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Biomedical subjects

A Wolff

Publications and source records attributed to A Wolff.

At least 19 recordsLinked to original sources

Diagnosis of a cardiac angiosarcoma by fluorine-18 fluordeoxyglucose positron emission tomography.

Cardiac angiosarcoma is a rare tumour entity with a poor prognosis. Early detection is difficult but important for the further course of the disease. We report on a young patient with a tumour of unknown origin and dignity of the right atrium. Magnetic resonance imaging, CT and echocardiography were sufficient in localisation, but no statement on the dignity was possible. Furthermore, staging led to ambiguous results. Malignancy could be proved by fluorine-18 fluordeoxyglucose positron emission tomography, leading to early surgery. Histology revealed a poorly differentiated angiosarcoma.

Adolescent↗

Evidence that wild-type p53 in neuroblastoma cells is in a conformation refractory to integration into the transcriptional complex.

Neuroblastoma (NB) cells reportedly accumulate wild-type p53 exclusively in the cytoplasm. However, immunofluorescence assays with five different antibodies showed that p53 accumulates in the nucleus of up to 10% of NB cells. PAb1801 detected cytoplasmic 'punctate structures' which were also found in p53-null cells, rendering this antibody unsuitable for p53 detection. A comparison of DO-1 and PAb1801 staining in NB tissue sections confirmed the results obtained with NB cells. Nuclear accumulation of p53 was induced in NB cells using substances which disturb p53's tertiary structure at its zinc finger motif, or by treatment with mitomycin C. Constitutive nuclear accumulation was observed in an SK-N-SH variant, AW-1, which has a point mutation in p53 at Cys176>Ser, disturbing the same motif. Even though p53 showed DNA-binding capability after mitomycin C treatment of NB cells, the target gene products MDM2 and p21(WAF1,CIP1,SDI1) were not synthesized and no p53 transactivating activity measured in a reporter gene assay. Therefore we suggest that p53 in NB cells might be predominantly in a conformation refractory to integration into the transcriptional complex, resulting in at least partial transcriptional inactivity, hyperactive nuclear export and resistance to degradation by exogenously expressed MDM2.

Animals↗

Five Nkx5 genes show differential expression patterns in anlagen of sensory organs in medaka: insight into the evolution of the gene family.

We report the identification and characterisation of five different Nkx5-related genes in medaka fish (Oryzias latipes). They constitute homologues of genes previously isolated in higher vertebrates, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3 and SOHo-1, and were named accordingly: OlNkx5--1.1, OlNkx5--2, OlNkx5--3 and OlSOHo. For the Nkx5--1 gene a new, second homologue, OlNkx5--1.2, was isolated. In medaka, Nkx5 and SOHo genes are differentially expressed in three developing sensory organs: eye, ear and lateral line and later in defined brain regions. Phylogenetic analyses of the entire Nkx5 family revealed that four paralogous Nkx5 groups, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3/GH6 and SOHo, are present in vertebrates. Only some of the Nkx5 family members have been identified in singular vertebrate species so far. Here we present, for the first time, the isolation of representatives of each Nkx5 subgroup in one species, the medaka fish. Based on similarities in sequence and expression patterns, and genomic organisation we propose a model of the evolutionary history of the Nkx5 family. The model predicts that the four vertebrate Nkx5 genes arose by a tandem duplication, followed by chromosomal duplication. The two Nkx5--1 genes identified so far exclusively in medaka most probably result from an additional genome duplication in the fish lineage.

Amino Acid Sequence↗

p53 in SV40-transformed DNA-damaged human cells binds to its cognate sequence but fails to transactivate target genes.

Human SV40-transformed cells contain high levels of stabilized p53 of which only a fraction is complexed with the SV40 large tumor antigen (T-antigen). This raises the question whether the p53 which is not complexed with T-antigen retains some biological activity. Two human SV40-transformed cell lines, BEAS and SV80, were investigated. A significant level of constitutive cognate-sequence-specific DNA-binding of p53 was detected by electrophoretic mobility shift assay (EMSA) of cell extracts. Upon DNA damage by treatment with mitomycin C the DNA-binding activity was increased, as known for cells with wild-type p53. However, in both cell lines, before and after DNA damage, p53 was not able to transactivate a target gene as shown by reporter gene assay. Hence, the capability of p53 to bind its cognate sequence is a prerequisite but no proof of p53 transactivating activity. Nuclear p53 levels were not further increased after mitomycin C treatment, occasionally rather slightly decreased, often accompanied by an even larger decrease in amount of T-antigen. In conclusion, SV40-transformation of human cells has caused a loss of essential features of wild-type p53 activity, even in that fraction of p53 not in physical complex with SV40 T-antigen.

