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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Induction of early endotoxin tolerance with atoxic endotoxin--a new method for preventing sepsis syndrome].

The induction of early-phase endotoxin tolerance in a procine endotoxin shock model by atoxic LPS from Rhodobacter sphaeroides led to a significant extension of the survival time (p < 0.0179). The protective effect of the non-specific tolerant state also led to an enhancement of cardiorespiratory parameters during the continuous endotoxin challenge. Non-specific stimulation of host defense mechanisms with atoxic endotoxin as prophylactic agent in surgical patients at risk may prove to be beneficial in the future.

Animals↗
PubMed1997

Altered 3'-terminal RNA structure in phage Qbeta adapted to host factor-less Escherichia coli.

The RNA phage Qbeta requires for the replication of its genome an RNA binding protein called Qbeta host factor or Hfq protein. Our previous results suggested that this protein mediates the access of replicase to the 3'-end of the Qbeta plus strand RNA. Here we report the results of an evolutionary experiment in which phage Qbeta was adapted to an Escherichia coli Q13 host strain with an inactivated host factor (hfq) gene. This strain initially produced phage at a titer approximately 10,000-fold lower than the wild-type strain and with minute plaque morphology, but after 12 growth cycles, phage titer and plaque size had evolved to levels near those of the wild-type host. RNAs isolated from adapted Qbeta mutants were efficient templates for replicase without host factor in vitro. Electron microscopy showed that mutant RNAs, in contrast to wild-type RNA, efficiently interacted with replicase at the 3'-end in the absence of host factor. The same set of four mutations in the 3'-terminal third of the genome was found in several independently evolved phage clones. One mutation disrupts the base pairing of the 3'-terminal CCCOH sequence, suggesting that the host factor stimulates activity of the wild-type RNA template by melting out its 3'-end.

Base Sequence↗
PubMed1997

Dinor-oxo-phytodienoic acid: a new hexadecanoid signal in the jasmonate family.

Jasmonic acid and its precursors are potent regulatory molecules in plants. We devised a method for the simultaneous extraction of these compounds from plant leaves to quantitate changes in the levels of jasmonate family members during health and on wounding. During our study, we identified a novel 16-carbon cyclopentenoic acid in leaf extracts from Arabidopsis and potato. The new compound, a member of the jasmonate family of signals, was named dinor-oxo-phytodienoic acid. Dinor-oxo-phytodienoic acid was not detected in the Arabidopsis mutant fad5, which is incapable of synthesizing 7Z,10Z, 13Z-hexadecatrienoic acid (16:3), suggesting that the metabolite is derived directly from plastid 16:3 rather than by beta-oxidation of the 18-carbon 12-oxo-phytodienoic acid. Simultaneous quantitation of jasmonate family members in healthy leaves of Arabidopsis and potato suggest that different plant species have different relative levels of jasmonic acid, oxo-phytodienoic acid, and dinor-oxo-phytodienoic acid. We term these profiles "oxylipin signatures." Dinor-oxo-phytodienoic acid levels increased dramatically in Arabidopsis and potato leaves on wounding, suggesting roles in wound signaling. Treatment of Arabidopsis with micromolar levels of dinor-oxo-phytodienoic acid increased the ability of leaf extracts to transform linoleic acid into the alpha-ketol 13-hydroxy-12-oxo-9(Z) octadecenoic acid indicating that the compound can regulate part of its own biosynthetic pathway. Tightly regulated changes in the relative levels of biologically active jasmonates may permit sensitive control over metabolic, developmental, and defensive processes in plants.

Arabidopsis↗
PubMed1997

Effect of exercise on sick leave due to low back pain. A randomized, comparative, long-term study.

