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Biomedical subjects

M Lazar

Publications and source records attributed to M Lazar.

At least 37 records · Page 2Linked to original sources

The beta enolase subunit displays three different patterns of microheterogeneity in human striated muscle.

In higher vertebrates, the glycolytic enzyme enolase (2-phospho-D-glycerate hydrolyase; EC 4.2.1.11) is active as a dimeric protein formed from three subunits--alpha: ubiquitous, beta: muscle specific, and gamma: neuron specific--encoded by different genes. In the present study, we have shown that an antiserum previously produced against the mouse beta beta enolase is also a specific reagent for the muscle specific human enolase. Using this antiserum to study human muscles, we demonstrated novel patterns of the beta subunit microheterogeneity which are distinctive from those observed previously in rodents and which appear to be independent of age, gender and muscular activity. Two variants of the beta subunit differing by their size have been detected: one heavy form of 46 kDa (beta H) and one light form of 45 kDa (beta L). Muscle biopsies expressed either beta H or beta L or beta H + beta L, and all muscles of an individual expressed the same variants. The products of in vitro translation of RNA prepared from human muscle displayed beta subunit variants identical to those of the protein present in the biopsy. Therefore the differences observed between individuals reveal a difference already present at the level of the RNA transcripts. These observations suggest the existence of an yet undescribed polymorphism of the human beta enolase gene which could affect the coding sequence. Comparative immunocytochemical and histochemical analyses of biopsies demonstrated that the beta subunit was expressed in all fast fibres (type II), but not in slow fibres (type I). No difference was observed in the intensity of beta enolase immunolabelling between the various types (IIA, IIAB, IIB) of fast fibres. No significant difference in fibre type composition and histological appearance was visible between muscles presenting either one of the three patterns of microheterogeneity.

Adult↗

Macular ring in a patient with Terson's syndrome.

PURPOSE: To report on a pigmented finding in the macula that is unique to Terson's syndrome, and was previously described only once. METHOD: A 49-year-old man underwent vitrectomy for vitreous hemorrhage due to Terson's syndrome. During surgery the retina was exposed, and a pigmentation was noticed around the macula. Follow-up of the macular finding is presented. RESULTS: At surgery a pigmented "ring" encircling the macula was revealed. Two and six months later, the pigmented line was still noticed, and an epiretinal membrane appeared in the temporal macula. CONCLUSION: Terson's syndrome may be associated with a pigmented "ring" encircling the macula, a finding that may be a result of a detachment of the internal limiting membrane (ILM). The epiretinal membrane that was later noticed, might also be related to the damage to the ILM.

Cerebral Hemorrhage↗

Cilioretinal artery occlusion during coronary catheterization.

PURPOSE: To report on a patient with cilioretinal artery occlusion during cardiac catheterization. METHODS: A 51-year-old man complained of blurred vision in the left eye immediately following cardiac catheterization. Visual acuity was 6/12 and the eye had a dense central scotoma. RESULTS: Mild retinal whitening of the posterior pole and segmented filling of the cilio-retinal artery established the diagnosis of cilioretinal artery occlusion. Immediate paracentesis was performed. Two weeks later, a tiny central scotoma could be observed and visual acuity was 6/6. CONCLUSIONS: Cardiac catheterization may result in retinal infarction. Awareness to any visual symptoms, immediate diagnosis and prompt intervention may prevent permanent visual impairment.

Cardiac Catheterization↗

Beta3-adrenergic relaxation of bovine iris sphincter.

Bovine iris sphincter in vitro responded to beta-adrenergic stimulation with pronounced relaxation (EC50 of isoproterenol = 0.3 nM), which was potentiated by the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, and mimicked by the adenylyl cyclase activator, forskolin. The beta1/beta2 antagonist, propranolol, exhibited low potency with calculated Ki of 200 nM. The beta3-selective antagonist, bupranolol, exhibited a biphasic inhibition profile, with calculated Kis of approximately 20-50 and 200-300 nM. The beta3-selective agonist, BRL 37344, elicited 70% of maximal relaxation (EC50 = 30 nM). When relaxation was induced by BRL 37344, bupranolol exhibited much higher potency (calculated Ki = 1 nM). Our data suggest that the beta-adrenergic relaxation response in bovine iris sphincter is mediated by a mixed population of beta-adrenergic receptors, with a predominant contribution of atypical, most likely beta3 subtype, receptors.

Adrenergic beta-Agonists↗

Low-frequency submicron fluctuations of red blood cells in diabetic retinopathy.