Animals↗

Mouse peripherin isoforms.

Three distinct mRNAs have been shown to be produced by alternative splicing from the unique mouse peripherin gene. They generate three translation products, one major form, Pe-58, and two minor forms, Pe-56 which possess a shorter C-terminal sequence, and Pe-61 in which an additional sequence has been inserted in the central rod domain (Landon et al., 1989, EMBO J. 8, 1719-1726). In this study, the simultaneous occurrence of multiple transcripts in murine nervous tissues and neuroblastoma cell lines was shown by PCR amplification of fragments overlapping the sites of alternative splicing. Recombinant peripherin isoforms were purified from E. coli expressing full-length cDNAs. Rabbit antisera were raised against synthetic peptides mimicking parts of the two C-terminal sequences and of the inserted sequence of Pe-61 and were immunoadsorbed until they became monoreactive. By western blot analysis, the peripherin isoforms were localised in neuroblastoma NB2a cell lysates and detergent insoluble fractions separated by two-dimensional electrophoresis. In addition, each isoform was resolved into several charge variants. At the cellular level, each antibody decorated the filament array of the NB2a cells, suggesting the participation of the minor peripherin isoforms in the intermediate filament network.

Animals↗

Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure.

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

Adult↗

NCCN Practice Guidelines for Breast Cancer.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients.

Breast Neoplasms↗

Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study.

OBJECTIVE: To compare the effect of unmodified cows' milk and iron supplemented formula milk on psychomotor development in infants from inner city areas when used as the main milk source. DESIGN: Double blind, randomised intervention trial. SETTING: Birmingham health centre. SUBJECTS: 100 infants, mean age 7.8 months (range 5.7 to 8.6 months), whose mothers had already elected to use unmodified cows' milk as their infant's milk source. INTERVENTION: Changing to an iron supplemented formula milk from enrolment to 18 months of age, or continuing with unmodified cows' milk. MAIN OUTCOME MEASURES: Developmental assessments using Griffiths scales at enrolment and at 18 and 24 months. RESULTS: 85 participants completed the trial. There were no significant differences in haemoglobin concentration between the two groups at enrolment, but by 18 months of age 33% of the unmodified cows' milk group, but only 2% of the iron supplemented group, were anaemic (P<0.001). The experimental groups had Griffiths general quotient scores that were not significantly different at enrolment, but the scores in both groups declined during the study. By 24 months the decrease in the mean scores in the unmodified cows' milk group was 14.7 whereas the decrease in the mean scores in the iron supplemented group was 9.3 (P<0.02, 95% confidence interval 0.4 to 10.4). Mean subquotient scores were considerably lower in the unmodified cows' milk group at 24 months; significantly so for personal and social scores (P<0.02, 1.2 to 16.8 [corrected]). CONCLUSION: Replacing unmodified cows' milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year.

Anemia, Iron-Deficiency↗

Understanding the influence of temperature change and cosolvent addition on conversion rate of enzymatic suspension reactions based on regime analysis.

It is a commonly held belief that enzymatic conversions of substrate in aqueous suspensions can be speeded up by raising the temperature or adding organic solvents to promote dissolution of the substrate. To quantify the impact of such changes, we studied the alpha-chymotrypsin-catalyzed hydrolysis of dimethyl benzylmethylmalonate as a model system. It was found that, upon addition of organic cosolvents, longer process times were actually required, even though the substrate solubility increased severalfold as expected. Upon raising the temperature from 25 degrees C to 37 degrees C, on the other hand, both the substrate solubility, the substrate dissolution rate, and the enzymatic reaction rate increased, leading to shorter process times. A dissolution-reaction model incorporating the kinetics of enzyme deactivation could be developed. A simple relation for the prediction of the overall process time was established by evaluating the time constants for the subprocesses: substrate dissolution; enzymatic conversion; and enzyme deactivation. Using regime analysis, rules of thumb for the optimization of an enzymatic suspension reaction were derived.

Animals↗

Potential of enzymatic kinetic resolution using solid substrates suspension: improved yield, productivity, substrate concentration, and recovery

In the literature the enzymatic kinetic resolution of a suspension of a solid substrate has largely been treated as a conventional kinetic resolution of a fully dissolved substrate. In this paper it is shown that this type of kinetic resolution is different in several important aspects. Quantitative models are developed for two types of such suspension processes. These models are used to compare the merits of these processes with the conventional kinetic resolution process where fully dissolved substrate is used. In the suspension processes the liquid phase concentration of substrate enantiomer that should be converted can be kept close to the maximum value, i.e., the solubility, when process conditions are properly chosen, whereas in a conventional process this concentration gradually decreases. Calculations show that this leads to a productivity that is about 6-fold higher in the suspension processes. Also, for enzymes with a low enantioselectivity, a severalfold increase in yield of remaining enantiopure substrate is predicted compared to the conventional kinetic resolution of dissolved enantiomers. Other potential advantages of using suspension reactions are that the initial substrate concentration may be higher (up to 25% (w/w)) and that the desired remaining substrate may be recovered by simply filtering off the solid crystals. Experimental evidence that these merits can be exploited is only partly given, using the few available examples from the literature.