STUDY DESIGN: The study was carried out as an open, randomized, multicenter, parallel-group study with an observation period of 12 months. Four norwegian physiotherapy institutes took part. Patients were subsequently followed for 12 months of home exercise on their own, without for 12 months of home exercise on their own, without the supervision of a physiotherapist. OBJECTIVES: 1) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1-year training program under the supervision of a physiotherapist. 2) To investigate the effect supervision by, and motivation from, physiotherapists has on training compliance and efficacy. SUMMARY OF BACKGROUND DATA: After ordinary physiotherapy treatment for low back problems, patients were randomly allocated either to a conventional training program designed by physiotherapists or to a training program using a new Norwegian-developed training apparatus called the TerapiMaster. The study included 153 patients with low back problems, all of whom had been referred to physiotherapy by their general practitioners. One hundred twenty-six patients were followed for an additional 12 months when performing home exercise programs on their own. METHODS: Monitoring patient satisfaction with the training program, compliance with the program, and absenteeism from work during the training period. RESULTS: Patient satisfaction with both training programs was high, with about 83% of participating patients completing the study in accordance with the protocol. Mean absenteeism (SD) during the preceding year totaled 82.5 days (19.8) in the conventional training group and 61.6 days (14.7) in the TerapiMaster group. Significant reductions to 17.2 days (6.0) and 16.4 days (5.3) in the two groups, respectively, were recorded during the training period, corresponding to a 75% to 80% reduction compared with the preceding 1-year period. Mean absenteeism showed a further significant decline during the 12-month period without supervised training. The average values were 9.9 days (3.2) for conventional training and 9.3 days (3.1) for the TerapiMaster, respectively. CONCLUSIONS: Both exercise programs reduced absenteeism significantly (75-80%). No difference in the effects of the two different programs was discernible. Regular follow-up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems. This thesis was corroborated by the 12-month study of unsupervised exercise.

Adult↗
PubMed1997

Recognition of bacteriophage Qbeta plus strand RNA as a template by Qbeta replicase: role of RNA interactions mediated by ribosomal proteins S1 and host factor.

RNA-protein interactions between bacteriophage Qbeta plus strand RNA and the components of the Qbeta replicase system were studied by deletion analysis. Internal, 5'-terminal and 3'-terminal deletions were assayed for template activity with replicase in vitro. Of the two internal binding sites previously described for replicase, we found that the S-site (map position 1247 to 1346) could be deleted without any significant effect on template activity, whereas deletion of the M-site (map position 2545 to 2867) resulted in a strong inactivation and a high salt sensitivity of the residual activity. Binding complexes of the deletion mutant RNAs with the different proteins involved in Qbeta RNA replication were analysed by electron microscopy. The formation of looped complex structures, previously reported and explained as simultaneous interactions with replicase at the S and the M-site, was abolished by deleting the S-site but, surprisingly, not by deleting the M-site. The same types of complexes observed with replicase were also formed with purified protein S1 (the alpha subunit of replicase), suggesting that these internal interactions with Qbeta RNA are mediated by the S1 protein. The Qbeta host factor, a protein required for the template activity of the Qbeta plus strand, was reported earlier to form similar complexes by binding to the S and M-sites (or adjacent sites) and in addition to the 3'-end, resulting in double-looped structures. The patterns of looped complexes observed with the deletion mutant RNAs suggest that the binding of host factor might not involve the S and M-sites themselves but adjacent downstream sites. An additional internal host factor interaction near map position 2300 was detected with several mutant RNAs. Qbeta RNA molecules with 3'-truncations formed 3'-terminal loops with similar efficiency as wild-type RNA, indicating that recognition of the 3'-end by host factor is not dependent on a specific 3'-terminal base sequence.

Allolevivirus↗
PubMed1997

Nitric oxide mediates intracytoplasmic and intranuclear zinc release.

