Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
Add more filters










Publication year range
1.
Hand (N Y) ; : 15589447231174044, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37222280

ABSTRACT

BACKGROUND: Saw injuries are common, with more 75 000 occurring each year in the United States alone. While these injuries occur frequently, management strategies are not universally agreed upon, and data regarding outcomes and complications are lacking. We propose to provide a comprehensive picture of upper extremity saw injury patterns, management strategies, complications, and outcomes. METHODS: Patients presenting to a single level 1 trauma center between 2012 and2019 with upper extremity laceration, crush, or amputation were identified. In all, 10 721 patients were reviewed, and those without wood saw injuries were excluded. Patient demographic information, injury details, management strategy, and outcomes were collected. RESULTS: In all, 283 upper extremity wood saw injuries were analyzed. Injuries most commonly affected the fingers (92.2%), and the frequencies of simple lacerations and complicated injuries were nearly identical. The table saw was the most commonly implicated saw (48%) with more than half of the injuries being complicated, the most common being bone injury. Most patients were treated nonsurgically (81.3%), with the majority undergoing wound care in the emergency department followed by home antibiotics (68.2%). Subsequent complications were exceedingly rare (4.2%), with wound infection occurring in 5 patients. Amputations occurred in 19.4% of patients, leading to permanent functional impairment. CONCLUSIONS: Wood saw injuries are common, generating functional and financial burden. While injuries range in severity, management can typically be conducted within the emergency department with local wound care and outpatient oral antibiotics. Injury complications and long-term issues are rare. Ongoing efforts to promote saw safety are required to minimize the burden of these injuries.

2.
Physiol Rep ; 5(23)2017 Dec.
Article in English | MEDLINE | ID: mdl-29192064

ABSTRACT

The renal podocyte is central to the filtration function of the kidney that is dependent on maintaining both highly organized, branched cell structures forming foot processes, and a unique cell-cell junction, the slit diaphragm. Our recent studies investigating the developmental formation of the slit diaphragm identified a novel claudin family tetraspannin, TM4SF10, which is a binding partner for ADAP (also known as Fyn binding protein Fyb). To investigate the role of ADAP in podocyte function in relation to Fyn and TM4SF10, we examined ADAP knockout (KO) mice and podocytes. ADAP KO mice developed glomerular pathology that began as hyalinosis and progressed to glomerulosclerosis, with aged male animals developing low levels of albuminuria. Podocyte cell lines established from the KO mice had slower attachment kinetics compared to wild-type cells, although this did not affect the total number of attached cells nor the ability to form focal contacts. After attachment, the ADAP KO cells did not attain typical podocyte morphology, lacking the elaborate cell protrusions typical of wild-type podocytes, with the actin cytoskeleton forming circumferential stress fibers. The absence of ADAP did not alter Fyn levels nor were there differences between KO and wild-type podocytes in the reduction of Fyn activating phosphorylation events with puromycin aminonucleoside treatment. In the setting of endogenous TM4SF10 overexpression, the absence of ADAP altered the formation of cell-cell contacts containing TM4SF10. These studies suggest ADAP does not alter Fyn activity in podocytes, but appears to mediate downstream effects of Fyn controlled by TM4SF10 involving actin cytoskeleton organization.


Subject(s)
Actin Cytoskeleton/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Podocytes/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Cell Line , Female , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Podocytes/ultrastructure , Proteinuria/genetics , Proteinuria/metabolism , Proteinuria/pathology , Proto-Oncogene Proteins c-fyn/metabolism
3.
Dev Dyn ; 245(6): 653-66, 2016 06.
Article in English | MEDLINE | ID: mdl-26990309