Journal Article↗

A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig.

1. The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-510), and the prototypical calcium channel blocker diltiazem. 2. In the atrial-paced isolated heart, CVT-510 was approximately 5 fold more potent to prolong the stimulus-to-His bundle (S-H interval), a measure of slowing AV nodal conduction (EC50 = 41 nM) than to increase coronary conductance (EC50 = 200 nM). At concentrations of CVT-510 (40 nM) and diltiazem (1 microM) that caused equal prolongation of S-H interval (approximately 10 ms), diltiazem, but not CVT-510, significantly reduced left ventricular developed pressure (LVP) and markedly increased coronary conductance. CVT-510 shortened atrial (EC50 = 73 nM) but not the ventricular monophasic action potentials (MAP). 3. In atrial-paced anaesthetized guinea-pigs, intravenous infusions of CVT-510 and diltiazem caused nearly equal prolongations of P-R interval. However, diltiazem, but not CVT-510, significantly reduced mean arterial blood pressure. 4. Both CVT-510 and diltiazem prolonged S-H interval, i.e., slowed AV nodal conduction. However, the A1 receptor-selective agonist CVT-510 did so without causing the negative inotropic, vasodilator, and hypotensive effects associated with diltiazem. Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium.

Action Potentials↗

Cortical and medullary somatosensory projections to the cochlear nuclear complex in the hedgehog tenrec.

Various tracer substances were injected into the spinal cord, the dorsal column nuclei, the trigeminal nuclear complex and the somatosensory cortex in Madagascan hedgehog tenrecs. With the exception of the cases injected exclusively into the spinal cord all injections gave rise to sparse, but distinct anterograde projections to the cochlear nuclear complex, particularly the granular cell domain within and outside of the dorsal cochlear nucleus. Among these cochlear afferents the projection from the primary somatosensory cortex is the most remarkable because the hedgehog tenrec has one of the lowest encephalisation indices among mammals and a similar cortico-cochlear connection has not been demonstrated so far in other species.

Afferent Pathways↗

A novel system of human submandibular/sublingual saliva collection.

The assessment of submandibular/sublingual (sm/sl) saliva is a procedure of increasing significance. However, the collection of these fluids by traditional techniques is difficult and therefore often neglected. To collect sm/sl saliva, we have assembled a novel, universal system consisting of four parts-collecting tubing, a buffering chamber, a storing tube, and a suction device. Submandibular/sublingual saliva samples were collected from ten healthy and ten xerostomic individuals. The system showed intra-examiner reproducibility of 0.92 for healthy and 0.89 for xerostomic subjects, and inter-examiner reproducibility of 0.93 for normal subjects and 0.80 for xerostomic individuals. The flow rates obtained by the present collecting set-up were similar to those measured by all known previous methods that were published during the last 40 years. The system was also efficient, in that more than 90% of the fluid that entered the system was eventually collected in the storing tube for analysis. The system appears to collect relatively pure sm/sl fluids, since contamination of the collected sample by a stimulant solution swabbed repeatedly over the tongue during saliva collection was minimal. The system is reliable, safe, practical, and comfortable for the patient.

Adult↗

The combination of two semen preparation techniques (glass wool filtration and swim-up) and their effect on the morphology of recovered spermatozoa and outcome of IVF-ET.

The aim of this prospective study was to relate sperm quality, especially sperm morphology, to the outcome of IVF results, when glass wool filtration (GWF) and swim-up were used in combination for the preparation of spermatozoa. A total of 60 ejaculates were analysed. GWF was compared with glass wool filtration/swim-up (GWF-SU) by using aliquots from the same semen samples to increase the precision of the comparison and to establish the cumulative effect of these two semen preparation methods on the morphology of the recovered spermatozoa. Sperm parameters were examined in native semen, in semen preparation samples after GWF and GWF-SU. The mean percentages for motility, morphology and velocity were improved significantly over those in fresh semen only when GWF-SU was used. GWF alone resulted only in a significantly higher recovery of motile spermatozoa. In semen preparation, 10% of spermatozoa with normal morphology appeared to be the cut-off point as there was a significantly higher recovery in fresh semen samples containing > 10% morphologically normal spermatozoa after GWF-SU. Outcome of IVF-ET following preparation with GWF-SU showed better results in comparison to the swim-up procedure alone, though this difference was not statistically significant. The cut-off point was also > 10% morphologically normal spermatozoa. Improvement in all aspects of IVF-ET occurred when native semen contained > 10% morphologically normal spermatozoa. It is concluded that GWF alone did not produce significantly better results but, in combination with swim-up, it resulted in significantly better sperm morphology and in an improved outcome of IVF-ET for fresh semen samples with > 10% morphologically normal spermatozoa.