We previously described that NO. leads to destruction of ZnS clusters and release of Zn2+ from various proteins including zinc finger transcription factors. To assess the relevance in living cells, we investigated, whether exogenous NO. leads to an increase of cytoplasmic and nuclear free Zn2+. L929 cells, mouse splenocytes, or rat aorta endothelial cells were labeled with Zinquin-E, a Zn2+-specific fluorophore, and were treated with two different spontaneous NO donors, S-nitrosocysteine or DETA/NO. Both NO donors strongly increased the Zn2+-dependent fluorescence in the cellular cytosol and also in nuclei as compared to controls. NO-dependent Zn2+ release in splenocytes was quantitated by flow cytometry. These results show for the first time, that nitrosative stress mediates intracellular and intranuclear Zn2+ release which may be relevant in altering gene expression patterns.

Animals↗
PubMed1997

Comparison of arbutamine and exercise echocardiography in diagnosing myocardial ischemia.

Arbutamine is a new catecholamine designed for use as a pharmacologic stress agent. This study compared the sensitivity of arbutamine with symptom-limited exercise to induce echocardiographic signs of ischemia. Arbutamine was administered by a computerized closed-loop delivery system that controls the infusion rate of arbutamine toward a predefined rate of heart rate increase and maximum heart rate limit. Beta blockers were stopped > or = 48 hours before both tests. Stress was stopped for intolerable symptoms, or clinical, electrocardiographic or echocardiographic signs of ischemia (new or worsening wall motion abnormality), target heart rate (> or = 85% age predicted maximum heart rate), or plateau of heart rate response. Thirty-seven patients were entered into the study (35 arbutamine and exercise, 1 arbutamine only, 1 exercise only), of which 30 had angiographic evidence of coronary artery disease (> or = 50% lumen diameter narrowing). Rate-pressure product increased significantly in response to both stress modalities (p < 0.001) and was significantly greater with exercise (11,308 +/- 2,443) than with arbutamine (9,486 +/- 2,479, p < 0.001). The time to maximum heart rate was longer during arbutamine stress echocardiography than during exercise testing (17.3 +/- 9.4 versus 9.3 +/- 4.2 minutes, respectively, p < 0.001). There were more patients with interpretable echo data for arbutamine (82%) than for exercise (67%). Sensitivity for recognition of myocardial ischemia was 94% (95% confidence interval 70% to 100%) and 88% (95% confidence interval 62% to 98%), respectively. The most frequent adverse events during arbutamine (n = 36) were dyspnea (5.6%) and tremor (5.6%). Two arbutamine stress tests were discontinued due to arrhythmias: 1 patient had premature atrial and ventricular beats, and the other had premature atrial contractions and atrial fibrillation. Arrhythmias were well tolerated and resolved without sequelae. In conclusion, the sensitivity of arbutamine to induce echocardiographic signs of ischemia was similar to that of exercise despite a lower rate-pressure product. Arbutamine was well tolerated and provides a reliable alternative to exercise echocardiography.

Adult↗
PubMed1997

Strongly reduced phage Qbeta replication, but normal phage MS2 replication in an Escherichia coli K12 mutant with inactivated Qbeta host factor (hfq) gene.

RNA phage production was observed in Escherichia coli hfq mutant strains transformed with plasmids containing genomic cDNA of phages Qbeta or MS2. Qbeta production was reduced 5000-fold in an insertional mutant containing an omega cassette in the middle of hfq, but was unaffected in a mutant with the cassette near the end of hfq. The insertions had no effect on MS2 replication.

Carrier Proteins↗
PubMed1997

Vasospasm in smooth coronary arteries as a cause of asystole and syncope.

In a patient with proven myocardial infarction, coronary artery disease was excluded angiographically. Four weeks later the patient experienced recurrent syncope of unknown cause. By means of Holter monitoring, ST-segment elevation with subsequent first-degree AV block progressing to asystole and resulting in loss of consciousness were documented. Treatment with gallopamil and a VVI-pacemaker led to complete relief of all symptoms. Hence, Prinzmetal's angina may be a rare cause of syncope even in smooth coronary arteries.

