found. The first is a segment in the 5'-terminal region (map segment 4078 to 4132) containing a potential stem-loop structure, whose sequence was previously recognized to be highly conserved in the small variant MDV-1 RNA and suggested to be involved in its template recognition. The second element is defined by two partially complementary sequence segments in the 3'-terminal region (map positions 557 to 576 and 24 to 35), that appear to be engaged in long-range base-pairing and may form the stem of a large secondary structure domain, whose branches are not necessary for template recognition. The results obtained with replicase holoenzyme and core enzyme were identical within the accuracy of the method. They confirm the absence of any role of S1 protein in the interaction of replicase with minus strand RNA and further emphasize the profound difference in the interactions of replicase with the plus and minus strand.

Allolevivirus↗

The natural history of disc herniation and the influence of intervention.

The natural history of lumbar disc herniation must be considered when evaluating the influence and outcome of intervention. The combination of clinical signs and symptoms and corresponding radiologic findings permits a more certain diagnostic conclusion compared with many other obscure back disorders. The relationship between low back pain and a herniated disc is unclear. Mechanical compression and chemical changes may be the source of nerve root symptoms. Studies have shown that the natural course of acute radiculopathy has a good prognosis. Bed rest, information, and analgesics usually are sufficient therapeutic measures. Prolongation of symptoms requires radiologic examination. The decision regarding continued conservative therapy versus surgical intervention must be evaluated. Chemonucleolysis and percutaneous nucleotomy are being used, but the indications are uncertain.

Adult↗

Are there two DNA methyltransferase gene families in plant cells? A new potential methyltransferase gene isolated from an Arabidopsis thaliana genomic library.

Using the 1kb 3' terminal DNA fragment of the mouse methyltransferase cDNA as a probe and low stringent hybridisation conditions, a new potential methyltransferase (MTase) gene family was isolated from an Arabidopsis thaliana genomic DNA library. One clone (MTase-11), which gave the strongest signal at the Northern blot, was entirely sequenced (11483 bp) and further characterised. Under consideration of the likely open reading frames and our preliminary cDNA experiments we propose that the clone 11 gene encodes for an approximately 90 kD protein. As deduced form the DNA sequence this protein contains all conserved sequence motifs specific for the 5m cytosine MTases. MTase-11 gene expression was demonstrable in callus and during germination but not in one month old plants or in leaves.

Amino Acid Sequence↗

Lowered amounts of the tissue-specific transcription factor LFB1 (HNF1) correlate with decreased levels of glutathione S-transferase alpha messenger RNA in human renal cell carcinoma.

Human renal cell carcinoma is characterized by the loss of differentiation markers such as glutathione S-transferase alpha (GST-alpha). In this paper we show that the promoter of a GST-alpha gene contains a functional binding site for the cell-specific transcription factor LFB1 (HNF1). To investigate the potential role of LFB1 in the down-regulation of GST-alpha expression, we have compared the amount and the binding activity of the LFB1 protein between normal kidney and tumor tissue. By Western analysis and gel retardation assay using a monoclonal antibody specific for LFB1 we show that in 11 of 14 carcinomas the amount of LFB1 is clearly reduced compared to the corresponding normal tissue and that in all 14 renal carcinomas LFB1 binding activity is diminished. As in the same samples the abundance of GST-alpha mRNA is lower than in the normal tissue, we postulate that the loss of LFB1 binding activity might be responsible for the decreased expression of the GST-alpha gene in renal cell carcinoma.

Antibodies, Monoclonal↗

[Esters of naproxen as potential prodrugs for skin penetration. 1. Synthesis and physico-chemical properties].

Several esters of the nonsteroidal antiinflammatory drug Naproxen [2-(6-methoxy-2-naphthyl)propionic acid] were synthesized by standard procedures. Melting points and enthalpies of melting were obtained by differential scanning calorimetry. Solubilities in water were measured using HPLC. The partition coefficients (octanol/water) were calculated according to Rekker and Mannhold and Rm-values were determined by RP-TLC. The two latter parameters were correlated with high significance.

Chemical Phenomena↗

Severe complications following thrombolytic therapy of an acute thrombosis of a prosthetic mitral valve.

