Science.gov

Sample records for aldosterone-sensitive distal nephron

  1. In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron.

    PubMed

    Nesterov, Viatcheslav; Krueger, Bettina; Bertog, Marko; Dahlmann, Anke; Palmisano, Ralf; Korbmacher, Christoph

    2016-06-01

    The epithelial sodium channel (ENaC) is rate limiting for Na(+) absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na(+) reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control.

  2. In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron.

    PubMed

    Nesterov, Viatcheslav; Krueger, Bettina; Bertog, Marko; Dahlmann, Anke; Palmisano, Ralf; Korbmacher, Christoph

    2016-06-01

    The epithelial sodium channel (ENaC) is rate limiting for Na(+) absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na(+) reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control. PMID:27170740

  3. An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron.

    PubMed

    Carrisoza-Gaytan, Rolando; Carattino, Marcelo D; Kleyman, Thomas R; Satlin, Lisa M

    2016-02-15

    Flow-induced K secretion (FIKS) in the aldosterone-sensitive distal nephron (ASDN) is mediated by large-conductance, Ca(2+)/stretch-activated BK channels composed of pore-forming α-subunits (BKα) and accessory β-subunits. This channel also plays a critical role in the renal adaptation to dietary K loading. Within the ASDN, the cortical collecting duct (CCD) is a major site for the final renal regulation of K homeostasis. Principal cells in the ASDN possess a single apical cilium whereas the surfaces of adjacent intercalated cells, devoid of cilia, are decorated with abundant microvilli and microplicae. Increases in tubular (urinary) flow rate, induced by volume expansion, diuretics, or a high K diet, subject CCD cells to hydrodynamic forces (fluid shear stress, circumferential stretch, and drag/torque on apical cilia and presumably microvilli/microplicae) that are transduced into increases in principal (PC) and intercalated (IC) cell cytoplasmic Ca(2+) concentration that activate apical voltage-, stretch- and Ca(2+)-activated BK channels, which mediate FIKS. This review summarizes studies by ourselves and others that have led to the evolving picture that the BK channel is localized in a macromolecular complex at the apical membrane, composed of mechanosensitive apical Ca(2+) channels and a variety of kinases/phosphatases as well as other signaling molecules anchored to the cytoskeleton, and that an increase in tubular fluid flow rate leads to IC- and PC-specific responses determined, in large part, by the cell-specific composition of the BK channels.

  4. Opening lines of communication in the distal nephron.

    PubMed

    Kleyman, Thomas R; Satlin, Lisa M; Hallows, Kenneth R

    2013-10-01

    The distal nephron is composed of two main cell types: principal cells and intercalated cells. These cells have distinct morphologic features that allow them to be readily distinguished by light microscopy, as well as distinct suites of proteins that facilitate cell-specific transport properties. In this issue of the JCI, Gueutin and colleagues describe a new mechanism by which β-intercalated cells, via release of ATP and prostaglandin E2 (PGE2), influence the activity of transporters in principal cells.

  5. Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron.

    PubMed

    Nesterov, Viatcheslav; Dahlmann, Anke; Krueger, Bettina; Bertog, Marko; Loffing, Johannes; Korbmacher, Christoph

    2012-11-01

    Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na(+) channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (ΔI(ami)) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased ΔI(ami) in CNT/CCD but had little effect on ΔI(ami) in DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS(-/-)) mice that lack aldosterone. In CNT/CCD of AS(-/-) mice, ΔI(ami) was lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS(-/-) mice, ΔI(ami) was similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.

  6. Wnt signaling orients the proximal-distal axis of chick kidney nephrons.

    PubMed

    Schneider, Jenny; Arraf, Alaa A; Grinstein, Mor; Yelin, Ronit; Schultheiss, Thomas M

    2015-08-01

    The nephron is the fundamental structural and functional unit of the kidney. Each mature nephron is patterned along a proximal-distal axis, with blood filtered at the proximal end and urine emerging from the distal end. In order to filter the blood and produce urine, specialized structures are formed at specific proximal-distal locations along the nephron, including the glomerulus at the proximal end, the tubule in the middle and the collecting duct at the distal end. The developmental processes that specify these different nephron segments are not fully understood. Wnt ligands, which are expressed in the nephric duct and later in the nascent nephron itself, are well-characterized inducers of nephrons, and are both required and sufficient for initiation of nephron formation from nephrogenic mesenchyme. Here, we present evidence that Wnt signaling also patterns the proximal-distal nephron axis. Using the chick mesonephros as a model system, a Wnt ligand was ectopically expressed in the coelomic lining, thereby introducing a source of Wnt signaling that is at right angles to the endogenous Wnt signal of the nephric duct. Under these conditions, the nephron axis was re-oriented, such that the glomerulus was always located at a position farthest from the Wnt sources. This re-orientation occurred within hours of exposure to ectopic Wnt signaling, and was accompanied initially by a repression of the early glomerular podocyte markers Wt1 and Pod1, followed by their re-emergence at a position distant from the Wnt signals. Activation of the Wnt signaling pathway in mesonephric explant cultures resulted in strong and specific repression of early and late glomerular markers. Finally, cytoplasmic β-catenin, indicative of active canonical Wnt signaling, was found to be enriched in the distal as compared with the proximal region of the forming nephron. Together, these data indicate that Wnt signaling patterns the proximal-distal axis of the nephron, with glomeruli

  7. Nephrons require Rho-kinase for proximal-distal polarity development.

    PubMed

    Lindström, Nils O; Hohenstein, Peter; Davies, Jamie A

    2013-01-01

    Epithelial tubules must have the right length and pattern for proper function. In the nephron, planar cell polarity controls elongation along the proximal-distal axis. As the tubule lengthens, specialized segments (proximal, distal etc.) begin to differentiate along it. Other epithelia need Rho-kinase for planar cell polarity but it is not known whether Rho-kinase is involved in this way in the nephron. We show that Rho-kinase is essential for the morphogenesis of nephrons, specifically for correct cell orientation and volume. We use fluorescent reporter-models and progenitor-specific markers to demonstrate that inhibition of Rho-kinase prevents proper proximal-distal axis formation, causes segments to develop abnormally, and progenitor-cell segregation to fail. Our data demonstrate the importance of Rho-kinase in normal nephron tubulogenesis and patterning.

  8. Urinary tract obstruction in the mouse: the kinetics of distal nephron injury.

    PubMed

    Hiatt, Michael J; Ivanova, Larissa; Trnka, Peter; Solomon, Marc; Matsell, Douglas G

    2013-09-01

    Congenital urinary tract obstruction is the single most important cause of childhood chronic kidney disease. We have previously demonstrated that human and primate fetal obstruction impairs the development, differentiation, and maturation of the kidney. Research using postnatal rodent models has primarily focused upon the role of proximal tubular injury, with few reports of collecting duct system pathology or the suitability of the postnatal models for examining injury to the distal nephron. We have employed the mouse unilateral ureteric obstruction (UUO) model and examined time points ranging from 1 to 14 days of obstruction. Many of the key features of fetal collecting duct injury are replicated in the postnatal mouse model of obstruction. Obstruction causes a sixfold increase in myofibroblast accumulation, two- to threefold dilatation of tubules of the distal nephron, 65% reduction of principal cell aquaporin 2 expression, 75% reduction of collecting duct intercalated cell abundance, and disruption of E-cadherin- and βcatenin-mediated collecting duct epithelial adhesion. Notably, these features are shared by the distal and connecting tubules. This work confirms that distal nephron pathology is a significant component of postnatal mouse UUO. We have highlighted the utility of this model for investigating collecting duct and distal tubule injury and for identifying the underlying mechanisms of the distal nephron's contribution to the repair and fibrosis.