OBJECTIVE: To characterize cell membrane mechanical fluctuations of red blood cells (RBCs) in patients with diabetic retinopathy. METHODS: Point dark-field microscopy-based recordings of these local displacements of the cell membrane in human erythrocytes were compared between patients with severe proliferative diabetic retinopathy and healthy controls. The study was performed on discoid RBCs. RESULTS: The average of the maximal displacement amplitude in the diabetic patients was 13.9% +/- 1.7% (236 +/- 29 nm) compared with 18.7% +/- 1.75% (318 +/- 30 nm) for the controls (P<.001). The decrease of the RBCs' average displacement amplitude was not correlated with the variation in negative curvature of the central area of discoid cells. CONCLUSIONS: Microdisplacements of the cell membrane, which reflect the bending deformability of the RBCs, are directly connected with its efficiency in passing through capillaries narrower than its own diameter. These microdisplacements were significantly reduced in patients with severe diabetic retinopathy because of an increase in viscoelasticity of the cell membrane. Such reduced cell membrane microdisplacements, which reflect lower bending deformability of the RBC, reduce the ability of the cell to enter and pass through small capillaries, increasing tissue ischemia and consequently contributing to the development of diabetic retinopathy.

Diabetic Retinopathy↗

Capsular bag distension associated with sulcus implantation of intraocular lenses.

Capsular bag distension syndrome after endophacoemulsification and in-the-bag intraocular lens (IOL) implantation has been reported. We describe 2 cases in which sulcus implantation of a posterior chamber IOL caused marked capsular bag distension. Both cases resolved with conservative treatment or a neodymium:YAG posterior capsulotomy.

Aged↗

Iris retraction syndrome associated with nonrhegmatogenous retinal detachment.

PURPOSE: To present the first documentation of iris retraction syndrome in eyes with nonrhegmatogenous retinal detachment. PATIENTS AND METHODS: One patient with age-related macular degeneration and another with panuveitis developed exudative retinal detachment with iris retraction configuration. Ultrasound biomicroscopy was performed to investigate the anatomic relationship of structures in the anterior segment of the eye. RESULTS: Ultrasound biomicroscopy demonstrated a severe backward bowing of the peripheral iris with irido-ciliary body and irido-zonular contact as well as broad iris lens touch. The iris retraction syndrome resolved after pupil dilation and disruption of the pupillary adhesions in both cases. The retinal detachment resolved several months later, without surgery. CONCLUSION: Iris retraction syndrome appears not to be exclusive to rhegmatogenous retinal detachment but can present in eyes with exudative - nonrhegmatogenous retinal detachment. Thus, when the configuration of the iris shows bowing in patients with retinal detachment, iris retraction syndrome should be considered and prompt pupil dilation should be carried out.

Aged↗

Reproducibility of topographic measures of the glaucomatous optic nerve head.

AIMS/BACKGROUND: Laser scanning tomography provides an assessment of three dimensional optic disc topography. For the clinical purpose of follow up of glaucoma patients, the repeatability of the various measured variables is essential. In the present study, the reproducibility of morphometric variables calculated by the topographic scanning system, TopSS (Laser Diagnostic Technology, San Diego, CA) was investigated. METHODS: Two independent measurements (30 minutes apart) each consisting of three complete images of the optic disc were performed on 16 eyes of 16 glaucoma patients using a TopSS. The instrument calculates 14 morphometric variables for the characterisation of the optic disc. RESULTS: From the two tailed paired tests, all variables were seen to have good reproducibility. However, correlation and regression analyses showed that only the three variables, volume below, half depth area, and average cup depth, are acceptably reproducible. CONCLUSION: The TopSS provides three variables which describe the physiological shape of the optic disc that have high reproducibility. These three variables might be useful for following the progression of optic disc changes in glaucoma patients.

Aged↗

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins.