Thrombosis of prosthetic cardiac valves is a rare but potentially lethal complication. As emergency surgical intervention of thrombotic prosthetic cardiac valves is correlated with high mortality, fibrinolytic therapy has been recently recommended as a therapy with high efficacy and no severe side effects. We report on a patient with thrombosis of a prosthetic mitral valve who developed severe embolic complications following the administration of the thrombolytic agent. On admission the patient showed signs of incipient cardiogenic shock. The diagnosis of thrombotic obstruction of the prosthetic mitral valve was confirmed by transesophageal echocardiography. The effective valve area was 0.41 cm2. Pulmonary arterial blood pressure and wedge pressure were significantly elevated. A fibrinolytic therapy with recombinant tissue-type plasminogen activator according to the Neuhaus scheme was attempted. Within 60 min after start of treatment the effective valve area increased (1.41 cm2), and the pulmonary capillary wedge pressure decreased. However, peripheral and cerebral embolism occurred. Occlusion of the right brachial and right femoral artery was ascertained by Doppler ultrasound. Embolism into the right leg made an embolectomy with a Fogarty catheter necessary. Computed tomography revealed two lesions located in the occipital and left temporal area of the brain. Correlated with the lesions evaluated in computed tomography, right hemiplegia and complete aphasia was observed. The neurological status of the patient has only slightly improved to the present. To our knowledge no severe persistent neurological deficits following thrombolytic therapy have been reported. We therefore assume that the risk of severe neurological complications is underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Differential effects of non-target stimuli on the occurrence of express saccades in man.

The effect of competing non-target stimuli (distractors) presented together with a target for saccades was investigated with special emphasis on saccadic reaction time. Using the gap task (fixation point offset preceding target onset by 200 msec) high numbers of express saccades were obtained from four human subjects. A single non-target stimulus in the visual hemifield contralateral to the target reduced the number of express saccades. The extend of reduction increased with increasing stimulus size leading to a situation where express saccades were replaced entirely with saccades having a latency mode 30 msec later. Non-target stimuli occurring in the hemifield ipsilateral to the saccade target could also reduce the number of express saccades in favour of fast regular saccades. The effect of ipsilateral non-target stimuli depended mainly on their position in the visual field: ipsilateral non-target stimuli outside the dead zone for express saccades caused only a slight reduction of express saccades. Non-target stimuli invading the dead zone, however, suppressed express saccades almost completely, even though the saccade target appeared well outside the dead zone. The onset of a whole field of bars of one orientation (serving as distractors) simultaneously with the target (consisting of a single bar of another orientation = pop-out condition), suppressed express saccades completely. The same result, however, was obtained with only two distractor bars presented ipsilateral and contralateral within the dead zone for express saccades. Express saccades were present, however, when the whole field of distracting bars was continuously visible throughout the whole trial.

Attention↗

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

OBJECTIVE: To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DESIGN: Prospective, placebo-controlled, randomized, single-blind study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). INTERVENTIONS: Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. MEASUREMENTS AND MAIN RESULTS: The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. CONCLUSION: PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.

Alprostadil↗

Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin.

By means of a rat aortic smooth muscle (RASM) cell culture model, the effects of angiotensin II (AII) on early proto-oncogene gene expression, DNA synthesis, and cell proliferation were measured and compared to known mitogens. In 24-h [3H]-thymidine incorporation assays, AII was found to be a weak mitogen when compared to potent mitogens such as fetal bovine serum and platelet-derived growth factor (PDGF). In contrast, when assays were carried out for 48 h, AII induced a significant dose-dependent stimulation of DNA synthesis, which more than doubled at 3 nM AII, and was maximal (five- to eightfold above control) at 100 nM AII. Treatment of cells with the AII type 1 receptor antagonist losartan inhibited the mitogenic effects of AII. AII also stimulated smooth muscle cell proliferation, as indicated by an absolute increase in cell number after AII stimulation of RASM cells for 5 d. AII stimulation of RASM cell growth correlated with the increased expression of specific endogenous growth factors, including transforming growth factor beta 1 (TGF-beta 1) and PDGF A-chain. However, addition of either PDGF- or TGF-beta 1-neutralizing antibodies failed to significantly reduce the delayed mitogenic effects induced by AII. In contrast, we found that AII-stimulated mitogenesis could be inhibited in a dose-dependent manner by the growth factor inhibitor drug suramin. Taken together, our results indicate that enhanced endogenous growth factor expression may represent the direct mechanism by which AII promotes smooth muscle cell growth in some vascular hyperproliferative diseases.

3T3 Cells↗

Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for common signaling mechanisms.

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. All treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ETA and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ETA receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ETA receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44mapk and p42mapk was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.

Angiotensin II↗