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Biomedical subjects

M Ehrenberg

Publications and source records attributed to M Ehrenberg.

At least 91 records · Page 5Linked to original sources

Vitreous hemorrhage nontoxic to retina as a stimulator of glial and fibrous proliferation.

To test the belief that blood is toxic to the retina, we developed an experimental model of vitreous hemorrhage in rabbits by injecting various amounts of autologous, uncoagulated , whole blood into their vitreous cavities, with the vitreous humor either intact or previously compressed by an expanding perfluoropropane gas bubble. Blood in the eyes with compressed vitreous cleared in half the time required for the same volume injected into eyes with intact vitreous (75.6 days vs 39.2 days). Large volumes of intravitreal blood (0.25 to 0.50 ml) were never toxic to the retina by ganzfeld and bright-flash electroretinography throughout a four-month observation period. The results indicated that massive vitreous hemorrhage has a dense filtering effect that can extinguish the ganzfeld but not the bright-flash electroretinogram. Blood caused moderate hemoglobin staining of the retina, without significant iron staining (confirmed by X-ray microprobe analysis). Hemoglobin residues accumulated within cells of the inner retina, especially Müller's cells. Blood clot retraction after the injection of large volumes of fresh blood (1 ml) produced traction retinal detachment, hole formation, and subretinal accumulation of blood. This correlated with a complete and persistent extinction of the ganzfeld and bright-flash electroretinograms throughout the four-month observation period. A striking finding was that almost all eyes developed glial membranes on the peripheral retina. Fibrous membranes, causing local retinal contraction, were found over the medullary wings and optic disk in eyes with vitreous compression.

Animals↗

Rubeosis iridis: preoperative iris fluorescein angiography and periocular steroids.

To study the risk of developing rubeosis iridis following vitrectomy, the use of preoperative iris fluorescein angiography was prospectively investigated on patients with diabetes mellitus, without any clinically detectable iris or angle neovascularization. With increasing severity of fluorescein leakage, the risk of iris neovascularization with or without glaucoma, six months after vitreous surgery, is significantly increased. It was also determined whether postoperative steroid therapy (periocular triamcinolone acetonide and topical prednisolone phosphate) reduces the risk of developing iris neovascularization after vitrectomy. Controlled and treated patient eyes did not differ significantly in the degree of rubeosis. However, neovascular glaucoma statistically occurred more frequently in the nonsteroid group.

Diabetic Retinopathy↗

Bilateral nodular sarcoid choroiditis with vitreous haemorrhage.

A 21-year-old black man with presumed systemic sarcoidosis had bilateral choroidal nodules, unilateral retinal neovascularisation and vitreous haemorrhage, and non-caseating granulomas on percutaneous liver biopsy. The choroidal nodules were serially documented by fundus photography and fluorescein angiography over a 22-month period. Fluorescein angiography was more accurate than ophthalmoscopy in demonstrating choroidal inflammation. The choroidal nodules resolved after systemic corticosteroid therapy. A vitreous haemorrhage occurred probably secondary to neovascularisation related to occlusion of an inferotemporal branch vein. The non-resolving vitreous haemorrhage and associated traction retinal detachment were treated with vitrectomy and membrane sectioning.

Adult↗

Rapidly progressive proptosis secondary to Burkitt's lymphoma. Origin in the ethmoidal sinuses.

A case of unilateral proptosis secondary to Burkitt's lymphoma occurred in the ethmoidal sinuses. Involvement of the skull and paranasal sinuses by Burkitt's lymphoma may masquerade initially as an infectious process delaying diagnosis and treatment. The tumor's rapid growth and dramatic response to therapy with the potential for long-term remission and cure emphasize the need for prompt diagnosis and treatment.

Burkitt Lymphoma↗

Postoperative emesis in vitreoretinal surgical patients.

We studied, prospectively, the incidence of emesis in 64 consecutive patients undergoing retinal and vitreous surgery performed either under local or general anesthesia. Of these patients 19% had at least one episode of emesis within 12 h after surgery. 30% of the patients who underwent general anesthesia had emesis, whereas only 4% of the patients with local anesthesia vomited. These results were statistically significant. Unless special attention is paid to minimize emesis, we recommend the use of local anesthesia, especially in patients with unstable metabolic disorders such as diabetes mellitus. Emesis and its potential ocular and systemic complications add to the postoperative malaise of general anesthesia.

Adult↗

Microscopic diffusion-reaction coupling in steady-state enzyme kinetics.

The theory of diffusion-controlled processes is applied to describe the steady state of a reversible enzymatic reaction with special emphasis on the effects of enzyme saturation. A standard macroscopic steady-state treatment requires only that the average diffusional influx of substrate equals the net reaction flux as well as the average diffusional efflux of product. In contrast, the microscopic diffusion-reaction coupling used here takes properly into account the conditional concentration distributions of substrate and product: Only when the enzyme is unoccupied will there be a diffusional association flux; when the enzyme is occupied, the concentration distributions will relax towards their homogeneous bulk values. In this way the relaxation effects of the non-steady state will be constantly reoccurring as the enzyme shifts between unoccupied and occupied states. Thus, one is forced to describe the steady state as the weighted sum of properly time-averaged non-stationary conditional distributions. The consequences of the theory for an appropriate assessment of the parameters obtained in Lineweaver-Burk plots are discussed. In general, our results serve to justify the simpler macroscopic coupling scheme. However, considerable deviations between the standard treatment and our analysis can occur for fast enzymes with an essentially irreversible product release.

Diffusion↗

Catalytic effects of elongation factor Ts on polypeptide synthesis.