  9. Invasion of distal nephron precursors associates with tubular interconnection during nephrogenesis.

    PubMed

    Kao, Robert M; Vasilyev, Aleksandr; Miyawaki, Atsushi; Drummond, Iain A; McMahon, Andrew P

    2012-10-01

    Formation of a functional renal network requires the interconnection of two epithelial tubes: the nephron, which arises from kidney mesenchyme, and the collecting system, which originates from the branching ureteric epithelium. How this connection occurs, however, is incompletely understood. Here, we used high-resolution image analysis in conjunction with genetic labeling of epithelia to visualize and characterize this process. Although the focal absence of basal lamina from renal vesicle stages ensures that both epithelial networks are closely apposed, we found that a patent luminal interconnection is not established until S-shaped body stages. Precursor cells of the distal nephron in the interconnection zone exhibit a characteristic morphology consisting of ill-defined epithelial junctional complexes but without expression of mesenchymal markers such as vimentin and Snai2. Live-cell imaging revealed that before luminal interconnection, distal cells break into the lumen of the collecting duct epithelium, suggesting that an invasive behavior is a key step in the interconnection process. Furthermore, loss of distal cell identity, which we induced by activating the Notch pathway, prevented luminal interconnection. Taken together, these data support a model in which establishing the distal identity of nephron precursor cells closest to the nascent collecting duct epithelium leads to an active cell invasion, which in turn contributes to a patent tubular interconnection between the nephron and collecting duct epithelia.

  10. Identification and localization of BK-beta subunits in the distal nephron of the mouse kidney.

    PubMed

    Grimm, P Richard; Foutz, Ruth M; Brenner, Robert; Sansom, Steven C

    2007-07-01

    Large-conductance, Ca(2+)-activated K(+) channels (BK), comprised of pore-forming alpha- and accessory beta-subunits, secrete K(+) in the distal nephron under high-flow and high-K(+) diet conditions. BK channels are detected by electrophysiology in many nephron segments; however, the accessory beta-subunit associated with these channels has not been determined. We performed RT-PCR, Western blotting, and immunohistochemical staining to determine whether BK-beta1 is localized to the connecting tubule's principal-like cells (CNT) or intercalated cells (ICs), and whether BK-beta2-4 are present in other distal nephron segments. RT-PCR and Western blots revealed that the mouse kidney expresses BK-beta1, BK-beta2, and BK-beta4. Available antibodies in conjunction with BK-beta1(-/-) and BK-beta4(-/-) mice allowed the specific localization of BK-beta1 and BK-beta4 in distal nephron segments. Immunohistochemical staining showed that BK-beta1 is localized in the CNT but not ICs of the connecting tubule. The localization of BK-beta4 was discerned using an anti-BK-beta4 antibody on wild-type tissue and anti-GFP on GFP-replaced BK-beta4 mouse (BK-beta4(-/-)) tissue. Both antibodies (anti-BK-beta4 and anti-GFP) localized BK-beta4 to the thick ascending limb (TAL), distal convoluted tubule (DCT), and ICs of the distal nephron. It is concluded that BK-beta1 is narrowly confined to the apical membrane of CNTs in the mouse, whereas BK-beta4 is expressed in the TAL, DCT, and ICs.

  11. Ca2+ Imaging as a tool to assess TRP channel function in murine distal nephrons.

    PubMed

    Mamenko, Mykola; Zaika, Oleg; O'Neil, Roger G; Pochynyuk, Oleh

    2013-01-01

    Transient receptor potential (TRP) channels are expressed in almost every segment of renal nephron from the glomerulus to the inner medullary collecting duct. Serving as a route for Ca(2+) entry from the intratubular space into cells in response to external cues, TRP channels modulate water-electrolyte transport, thus determining functional properties of the renal tubule. In this chapter, we discuss technical aspects of using Ca(2+) imaging to monitor activity of TRP channels in situ, namely, in the freshly isolated distal nephrons, with a special emphasis on the mechanosensitive TRPV4 channel and its role in tubular flow sensing.

  12. Differential regulation of ROMK (Kir1.1) in distal nephron segments by dietary potassium.

    PubMed

    Wade, James B; Fang, Liang; Coleman, Richard A; Liu, Jie; Grimm, P Richard; Wang, Tong; Welling, Paul A

    2011-06-01

    ROMK channels are well-known to play a central role in renal K secretion, but the absence of highly specific and avid-ROMK antibodies has presented significant roadblocks toward mapping the extent of expression along the entire distal nephron and determining whether surface density of these channels is regulated in response to physiological stimuli. Here, we prepared new ROMK antibodies verified to be highly specific, using ROMK knockout mice as a control. Characterization with segmental markers revealed a more extensive pattern of ROMK expression along the entire distal nephron than previously thought, localizing to distal convoluted tubule regions, DCT1 and DCT2; the connecting tubule (CNT); and cortical collecting duct (CD). ROMK was diffusely distributed in intracellular compartments and at the apical membrane of each tubular region. Apical labeling was significantly increased by high-K diet in DCT2, CNT1, CNT2, and CD (P < 0.05) but not in DCT1. Consistent with the large increase in apical ROMK, dramatically increased mature glycosylation was observed following dietary potassium augmentation. We conclude 1) our new antibody provides a unique tool to characterize ROMK channel localization and expression and 2) high-K diet causes a large increase in apical expression of ROMK in DCT2, CNT, and CD but not in DCT1, indicating that different regulatory mechanisms are involved in K diet-regulated ROMK channel functions in the distal nephron. PMID:21454252

  13. Differential regulation of ROMK (Kir1.1) in distal nephron segments by dietary potassium.

    PubMed

    Wade, James B; Fang, Liang; Coleman, Richard A; Liu, Jie; Grimm, P Richard; Wang, Tong; Welling, Paul A

    2011-06-01

    ROMK channels are well-known to play a central role in renal K secretion, but the absence of highly specific and avid-ROMK antibodies has presented significant roadblocks toward mapping the extent of expression along the entire distal nephron and determining whether surface density of these channels is regulated in response to physiological stimuli. Here, we prepared new ROMK antibodies verified to be highly specific, using ROMK knockout mice as a control. Characterization with segmental markers revealed a more extensive pattern of ROMK expression along the entire distal nephron than previously thought, localizing to distal convoluted tubule regions, DCT1 and DCT2; the connecting tubule (CNT); and cortical collecting duct (CD). ROMK was diffusely distributed in intracellular compartments and at the apical membrane of each tubular region. Apical labeling was significantly increased by high-K diet in DCT2, CNT1, CNT2, and CD (P < 0.05) but not in DCT1. Consistent with the large increase in apical ROMK, dramatically increased mature glycosylation was observed following dietary potassium augmentation. We conclude 1) our new antibody provides a unique tool to characterize ROMK channel localization and expression and 2) high-K diet causes a large increase in apical expression of ROMK in DCT2, CNT, and CD but not in DCT1, indicating that different regulatory mechanisms are involved in K diet-regulated ROMK channel functions in the distal nephron.

  14. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis.

    PubMed

    Terker, Andrew S; Zhang, Chong; Erspamer, Kayla J; Gamba, Gerardo; Yang, Chao-Ling; Ellison, David H

    2016-01-01

    Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low-potassium diet. Recent data suggest that plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the with-no-lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK) pathway. As previous studies used extreme dietary manipulations, we sought to determine whether the relationship between potassium and NaCl cotransporter (NCC) is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride concentration. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable it to mediate effects of potassium on NCC in vivo.

  15. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis

    PubMed Central

    Terker, Andrew S.; Zhang, Chong; Erspamer, Kayla J.; Gamba, Gerardo; Yang, Chao-Ling; Ellison, David H.