Angina Pectoris, Variant↗
PubMed1997

Effects of stimulus conditions on the performance of antisaccades in man.

We investigated the effect of different spatial and temporal parameters on the saccadic reaction times (SRTs) of the antisaccades and on the frequency and the SRTs of erratic prosaccades in five adult human subjects. The subjects were instructed to aim their saccades to the side opposite to where a visual go-stimulus occurred. Parameters under consideration were: the gap duration (between 0 and 600 ms, and an overlap paradigm); the stimulus size (sizes of 0.1 degrees, 0.2 degrees, and 0.4 degrees, using the gap 200-ms paradigm); and the stimulus eccentricity (1 degree, 2 degrees, 4 degrees, 8 degrees, and 12 degrees, with the gap 200-ms paradigm). A decrease in the anti SRTs and an increase in the error rate were observed with medium gap durations (200 ms, 250 ms), while the anti-SRTs were longer and the error rates lower with the shorter values (0 ms, 100 ms, and with the overlap paradigm) and with the long values (600 ms). A slight decrease in the anti-SRTs and an increase in the error frequency occurred with increasing eccentricity; the SRT distributions of the errors resembled closely those of prosaccades in corresponding prosaccade tasks with the same eccentricities. The stimulus size had only modest or no effects at all. Analysis of the distributions of the correction times of the erratic prosaccades showed that the intersaccadic intervals could be very short: in the range of express saccades, with a peak at 100 ms or in some subjects even shorter, with a peak at 40-50 ms. It is concluded that the performance of antisaccades is influenced by parameters that interact with the fixation and/or attention system of oculomotor control. Parameters supporting a disengagement of fixation at the time of stimulus onset provoke a reduction of the saccadic reaction times not only of prosaccades but also of antisaccades. Moreover, a certain state of disengagement seems to facilitate the occurrence of reflex-like errors.

Adult↗
PubMed1997

Patterning the expression of a tissue-specific transcription factor in embryogenesis: HNF1 alpha gene activation during Xenopus development.

Tissue-specific transcription factors play an essential role in establishing cell identity during development. We review our knowledge of the molecular events involved in the activation of the gene encoding the tissue-specific transcription factor HNF1 alpha (LFB1). The available data suggest that the maternal factors OZ-1, HNF4 alpha and HNF4 beta act as initial activators of the HNF1 alpha promoter. We present evidence suggesting that the mesoderm-inducing factor activin A plays a critical role by acting through the HNF4 binding site of the HNF1 alpha promoter. The activity of this embryonic morphogen seems to form a gradient opposing the distribution of the maternal HNF4 proteins that are concentrated at the animal pole of the egg. After zygotic gene transcription the HNF1 alpha-related transcription factor HNF1 beta accumulates faster than HNF1 alpha itself and thus is likely to contribute to the activation of the HNF1 alpha transcription via the HNF1 binding site. The cofactor of the HNF1 proteins (DCoH) is present throughout development and thus cannot limit the activation potential of HNF1 alpha in early development. Our results provide a detailed description of setting up the expression pattern of a tissue-specific transcription factor during embryogenesis.

Activins↗
PubMed1997

Prevalence of hepatitis G virus and its strain variant, the GB agent, in blood donations and their transmission to recipients.