Adult↗

Increased major salivary gland secretion in familial dysautonomia.

Familial dysautonomia (FD), an autosomal recessive peripheral nervous system disorder, affects almost exclusively children of Jewish Ashkenazi origin and causes profound generalized autonomic dysfunction. Excessive drooling is frequent and is traditionally attributed to swallowing difficulties. Although true hypersalivation has been postulated, no quantitative assessment of the salivary secretion rate has yet been reported. The authors determined this rate in 13 children with FD and 28 healthy controls. Resting parotid, submandibular/sublingual and unstimulated whole salivary secretion rates were significantly elevated in children with FD. The known relation of salivary function with age was found in controls only. This apparently major contribution of salivary hyperfunction to excessive drooling in FD may be attributable to salivary gland denervation supersensitivity, as this mechanism is present in the cardiovascular system and the pupil in FD.

Adolescent↗

Synaptic and non-synaptic cholinergic innervation of the various types of neurons in the main olfactory bulb of adult rat: immunocytochemistry of choline acetyltransferase.

The cholinergic neuronal structures and their synaptic connections in the main olfactory bulb of adult rats were analysed by using choline acetyltransferase immunocytochemistry. Within the glomeruli, cholinergic nerve fibers were restricted to strands which subdivided the neuropil into small compartments, the interior of which contained sensory axons but was devoid of cholinergic axons. Small numbers of choline acetyltransferase neurons were detected in all layers. Ultrastructural analysis revealed selective triadic synaptic relationships with different neuron classes in the intraglomerular area and in the external plexiform layer. These triads were made up of (i) a cholinergic axon, (ii) one or several periglomerular or granule cell dendrites, and (iii) usually one relay cell dendrite. In these triads, asymmetric cholinergic synapses were selectively focused on dendrites (gemmules and spines) of periglomerular or granule cells. Within the glomerulus, mitral and tufted cell dendrites were closely apposed to some cholinergic axon varicosities, most abundantly near arborizations of the apical dendrites. However, cholinergic synapses were never seen on any relay cell dendrite. In the external plexiform layer, cholinergic synapses were present on all parts of the superficial short-axon cells. In the internal plexiform layer and the granule cell layer, cholinergic axon varicosities exhibited close apposition or asymmetric synapses with granule cell gemmules. The data suggest that cholinergic projections from the basal forebrain to the main olfactory bulb focus synaptic innervation on interneurons. On relay cells, direct acetylcholine effects may occur, but these must be based on non-synaptic acetylcholine release at the surface of their dendrites.

Animals↗

A novel antibiofilm technology for contact lens solutions.

PURPOSE: Nonsteroidal anti-inflammatory drugs, including sodium salicylate, inhibit extracellular bacterial biofilm production. The authors studied the effect of the addition of sodium salicylate on bacterial adherence and biofilm formation on contact lenses and cases and commonly used medical polymers. METHODS: The study was done in vitro with bacterial adherence and biofilm measured on lenses and cases that were exposed to saline contaminated with Staphylococcus epidermidis and Pseudomonas aeruginosa with and without 1 and 3 mm sodium salicylate. Bacterial adherence to contact lenses was quantitated by a vortex assay and by scanning electron microscopy. Biofilm formation on contact lens cases and other polymers was measured by an optical density assay and a radiolabeling assay. RESULTS: Inhibition of biofilm formation was demonstrated on plastic contact lens cases in a dose-related manner with 1 and 3 mm sodium salicylate. A dose-related decrease in bacterial adherence also was noted. Assays with contact lenses also demonstrated less adherence in the presence of sodium salicylate. Electron micrographs of the contact lens showed less biofilm, most noticeable with 3 mm salicylate. Other studies demonstrated decreased adherence of S. epidermidis to polyethylene and polystyrene. Sodium salicylate also decreased biofilm on plastic tissue culture wells, but sorbic acid paradoxically increased deposition. CONCLUSION: The authors found that the addition of low-dose sodium salicylate to saline decreased the adherence of S. epidermidis and P. aeruginosa to contact lenses and lens cases. Biofilm production also was decreased on the lens cases and on medical polymers used to make plastic cases. These studies suggest that sodium salicylate deserves additional study to determine its use in contact lens solutions.

Bacterial Adhesion↗