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Biomedical subjects

A Weber

Publications and source records attributed to A Weber.

At least 271 records · Page 15Linked to original sources
PubMed1994

DNase I increases the rate constant of depolymerization at the pointed (-) end of actin filaments.

We show here that DNase is distinguished from other known actin-binding proteins by its unique ability to increase the depolymerization rate constant of actin at the pointed filament end, thereby speeding up depolymerization of filaments capped at their barbed ends. This action requires relatively high DNase concentrations, 3 orders of magnitude higher than those needed to block elongation, although 10 times lower than those needed for DNase binding to the side of the filament. We propose that a high DNase concentrations, steric interference between the two DNase molecules, bound to the ends of both strands of the two-start actin helix, destabilizes actin binding to the filament.

Actins↗
PubMed1994

spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.

The region specific homeotic gene spalt (sal) of Drosophila melanogaster promotes the specification of terminal pattern elements as opposed to segments in the trunk. Our results show that the previously reported sal transcription unit was misidentified. Based on P-element mediated germ line transformation and DNA sequence analysis of sal mutant alleles, we identified the transcription unit that carries sal function. sal is located close to the misidentified transcription unit, and it is expressed in similar temporal and spatial patterns during embryogenesis. The sal gene encodes a zinc finger protein of novel structure composed of three widely spaced 'double zinc finger' motifs of internally conserved sequences and a single zinc finger motif of different sequence. Antibodies produced against the sal protein show that sal is first expressed at the blastoderm stage and later in restricted areas of the embryonic nervous system as well as in the developing trachea. The antibodies detect sal homologous proteins in corresponding spatial and temporal patterns in the embryos of related insect species. Sequence analysis of the sal gene of Drosophila virilis, a species which is phylogenetically separated by approximately 60 million years, suggests that the sal function is conserved during evolution, consistent with its proposed role in head formation during arthropod evolution.

Amino Acid Sequence↗
PubMed1994

Nebulizer delivery of tobramycin to the lower respiratory tract.

We characterized a tobramycin aerosol generated by five nebulizers: Micron One, Pulmosonic, Pulmo-Aide, DeVilbiss Model 65, and UltraNeb 100 by particle size and drug concentration. The Micron One nebulizer did not produce a recoverable aerosol, while the Pulmosonic had a minimal output; therefore three machines were examined for their ability to deliver tobramycin to the lower respiratory tract of patients with cystic fibrosis (CF). The DeVilbiss 65 had the greatest output: with air as the carrier gas it produced an aerosol with > 60% of the particles having a mean mass aerodynamic diameter (MMAD) of > 5.5 microns. Using helox shifted the MMAD so that > 65% of the particles were < 5.5 microns. Increasing the power in the DeVilbiss 65 increased the output of particles > 9.2 microns, without a change in the particles < 3.3 microns. With air as the carrier gas the Pulmo-Aide and the UltraNeb 100 produced an aerosol with > 60% particles, < 3.3 microns MMAD. Using helox the UltraNeb 100 increased the amount of aerosol with a < 3.3 microns MMAD to 98%. Tobramycin delivery to the lower respiratory tract with the Pulmo-Aide and UltraNeb 100 was compared using air or helox by measuring sputum drug concentration. Pulmo-Aide failed to produce detectable tobramycin in sputum in 2 out of 9 patients with CF. With the UltraNeb 100, all patients had measurable sputum tobramycin immediately after administration (range, 16.2-3385 micrograms/g), but no statistically significant difference was found when using either compressed air, helox, or ambient air.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The 24 kDa outer envelope membrane protein from spinach chloroplasts: molecular cloning, in vivo expression and import pathway of a protein with unusual properties.

The 24 kDa outer envelope membrane protein of spinach chloroplasts (omp24) represents a major constituent of this membrane. Sequences of tryptic and endoprotease Glu-C peptides derived from omp24 allowed the design of oligonucleotides which were used to generate a DNA fragment by polymerase chain reaction using spinach cDNA as template. This fragment served as a probe to screen a cDNA library for a full-length clone of the omp24 coding sequence. The protein predicted from the complete sequence only has 148 amino acids and a molecular mass of 16294 Da. It is an acidic protein (calculated isoelectric point 4.8) with a high content of proline residues. Expression of the coding sequence in Escherichia coli and characterization of the purified recombinant protein produced revealed that the overestimation of its molecular mass by SDS-PAGE (ca. 25 kDa) is due to its abnormal amino acid composition. Despite its rather low hydrophobicity (polarity index 49%), omp24 appears to be deeply embedded in the outer membrane. Insertion of omp24 into the membrane proceeds almost independently of surface receptors or targeting sequence but, in contrast to other known outer envelope membrane proteins, is stimulated by ATP.