BACKGROUND: Hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) are independent isolates of a recently identified non-A through -E hepatitis virus. Prevalence in United States volunteer blood donors is 1.5 to 1.9 percent, but no data on European blood donors are available. Epidemiologic data suggest a preferred parenteral transmission route. The prevalence of HGV/GBV-C in European blood donors and the efficiency of transmission to transfusion recipients were investigated. STUDY DESIGN AND METHODS: Plasma samples from unpaid volunteer German blood donors were tested for HGV/GBV-C by in-house reverse transcription-polymerase chain reaction. Positive donors were independently retested and interviewed for parenteral transmission risks. Amplification products were sequenced and subjected to phylogenetic analysis. Recipients of reverse transcription-polymerase chain reaction-positive donations were traced and tested for HGV/GBV-C infection. RESULTS: A total of 14 (1.34%) of 1048 donors (alanine aminotransferase < 45 IU/L) were repeatedly positive for HGV/GBV-C with 9 (2.18%) of 413 urban and 5 (0.78%) of 635 rural donors (chi 2-test; p = 0.04). Isolates differed in nucleotide sequence homology over a range of 12.5 to 19.6 percent. All but one positive donor reported parenteral transmission risks. Transmission of HGV/GBV-C was detected in 4 of 9 transfusion recipients. The prevalence of HGV/GBV-C in donors with an alanine aminotransferase level > 45 IU per L was 3 percent (3/100). Two mother/child pairs were identified with highly homologous isolates. CONCLUSION: A significantly greater prevalence of HGV/GBV-C was detected in urban volunteer blood donors than in rural donors. The high prevalence in urban donors (2.18%) suggests specific transmission risks for this group. The less than 50-percent efficiency of HGV/GBV-C transmission via blood components may indicate the presence of defective viruses with reduced infectivity. There is evidence for vertical transmission.

Adult↗
PubMed1997

An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection.

The gene for the most common and severe form of autosomal dominant polycystic kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to result in an integral membrane protein of 4302 amino acids. The major challenge faced by researchers attempting to complete mutation analysis of the PKD1 gene has been the presence of several homologous loci also located on chromosome 16. Because the sequence of PKD1 and its homologs is nearly identical in the 5' region of the gene, most traditional approaches to mutation analysis cannot distinguish sequence variants occurring uniquely in PKD1. Therefore, only a small number of mutations have been identified to date and these have all been found in the 3', unique portion of the gene. In order to begin analysis of the duplicated region of PKD1, we have devised a novel strategy that depends on long-range PCR and a single gene-specific primer from the unique region of the gene to amplify a PKD1-specific template that spans exons 23-34. This 10 kb template, amplified from genomic DNA, can be employed for mutation analysis using a wide variety of sequence-based approaches. We have used our long-range PCR strategy to begin screening for sequence variants with heteroduplex analysis, and several affected individuals were discovered to have clusters of base pair substitutions in exons 23 and 25. In two patients, these changes, identified in exon 23, would be predicted to result in multiple amino acid substitutions in a short stretch of the protein. This clustering of base pair substitutions is unusual and suggests that mutation may result from unique structural features of the PKD1 gene.

Amino Acid Sequence↗
PubMed1997

Similar morphological and intracellular biochemical changes in alcoholic acute pancreatitis and ischemic acute pancreatitis in rats.

Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the typical features of acute pancreatitis, therefore the role of an additional challenge, such as either ethanol intoxication or short-term ischemia, was studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of cholecystokinin and secretin each). Ischemic pancreatitis was performed by obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the supplying arteries for 40 min. The macro- and microscopic alterations were evaluated and graded by a scoring system. Additionally, the pancreas was removed in 50% of the animals and the pancreatic acini were prepared. From those acini the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase, glucuronidase, and acidic phosphatases were determined. While obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce acute pancreatitis, a combination of obstruction/hyperstimulation with either ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats, respectively. Similarly, both models were characterized by extrapancreatic fat necrosis and acinar necrosis at the periphery of the lobules. Almost all intracellular enzymes were elevated in both pancreatitis models compared to sham-operated controls. Both alcohol and ischemia were insults that sensitize the pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since the observed morphologic and enzymatic alterations in both models are very similar, alcohol and ischemia might have some common pathways by which they make the pancreas vulnerable to enzymatic attacks.

Acute Disease↗
PubMed1997

Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions.

