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Biomedical subjects

E Rosen

Publications and source records attributed to E Rosen.

At least 37 records · Page 2Linked to original sources

The arabidopsis thaliana AGRAVITROPIC 1 gene encodes a component of the polar-auxin-transport efflux carrier.

Auxins are plant hormones that mediate many aspects of plant growth and development. In higher plants, auxins are polarly transported from sites of synthesis in the shoot apex to their sites of action in the basal regions of shoots and in roots. Polar auxin transport is an important aspect of auxin functions and is mediated by cellular influx and efflux carriers. Little is known about the molecular identity of its regulatory component, the efflux carrier [Estelle, M. (1996) Current Biol. 6, 1589-1591]. Here we show that mutations in the Arabidopsis thaliana AGRAVITROPIC 1 (AGR1) gene involved in root gravitropism confer increased root-growth sensitivity to auxin and decreased sensitivity to ethylene and an auxin transport inhibitor, and cause retention of exogenously added auxin in root tip cells. We used positional cloning to show that AGR1 encodes a putative transmembrane protein whose amino acid sequence shares homologies with bacterial transporters. When expressed in Saccharomyces cerevisiae, AGR1 promotes an increased efflux of radiolabeled IAA from the cells and confers increased resistance to fluoro-IAA, a toxic IAA-derived compound. AGR1 transcripts were localized to the root distal elongation zone, a region undergoing a curvature response upon gravistimulation. We have identified several AGR1-related genes in Arabidopsis, suggesting a global role of this gene family in the control of auxin-regulated growth and developmental processes.

Amino Acid Sequence↗

Staar Collamer posterior chamber phakic intraocular lens to correct myopia and hyperopia.

PURPOSE: To evaluate the efficacy, safety, stability, and predictability of implanting a collagen polymer (Staar Collamer), posterior chamber phakic intraocular lens (IOL) to correct myopia and hyperopia. SETTING: Centre for Advanced Refractive Eye Surgery at the BMI Alexandra Hospital, Cheadle, Manchester, United Kingdom. METHODS: A Staar Collamer posterior chamber phakic IOL was implanted in 25 eyes of 14 patients with a mean age of 37.9 years (range 20 to 50 years). Seven patients were men and seven, women. Sixteen were myopic and 9, hyperopic. Before treatment, each patient had a thorough evaluation including refractive, general, ocular, and social and personal histories. The examination included visual acuity, refraction, tonometry, topography, biometry, biomicroscopy, pupil size in dim illumination, and posterior segment evaluation by a vitreoretinal specialist. Patients were informed about the surgical process and expected outcome, their own expectations were discussed, and their consent to surgery was obtained. Surgical implantation was performed through a less than 3.0 mm clear corneal sutureless incision using brief general anesthesia on a day-case surgical basis. RESULTS: At 3 months postoperatively, all eyes had a significant increase in uncorrected visual acuity, allowing all but two patients (three eyes) to manage most activities without spectacles. Adjustment by incisional corneal surgery was planned for undercorrected myopic eyes (n = 3). Pupil block glaucoma and pigment deposits occurred in one patient each. CONCLUSION: In this short-term study, the posterior chamber phakic IOL was predictable, safe, and efficacious in the correction of myopic and hyperopic refractive errors, with good refractive stability. Long-term follow-up is required to validate that the absence of significant complications in most patients is a lasting phenomenon.

Adult↗

Lens epithelial cell proliferation, migration, and metaplasia following capsulorhexis.

AIM: To study the behaviour of residual lens epithelial cells after capsulorhexis and expression of material from the isolated lens. METHODS: Human and bovine lens capsules were isolated, sterile non-toxic silicone rings inserted, and the preparations placed in organ culture for up to 12 weeks. Cell coverage of the posterior lens capsule was recorded and the capsules were examined, both pre- and post-coverage, for (a) proliferative activity and (b) cytoskeletal components. RESULTS: After a lag period outgrowth was observed across the posterior capsule. The rate of cell coverage was dependent upon both species and the presence or absence of serum. The proliferative activity of the cells was greatest at or near the leading edge and decreased once covered. Wrinkles became visible in the posterior capsule during the late stages of precoverage and increased in both number and complexity. All cells on both the human and bovine posterior capsules contained F-actin and vimentin and the majority were immunolabelled for alpha-smooth muscle actin (alpha-SMA). CONCLUSIONS: This model exhibits many of the in vivo characteristics of the lens capsule after extracapsular surgery and may prove useful in further elucidating the cellular mechanisms of posterior capsule opacification.

Aged↗

Taking Web medicine.

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Academic Medical Centers↗

Video publishing.

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Echocardiography↗

Milia en plaque in a bilateral submandibular distribution.

Milia en plaque typically occurs in the retroauricular area. We report the case of an 84-year-old woman with this disorder occurring bilaterally in the submandibular region. The diagnosis was confirmed by histological examination.

Aged↗

Molecular genetics of root gravitropism and waving in Arabidopsis thaliana.