    2015-01-01

    Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low potassium diet. Recent data suggest plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the With no lysine kinase (WNK)-Ste20p-related proline-and alanine-rich kinase (SPAK) pathway. Since previous studies used extreme dietary manipulations, we sought to determine if the relationship between potassium and NCC is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect the thiazide-sensitive sodium-chloride cotransporter, NCC, in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3 and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable kinase mediating effects of potassium on NCC in vivo. PMID:26422504

  16. Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6).

    PubMed

    Marunaka, Y; Hagiwara, N; Tohda, H

    1992-09-01

    Using the patch-clamp technique, we studied the effect of insulin on an amiloride-blockable Na channel in the apical membrane of a distal nephron cell line (A6) cultured on permeable collagen films for 10-14 days. NPo (N, number of channels per patch membrane; Po, average value of open probability of individual channels in the patch) under baseline conditions was 0.88 +/- 0.12 (SE)(n = 17). After making cell-attached patches on the apical membrane which contained Na channels, insulin (1 mU/ml) was applied to the serosal bath. While maintaining the cell-attached patch, NPo significantly increased to 1.48 +/- 0.19 (n = 17; P less than 0.001) after 5-10 min of insulin application. The open probability of Na channels was 0.39 +/- 0.01 (n = 38) under baseline condition, and increased to 0.66 +/- 0.03 (n = 38, P less than 0.001) after addition of insulin. The baseline single-channel conductance was 4pS, and neither the single-channel conductance nor the current-voltage relationship was significantly changed by insulin. These results indicate that insulin increases Na absorption in the distal nephron by increasing the open probability of the amiloride-blockable Na channel.

  17. Vasopressin regulation of sodium transport in the distal nephron and collecting duct.

    PubMed

    Kortenoeven, M L A; Pedersen, N B; Rosenbaek, L L; Fenton, R A

    2015-08-15

    Arginine vasopressin (AVP) is released from the posterior pituitary gland during states of hyperosmolality or hypovolemia. AVP is a peptide hormone, with antidiuretic and antinatriuretic properties. It allows the kidneys to increase body water retention predominantly by increasing the cell surface expression of aquaporin water channels in the collecting duct alongside increasing the osmotic driving forces for water reabsorption. The antinatriuretic effects of AVP are mediated by the regulation of sodium transport throughout the distal nephron, from the thick ascending limb through to the collecting duct, which in turn partially facilitates osmotic movement of water. In this review, we will discuss the regulatory role of AVP in sodium transport and summarize the effects of AVP on various molecular targets, including the sodium-potassium-chloride cotransporter NKCC2, the thiazide-sensitive sodium-chloride cotransporter NCC, and the epithelial sodium channel ENaC.

  18. Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron

    PubMed Central

    Mamenko, M.; Zaika, O.; Boukelmoune, N.; O'Neil, R. G.

    2014-01-01

    Long-standing experimental evidence suggests that epithelial cells in the renal tubule are able to sense osmotic and pressure gradients caused by alterations in ultrafiltrate flow by elevating intracellular Ca2+ concentration. These responses are viewed as critical regulators of a variety of processes ranging from transport of water and solutes to cellular growth and differentiation. A loss in the ability to sense mechanical stimuli has been implicated in numerous pathologies associated with systemic imbalance of electrolytes and to the development of polycystic kidney disease. The molecular mechanisms conferring mechanosensitive properties to epithelial tubular cells involve activation of transient receptor potential (TRP) channels, such as TRPV4, allowing direct Ca2+ influx to increase intracellular Ca2+ concentration. In this review, we critically analyze the current evidence about signaling determinants of TRPV4 activation by luminal flow in the distal nephron and discuss how dysfunction of this mechanism contributes to the progression of polycystic kidney disease. We also review the physiological relevance of TRPV4-based mechanosensitivity in controlling flow-dependent K+ secretion in the distal renal tubule. PMID:25503733

  19. Discrete control of TRPV4 channel function in the distal nephron by protein kinases A and C.

    PubMed

    Mamenko, Mykola; Zaika, Oleg L; Boukelmoune, Nabila; Berrout, Jonathan; O'Neil, Roger G; Pochynyuk, Oleh

    2013-07-12

    We have recently documented that the Ca(2+)-permeable TRPV4 channel, which is abundantly expressed in distal nephron cells, mediates cellular Ca(2+) responses to elevated luminal flow. In this study, we combined Fura-2-based [Ca(2+)]i imaging with immunofluorescence microscopy in isolated split-opened distal nephrons of C57BL/6 mice to probe the molecular determinants of TRPV4 activity and subcellular distribution. We found that activation of the PKC pathway with phorbol 12-myristate 13-acetate significantly increased [Ca(2+)]i responses to flow without affecting the subcellular distribution of TRPV4. Inhibition of PKC with bisindolylmaleimide I diminished cellular responses to elevated flow. In contrast, activation of the PKA pathway with forskolin did not affect TRPV4-mediated [Ca(2+)]i responses to flow but markedly shifted the subcellular distribution of the channel toward the apical membrane. These actions were blocked with the specific PKA inhibitor H-89. Concomitant activation of the PKA and PKC cascades additively enhanced the amplitude of flow-induced [Ca(2+)]i responses and greatly increased basal [Ca(2+)]i levels, indicating constitutive TRPV4 activation. This effect was precluded by the selective TRPV4 antagonist HC-067047. Therefore, the functional status of the TRPV4 channel in the distal nephron is regulated by two distinct signaling pathways. Although the PKA-dependent cascade promotes TRPV4 trafficking and translocation to the apical membrane, the PKC-dependent pathway increases the activity of the channel on the plasma membrane. PMID:23709216

  20. Salt handling in the distal nephron: lessons learned from inherited human disorders.

    PubMed

    Jeck, Nikola; Schlingmann, Karl P; Reinalter, Stephan C; Kömhoff, Martin; Peters, Melanie; Waldegger, Siegfried; Seyberth, Hannsjörg W

    2005-04-01

    The molecular basis of inherited salt-losing tubular disorders with secondary hypokalemia has become much clearer in the past two decades. Two distinct segments along the nephron turned out to be affected, the thick ascending limb of Henle's loop and the distal convoluted tubule, accounting for two major clinical phenotypes, hyperprostaglandin E syndrome and Bartter-Gitelman syndrome. To date, inactivating mutations have been detected in six different genes encoding for proteins involved in renal transepithelial salt transport. Careful examination of genetically defined patients ("human knockouts") allowed us to determine the individual role of a specific protein and its contribution to the overall process of renal salt reabsorption. The recent generation of several genetically engineered mouse models that are deficient in orthologous genes further enabled us to compare the human phenotype with the animal models, revealing some unexpected interspecies differences. As the first line treatment in hyperprostaglandin E syndrome includes cyclooxygenase inhibitors, we propose some hypotheses about the mysterious role of PGE(2) in the etiology of renal salt-losing disorders. PMID:15793031

  1. Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron.