The kinetic parameters which characterize the interaction between elongation factor Tu (EF-Tu) and elongation factor Ts (EF-Ts) have been determined in a poly(uridylic acid)-primed translation system. The EF-Ts catalyzed release of GDP from EF-Tu was measured independently in a nucleotide exchange assay. We conclude that the rate-limiting step for the EF-Tu cycle in protein synthesis in the absence of EF-Ts is the release of GDP. By adding EF-Ts the time of this step is reduced from 90 s to 30 ms. Half maximal rate is obtained at an EF-Ts concentration of 2.5 x 10 M.

Journal Article↗

Is there proofreading during polypeptide synthesis?

The stoichiometric efficiency with which ternary complexes containing Phe-tRNAphe and Leu-tRNAleu support polypeptide synthesis has been compared in a poly(U)-directed, steady-state translation system. When unfractionated tRNA is used to support synthesis, the number of discharged ternary complexes per peptide bond formed is an average of 48 times greater for leucine than for phenylalanine. When three purified leucine isoacceptor species are tested, they each show a characteristic ratio of ternary complexes discharged per missense insertion, normalized to that for phenylalanine: these are 103, 76, and 45 for Leu- tRNA2leu , Leu- tRNA3leu , and Leu- tRNA4leu , respectively. The data are consistent with the functioning of a proofreading mechanism during translation.

Escherichia coli↗

Kinetic suppression of translational errors by (p)ppGpp.

The effect of (p)ppGpp on the accuracy of translation was studied in vitro using a poly(U)-programmed poly(Phe)-synthesizing system operating at incorporation rates and missense error frequencies close to the values obtained in vivo. Simulation of a relaxed phenotype in vitro was accomplished by limitation of the cognate aminoacyl-tRNA synthetase, while the noncognate aminoacyl-tRNA synthetase was included at saturating concentrations. This protocol yielded a Phe-tRNA-starved steady state system displaying the expected decrease in Phe polymerization rates accompanied by a drastic increase in relative Leu misincorporation errors. The use of purified enzymes permitted us to assay for the effects of the individual nucleotides ppGpp and ppGpp as well as their potential targets, the elongation factors Tu and G, upon the missense error rates. Our results support the conclusion that ppGpp reduces misincorporation in a starved in vitro system by preferentially inhibiting EF-Tu. The details of the proposed mechanism and their relevance to an in vivo situation are discussed.

Cell-Free System↗

Association kinetics with coupled three- and one-dimensional diffusion. Chain-length dependence of the association rate of specific DNA sites.

The effective target size of a specific binding site on a long polymeric chain can be considerably enhanced if the associating molecules slide along the chain in a one-dimensional diffusion. Such a mechanism has been proposed to explain the "faster than diffusion controlled" association of the lac repressor protein with the operator site on a long DNA chain. An important experimental tool for investigating the properties of rate-enhancing mechanisms of this type is now becoming available. In these experiments the DNA chain length is varied and the association rate of the investigated protein is measured. Previous attempts to describe theoretically how such one-dimensional sliding processes behave under those conditions were either oversimplified or connected with fundamental errors. We present here a theory for the association rate of proteins with a specific site on DNA molecules with variable lengths. We use a steady-state approach as do Schranner and Richter (Biophys. Chem. 8 (1978)47) but, in contrast, use boundary conditions which appear to be physically more reasonable.

Chemical Phenomena↗

Rate of elongation of polyphenylalanine in vitro.

Ribosomes purified from Escherichia coli were preincubated with AcPhe-tRNA and poly(U). Then purified components necessary for polypeptide synthesis were added. Incubation of the complete system led to a burst of elongation which lasted for nearly 10 s. During the initial burst approximately 10% of the ribosomes participated in the elongation of poly(Phe) at an average rate per ribosome close to eight peptide bonds/s. The missense error rate with leucine was 4 x 10(-4) during the burst. Accordingly, the preincubated elongation system functions at a rate, as well as an accuracy, close to those of protein synthesis in vivo.

Amino Acyl-tRNA Synthetases↗

Pigmentary macular degeneration with multifocal necrotizing encephalopathy.

A previously healthy 10-year-old girl suffered sudden, binocular visual deterioration. During the next few years her neurologic and visual condition progressively worsened and she developed hypertension, seizures, ataxia, and lactic acidemia, leading to death at the age of 16 years. Bilateral optic disk pallor was followed by the loss of the foveal reflex and pigmentary maculopathy, manifested as disorganization of the retinal layers, loss of ganglion cells, degeneration of the photoreceptors and nuclei, and irregular infiltration of the retina by pigment epithelial cells. The optic nerves and tracts showed central axonal loss. Bilateral, multifocal symmetric areas of cerebral atrophy and necrosis of the neuropil and neurons in the cerebral cortex, basal ganglia, and thalamus were observed; neurons persisted in the dorsal medulla, despite neuropil degeneration.

Brain Diseases↗

Fluorescence relaxation of proflavin-deoxyribonucleic acid interaction. Kinetic properties of a base-specific reaction.

The kinetics of proflavin binding to Micrococcus lysodeicticus deoxyribonucleic acid (DNA [(G-C) content 72%], to Bacillus megaterium DNA [(A-T) content 70%], and to the polydeoxyribonucleotides poly[d(G-C)] and poly[d(A-T)] was studied with fluorescence temperature-jump methods. Poly[d(A-T)] binds proflavin in a two-step reaction with a preequilibrium. Poly[d(G-C)] is characterized by a bimolecular reaction. The binding of acridines to natural DNAs is shown to be characterized by different types of sites whose properties depend on the base composition. The sites have considerable enthalpic differences which result in exchange of dye molecules between them when the temperature is changed. Also, on natural DNAs A-T base pairs are associated with a rapidly equilibrating external complex which is absent or much weaker for G-C base pairs.

Acridines↗