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Biomedical subjects

A Wolff

Publications and source records attributed to A Wolff.

At least 37 records · Page 2Linked to original sources

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↗

Differential distribution of glutamylated tubulin during spermatogenesis in mammalian testis.

The distribution of glutamylated tubulin has been analyzed in mammalian testis using the specific mAb GT335 by immunoelectron microscopy and immunoblotting. In spermatozoa of various species, immunogold labeling showed the presence of glutamylated tubulin in all of the microtubules of axoneme and centrioles, whereas the microtubule network of the spermatid manchette was unlabeled. In earlier germ cells, centriole was the only microtubule structure to be labeled. A similar distribution was observed using the anti-acetylated tubulin antibody (6-11B-1), confirming previous results of Hermo et al. [Anat. Rec. 229:31-50, 1991]. However, among testicular somatic cells, microtubules of some Sertoli cell branches were not acetylated but glutamylated. 2-D PAGE of mouse and hamster sperm extracts showed a high level of alpha and beta-tubulin heterogeneity, comparable to that found in brain. Immunoblotting with GT335 revealed a large amount of glutamylated tubulin resolved into numerous alpha as well as beta-tubulin isoforms. This suggests that the major testis-specific tubulin isotypes (m alpha 3/7 and m beta 3) are also glutamylatable. These results show a subcellular sorting of posttranslationally modified tubulin isoforms in spermatids, glutamylation being associated with the most stable microtubule structures.

Amino Acid Sequence↗

Glutamylated tubulin probed in ciliates with the monoclonal antibody GT335.

Microtubular networks are extensively developed in many ciliate species. In several of them, we investigate the occurrence of the post-translational glutamylation of tubulin [Eddé et al., 1990: Science 247:82-85; Eddé et al., 1991: J. Cell. Biochem. 46:134-142] using as a probe for such modified tubulin, the monoclonal antibody GT335 [Wolff et al., 1992: Eur. J. Cell Biol. 59:425-432]. Results obtained in Paramecium strongly suggest that both axonemal and cytoplasmic tubulin are glutamylated. As in the vertebrate brain tubulin so far tested, the GT335 epitope is located at the carboxy-terminal fragment of cytoplasmic tubulin removed by subtilisin treatment. Immunoblotting and immunofluorescence experiments reveal that, unlike tubulin acetylation, glutamylation is not restricted to cold-resistant microtubules. In addition, immunofluorescence studies performed on dividing cells show that glutamylation takes place soon after the polymerization of microtubules. Finally, glutamylated tubulin is also detected in the ciliate species Euplotes, Tetrahymena, and Paraurostyla. Together with results obtained on flagellate species, this suggests that tubulin glutamylation came out early in the course of eukaryotic evolution and has been widely exploited in various cellular strategies.

Animals↗

Structure of the polyglutamyl chain of tubulin: occurrence of alpha and gamma linkages between glutamyl units revealed by monoreactive polyclonal antibodies.

Polyglutamylation, a posttranslational modification which consists of the sequential addition of one to six glutamyl units in the carboxy-terminal domain of both tubulin subunits, is a major event in neurons. Its structure has been investigated by using monoreactive polyclonal antibodies directed against distinct glutamylation motifs, ie alpha- and gamma-linkages between glutamyl units. It is shown that, beside alpha-linkages previously characterized, gamma-linkages also occur in glutamyl chains of brain tubulin. The co-existence of these two basic motifs leads to a conception of the polyglutamyl chain with a very sophisticated structure which could, through its complexity, help the microtubule to reach its structure and fulfil its functions.

Amino Acid Sequence↗

Distribution of GABA-immunoreactive nerve fibers and cells in the cervical and thoracic paravertebral sympathetic trunk of adult rat: evidence for an ascending feed-forward inhibition system.

Neurochemical and immunohistochemical evidence suggests that the superior cervical ganglion (SCG) contains all components of a gamma-aminobutyric acid (GABA)ergic transmission system, which includes GABAergic axons of unknown origin. The number of nerve fibers with and without GABA-like immunoreactivity was determined in interganglionic connectives at all cervical and thoracic levels of the paravertebral sympathetic trunk. In addition, the distribution of GABA-immunoreactive (IR) neurons was established within the ganglion chain and compared with the relative frequency of principal neurons richly innervated by GABA-IR axon terminals. The following results were obtained: 1) the total number of nerve fibers in cross sections did not significantly vary between the cervical levels, but it increased steadily from upper to lower thoracic segments; 2) in contrast, the number of GABA-IR fibers decreased from the cervical sympathetic trunk below the SCG (approximately 300 fibers) down to the seventh to tenth thoracic ganglion, below which no such fiber was seen; 3) GABA-IR nerve fibers originate from a subclass of GABA-IR cells; these are small, bipolar neurons with predominantly ascending, unmyelinated axon-like processes; 4) the number of principal neurons richly innervated by GABA-IR nerve fibers decreased from the SCG to the upper thoracic ganglia, and was very small below; and 5) apart from basket-like innervation, GABA-IR axons also formed diffuse networks around GABA-negative principal neurons predominantly in cervical and upper thoracic ganglia. These data suggest that the GABAergic innervation of paravertebral sympathetic ganglia is more complex than previously suspected. What appears as preganglionic afferents from several spinal segments (C8-Th7) innervate GABAergic neurons in the sympathetic trunk which have ascending axons and focus their inhibitory effects on the cervical sympathetic ganglia, predominantly the SCG. These data suggest that GABAergic small interganglionic neurons form a feed-forward inhibition system, which may be driven by multisegmental spinal input in the paravertebral sympathetic ganglion chain.

Afferent Pathways↗

Pre- and postnatal development of the primary visual cortex of the common marmoset. II. Formation, remodelling, and elimination of synapses as overlapping processes.

During ontogenesis changes in the numerical density of synapses are usually assumed to depend essentially on variations in the formation of synapses. Only the final adjustment to adult synapse densities is thought to include the elimination of synapses in some brain regions of certain species. Here, we focus attention on quantitative aspects of synapse elimination throughout development of area 17 of marmoset monkeys (Callithrix jacchus). Mature synapses, various precursor forms, and indicators of lysosomal degradation of synapses were quantitatively analysed by electron microscopy and morphometric methods. A total number of about 135 x 10(9) synapses was calculated for area 17 in each adult hemisphere corresponding to a volume density of 600 x 10(6) synapses/mm3. At 3 months of age, the respective values were 508 x 10(9)/area and 1,159 x 10(6)/mm3, while at birth these values were 69 x 10(9)/area and 328 x 10(6)/mm3. Consequently, at least three out of four synapses are eliminated between 3 months and adulthood. However, the real number of synapses being eliminated during development is probably much larger if the time course of lysosomal degradation is additionally taken into account. The frequency of lysosomes in presynaptic endings is highest before net-elimination of synapses occurs, i.e., between 1 and 3 months. This suggests that lysosomal degradation is not directly responsible for the majority of synapses removed during ontogenesis but apparently represents a second mechanism for synapse remodelling and elimination. Thus, it appears from this study that remodelling and elimination of synapses are quantitatively as important as their formation, and accompany synaptogenesis from its very onset onwards.

Animals↗