    PubMed

    Nguyen, Mien T X; Han, Jiyang; Ralph, Donna L; Veiras, Luciana C; McDonough, Alicia A

    2015-09-01

    In Sprague Dawley rats, 2-week angiotensin II (AngII) infusion increases Na(+) transporter abundance and activation from cortical thick ascending loop of Henle (TALH) to medullary collecting duct (CD) and raises blood pressure associated with a pressure natriuresis, accompanied by depressed Na(+) transporter abundance and activation from proximal tubule (PT) through medullary TALH. This study tests the hypothesis that early during AngII infusion, before blood pressure raises, Na(+) transporters' abundance and activation increase all along the nephron. Male Sprague Dawley rats were infused via osmotic minipumps with a subpressor dose of AngII (200 ng/kg/min) or vehicle for 3 days. Overnight urine was collected in metabolic cages and sodium transporters' abundance and phosphorylation were determined by immunoblotting homogenates of renal cortex and medulla. There were no significant differences in body weight gain, overnight urine volume, urinary Na(+) and K(+) excretion, or rate of excretion of a saline challenge between AngII and vehicle infused rats. The 3-day nonpressor AngII infusion significantly increased the abundance of PT Na(+)/H(+) exchanger 3 (NHE3), cortical TALH Na-K-2Cl cotransporter 2 (NKCC2), distal convoluted tubule (DCT) Na-Cl cotransporter (NCC), and cortical CD ENaC subunits. Additionally, phosphorylation of cortical NKCC2, NCC, and STE20/SPS1-related proline-alanine-rich kinase (SPAK) were increased; medullary NKCC2 and SPAK were not altered. In conclusion, 3-day AngII infusion provokes PT NHE3 accumulation as well as NKCC2, NCC, and SPAK accumulation and activation in a prehypertensive phase before evidence for intrarenal angiotensinogen accumulation. PMID:26347505

  2. New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

    PubMed Central

    Morla, Luciana; Edwards, Aurélie; Crambert, Gilles

    2016-01-01

    The renal handling of Na+ balance is a major determinant of the blood pressure (BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part (i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na+ excretion and are the target of many different regulatory processes that modulate Na+ retention more or less efficiently. G-protein coupled receptors (GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na+ absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na+ excretion, this review also highlights the complexity of these different pathways, and the connections between them. PMID:26981195

  3. Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron.

    PubMed

    Cornelius, Ryan J; Wen, Donghai; Hatcher, Lori I; Sansom, Steven C

    2012-12-01

    Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH(4)Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia.

  4. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.

    PubMed

    Georgas, Kylie; Rumballe, Bree; Valerius, M Todd; Chiu, Han Sheng; Thiagarajan, Rathi D; Lesieur, Emmanuelle; Aronow, Bruce J; Brunskill, Eric W; Combes, Alexander N; Tang, Dave; Taylor, Darrin; Grimmond, Sean M; Potter, S Steven; McMahon, Andrew P; Little, Melissa H

    2009-08-15

    While nephron formation is known to be initiated by a mesenchyme-to-epithelial transition of the cap mesenchyme to form a renal vesicle (RV), the subsequent patterning of the nephron and fusion with the ureteric component of the kidney to form a patent contiguous uriniferous tubule has not been fully characterized. Using dual section in situ hybridization (SISH)/immunohistochemistry (IHC) we have revealed distinct distal/proximal patterning of Notch, BMP and Wnt pathway components within the RV stage nephron. Quantitation of mitoses and Cyclin D1 expression indicated that cell proliferation was higher in the distal RV, reflecting the differential developmental programs of the proximal and distal populations. A small number of RV genes were also expressed in the early connecting segment of the nephron. Dual ISH/IHC combined with serial section immunofluorescence and 3D reconstruction revealed that fusion occurs between the late RV and adjacent ureteric tip via a process that involves loss of the intervening ureteric epithelial basement membrane and insertion of cells expressing RV markers into the ureteric tip. Using Six2-eGFPCre x R26R-lacZ mice, we demonstrate that these cells are derived from the cap mesenchyme and not the ureteric epithelium. Hence, both nephron patterning and patency are evident at the late renal vesicle stage. PMID:19501082

  5. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.

    PubMed

    Georgas, Kylie; Rumballe, Bree; Valerius, M Todd; Chiu, Han Sheng; Thiagarajan, Rathi D; Lesieur, Emmanuelle; Aronow, Bruce J; Brunskill, Eric W; Combes, Alexander N; Tang, Dave; Taylor, Darrin; Grimmond, Sean M; Potter, S Steven; McMahon, Andrew P; Little, Melissa H

    2009-08-15

    While nephron formation is known to be initiated by a mesenchyme-to-epithelial transition of the cap mesenchyme to form a renal vesicle (RV), the subsequent patterning of the nephron and fusion with the ureteric component of the kidney to form a patent contiguous uriniferous tubule has not been fully characterized. Using dual section in situ hybridization (SISH)/immunohistochemistry (IHC) we have revealed distinct distal/proximal patterning of Notch, BMP and Wnt pathway components within the RV stage nephron. Quantitation of mitoses and Cyclin D1 expression indicated that cell proliferation was higher in the distal RV, reflecting the differential developmental programs of the proximal and distal populations. A small number of RV genes were also expressed in the early connecting segment of the nephron. Dual ISH/IHC combined with serial section immunofluorescence and 3D reconstruction revealed that fusion occurs between the late RV and adjacent ureteric tip via a process that involves loss of the intervening ureteric epithelial basement membrane and insertion of cells expressing RV markers into the ureteric tip. Using Six2-eGFPCre x R26R-lacZ mice, we demonstrate that these cells are derived from the cap mesenchyme and not the ureteric epithelium. Hence, both nephron patterning and patency are evident at the late renal vesicle stage.

  6. Differential regulation of Na+ transporters along nephron during ANG II-dependent hypertension: distal stimulation counteracted by proximal inhibition.

    PubMed

    Nguyen, Mien T X; Lee, Donna H; Delpire, Eric; McDonough, Alicia A

    2013-08-15

    During angiotensin II (ANG II)-dependent hypertension, ANG II stimulates, while hypertension inhibits, Na(+) transporter activity to balance Na(+) output to input. This study tests the hypothesis that ANG II infusion activates Na(+) transporters in the distal nephron while inhibiting transporters along the proximal nephron. Male Sprague-Dawley rats were infused with ANG II (400 ng·kg(-1)·min(-1)) or vehicle for 2 wk. Kidneys were dissected (cortex vs. medulla) or fixed for immunohistochemistry (IHC). ANG II increased mean arterial pressure by 40 mmHg, urine Na(+) by 1.67-fold, and urine volume by 3-fold, evidence for hypertension and pressure natriuresis. Na(+) transporters' abundance and activation [assessed by phosphorylation (-P) or proteolytic cleavage] were measured by immunoblot. During ANG II infusion Na(+)/H(+) exchanger 3 (NHE3) abundance decreased in both cortex and medulla; Na-K-2Cl cotransporter 2 (NKCC2) decreased in medullary thick ascending loop of Henle (TALH) and increased, along with NKCC2-P, in cortical TALH; Na-Cl cotransporter (NCC) and NCC-P increased in the distal convoluted tubule; and epithelial Na(+) channel subunits and their cleaved forms were increased in both cortex and medulla. Like NKCC2, STE20/SPS1-related proline alanine-rich kinase (SPAK) and SPAK-P were decreased in medulla and increased in cortex. By IHC, during ANG II NHE3 remained localized to proximal tubule microvilli at lower abundance, and the differential regulation of NKCC2 and NKCC2-P in cortex versus medulla was evident. In summary, ANG II infusion increases Na(+) transporter abundance and activation from cortical TALH to medullary collecting duct while the hypertension drives a natriuresis response evident as decreased Na(+) transporter abundance and activation from proximal tubule through medullary TALH. PMID:23720346

  7. Proximal Nephron

    PubMed Central

    Zhuo, Jia L.; Li, Xiao C.

    2013-01-01

    The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches. PMID:23897681

  8. Bone morphogenetic protein-7 expression and activity in the human adult normal kidney is predominantly localized to the distal nephron.