When Arabidopsis thaliana seedlings grow embedded in an agar-based medium, their roots grow vertically downward. This reflects their ability to sense the gravity vector and to position their tip parallel to it (gravitropism). We have isolated a number of mutations affecting root gravitropism in Arabidopsis thaliana. One of these mutations, named arg1, affects root and hypocotyl gravitropism without promoting defects in starch content or in the ability of seedlings' organs to respond to plant hormones. The ARG1 gene was cloned and shown to code for a protein with a J domain at its amino terminus and a second sequence motif found in several cytoskeleton binding proteins. Mutations in the AGR1 locus promote a strong defect in root gravitropism. Some alleles also confer an increased root resistance to exogenous ethylene and an increased sensitivity to auxin. AGR1 was cloned and found to encode a putative transmembrane protein which might be involved in polar auxin transport, or in regulating the differential growth response to gravistimulation. When Arabidopsis seedlings grow on the surface of agar-based media tilted backward, their roots wave. That wavy pattern of root growth derives from a combined response to gravity, touch and other surface-derived stimuli. It is accompanied by a reversible rotation of the root tip about its axis. A number of mutations affect the presence or the shape of root waves on tilted agar-based surfaces. One of them, wvc1, promotes the formation of compressed root waves under these conditions. The physiological and molecular analyses of this mutant suggest that a tryptophan-derived molecule other than IAA might be an important regulator of the curvature responsible for root waving.

Arabidopsis↗

Scatter factor/hepatocyte growth factor expression enhances human glioblastoma tumorigenicity and growth.

We have shown previously that the multifunctional cytokine scatter factor/hepatocyte growth factor (SF/HGF) is elevated in human malignant gliomas. In this study we investigated how human SF/HGF expression affects the malignancy of the U373 human glioblastoma cell line in vivo and in vitro. Human SF/HGF gene transfer increased U373 glioblastoma tumorigenicity by > or = 20-fold and enhanced the growth rate of intracerebral U373 xenografts by 3- to 8-fold. SF/HGF expression had no effect on the proliferation of glioblastoma cell monolayers but increased their anchorage-independent colony formation in soft agar by 5- to 8-fold. These results are the first to show that SF/HGF expression by human glioblastoma cells enhances their growth dysregulation in vitro and malignancy in vivo.

Animals↗

The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.

Human secretory leukocyte protease inhibitor (hSLPI) is produced by epithelial cells at mucosal surfaces, where it regulates both the neutrophil-mediated inflammation that characterizes inflammatory diseases, and pathogens themselves via both antiprotease and "defensin-like" activities. Additionally, hSLPI may regulate other processes such as cutaneous desquamation and placental invasiveness. To better understand the primary physiologic roles of SLPI, it will be important to establish a genetically tractable animal model, the most attractive candidate being the mouse. In this report, the cloning and characterization of murine (m) SLPI is described. mSLPI is encoded by a single copy gene, and appears structurally highly similar to hSLPI. At the same time, significant differences between mSLPI and hSLPI are presented, notably a difference in expression pattern, and a structural difference in the protease binding site that correlates with a difference in the spectrum of protease inhibiton. Such species-specific evolution of this protease inhibitor is notable given that species-specific structure-function differences have previously been reported for the alpha-1 antitrypsin family.

Amino Acid Sequence↗

Early one-stage reconstruction of congenital vertical talus.

A simple, one-stage surgical reconstruction was performed on 20 feet with congenital vertical talus in 13 consecutive children. A newly devised outcome scoring system with seven clinical and eight radiographic parameters was utilized to determine correction of all feet at average follow-up of 41 months. There were no excellent, 17 good, 3 fair, and no poor results, with few associated perioperative complications. Clinically, mild postoperative stiffness of ankle and subtalar motion was occasionally noted. Radiographically, many feet had mild residual forefoot abduction with midfoot sagging at the talonavicular joint. Despite these mild postoperative abnormalities, good correction with plantigrade, painless feet was generally obtained when this procedure was performed in children younger than 27 months of age.

Child, Preschool↗

Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo.

Scatter factor (SF), also known as hepatocyte growth factor, is angiogenic in systemic tissue, and SF titers correlate with the malignancy and metastatic phenotype of certain systemic cancers. Human gliomas express SF and its receptor c-met, but their role in the malignant progression of these tumors has not been defined. To examine this, 9L glioma cells that express c-met but not SF were transfected with human SF cDNA, and their behavior in vitro and in vivo was examined. SF gene expression was detected in conditioned medium of 9L-SF but not in control 9L-neo-transfected cell lines, by reverse transcriptase-PCR, immunoblot, ELISA, and scatter activity assays. Gliomas derived from 9L-SF and control 9L-neo cell lines implanted in the caudate/putamen of Fisher 344 rats (intracranially) and in the flanks of SCID/Beige mice (subcutaneously) were examined. Extracts from intracranial (i.c.) gliomas contained elevated levels of SF protein as determined by ELISA (1 to 5.5 ng SF/mg protein), whereas no SF was detected in control tumors. Reverse transcriptase-PCR of RNA from i.c. gliomas revealed that only 9L-SF gliomas expressed SF and both 9L-neo and 9L-SF gliomas expressed the c-met SF receptor. By postimplantation Day 14, 9L-SF i.c. gliomas were approximately 5-fold larger than 9L-neo control tumors (p < 0.001). Subcutaneous 9L-SF glioma growth was also greater than that in controls, although the differences were more variable. SF-producing i.c. gliomas contained elevated levels of 48-kd urokinase (3.5-fold) and 92-kd type IV collagenase (2.8-fold), both enzymes that correlate with the malignant progression of human gliomas (p < 0.001). SF-producing and control 9L cell lines did not differ in rates of proliferation, thymidine incorporation, or adhesion-independent growth in vitro. Conditioned medium from 9L-SF cells stimulated thymidine incorporation into microvessel brain endothelial cells 3- to 4-fold higher than did CM from 9L-neo controls (p < 0.001). Intracranial 9L-SF gliomas were more angiogenic than controls based on elevated peak (2.25-fold; p < 0.005) and mean (1.7-fold; p < 0.008) blood vessel densities. These results suggest that SF production by glioma cells enhances glioma malignancy in vivo, in part, by paracrine mechanisms involving glioma-associated angiogenesis.

Animals↗