ABSTRACT

BACKGROUND: TMEM47 is the vertebrate orthologue of C. elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. VAB-9 regulates cell morphology and adhesion in C. elegans and TMEM47 is expressed during kidney development and regulates the activity of Fyn. The conserved functions of VAB-9 and TMEM47 are not well understood. RESULTS: expression of TMEM47 in C. elegans functionally rescues vab-9 mutations. Unlike Claudins, expression of TMEM47 in L fibroblasts does not generate tight junction strands; instead, membrane localization requires E-cadherin expression. Temporally, TMEM47 localizes at cell junctions first with E-cadherin before ZO-1 colocalization and in polarized epithelia, TMEM47 colocalizes with adherens junction proteins. By immunoprecipitation, TMEM47 associates with classical adherens junction proteins, but also with tight junction proteins Par6B and aPKCλ. Over-expression of TMEM47 in MDCK cells decreases apical surface area, increases activated myosin light chain at cell-cell contacts, disrupts cell polarity and morphology, delays cell junction reassembly following calcium switch, and selectively interferes with tight junction assembly. Reduced TMEM47 expression results in opposite phenotypes. CONCLUSIONS: TMEM47 regulates the localization of a subset of tight junction proteins, associated actomyosin structures, cell morphology, and participates in developmental transitions from adherens to tight junctions. Developmental Dynamics 245:653-666, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/cytology , Caenorhabditis elegans/metabolism , Membrane Proteins/metabolism , Tight Junction Proteins/metabolism , Animals , Blotting, Western , Cadherins/genetics , Cadherins/metabolism , Caenorhabditis elegans Proteins/genetics , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Line , Cell Polarity/genetics , Cell Polarity/physiology , Dogs , Immunoprecipitation , Intercellular Junctions/genetics , Intercellular Junctions/metabolism , Membrane Proteins/genetics , Morphogenesis/genetics , Morphogenesis/physiology , Tight Junction Proteins/genetics , Tight Junctions/metabolism , Zonula Occludens-1 Protein/metabolism
4.
Tissue Barriers ; 1(3): e25502, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-24665403

ABSTRACT

The claudin family of integral membrane proteins was identified as the major protein component of the tight junctions in all vertebrates. Since their identification, claudins, and their associated pfam00822 superfamily of proteins have been implicated in a wide variety of cellular processes. Claudin homologs have been identified in invertebrates as well, including Drosophila and C. elegans. Recent studies demonstrate that the C. elegans claudins, clc-1-clc- 5, and similar proteins in the greater PMP22/EMP/claudin/voltage-gated calcium channel γ subunit family, including nsy-4, and vab-9, while highly divergent at a sequence level from each other and from the vertebrate claudins, in many cases play roles similar to those traditionally assigned to their vertebrate homologs. These include regulating cell adhesion and passage of small molecules through the paracellular space, channel activity, protein aggregation, sensitivity to pore-forming toxins, intercellular signaling, cell fate specification and dynamic changes in cell morphology. Study of claudin superfamily proteins in C. elegans should continue to provide clues as to how claudin family protein function has been adapted to perform diverse functions at specialized cell-cell contacts in metazoans.

5.
Am J Physiol Cell Physiol ; 301(6): C1351-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21881001

ABSTRACT

TM4SF10 [transmembrane tetra(4)-span family 10] is a claudin-like cell junction protein that is transiently expressed during podocyte development where its expression is downregulated in differentiating podocytes coincident with the appearance of nephrin at the slit diaphragm. In a yeast two-hybrid screen, we identified adhesion and degranulation-promoting adaptor protein (ADAP), a well-known Fyn substrate and Fyn binding partner, as a TM4SF10 interacting protein in mouse kidney. Using coimmunoprecipitation and immunohistochemistry experiments in cultured human podocytes, we show that TM4SF10 colocalizes with Fyn and ADAP but does not form a stable complex with Fyn. Cytoskeletal changes and phosphorylation events mediated by Fyn activity were reversed by TM4SF10 overexpression, including a decrease in the activating tyrosine phosphorylation of Fyn (Y(421)), suggesting TM4SF10 may have a regulatory role in suppressing Fyn activity. In addition, TM4SF10 was reexpressed following podocyte injury by puromycin aminonucleoside treatment, and its expression enhanced the abundance of high-molecular-weight forms of nephrin indicating it may participate in a mechanism controlling nephrin's appearance at the plasma membrane. Therefore, these studies have identified ADAP as another Fyn adapter protein expressed in podocytes, and that TM4SF10, possibly through ADAP, may regulate Fyn activity. Since TM4SF10 expression is temporally regulated during kidney development, these studies may help define a mechanism by which the slit diaphragm matures as a highly specialized cell junction during podocyte differentiation.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Podocytes/metabolism , Proto-Oncogene Proteins c-fyn/metabolism , Animals , Blotting, Western , Cell Differentiation/physiology , Cell Line , Humans , Immunohistochemistry , Immunoprecipitation , Intercellular Junctions/metabolism , Mice , Phosphorylation , Podocytes/cytology , Polymerase Chain Reaction , Rats , Transduction, Genetic , Two-Hybrid System Techniques
6.
Methods Mol Biol ; 762: 147-69, 2011.
Article in English | MEDLINE | ID: mdl-21717355