Amino Acid Sequence↗
PubMed1994

Detection and clinical relevance of a type I allergy with occupational exposure to hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride.

Hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA) belong to the group of the acid anhydrides and, among other applications, are used in the production of epoxy resins. These substances are known as potent low-molecular allergens and induce predominantly type I allergies according to Coombs and Gell. We examined 110 employees exposed to HHPA and MTHPA. With all of them a RAST was carried out with the commercially available conjugates of phthalic anhydride (PA) and a skin prick test with 1% and 5% acetonic solutions of PA. In 109 of these sera a radio allergo sorbent test (RAST) was carried out with the not commercially available conjugates of HHPA and of MTHPA. With complaints connected with the workplace the working materials used (HHPA, MTHPA) were also checked by means of the skin prick test. With at least one positive immunological finding (in the RAST and/or skin prick test) in connection with complaints at the workplace, we performed a workplace-related inhalation test under experimental conditions. Specific IgE against acid anhydrides was detected in a total of 17 (15.4%) persons. In the challenge test, six (5.4%) sensitisations were shown to be clinically relevant. On inclusion of borderline positive findings with PA conjugates the RAST produced three false negative and one false positive finding compared with a RAST with HHPA and MTHPA conjugates. With the conjugates of trimellitic anhydride, in no case could specific IgE be detected. The skin prick test led, in comparison with the RAST, to three false positive and three false negative findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Time course of systemic and renal plasma prostanoid concentrations and renal function in ovine hyperdynamic sepsis.

1. We continuously recorded systemic and renal haemodynamic changes, and arterial, renal venous and urinary concentrations of thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E2, and determined their relationship to renal function in an ovine model of progressive hyperdynamic sepsis. 2. Nine chronically instrumented unanaesthetized sheep were given a continuous intravenous infusion of Escherichia coli endotoxin (20 ng min-1 kg-1) for 3 days. 3. Within the first 12 h of infusion, endotoxin induced a major hypotensive septic syndrome, including a persistent 30% reduction in mean arterial pressure, a 50% decrease in systemic vascular resistance and a 50% increase in mean pulmonary artery pressure, associated with severe lactacidaemia. 4. Renal blood flow decreased by 40%, and creatinine clearance, urine flow, and fractional sodium excretion decreased by more than 75%, of baseline values. After 12 h of endotoxin infusion, cardiac output increased two-fold and renal blood flow recovered to baseline values, whereas creatinine clearance remained depressed. Four sheep died between 13 and 22 h of endotoxaemia; these animals (allocated to group 1) presented a significantly and persistently more reduced renal blood flow (-23%) and creatinine clearance (-77%) after 4 h than the remaining five sheep (allocated to group 2), which survived more than 36 h (-16% and -21%, respectively), whereas systemic and pulmonary haemodynamic and gas exchange data remained similar in both groups. 5. The more pronounced decreases in renal blood flow, creatinine clearance and urine flow in group 1 were associated with higher plasma renin activity and plasma 6-keto-prostaglandin F1 alpha concentrations and a lower fractional urinary excretion of 6-keto-prostaglandin F1 alpha than in group 2, whereas plasma thromboxane B2 concentrations were similarly increased in both groups. Plasma prostaglandin E2 concentrations and urinary excretion were not notably affected by endotoxin infusion in either group. 6. Our results are not in favour of a significant renal production of any of these three prostanoids during endotoxaemia. In both groups, values of creatinine clearance were linearly correlated with simultaneous mean arterial pressure values after starting endotoxin infusion (group 1: creatinine clearance = 1.99 x mean arterial pressure--105, r = 0.95; group 2: creatinine clearance = 2.06 x mean arterial pressure--104, r = 0.80).(ABSTRACT TRUNCATED AT 400 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Morphological and clinical aspects of heterotopic ossification in sports. A case study.