    PubMed

    Wetzel, P; Haag, J; Câmpean, V; Goldschmeding, R; Atalla, A; Amann, K; Aigner, T

    2006-08-01

    Bone morphogenetic protein-7 (BMP)-7 plays an important role during fetal kidney development. In the adult, BMP-7 is most strongly expressed in the kidney compared to other organs, but the exact expression pattern as well as the function of BMP-7 is unclear. The major aim of the present study was to define which parts of the human kidney do physiologically express BMP-7 and which cells appear to be targets of BMP activity by showing phosphorylated BMP-receptor-associated Smads 1, 5, or 8 and inhibitor of differentiation factor 1 (ID1) expression. BMP-7 expression was localized by immunohistology to the epithelia of the distal tubule as well as the collecting ducts (CDs). Phospho-Smads 1/5/8 and ID1 expression largely colocalized with BMP-7 and was also localized in the epithelia of the distal tubule and the CDs. This was confirmed by polymerase chain reaction-based mRNA expression analysis. In vitro, proximal tubular cells (PTCs) expressed BMP receptors and BMP-receptor-associated Smads and were reactive to BMP-7. Our data indicate that BMP-7 expression in the adult human kidney appears to be more restricted than in the fetal situation and predominantly found in the distal nephron. Also, evidence of in vivo BMP signalling (i.e. phospho-Smads and ID1 expression) was found there. These findings suggest that BMP-7 plays a physiological role mostly in this part of the kidney. Still, as reported previously, PTCs are responsive to BMP-7, but presumably not in an autocrine or paracrine mode in normal adult kidneys. PMID:16807538

  9. Fulvene-5 inhibition of Nadph oxidases attenuates activation of epithelial sodium channels in A6 distal nephron cells.

    PubMed

    Trac, David; Liu, Bingchen; Pao, Alan C; Thomas, Sheela V; Park, Michael; Downs, Charles A; Ma, He-Ping; Helms, My N

    2013-10-01

    Nadph oxidase 4 is an important cellular source of reactive oxygen species (ROS) generation in the kidney. Novel antioxidant drugs, such as Nox4 inhibitor compounds, are being developed. There is, however, very little experimental evidence for the biological role and regulation of Nadph oxidase isoforms in the kidney. Herein, we show that Fulvene-5 is an effective inhibitor of Nox-generated ROS and report the role of Nox isoforms in activating epithelial sodium channels (ENaC) in A6 distal nephron cells via oxidant signaling and cell stretch activation. Using single-channel patch-clamp analysis, we report that Fulvene-5 blocked the increase in ENaC activity that is typically observed with H2O2 treatment of A6 cells: average ENaC NPo values decreased from a baseline level of 1.04 ± 0.18 (means ± SE) to 0.25 ± 0.08 following Fulvene-5 treatment. H2O2 treatment failed to increase ENaC activity in the presence of Fulvene-5. Moreover, Fulvene-5 treatment of A6 cells blocked the osmotic cell stretch response of A6 cells, indicating that stretch activation of Nox-derived ROS plays an important role in ENaC regulation. Together, these findings indicate that Fulvene-5, and perhaps other classes of antioxidant inhibitors, may represent a novel class of compounds useful for the treatment of pathological disorders stemming from inappropriate ion channel activity, such as hypertension. PMID:23863470

  10. Morphological and molecular investigations of the holocephalan elephant fish nephron: the existence of a countercurrent-like configuration and two separate diluting segments in the distal tubule.

    PubMed

    Kakumura, Keigo; Takabe, Souichirou; Takagi, Wataru; Hasegawa, Kumi; Konno, Norifumi; Bell, Justin D; Toop, Tes; Donald, John A; Kaneko, Toyoji; Hyodo, Susumu

    2015-12-01

    In marine cartilaginous fish, reabsorption of filtered urea by the kidney is essential for retaining a large amount of urea in their body. However, the mechanism for urea reabsorption is poorly understood due to the complexity of the kidney. To address this problem, we focused on elephant fish (Callorhinchus milii) for which a genome database is available, and conducted molecular mapping of membrane transporters along the different segments of the nephron. Basically, the nephron architecture of elephant fish was similar to that described for elasmobranch nephrons, but some unique features were observed. The late distal tubule (LDT), which corresponded to the fourth loop of the nephron, ran straight near the renal corpuscle, while it was convoluted around the tip of the loop. The ascending and descending limbs of the straight portion were closely apposed to each other and were arranged in a countercurrent fashion. The convoluted portion of LDT was tightly packed and enveloped by the larger convolution of the second loop that originated from the same renal corpuscle. In situ hybridization analysis demonstrated that co-localization of Na(+),K(+),2Cl(-) cotransporter 2 and Na(+)/K(+)-ATPase α1 subunit was observed in the early distal tubule and the posterior part of LDT, indicating the existence of two separate diluting segments. The diluting segments most likely facilitate NaCl absorption and thereby water reabsorption to elevate urea concentration in the filtrate, and subsequently contribute to efficient urea reabsorption in the final segment of the nephron, the collecting tubule, where urea transporter-1 was intensely localized.

  11. RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron.

    PubMed

    Quentin, Fabienne; Eladari, Dominique; Cheval, Lydie; Lopez, Claude; Goossens, Dominique; Colin, Yves; Cartron, Jean-Pierre; Paillard, Michel; Chambrey, Régine

    2003-03-01

    Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies with specific ammonia transporters in primitive organisms and plants, could represent members of a new family of proteins involved in ammonia transport in the mammalian kidney. Consistent with this hypothesis, the expression of RhCG was recently reported at the apical pole of all connecting tubule (CNT) cells as well as in intercalated cells of collecting duct (CD). To assess the localization along the nephron of RhBG, polyclonal antibodies against the Rh type B glycoprotein were generated. In immunoblot experiments, a specific polypeptide of Mr approximately 50 kD was detected in rat kidney cortex and in outer and inner medulla membrane fractions. Immunocytochemical studies revealed RhBG expression in distal nephron segments within the cortical labyrinth, medullary rays, and outer and inner medulla. RhBG expression was restricted to the basolateral membrane of epithelial cells. The same localization was observed in rat and mouse kidney. RT-PCR analysis on microdissected rat nephron segments confirmed that RhBG mRNAs were chiefly expressed in CNT and cortical and outer medullary CD. Double immunostaining with RhCG demonstrated that RhBG and RhCG were coexpressed in the same cells, but with a basolateral and apical localization, respectively. In conclusion, RhBG and RhCG are present in a major site of ammonia secretion in the kidney, i.e., the CNT and CD, in agreement with their putative role in ammonium transport.

  12. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting

    PubMed Central

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X.; Smith, Roger D.; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  13. Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH.

    PubMed

    Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Lourdel, Stéphane; Teulon, Jacques; Paulais, Marc

    2016-09-01

    ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. PMID:27574292

  14. Induction and patterning of the metanephric nephron.

    PubMed

    O'Brien, Lori L; McMahon, Andrew P

    2014-12-01

    The functional unit of the mammalian metanephric kidney is the nephron: a complex tubular structure dedicated to blood filtration and maintenance of several important physiological functions. Nephrons are assembled from a nephron-restricted pool of mesenchymal progenitors over an extensive developmental period that is completed prior to (human), or shortly after (mouse), birth. An appropriate balance in the expansion and commitment of nephron progenitors to nephron formation is essential for normal kidney function. Too few nephrons increase risk of kidney disease later in life while the failure of normal progenitor differentiation in Wilm's tumor patients leads to massive growth of a nephroblast population often necessitating surgical removal of the kidney. An inductive process within the metanephric mesenchyme leads to the formation of a pretubular aggregate which transitions into an epithelial renal vesicle: the precursor for nephron assembly. Growth, morphogenesis and patterning transform this simple cyst-like structure into a highly elongated mature nephron with distinct cell types positioned along a proximal (glomerular) to distal (connecting segment) axis of functional organization. This review discusses our current understanding of the specification, maintenance and commitment of nephron progenitors, and the regulatory processes that transform the renal vesicle into a nephron.