ABSTRACT

In the last decade, the claudin family of integral membrane proteins has been identified as the major protein component of the tight junctions in all vertebrates. The claudin superfamily proteins also function to regulate channel activity, intercellular signaling, and cell morphology. Subsequently, claudin homologues have been identified in invertebrates, including Drosophila and Caenorhabditis elegans. Recent studies demonstrate that the C. elegans claudins, clc-1 to clc-5, and similar proteins in the greater PMP22/EMP/claudin/calcium channel γ subunit family, including nsy-1-nsy-4 and vab-9, while highly divergent at a sequence level from each other and from the vertebrate claudins, in some cases play roles similar to those traditionally assigned to their vertebrate homologues. These include regulating cell adhesion and passage of small molecules through the paracellular space. The claudin superfamily proteins also function to regulate channel activity, intercellular signaling, and cell morphology. Study of claudin superfamily proteins in C. elegans should continue to provide clues as to how core claudin protein function can be modified to serve various specific roles at regions of cell-cell contact in metazoans.


Subject(s)
Caenorhabditis elegans/genetics , Cell Adhesion/physiology , Claudins/physiology , Ion Channels/metabolism , Signal Transduction/physiology , Tight Junctions/metabolism , Animals , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Chloride Channels/genetics , Chloride Channels/metabolism , Claudins/genetics , Conserved Sequence/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Species Specificity
7.
Dev Dyn ; 236(2): 596-605, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17195181

ABSTRACT

Cell junctions in the nephron are highly specialized to perform specific and distinct filtration and reabsorption functions. The mature kidney forms complex cell junctions including slit diaphragms that prevent the passage of serum proteins into the filtrate, and tubule cell junctions that regulate specific paracellular ion reuptake. We have investigated the expression of TM4SF10 (Trans-Membrane tetra(4)-Span Family 10) in mouse kidneys. TM4SF10 is the vertebrate orthologue of Caenorhabditis elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. We found that TM4SF10 localizes at the basal-most region of podocyte precursors before the capillary loop stage, at some tubule precursors, and at the ureteric bud junction with S-shaped bodies. Overall expression of TM4SF10 peaked at postnatal day 4 and was virtually absent in adult kidneys. The very limited expression of TM4SF10 protein that persisted into adulthood was restricted to a few tubule segments but remained localized to the basal region of lateral membranes. In undifferentiated cultured podocytes, TM4SF10 localized to the perinuclear region and translocated to the cell membrane after Cadherin appearance at cell-cell contacts. TM4SF10 colocalized with ZO1 and p120ctn in undifferentiated confluent podocytes and also colocalized with the tips of actin filaments at cell contacts. Upon differentiation of cultured podocytes, TM4SF10 protein disappeared from cell contacts and expression ceased. These results suggest that TM4SF10 functions during differentiation of podocytes and may participate in the maturation of cell junctions from simple adherens junctions to elaborate slit diaphragms. TM4SF10 may define a new class of Claudin-like proteins that function during junctional development.


Subject(s)
Cell Differentiation/physiology , Intercellular Junctions/metabolism , Kidney/embryology , Membrane Proteins/metabolism , Podocytes/cytology , Animals , Blotting, Western , Cell Differentiation/genetics , Cell Line , DNA Primers , Immunohistochemistry , Kidney/metabolism , Membrane Proteins/genetics , Mice , Podocytes/metabolism , Reverse Transcriptase Polymerase Chain Reaction
8.
Curr Biol ; 14(20): 1882-7, 2004 Oct 26.
Article in English | MEDLINE | ID: mdl-15498499

ABSTRACT

Polarized migration and spreading of epithelial sheets is important during many processes in vivo, including embryogenesis and wound healing. However, the signaling pathways that regulate epithelial migrations are poorly understood. To identify molecular components that regulate the spreading of epithelial sheets, we performed a screen for mutations that perturb epidermal cell migration during embryogenesis in Caenorhabditis elegans. We identified one mutant (jc5) as a weak mutation in itr-1, which encodes the single inositol 1,4,5-trisphosphate receptor (ITR) in C. elegans. During the migration of the embryonic epidermis, jc5 embryos display defects including misdirected migration or premature cessation of migration. Cells that halt their migration have disorganized F-actin and display reduced filopodial protrusive activity at their leading edge. Furthermore, some filopodia formed by epidermal cells in itr-1(jc5) embryos exhibit abnormally long lifetimes. Pharmacological studies with the inositol 1,4,5-trisphosphate antagonist xestospongin C phenocopy these defects, confirming that ITR function is important for proper epidermal migration. Our results provide the first molecular evidence that movements of embryonic epithelial cell sheets can be controlled by ITRs and suggest that such regulation may be a widespread mechanism for coordinating epithelial cell movements during embryogenesis.