Heterotopic ossification (HO) caused through sport injuries is a rare, clearly defined lesion. In a considerable number of cases, however, no adequate trauma can be remembered or otherwise established in the "sporting history". Differential diagnosis of this non-traumatic HO variant often presents many problems which may lead to the wrong diagnosis of sarcoma. We looked at 28 cases, in which in more than 50% a sarcoma was discussed as primary diagnosis. These difficulties arise mainly in cases where clinical features suggest a tumor, radiological changes are unspecific, and the diagnosis is based on a small biopsy sample. We demonstrate and discuss the problems involved in differential diagnosis using the history of a matchgrade sportsman as a sample. Unlike in sarcoma, patients with HO usually suffer severe pain, and well over 50% of all patients develop the disease during the 2nd or 3rd decade. Over 90% of all patients with soft tissue sarcoma, however, are over the age of 30. From the morphological point of view, the different histological pattern of HO has to be taken into account, since early stages may mimick a sarcomatous lesion. If the clinical findings suggest the presence of HO, surgical intervention including the taking of biopsy sample should be postponed, so that instead of early highly mitotic active phases more mature bone structures, which are easier to classify, will be available for evaluation. Only a profound knowledge of the different phases of HO, together with clinical and radiological features, will clarify the differential diagnostic problems of the non-traumatic variant of this lesion in sportsmen.

Adult↗
PubMed1994

Tropomodulin caps the pointed ends of actin filaments.

Many proteins have been shown to cap the fast growing (barbed) ends of actin filaments, but none have been shown to block elongation and depolymerization at the slow growing (pointed) filament ends. Tropomodulin is a tropomyosin-binding protein originally isolated from red blood cells that has been localized by immunofluorescence staining to a site at or near the pointed ends of skeletal muscle thin filaments (Fowler, V. M., M. A., Sussman, P. G. Miller, B. E. Flucher, and M. P. Daniels. 1993. J. Cell Biol. 120: 411-420). Our experiments demonstrate that tropomodulin in conjunction with tropomyosin is a pointed end capping protein: it completely blocks both elongation and depolymerization at the pointed ends of tropomyosin-containing actin filaments in concentrations stoichiometric to the concentration of filament ends (Kd < or = 1 nM). In the absence of tropomyosin, tropomodulin acts as a "leaky" cap, partially inhibiting elongation and depolymerization at the pointed filament ends (Kd for inhibition of elongation = 0.1-0.4 microM). Thus, tropomodulin can bind directly to actin at the pointed filament end. Tropomodulin also doubles the critical concentration at the pointed ends of pure actin filaments without affecting either the rate of extent of polymerization at the barbed filament ends, indicating that tropomodulin does not sequester actin monomers. Our experiments provide direct biochemical evidence that tropomodulin binds to both the terminal tropomyosin and actin molecules at the pointed filament end, and is the long sought-after pointed end capping protein. We propose that tropomodulin plays a role in maintaining the narrow length distributions of the stable, tropomyosin-containing actin filaments in striated muscle and in red blood cells.

Actin Cytoskeleton↗
PubMed1994

The isolated perfused kidney of the pig: new model to evaluate shock wave-induced lesions.

Little is known about the mechanisms and determining factors of shock wave-induced kidney trauma. After classification of the renal lesion in a canine model, we attempted to establish an ex vivo model using the isolated kidney of the pig perfused by Tyrode's solution under physiologic conditions. After shock wave application on the Modulith SL 20, vessel lesions were evaluated by microangiography to determine the size and frequency of dye extravasation in the different areas of the organ. Variation of the focus localization caused different patterns of lesions that characterized the pathway of the shock wave. In particular, constant petechial extravasation in the cortex was observed. The generator voltage correlated with the diameter and the frequency of the lesion area. The number of shock waves primarily affected the incidence of vessel rupture in the regions adjacent to the focal zone. Light microscopy revealed dose-dependent necrosis of tubular cells up to gap-like parenchymal defects. Even after application of the minimal shock wave doses, electron microscopy demonstrated vacuolization of tubular cells in the shock wave focus. Traumatic junctions between capillaries and the tubulur system can explain clinically observed macrohematuria without renal hematomas. With this model, it was possible to evaluate localization and dose dependence of shock wave-induced kidney trauma with high sensitivity and reproducibility. Further advantages of the model were easy availability and the fact that studies on living animals were not necessary. Therefore, standardization and comparison of different lithotripters becomes possible.

Angiography↗
PubMed1994

Mutations of the ACTH receptor gene are only one cause of familial glucocorticoid deficiency.