  15. Hnf1beta and nephron segmentation.

    PubMed

    Naylor, Richard W; Davidson, Alan J

    2014-04-01

    The nephron is the functional unit that executes the homeostatic roles of the kidney in vertebrates. Critical to this function is the physical arrangement of the glomerular blood filter attached to a tubular epithelium that is subdivided into specialized proximal and distal segments. During embryogenesis, nephron progenitors undergo a mesenchymal-epithelial transition (MET) and adopt different segment-specific cell fates along the proximo-distal axis of the nephron. The molecular basis of how these segments arise remains largely unknown. Recent studies using the zebrafish have identified the Hnf1beta transcription factor (Hnf1b) as a major regulator of tubular segmentation. In Hnf1b-deficient zebrafish embryos, nephron progenitors fail to adopt the proximo-distal segmentation pattern of the nephron, yet still undergo MET. This observation suggests that the functional segmentation of renal tubular epithelial cells is independent of pathways that induce their epithelialization. Here we review this new role of Hnf1b for nephron segmentation during zebrafish and mouse kidney development.

  16. Remnant nephron physiology and the progression of chronic kidney disease.

    PubMed

    Schnaper, H William

    2014-02-01

    In chronic kidney disease, ongoing failure of individual nephrons leads to the progressive loss of renal function. This process results in part from a cellular and molecular response to injury that represents an attempt to maintain homeostasis but instead initiates a program that damages the nephron. As nephrons are lost, compensation by the remaining nephrons exacerbates glomerular pathophysiology. The delivery of excessive amounts of biologically active molecules to the distal nephron and tubulointerstitium generates inflammation and cellular dedifferentiation. Energy requirements of hyperfunctioning nephrons exceed the metabolic substrate available to the renal tubule, and inadequacy of the local vascular supply promotes hypoxia/ischemia and consequent acidosis and reactive oxygen species generation. In this way, mechanisms activated to maintain biological balance ultimately lead to demise of the nephron.

  17. Local inputs to aldosterone-sensitive neurons of the nucleus tractus solitarius.

    PubMed

    Sequeira, S M; Geerling, J C; Loewy, A D

    2006-09-15

    Aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) become activated during sodium depletion and could be key neural elements regulating sodium intake. The afferent inputs to these neurons have not yet been defined, but one source may be neurons in the area postrema, a neighboring circumventricular organ that innervates the NTS and exerts a powerful inhibitory influence on sodium appetite [Contreras RJ, Stetson PW (1981) Changes in salt intake after lesions of the area postrema and the nucleus of the solitary tract in rats. Brain Res 211:355-366]. After an anterograde axonal tracer was injected into the area postrema in rats, sections through the NTS were immunolabeled for the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), a marker for aldosterone-sensitive neurons, and examined by confocal microscopy. We found that some of the aldosterone-sensitive neurons received close appositions from processes originating in the area postrema, suggesting that input to the HSD2 neurons could be involved in the inhibition of sodium appetite by this site. Axonal varicosities originating from the area postrema also made close appositions with other neurons in the medial NTS, including the neurotensin-immunoreactive neurons in the dorsomedial NTS. Besides these projections, a dense field of neurotensinergic axon terminals overlapped the distribution of the HSD2 neurons. Neurotensin-immunoreactive axon terminals were identified in close apposition to the dendrites and cell bodies of some HSD2 neurons, as well as unlabeled neurons lying in the same zone within the medial NTS. A local microcircuit involving the area postrema, HSD2 neurons, and neurotensinergic neurons may play a major role in the regulation of sodium appetite.

  18. WNK1-related Familial Hyperkalemic Hypertension results from an increased expression of L-WNK1 specifically in the distal nephron.

    PubMed

    Vidal-Petiot, Emmanuelle; Elvira-Matelot, Emilie; Mutig, Kerim; Soukaseum, Christelle; Baudrie, Véronique; Wu, Shengnan; Cheval, Lydie; Huc, Elizabeth; Cambillau, Michèle; Bachmann, Sebastian; Doucet, Alain; Jeunemaitre, Xavier; Hadchouel, Juliette

    2013-08-27

    Large deletions in the first intron of the With No lysine (K) 1 (WNK1) gene are responsible for Familial Hyperkalemic Hypertension (FHHt), a rare form of human hypertension associated with hyperkalemia and hyperchloremic metabolic acidosis. We generated a mouse model of WNK1-associated FHHt to explore the consequences of this intronic deletion. WNK1(+/FHHt) mice display all clinical and biological signs of FHHt. This phenotype results from increased expression of long WNK1 (L-WNK1), the ubiquitous kinase isoform of WNK1, in the distal convoluted tubule, which in turn, stimulates the activity of the Na-Cl cotransporter. We also show that the activity of the epithelial sodium channel is not altered in FHHt mice, suggesting that other mechanisms are responsible for the hyperkalemia and acidosis in this model. Finally, we observe a decreased expression of the renal outer medullary potassium channel in the late distal convoluted tubule of WNK1(+/FHHt) mice, which could contribute to the hyperkalemia. In summary, our study provides insights into the in vivo mechanisms underlying the pathogenesis of WNK1-mediated FHHt and further corroborates the importance of WNK1 in ion homeostasis and blood pressure. PMID:23940364

  19. Distal Convoluted Tubule

    PubMed Central

    Ellison, David H.

    2014-01-01

    The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. PMID:24855283

  20. Nephron formation adopts a novel spatial topology at cessation of nephrogenesis.

    PubMed

    Rumballe, Bree A; Georgas, Kylie M; Combes, Alexander N; Ju, Adler L; Gilbert, Thierry; Little, Melissa H

    2011-12-01

    Nephron number in the mammalian kidney is known to vary dramatically, with postnatal renal function directly influenced by nephron complement. What determines final nephron number is poorly understood but nephron formation in the mouse kidney ceases within the first few days after birth, presumably due to the loss of all remaining nephron progenitors via epithelial differentiation. What initiates this event is not known. Indeed, whether nephron formation occurs in the same way at this time as during embryonic development has also not been examined. In this study, we investigate the key cellular compartments involved in nephron formation; the ureteric tip, cap mesenchyme and early nephrons; from postnatal day (P) 0 to 6 in the mouse. High resolution analyses of gene and protein expression indicate that loss of nephron progenitors precedes loss of ureteric tip identity, but show spatial shifts in the expression of cap mesenchyme genes during this time. In addition, cap mesenchymal volume and rate of proliferation decline prior to birth. Section-based 3D modeling and Optical Projection Tomography revealed a burst of ectopic nephron induction, with the formation of multiple (up to 5) nephrons per ureteric tip evident from P2. While the distal-proximal patterning of these nephrons occurred normally, their spatial relationship with the ureteric compartment was altered. We propose that this phase of nephron formation represents an acceleration of differentiation within the cap mesenchyme due to a displacement of signals within the nephrogenic niche.

