Two arcane areas in liposuction: The banana and the sensuous triangle

Two new approaches in suction lipectomy of the buttocks region are described: liposuction of the banana and liposuction of the sensuous triangle. The banana is the highest part of the posterior thigh just below the buttocks crease. It appears only in certain individuals and appears as a buldge under the buttocks crease. The preferred approach to liposuction of the banana is discussed as well as a theory as to its etiology. A common complication of liposuction of this area is ptosis of the buttocks crease. Methods of treatment of this complication are also discussed. The second topic addressed is liposuction of the sensuous triangle which is at the junction of the lateral buttocks, lateral thigh, and posterior thigh. The result of suctioning this area is a more athletic-appearing buttocks region.Presented at the 7th Annual Meeting of the Lipoplasty Society of North America, San Francisco, California, October 29, 1989     

Factors affecting the availability and use of hemodialysis facilities

This article describes factors related to the geographic distribution of hemodialysis facilities and the relationship between availability and use. Such facilities tend to be concentrated in the same types of areas as other medical resources, and the number of medical specialists in an area is related to the rate of treatment for renal diseases. The proportion of treatment stations in an area owned by for-profit organizations is not related to the total treatment rate, but the market share of for-profit facilities is positively related to in-center treatment and negatively related to home treatment.     

Mitral stenosis obscuring the diagnosis of plexogenic pulmonary arteriopathy and familial pulmonary hypertension

A patient who died after surgery for critical mitral stenosis was found to have underlying unrecognised plexogenic pulmonary arteriopathy and familial pulmonary hypertension. The importance of recognising familial pulmonary hypertension is discussed, together with the contribution of genetic and other risk factors to plexogenic pulmonary arteriopathy.     

Pentobarbital has curare-like effects on adult-type nicotinic acetylcholine receptor channel currents

Pentobarbital (PB) is widely used as a short-term sedative and anticonvulsive drug with a side-effect of relaxing muscle tone. We investigated block of nicotinic acetylcholine receptor (nAChR) channel currents by PB using the patch-clamp technique in combination with an ultrafast system for solution exchange. As a preparation, recombinant rat adult-type nAChR channels transiently expressed in HEK293 cells were used. Appli-cation of 1 mM acetylcholine to small cells or outside-out patches showed a transient current with fast activation and desensitization kinetics. Adding PB to the acetylcholine-containing solution resulted in a decrease of the time constant of current decay and of the peak current amplitude starting at concentrations >0.01 mM PB. Preincubation of nAChR channels with PB led to a decrease of the peak current amplitude without alteration of activation and desensitization kinetics caused by competitive block of nAChR channels. In conclusion, similar to the effect of d-Tubocurarine, block of nAChR channel currents by PB can be explained by a combination of open-channel and competitive block. IMPLICATIONS: The interaction between adult-type nicotinic acetylcholine receptors, acetylcholine, and pentobarbital was biophysically investigated by using the patch-clamp technique in combination with tools for ultrafast solution exchange. PB elicited open-channel block and competitive block of nicotinic acetylcholine receptor channel currents, whereas the latter seems to be effective in clinically relevant concentrations.     

Evaluating the Health Risk from Secondary Sulfates in Eastern North American Regional Ambient Air Particulate Matter

Epidemiological studies of particulate matter (PM) using central area monitors have associated total PM mass, as well as certain individual components of PM, including sulfate, with adverse human health effects. However, some recent studies that used concentrated ambient particles (CAPs) or analyzed the effects of air pollution from different sources or geographic areas suggest that while some particles may be harmful, other particulate species including secondary sulfates may have negligible health effects. Toxicology studies to date also suggest that secondary sulfates pose little health risk. While studies using central-area monitors implicitly assume that all residents of the area are exposed to the same levels of pollution, newer studies find substantial health effects for those in close proximity to major roads. These latter studies recognize that although population exposure to widespread pollutants, such as total PM mass and sulfates, may be relatively uniform over a wide area, exposure to pollutants from local sources is not. While there is an emerging literature associating several adverse health effects with proximity to local pollution sources, the current database provides limited information that allows identification of specific particulate species that may cause little to no harm. In this article, we suggest that ambient secondary sulfates, and eastern North American regional air masses generally, appear to have little adverse impact on public health. This suggestion is based on evidence gleaned from eight avenues of investigation: (1) recent non-central-area monitor studies, including exposure gradient or proximity studies; (2) CAPs studies; (3) studies that examine effects related to different geographic areas or sources; (4) toxicology studies; (5) the limited number of studies that analyze existing central-area monitor data to explicitly examine the health impacts of sulfate and acidity versus PM mass; (6) “modern” area monitor studies with additional capabilities to distinguish among sources of pollution; (7) partial reinterpretation of two pivotal cohort studies; and (8) studies separating effects of secondary sulfates from those of primary metal sulfates. However, uncertainties remain regarding the role that secondary sulfates may play in ambient PM chemistry pathways leading to potentially harmful products, such as the possible effects of secondary organic aerosols that may be the product of acid catalysis of sulfur dioxide. Thus, more targeted study is needed, and some research suggestions are made in this regard.     

Molecular composition of the alveolar lining fluid in the aging lung

As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.     