Familial glucocorticoid deficiency (FGD) is an autosomal recessive syndrome of failure of adrenal cortisol responsiveness to adrenocorticotropin (ACTH). Defects in the ACTH receptor have been suggested as a possible cause, and we have previously reported a point mutation in this gene in a family with FGD. Investigation of seven additional families has revealed a number of novel mutations in the ACTH receptor in some, but a normal gene in others suggesting that the aetiology of FGD may be heterogeneous. Using a highly polymorphic CA repeat marker (D18S40) closely linked to the ACTH receptor locus, we are now able to confirm that some cases of FGD result from defects at another locus. FGD provides an example of a single relatively homogeneous clinical syndrome resulting from two different molecular aetiologies.

Adrenal Insufficiency↗
PubMed1994

Young hospital doctors after night duty: their task-specific cognitive status and emotional condition.

Sleep deprivation is an unpleasant burden of young hospital doctors during their medical training. It may disrupt the balance between coping strategies available to them and the professional demands encountered. Impaired medical care offered by sleep-deprived juniors may be a consequence. Valid research work on this subject is rare and surprisingly contradictory. Therefore, we evaluated the task-specific cognitive status and emotional condition of 40 young hospital doctors (27 men and 13 women, 29.9 +/- 2.9 years of age) at the University of Tuebingen, all of whom were in the beginning of their academic career. Subjects were tested twice acting as their own control, once at 8.00 am after a night off duty (OD) (at least 6 hours of uninterrupted sleep), and once at a similar time after a night on call (OC) being in the hospital for 24 hours. Standardized and reliable psychometric tests thought to represent daily routine medical function were performed. On-call activities were recorded by means of a sleep diary, whereas a questionnaire interrogated aspects of private and professional life. Neuropsychological function deteriorated significantly: number connection test (per cent of norms +/- SD, 103.2 +/- 9.8 OC vs 107.8 +/- 10.5 OD, F = 27.7, P < 0.001), things-to-do list (correct items +/- SD, 6.7 +/- 1.2 OC vs 7.4 +/- 1.5 OD, F = 12.7, P < 0.01), Vienna reaction timer (per cent of norms +/- SD, 95.6 +/- 9.0 OC vs 97.7 +/- 10.4 OD, F = 4.8, P < 0.05), Stroop test (T-values +/- SD, 59.7 +/- 6.3 OC vs 64.6 +/- 7.1 OD, F = 37.1, P < 0.001), ECG test (correct responses +/- SD, 38.3 +/- 7.3 OC vs 43.4 +/- 6.5 OD, F = 45.2, P < 0.001) and status of mood (T-value +/- SD, 60.3 +/- 9.0 OC vs 54.0 +/- 6.6 OD, F = 19.6, P < 0.001). Cognitive function and mood status of young hospital doctors after a night on call decrease considerably. In view of the special vulnerability of medical trainees to occupational stress all efforts are warranted to reduce sleep deprivation in the medical profession.

Adaptation, Psychological↗
PubMed1994

A rapid method for measuring organelle-specific substrate transport in homogenates from plant tissues.

A rapid method is described for measuring organelle-specific metabolite transport systems in crude homogenates from plants. The tissues were homogenized in liquid nitrogen, extracted with buffer and reconstituted into artificial membranes. The method allowed demonstration of the known different substrate specificities of chloroplast triose phosphate/phosphate translocators from C3- and C4-plants, of the triose phosphate/phosphate translocator from non-green tissue, and of the dicarboxylate translocator. It thus by-passes the necessity to isolate intact plant organelles and, in addition, only a low amount of tissue material is required for transport measurements.

Biological Transport↗
PubMed1994

[The detection of salmonellas using Rambach agar].

Selective enrichment in Rappaport-Vassiliadis medium of 1595 animal fed samples and of 82 feedstuff and carcass meal was streaked simultaneously onto water-blue-metachrome-yellow-lactose-agar acc. to Gassner, onto brilliant-green-phenol-red-lactose-agar acc. to Kauffmann and onto Rambach agar. Salmonellae were isolated in 34 cases with Rambach agar (sensitivity 94.4%), in 33 cases with water-blue-metachrome-yellow-lactose-agar acc. to Gassner (sensitivity 91.7%) and in 31 cases with brilliant-green-phenol-red-lactose-agar acc. to Kauffmann (sensitivity 86.1%). The high specificity (99.87%) recommends the use of Rambach agar for isolation of Salmonellae from selective enrichment.

Animal Feed↗