  1. Nephron Patterning: Lessons from Xenopus, Zebrafish, and Mouse Studies

    PubMed Central

    Desgrange, Audrey; Cereghini, Silvia

    2015-01-01

    The nephron is the basic structural and functional unit of the vertebrate kidney. To ensure kidney functions, the nephrons possess a highly segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. During embryogenesis, nephron progenitors undergo a mesenchymal-to-epithelial transition (MET) and acquire different segment-specific cell fates along the proximo-distal axis of the nephron. Even if the morphological changes occurring during nephrogenesis are characterized, the regulatory networks driving nephron segmentation are still poorly understood. Interestingly, several studies have shown that the pronephric nephrons in Xenopus and zebrafish are segmented in a similar fashion as the mouse metanephric nephrons. Here we review functional and molecular aspects of nephron segmentation with a particular interest on the signaling molecules and transcription factors recently implicated in kidney development in these three different vertebrate model organisms. A complete understanding of the mechanisms underlying nephrogenesis in different model organisms will provide novel insights on the etiology of several human renal diseases. PMID:26378582

  2. Three-dimensional reconstruction of the mouse nephron.

    PubMed

    Zhai, Xiao-Yue; Thomsen, Jesper S; Birn, Henrik; Kristoffersen, Inger B; Andreasen, Arne; Christensen, Erik I

    2006-01-01

    Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture, including the spatial course of the tubules, lengths of different segments of nephrons, histotopography of tubules and vascular bundles, and epithelial ultrastructure at well-defined positions along Henle's loop and the distal convolution of nephrons. Three-dimensional reconstruction of 200 nephrons and collecting ducts was performed on aligned digital images, obtained from 2.5-mum-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons contributed to a 27% average increase in the lengths of the corresponding segments, (2) the thick-walled tubules incorporated in the central part of the vascular bundles in the inner stripe of the outer medulla were identified as thick ascending limbs of long-looped nephrons, and (3) three types of short-looped nephron bends were identified to relate to the length and the position of the nephron and its corresponding glomerulus. The ultrastructure of the tubule segments was identified and suggests important implications for renal transport mechanisms that should be considered when evaluating the segmental distribution of water and solute transporters within the normal and diseased kidney.

  3. Visualization of Three-Dimensional Nephron Structure With Microcomputed Tomography

    SciTech Connect

    Bentley,M.; Jorgensen, S.; Lerman, L.; Ritman, E.; Romero, J.

    2007-01-01

    The three-dimensional architecture of nephrons in situ and their interrelationship with other nephrons are difficult to visualize by microscopic methods. The present study uses microcomputed X-ray tomography (micro-CT) to visualize intact nephrons in situ. Rat kidneys were perfusion-fixed with buffered formalin and their vasculature was subsequently perfused with radiopaque silicone. Cortical tissue was stained en bloc with osmium tetroxide, embedded in plastic, scanned, and reconstructed at voxel resolutions of 6, 2, and 1 {mu}m. At 6 {mu}m resolution, large blood vessels and glomeruli could be visualized but nephrons and their lumens were small and difficult to visualize. Optimal images were obtained using a synchrotron radiation source at 2 {mu}m resolution where nephron components could be identified, correlated with histological sections, and traced. Proximal tubules had large diameters and opaque walls, whereas distal tubules, connecting tubules, and collecting ducts had smaller diameters and less opaque walls. Blood vessels could be distinguished from nephrons by the luminal presence of radiopaque silicone. Proximal tubules were three times longer than distal tubules. Proximal and distal tubules were tightly coiled in the outer cortex but were loosely coiled in the middle and inner cortex. The connecting tubules had the narrowest diameters of the tubules and converged to form arcades that paralleled the radial vessels as they extended to the outer cortex. These results illustrate a potential use of micro-CT to obtain three-dimensional information about nephron architecture and nephron interrelationships, which could be useful in evaluating experimental tubular hypertrophy, atrophy, and necrosis.

  4. Visualization of three-dimensional nephron structure with microcomputed tomography.

    PubMed

    Bentley, Michael D; Jorgensen, Steven M; Lerman, Lilach O; Ritman, Erik L; Romero, J Carlos

    2007-03-01

    The three-dimensional architecture of nephrons in situ and their interrelationship with other nephrons are difficult to visualize by microscopic methods. The present study uses microcomputed X-ray tomography (micro-CT) to visualize intact nephrons in situ. Rat kidneys were perfusion-fixed with buffered formalin and their vasculature was subsequently perfused with radiopaque silicone. Cortical tissue was stained en bloc with osmium tetroxide, embedded in plastic, scanned, and reconstructed at voxel resolutions of 6, 2, and 1 microm. At 6 microm resolution, large blood vessels and glomeruli could be visualized but nephrons and their lumens were small and difficult to visualize. Optimal images were obtained using a synchrotron radiation source at 2 microm resolution where nephron components could be identified, correlated with histological sections, and traced. Proximal tubules had large diameters and opaque walls, whereas distal tubules, connecting tubules, and collecting ducts had smaller diameters and less opaque walls. Blood vessels could be distinguished from nephrons by the luminal presence of radiopaque silicone. Proximal tubules were three times longer than distal tubules. Proximal and distal tubules were tightly coiled in the outer cortex but were loosely coiled in the middle and inner cortex. The connecting tubules had the narrowest diameters of the tubules and converged to form arcades that paralleled the radial vessels as they extended to the outer cortex. These results illustrate a potential use of micro-CT to obtain three-dimensional information about nephron architecture and nephron interrelationships, which could be useful in evaluating experimental tubular hypertrophy, atrophy, and necrosis.

  5. [The assessment of the regularity of the nephron anlage tubule formation on the basis of provisionality principle].

    PubMed

    Panteleev, S M; Vikhareva, L V; Mal'tseva, N G; Ushakov, A L; Khamoshina, I Ia; Iaroslavtseva, O F; Chivshina, R V; Pal'chenkova, N O; Margarian, A V; Belkhoroeva, M M

    2011-01-01

    The study of the definitive kidneys of 94 human embryos and fetuses at 4.5 to 12 weeks of gestation, has demonstrated that the formation of the proximal nephron tubules resulted from the cellular proliferation in the area of transition of the capsule of the renal corpuscle into the tubular part of the nephron that occurs only after the completion of the segregation of the renal corpuscle and the distal tubule within the nephron anlage. The formation of the renal tubules in the nephron anlage seems to be determined phylogenetically, while the initial differentiation of the distal tubule is a provisional feature.

  6. Genetics and the nephron.

    PubMed

    Marlais, M; Coward, R J

    2014-04-01

    There have been phenomenal advances in our understanding of renal biology over the last 20 years through our ability to define the genetic mutations causing kidney disease in children. This review will take you through a trip down the nephron and highlight how these conditions may present to the paediatrician and the molecular basis for their biological effects.

  7. Nephron organoids derived from human pluripotent stem cells model kidney development and injury.

    PubMed

    Morizane, Ryuji; Lam, Albert Q; Freedman, Benjamin S; Kishi, Seiji; Valerius, M Todd; Bonventre, Joseph V

    2015-11-01

    Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) may enable organ regeneration, disease modeling and drug screening. We report an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+ SALL1+ WT1+ PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+ LHX1+ renal vesicles that self-organize into nephron structures. In both two- and three-dimensional culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.

  8. Development of the metanephros in the chick: maturation of glomerular size and nephron length.

    PubMed

    Gambaryan, S P

    1992-01-01

    In the avian kidney three nephron types may be identified: mammalian-type nephrons with long (MTN-I) and short (MTN-II) loops of Henlé, and reptilian-type nephrons (RTN). By the method of microdissection the maturation of the nephrons of domestic fowl kidney has been studied. From the 14th day of incubation it is possible to isolate the MTN-I which appear first; all three nephron types may be isolated after 18 days of incubation. The thin limb of Henlé's loop in MTN-I appears after hatching, and the length of this segment in 1-day-old chicks is 0.1-0.13 mm. In 60-day-old chicks its length has approximately doubled. The transition of the thin segment to the thick segment is situated in the descending part of Henlé's loop. In the course of development, the relative length of all nephron segments in MTN-I increases uniformly, while in MTN-II and in RTN the relative length of the proximal and distal convoluted tubules increases. At all stages of development, MTN-I are the longest among the three groups of nephrons and have the largest glomeruli. The comparison between developing avian and mammalian kidneys shows great similarities in the process of maturation in analogous nephron types in these two classes of vertebrates.