Formation of Sindbis Virus Capsid Protein in Mammalian Cell-Free Extracts Programmed with Viral Messenger RNA

Extracts from Krebs II ascites cells and rabbit reticulocytes effectively synthesize viral proteins with Sindbis viral mRNA isolated from Sindbis-infected BHK cells. The major product is identical to Sindbis capsid protein on the basis of its electrophoretic mobility in sodium dodecyl sulfate-acrylamide gels and two-dimensional tryptic-peptide fingerprints. Various amounts of several additional discrete polypeptides are formed, depending on the components of the cell-free extracts. One of these polypeptides may be a prematurely terminated part of the viral-capsid protein, while another is larger in molecular weight than capsid protein but contains the capsid tryptic peptides. Several of the proteins formed in vitro also are detected in extracts of Sindbis-infected BHK cells labeled with [(35)S]methionine.The three proteins found in Sindbis virions are postulated to originate by proteolytic cleavage from a larger molecular weight polypeptide precursor that is translated from a polycistronic mRNA presumed to contain a single site for initiation of protein synthesis. The two in vitro systems appear to translate this polycistronic viral mRNA to yield specific viral capsid although no evidence was found for post-translational proteolysis. Other mechanisms for production of the capsid protein in the cell-free extracts are considered, and some of these may function in the viral-infected cell where unusually large amounts of viral capsid proteins are frequently detected.     

Bronchiolitis: update 2001

In this review, reports from last year on the following topics are summarized: (1) reviews of bronchiolitis in infants; respiratory syncytial virus (RSV)-associated illness, including possible viral mechanisms of alteration of airway function and results of an epidemiologic study of bronchiolitis-associated mortality. Studies evaluating (2) the use of serum eosinophilic cationic protein as a marker for development of subsequent persistent wheezing infants; (3) parental bronchial responsiveness as an indicator of genetic susceptibility to acute bronchiolitis; (4) prophylactic use of monoclonal antibody (Palivizumab) to control an outbreak of RSV in a hospital nursery; (5) a controlled clinical trial of ribaviron in acutely ill children; (6) reports of new associations with bronchiolitis obliterans organizing pneumonia (BOOP); (7) case reports of use of methotrexate as an alternate to corticosteroids in treatment of BOOP; (8) a newly described entity, eosinophilic bronchiolitis.     

Evolutionarily related small viral fusogens hijack distinct but modular actin nucleation pathways to drive cell-cell fusion

Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP–mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.

Aquareovirus and orthoreovirus are two genera of the Reoviridae family of segmented double-stranded RNA viruses that form multinucleated syncytia after infection, which can increase viral spread and pathogenicity (1–4). To drive cell-cell fusion, both aquareovirus and orthoreovirus express a nonstructural, fusion-associated small transmembrane (FAST) protein on the plasma membrane of infected cells. The FAST protein is not required for viral entry, and expression of FAST protein alone is sufficient to cause cells to fuse with naïve neighboring cells, forming large multinucleated syncytium (1, 2, 5–12), confirming they are bona fide cell-cell fusogens. Although they have similar function and topology in the membrane, FAST proteins from aquareovirus and orthoreovirus share minimal sequence identity (13). Based on phylogenetic analysis, they are hypothesized to have evolved from a common, likely nonfusogenic, ancestor 510 million years ago (4, 13, 14). Separate gain-of-function events are believed to have produced fusogenic proteins in both aquareovirus and orthoreovirus, with further divergence or acquisition events resulting in the diversity of FAST proteins found in reoviruses today (13).Aquareovirus and orthoreovirus FAST proteins are single-pass membrane proteins of fewer than 200 residues comprised of a mostly disordered cytoplasmic tail, a transmembrane domain, and a small ectodomain of fewer than 40 residues (1, 2). The membrane-disruptive ectodomains of FAST proteins typically have solvent-exposed hydrophobic residues and/or myristoylation motifs that are necessary for cell-cell fusion (5, 15–17). In contrast to other cell-cell fusogens that fuse membranes by pulling them together using conformational changes in their ∼10 nm-tall ectodomains, the ectodomains of FAST proteins have minimal predicted secondary structure, are unlikely to undergo conformational changes to drive membrane fusion (1, 2), and extend only ∼1 nm above the bilayer (5, 18). How such short fusogens can overcome the ∼2 nm repulsive hydration barrier and larger barrier presented by cell surface proteins to reach and fuse with an opposing membrane (5, 18) has been a long-standing question for FAST proteins and other short cell-cell fusogens, such as myomixer and myomaker that are involved in myoblast fusion (19–22).Recently, we found that the FAST protein from reptilian orthoreovirus, p14, hijacks the host cell actin cytoskeleton to drive cell-cell fusion by forming localized branched actin networks (23). This is accomplished through a c-src phosphorylated tyrosine motif, YVNI, in p14’s disordered cytoplasmic tail that binds to a host adaptor protein, Grb2, which then binds to N-WASP and nucleates branched actin assembly. We hypothesize that this directly couples local actin-generated forces to push p14’s short, fusogenic ectodomain into the opposing cell’s plasma membrane (23). While all FAST family proteins have similarly short ectodomains, it is unclear if this is a general strategy used by other FAST proteins to drive cell-cell fusion.Here, we report that a FAST protein from the divergent aquareovirus, p22, also hijacks the host actin cytoskeleton but does so using a molecular strategy distinct from that of the orthoreovirus FAST protein p14. Instead of binding to Grb2, we find that p22 binds to Intersectin-1 through an SH3 binding motif in its cytoplasmic tail, which binds Cdc42 to activate N-WASP–mediated branched actin assembly. We show that despite minimal sequence identity, the p22 cytoplasmic tail can be functionally swapped with that of p14, suggesting that while the cytoplasmic tails of the two FAST proteins evolved independently, they serve a similar function. By directly coupling the ectodomain to a different actin nucleator, we suggest that actin’s functional role is applying mechanical pressure to a fusogenic ectodomain at the plasma membrane. This biophysical role may be shared across other members of the FAST protein family and could be more generally employed by other cell-cell fusogens.