The glycolytic enzyme enolase (EC 4.2.1.11) is active as dimers formed from three subunits encoded by different genes. The embryonic alphaalpha isoform remains distributed in many adult cell types, whereas a transition towards betabeta and gammagamma isoforms occurs in striated muscle cells and neurons respectively. It is not understood why enolase exhibits tissue-specific isoforms with very close functional properties. We approached this problem by the purification of native betabeta-enolase from mouse hindlimb muscles and by raising specific antibodies of high titre against this protein. These reagents have been useful in revealing a heterogeneity of the beta-enolase subunit that changes with in vivo and in vitro maturation. A basic carboxypeptidase appears to be involved in generating an acidic beta-enolase variant, and may regulate plasminogen binding by this subunit. We show for the first time that pure betabeta-enolase binds with high affinity the adjacent enzymes in the glycolytic pathway (pyruvate kinase and phosphoglycerate mutase), favouring the hypothesis that these three enzymes form a functional glycolytic segment. betabeta-Enolase binds with high affinity sarcomeric troponin but not actin and tropomyosin. Some of these binding properties are shared by the alphaalpha-isoenolase, which is also expressed in striated muscle, but not by the neuron-specific gammagamma-enolase. These results support the idea that specific interactions with macromolecules will address muscle enolase isoforms at the subcellular site where ATP, produced through glycolysis, is most needed for contraction. Such a specific targeting could be modulated by post-translational modifications.

Animals↗

Bilateral retinal vein occlusion associated with 5,10-methylenetetrahydrofolate reductase mutation.

PURPOSE: To report on the occurrence of 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency, known to cause mild to moderate hyperhomocystinemia and increased risk of vascular occlusive disease, in a young patient with bilateral central retinal vein occlusion. METHODS: A 25-year-old man was initially examined with central retinal vein occlusion in the right eye, followed 4 months later by a central retinal vein occlusion in the left eye. Studies for risk factors predisposing to thrombosis were performed. RESULTS: Hematologic studies failed to detect any pathology. However, the patient was found to be homozygous for 677C-T mutation in MTHFR enzyme. CONCLUSION: Central retinal vein occlusion may be associated with a mutation in MTHFR.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Late onset corneal haze after photorefractive keratectomy for moderate and high myopia.

BACKGROUND: Corneal haze after photorefractive keratectomy (PRK) usually appears within 4 weeks after the procedure. A new type of corneal haze, starting relatively late after PRK, is reported. METHODS: The authors reviewed the files of their first 1000 consecutive patients who completed a follow-up of 12 months or more and identified all those who had clear corneas for at least 4 months, after which corneal haze appeared. The clinical course in these patients was evaluated. RESULTS: Late onset corneal haze (LOCH) had occurred in 18 eyes of 17 patients (incidence, 1.8%), appearing 4 to 12 months after PRK and resulting in decreased visual acuity and regression. Treatment with topical steroids or reoperation resulted in partial reversibility of haze and regression. CONCLUSIONS: A new entity of LOCH is described. The appearance of LOCH suggests that corneal healing and remodeling continue for at least 1 year after PRK.

Administration, Topical↗

Delay of corneal wound healing in patients treated with colchicine.

BACKGROUND: Colchicine has a known adverse effect on wound healing through its inhibitory effect on tubulin-dependent cell functions and through collagenase activation. In the cornea, it has been shown in animal and in vitro studies to inhibit epithelium mitosis, fibroblast mitosis and migration, as well as to reduce collagen deposition. The authors report on two patients with corneal ulcers refractory to conventional treatment while the patients were undergoing oral colchicine therapy. CASE REPORTS: The first patient was an 86-year-old woman who had been treated with oral colchicine because of rheumatoid arthritis. She was admitted to the authors' department with a deep corneal ulcer in the right eye for which she had been treated for 3 weeks with local antibiotics without any improvement. The second patient, a 60-year-old woman, was hospitalized because of a corneal ulcer in her left eye. She had been receiving oral colchicine therapy for mixed connective tissue disease. Treatment with local antibiotics was initiated but the condition of the eye worsened, ultimately resulting in corneal perforation. RESULTS: Withdrawal of oral colchicine therapy was followed by rapid corneal wound healing in both patients. CONCLUSION: The findings in these two patients suggest that colchicine may delay corneal wound healing. The authors suggest that in patients with corneal ulcers refractory to conventional treatment who are receiving colchicine, cessation of colchicine therapy should be considered.

Aged↗

Macular hemorrhage after excimer laser photorefractive keratectomy.

We describe three patients with high myopia, 13.0 to 20.0 diopters (D), who had typical myopic macular hemorrhages 1 to 6 months after photorefractive keratectomy (PRK). The hemorrhages eventually resolved, with resultant permanent decrease in vision and pigmentary and atrophic changes in the macula. Highly myopic eyes are predisposed to bleeding in areas of lacquer cracks and to myopic choroidal neovascularization formation. Awareness of potential retinal pathology in patients having PRK and follow-up retinal examinations are warranted.

Adult↗