Subject(s)
Caenorhabditis elegans/embryology , Calcium Channels/metabolism , Cell Movement/physiology , Epidermis/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction , Animals , Blotting, Western , Calcium Channels/genetics , Calcium Channels/physiology , Cell Movement/drug effects , DNA Primers , Epidermal Cells , Epidermis/physiology , Gene Components , Immunohistochemistry , Inositol 1,4,5-Trisphosphate Receptors , Macrocyclic Compounds , Microscopy, Confocal , Microscopy, Video , Mutation/genetics , Oxazoles/pharmacology , Pseudopodia/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/physiology , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA
9.
Curr Opin Nephrol Hypertens ; 12(4): 415-21, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12815338

ABSTRACT

PURPOSE OF REVIEW: Messenger RNA, transfer RNA and ribosomal RNA were defined long ago as essential components for transmission of genetic code from DNA. However, there are many other, less commonly recognized RNAs, such as ribozymes and small interfering RNAs, which are distinguished by their ability to inhibit RNA function. This review describes the basic molecular concepts and potential therapeutic applications of RNA inhibition by a variety of molecules, including ribozymes, antisense oligonucleotides, aptamers and small interfering RNAs. RECENT FINDINGS: A tremendous amount of data has recently emerged about double-stranded small interfering RNAs, which bind and degrade corresponding messenger RNAs by a process called RNA interference. Though native small interfering RNAs have been shown to be biologically relevant in animals and plants, synthetic types have rapidly become powerful tools for post-transcriptional inhibition of specific gene products to determine functional consequences in simple organisms and in-vitro model systems. More established means of RNA inhibition, such as with ribozyme and antisense strategies, continue to be viable options for in-vitro experiments, and form the basis for many ongoing clinical trials. SUMMARY: Ribozymes, antisense oligonucleotides, aptamers and small interfering RNAs are potentially useful reagents for in-vitro investigation and for treatment of kidney and hypertension diseases.


Subject(s)
Gene Silencing , Oligonucleotides, Antisense/metabolism , RNA Processing, Post-Transcriptional , RNA, Catalytic/metabolism , RNA, Small Interfering/metabolism , RNA/metabolism , Animals , Genetic Therapy/methods , Humans , Hypertension/therapy , Kidney Diseases/therapy
10.
Nat Cell Biol ; 5(7): 619-25, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12819787

ABSTRACT

Epithelial cell junctions are essential for cell polarity, adhesion and morphogenesis. We have analysed VAB-9, a cell junction protein in Caenorhabditis elegans. VAB-9 is a predicted four-pass integral membrane protein that has greatest similarity to BCMP1 (brain cell membrane protein 1, a member of the PMP22/EMP/Claudin family of cell junction proteins) and localizes to the adherens junction domain of C. elegans apical junctions. Here, we show that VAB-9 requires HMR-1/cadherin for localization to the cell membrane, and both HMP-1/alpha-catenin and HMP-2/beta-catenin for maintaining its distribution at the cell junction. In vab-9 mutants, morphological defects correlate with disorganization of F-actin at the adherens junction; however, localization of the cadherin-catenin complex and epithelial polarity is normal. These results suggest that VAB-9 regulates interactions between the cytoskeleton and the adherens junction downstream of or parallel to alpha-catenin and/or beta-catenin. Mutations in vab-9 enhance adhesion defects through functional loss of the cell junction genes apical junction molecule 1 (ajm-1) and discs large 1 (dlg-1), suggesting that VAB-9 is involved in cell adhesion. Thus, VAB-9 represents the first characterized tetraspan adherens junction protein in C. elegans and defines a new family of such proteins in higher eukaryotes.


Subject(s)
Caenorhabditis elegans Proteins/isolation & purification , Caenorhabditis elegans/metabolism , Cell Adhesion/genetics , Epidermis/metabolism , Epithelial Cells/metabolism , Intercellular Junctions/metabolism , Membrane Proteins/isolation & purification , Actin Cytoskeleton/metabolism , Adherens Junctions/genetics , Adherens Junctions/metabolism , Animals , Cadherins/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/ultrastructure , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cell Size/genetics , Claudin-1 , Cytoskeletal Proteins/metabolism , DNA, Complementary/analysis , DNA, Complementary/genetics , Epidermis/ultrastructure , Epithelial Cells/ultrastructure , Intercellular Junctions/genetics , Intercellular Junctions/ultrastructure , Membrane Proteins/genetics , Membrane Proteins/metabolism , Microscopy, Electron , Molecular Sequence Data , Mutation/genetics , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Trans-Activators/metabolism , alpha Catenin , beta Catenin
SELECTION OF CITATIONS
SEARCH DETAIL
...