Dibutyltin dichloride (DBTC; 6 mg/kg body weight, i.v.) induced acute interstitial pancreatitis in rats. The course of the pancreatitis was examined within 28 days by light and electron microscopy as well as by pathobiochemistry (amylase, lipase, alkaline phosphatase, and bilirubin in serum; tin concentration in biliopancreatic juice, tissue, and concretions). The pathogenesis of the DBTC-induced pancreatitis in rats was studied by different experimental designs (in intact animals, after bile duct ligation, after surgical bypass of the bile duct). DBTC caused toxic necrosis of the biliopancreatic duct epithelium, which is then shed into the duct and forms obstructing plugs in the distal common bile duct. Interstitial pancreatitis occurred during the first 4 days, accompanied by significantly increased activities of serum alpha-amylase and lipase. After 7 days extensive infiltration of the pancreatic interstitium with mononuclear cells was observed. Twenty-eight days after administration of DBTC one-third of the rats showed periductal and interstitial fibrosis as well as an active inflammatory process in the pancreas. The findings suggest a twofold pathogenesis of the DBTC-induced pancreatitis: first, the cytotoxic effects on the biliopancreatic duct epithelium lead to epithelial necrosis with obstruction of the duct, subsequent cholestasis, and interstitial pancreatitis; and second, the hematogenic DBTC effects cause direct injury of pancreatic cells (mitochondrial damage, autophagy, cell necrosis) followed by interstitial edema and inflammation. Both processes lead to this special type of DBTC-induced acute pancreatitis with a tendency to a chronic course, when the obstruction of the duct and cholestasis persist.

Acute Disease↗
PubMed1997

A role for sugar transporters during seed development: molecular characterization of a hexose and a sucrose carrier in fava bean seeds.

To analyze sugar transport processes during seed development of fava bean, we cloned cDNAs encoding one sucrose and one hexose transporter, designated VfSUT1 and VfSTP1, respectively. sugar uptake activity was confirmed after heterologous expression in yeast. Gene expression was studied in relation to seed development. Transcripts were detected in both vegetative and seed tissues. In the embryo, VfSUT1 and VfSTP1 mRNAs were detected only in epidermal cells, but in a different temporal and spatial pattern. VfSTP1 mRNA accumulates during the midcotyledon stage in epidermal cells covering the mitotically active parenchyma, whereas the VfSUT1 transcript was specific to outer epidermal cells showing transfer cell morphology and covering the storage parenchyma. Transfer cells developed at the contact area of the cotyledonary epidermis and the seed coat, starting first at the early cotyledon stage and subsequently spreading to the abaxial region at the late cotyledon stage. Feeding high concentrations of sugars suppressed both VfSUT1 expression and transfer cell differentiation in vitro, suggesting a control by carbohydrate availability.

Carbohydrate Metabolism↗
PubMed1997

Caerulein pancreatitis increases mRNA but reduces protein levels of rat pancreatic heat shock proteins.

We have recently reported that preconditioning through hyperthermia induces expression of pancreatic heat shock proteins (HSPs) and protects against caerulein pancreatitis. Here, we investigate caerulein-mediated effects on pancreatic HSPs without prior hyperthermia. Caerulein time and dose dependently increased pancreatic mRNA levels of the constitutive isoform of HSP70 (HSC70). However, pancreatic HSC70 protein levels were decreased, as were HSP60 protein levels. Also, in contrast to hyperthermia preconditioning, caerulein did not induce measurable levels of mRNA or protein of the inducible isoform of HSP70. Thus the pancreas reacts to different kinds of stress (hyperthermia vs. hyperstimulation) with differential induction of HSP mRNAs. Clearly, hyperthermia leads to induction of HSP protein expression, whereas caerulein treatment does not. Therefore, our current study further supports the idea that hyperthermia-induced protection against caerulein pancreatitis may be mediated through increased protein levels of pancreatic HSPs. It is further tempting to hypothesize that failure to appropriately increase HSP protein levels in response to high doses of caerulein might be a factor in the development of pancreatitis.

Acute Disease↗