Strategies for a successful corrective Asian blepharoplasty after previously failed revisions

Asian blepharoplasty, although a common procedure, has a relatively high rate of complications. Subtle imperfections and more serious iatrogenic complications often require immediate attention by the aesthetic surgeon. After attempted correction of the deformities, residual problems or new ones can arise. Blepharoptosis, supratarsal depression, an excessively high or low crease, a short or discontinuous crease, multiple creases, and asymmetric creases are the most commonly encountered complications that require special attention in this group, which has already undergone more than one surgical procedure. Between January of 1996 and December of 2002, 168 Asian blepharoplasty revisions were performed by one surgeon (S. H.-T. Chen); of these, 36 patients (21 percent) had previously undergone failed revisions. This subgroup of patients consisted of six with blepharoptosis, six with asymmetrical eyelid creases, three with supratarsal depressions, three with high creases, two with short creases, and 16 with combinations of these deformities. The results were graded as excellent, good, fair, or poor, based on the symmetry of the eyelids, palpebral fissures, crease heights, lengths, shapes, eyelid fullness, and overall aesthetics of the final outcome. A survey was performed of patient and surgeon satisfaction and factored into the grading system. With an average follow-up period of 16 months (6 to 60 months), 22 patients (61 percent) were found to have excellent results, 10 (28 percent) had good results, two (5.6 percent) had fair results, and two (5.6 percent) had poor results. Corrective procedures after failed revision Asian blepharoplasty require special strategic considerations because of the presence of extensive scarring and inadequate skin, muscle, and preaponeurotic fat and because of the occasional presence of dehiscence of the levator aponeurosis. By using careful preoperative evaluation, accurate measurements, precise preoperative planning, intraoperative fat repositioning or grafting, skin excision or redraping, and proper placement of anchoring sutures, successful outcomes can be achieved. The authors evaluate the outcomes and detail the surgical procedures that were used to achieve successful outcomes in this particularly challenging group of patients.     

Characterization of a branch of the phylogenetic tree

We use a combination of analytic models and computer simulations to gain insight into the dynamics of evolution. Our results suggest that certain interesting phenomena should eventually emerge from the fossil record. For example, there should be a "tortoise and hare effect": those genera with the smallest species death rate are likely to survive much longer than genera with large species birth and death rates. A complete characterization of the behavior of a branch of the phylogenetic tree corresponding to a genus and accurate mathematical representations of the various stages are obtained. We apply our results to address certain controversial issues that have arisen in paleontology such as the importance of punctuated equilibrium and whether unique Cambrian phyla have survived to the present.     

Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites

Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are potent inhibitors of HIV infection. Here we report new findings on the mechanism of inhibition of a N-HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mutation in the N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development.     

Interaction between heme oxygenase-1 and -2 proteins

The three isoforms of heme oxygenase (HO), the rate-limiting enzyme in heme degradation, are the products of different genes that show marked differences in regulation and expression. Why is there redundancy in the heme degradation pathway, and why are there differences in tissue expression of HO isoenzymes are unanswered questions? An interaction between HO-1 and HO-2 is suspected by the co-localization of these enzymes in the lung and regions of the brain. Using multiple models and assays, we demonstrated an interaction between HO-1 and HO-2 at amino acids 0-45 of HO-2 and amino acids 58-80 of HO-1. The latter corresponds to a highly conserved, hydrophilic, and exposed region of the protein. Furthermore, the observed activity of the HO-1.HO-2 complex was lower than that expected from the sum of HO-1- and HO-2-derived activities, suggesting that this interaction serves to limit HO enzymatic activity. We speculate that this HO-1.HO-2 protein interaction may promote non-enzymatic functions of HO.     

Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium

Retinal pigment epithelium (RPE)possesses regulated chloride channels that are crucial fortransepithelial fluid and ion transport. At present, little is knownabout the molecular nature of chloride channels in human adult RPE(haRPE) or the effects of oxidative stress on membrane conductanceproperties. In the present study, we assessed ClC channel and cysticfibrosis transmembrane conductance regulator (CFTR) expression andmembrane chloride conductance properties in haRPE cells. ClC-5, ClC-3,ClC-2, and CFTR mRNA expression was confirmed with RT-PCR analysis, andprotein expression was detected with Western blot analysis andimmunofluorescence microscopy. Whole cell recordings of primarycultures of haRPE showed an outwardly rectifying chloride current thatwas inhibited by the oxidant H₂O₂. Theinhibitory effects of H₂O₂ were reduced incultured human RPE cells that were incubated with precursors ofglutathione synthesis or that were stably transfected to overexpress glutathione S-transferase. These findings indicate apossible role for ClC channels in haRPE cells and suggest possibleredox modulation of human RPE chloride conductances.

     

Comparison of homoeologous group-6 short arm physical maps of wheat and barley reveals a similar distribution of recombinogenic and gene-rich regions

Eighty two new loci, mapped with 51 DNA clones, were added to the earlier deletion maps of the homoeologous group-6 short arms of hexaploid wheat ( Triticum aestivum L. em Thell., 2n = 6 x = 42, AABBDD). There are now 41, 56 and 52 loci mapped on deletion maps of 6AS, 6BS and 6DS, respectively. The linear order of orthologous loci in all three arms appears to be identical. The majority of the loci are located in the distal one-half of the three arms. There seems to be an increased marker/gene density from the centromeric to the telomeric regions in each arm, and the marker density in comparable physical regions is similar on all three maps. Recombination is not uniformly distributed along the chromosome arms; 60% of recombination occurs in the distal one-third of each arm. Recombination increases from the proximal region to the distal end in a nonlinear pattern. The distribution of loci and recombination along each of the three chromosome arms is highly correlated. Comparison of the 6BS deletion map from this study and a 6HS physical map of barley ( Hordeum vulgare L., 2n = 2 x = 14, HH) reveals a remarkably similar distribution of recombinogenic and gene-rich regions between the two chromosome arms, suggesting that the distribution patterns of genes may be conserved in the homoeologous group-6 chromosome short arms of wheat and barley. A consensus map of wheat group-6 short arms containing 46 orthologous loci was constructed. Comparison of the consensus map with published linkage maps of Triticeae group-6 chromosome short arms indicates that the linear order of the loci on the maps has been largely conserved. Evidence from this study does not support the existence of a 2BS-6BS reciprocal terminal translocation.     

The murine macrophage apoB-48 receptor gene (Apob-48r): homology to the human receptor

Previously we cloned the human macrophage apolipoprotein B-48 receptor (ApoB-48R) and documented its expression in human atherosclerotic foam cells (1). Now we have identified and characterized the murine macrophage apob-48r cDNA gene sequence and its chromosomal location. The cDNA (3,615 bp) -deduced amino acid (aa) sequence (942 aa) is approximately 45% identical to the human macrophage APOB-48R, but not to other known gene families. The murine Apob-48r gene, like the human APOB-48R gene, consists of four exons interrupted by three small introns and is syntenically located on chromosome 7. Functionally significant conserved domains include an N-terminal hydrophobic domain, a glycosaminoglycan attachment site, an N-glycosylation site, and an ExxxLL internalization motif C-terminal to the putative internal transmembrane domain. Two conserved coiled-coil domains are likely involved in the spontaneous homodimerization that generates the active dimeric ligand binding species (mouse, approximately 190 kDa; human, approximately 200 kDa). Transfection of the murine apoB-48R into Chinese hamster ovary cells (CHOs) confers apoB-48R function: rapid, high-affinity, specific uptake of known triglyceride-rich lipoprotein ligands of the apoB-48R and, of note, uptake of the cholesteryl ester-rich apoB-48-containing very low density lipoproteins that accumulate in atherosclerosis-prone apoE-deficient mice. Uptake of these ligands by murine apoB-48R-transfected CHOs causes saturable, visible cellular triglyceride and cholesterol accumulation in vitro that resemble foam cells of atherosclerotic lesions. In aggregate, the data presented here and that previously published suggest that the apoE-independent murine apoB-48R pathway may contribute to the spontaneous development of atherosclerotic lesions rich in macrophage-derived foam cells observed in apoE-deficient mice, a murine model of human atherosclerosis.     

A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78

Neuroleukin (NLK) is a multifunctional protein involved in neuronal growth and survival, cell motility and differentiation, and glucose metabolism. We report herein that hippocampal expression of NLK and its receptor gp78 is associated with maze learning in rats. First, mRNA levels of NLK and gp78 were significantly increased in hippocampi of male Fischer-344 rats following training in the Stone T-maze and the Morris water maze. Second, a parallel increase was found in hippocampal NLK and gp78 proteins after maze learning. Third, NLK and gp78 mRNA and protein expression in hippocampus was reduced in a group of aged rats that showed more errors during the acquisition of the Stone maze task as compared with young rats. Finally, application of recombinant NLK to hippocampal neurons significantly enhanced glutamate-induced ion currents, functional molecular changes that have been correlated with learning in vivo. Taken together, our results identify a novel association of hippocampal expression of NLK and its receptor gp78 with rat maze learning. Interaction of NLK with gp78 and subsequent signaling may strengthen synaptic mechanisms underlying learning and memory formation.