  9. Reevaluation of erythropoietin production by the nephron.

    PubMed

    Nagai, Takanori; Yasuoka, Yukiko; Izumi, Yuichiro; Horikawa, Kahori; Kimura, Miho; Nakayama, Yushi; Uematsu, Takayuki; Fukuyama, Takashi; Yamazaki, Taiga; Kohda, Yukimasa; Hasuike, Yukiko; Nanami, Masayoshi; Kuragano, Takahiro; Kobayashi, Noritada; Obinata, Masuo; Tomita, Kimio; Tanoue, Akito; Nakanishi, Takeshi; Kawahara, Katsumasa; Nonoguchi, Hiroshi

    2014-06-27

    Erythropoietin production has been reported to occur in the peritubular interstitial fibroblasts in the kidney. Since the erythropoietin production in the nephron is controversial, we reevaluated the erythropoietin production in the kidney. We examined mRNA expressions of erythropoietin and HIF PHD2 using high-sensitive in situ hybridization system (ISH) and protein expression of HIF PHD2 using immunohistochemistry in the kidney. We further investigated the mechanism of erythropoietin production by hypoxia in vitro using human liver hepatocell (HepG2) and rat intercalated cell line (IN-IC cells). ISH in mice showed mRNA expression of erythropoietin in proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs) and cortical collecting ducts (CCDs) but not in the peritubular cells under normal conditions. Hypoxia induced mRNA expression of erythropoietin largely in peritubular cells and slightly in PCTs, DCTs, and CCDs. Double staining with AQP3 or AE1 indicated that erythropoietin mRNA expresses mainly in β-intercalated or non α/non β-intercalated cells of the collecting ducts. Immunohistochemistry in rat showed the expression of HIF PHD2 in the collecting ducts and peritubular cells and its increase by anemia in peritubular cells. In IN-IC cells, hypoxia increased mRNA expression of erythropoietin, erythropoietin concentration in the medium and protein expression of HIF PHD2. These data suggest that erythropoietin is produced by the cortical nephrons mainly in the intercalated cells, but not in the peritubular cells, in normal hematopoietic condition and by mainly peritubular cells in hypoxia, suggesting the different regulation mechanism between the nephrons and peritubular cells.

  10. Reevaluation of erythropoietin production by the nephron.

    PubMed

    Nagai, Takanori; Yasuoka, Yukiko; Izumi, Yuichiro; Horikawa, Kahori; Kimura, Miho; Nakayama, Yushi; Uematsu, Takayuki; Fukuyama, Takashi; Yamazaki, Taiga; Kohda, Yukimasa; Hasuike, Yukiko; Nanami, Masayoshi; Kuragano, Takahiro; Kobayashi, Noritada; Obinata, Masuo; Tomita, Kimio; Tanoue, Akito; Nakanishi, Takeshi; Kawahara, Katsumasa; Nonoguchi, Hiroshi

    2014-06-27

    Erythropoietin production has been reported to occur in the peritubular interstitial fibroblasts in the kidney. Since the erythropoietin production in the nephron is controversial, we reevaluated the erythropoietin production in the kidney. We examined mRNA expressions of erythropoietin and HIF PHD2 using high-sensitive in situ hybridization system (ISH) and protein expression of HIF PHD2 using immunohistochemistry in the kidney. We further investigated the mechanism of erythropoietin production by hypoxia in vitro using human liver hepatocell (HepG2) and rat intercalated cell line (IN-IC cells). ISH in mice showed mRNA expression of erythropoietin in proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs) and cortical collecting ducts (CCDs) but not in the peritubular cells under normal conditions. Hypoxia induced mRNA expression of erythropoietin largely in peritubular cells and slightly in PCTs, DCTs, and CCDs. Double staining with AQP3 or AE1 indicated that erythropoietin mRNA expresses mainly in β-intercalated or non α/non β-intercalated cells of the collecting ducts. Immunohistochemistry in rat showed the expression of HIF PHD2 in the collecting ducts and peritubular cells and its increase by anemia in peritubular cells. In IN-IC cells, hypoxia increased mRNA expression of erythropoietin, erythropoietin concentration in the medium and protein expression of HIF PHD2. These data suggest that erythropoietin is produced by the cortical nephrons mainly in the intercalated cells, but not in the peritubular cells, in normal hematopoietic condition and by mainly peritubular cells in hypoxia, suggesting the different regulation mechanism between the nephrons and peritubular cells. PMID:24832733

  11. Glomerular and tubular adaptive responses to acute nephron loss in the rat. Effect of prostaglandin synthesis inhibition.

    PubMed Central

    Pelayo, J C; Shanley, P F

    1990-01-01

    These studies, using in vivo micropuncture techniques in the Munich-Wistar rat, document the magnitude of changes in glomerular and tubular function and structure 24 h after approximately 75% nephron loss (Nx) and compared these results with those obtained in sham-operated rats. The contribution of either nephron hypertrophy or renal prostaglandin to these adjustments in nephron function was also explored. After acute Nx, single nephron GFR (SNGFR) was increased, on average by approximately 30%, due primarily to glomerular hyperperfusion and hypertension. The approximately 45% reduction in preglomerular and the constancy in postglomerular vascular resistances was entirely responsible for these adaptations. Although increases in fluid reabsorption in proximal convoluted tubules correlated closely with increase in SNGFR, the fractional fluid reabsorption between late proximal and early distal tubular segments was depressed. Nephron hypertrophy could not be substantiated based on either measurements of protein content in renal tissue homogenates or morphometric analysis of proximal convoluted tubules. However, acute Nx was associated with increased urinary excretory rates per functional nephron for 6-keto-PGF1 alpha and TXB2. Prostaglandin synthesis inhibition did not affect function in control nephrons, but this maneuver was associated with normalization of glomerular and tubular function in remnant nephrons. The results suggest that enhanced synthesis of cyclooxygenase-dependent products is one of the earliest responses to Nx, and even before hypertrophy the pathophysiologic effects of prostaglandin may be important contributors to the adaptations in remnant nephron function. PMID:1693376

  12. Caudal migration and proliferation of renal progenitors regulates early nephron segment size in zebrafish

    PubMed Central

    Naylor, Richard W.; Dodd, Rachel C.; Davidson, Alan J.

    2016-01-01

    The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca. Laser-mediated severing of the tubule, such that the DE and DL are disconnected or that the DL and cloaca do not fuse, results in a reduction in tubule cell proliferation and significantly shortens the DE segment while the caudal movement of the DL is unaffected. These results suggest that the DL mechanically pulls the more proximal segments, thereby driving both their caudal extension and their proliferation. Together, these data provide new insights into early nephron morphogenesis and demonstrate the importance of cell movement and proliferation in determining initial nephron segment size. PMID:27759103

  13. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment.

    PubMed

    Cebrian, Cristina; Asai, Naoya; D'Agati, Vivette; Costantini, Frank

    2014-04-10

    Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover. The reduction in CM cell number decreased the rate of branching, which in turn allowed the number of CM cells per UB tip to normalize, revealing a self-correction mechanism. However, the retarded UB branching impaired kidney growth, leaving a permanent nephron deficit. Thus, the number of fetal nephron progenitor cells is an important determinant of nephron endowment, largely via its effect on UB branching.

  14. Morphology and histochemistry of juvenile American alligator (Alligator mississippiensis) nephrons.

    PubMed

    Moore, Brandon C; Hyndman, Kelly A; Cox, Ashley; Lawler, Ashley; Mathavan, Ketan; Guillette, Louis J

    2009-10-01

    Here we present a detailed morphological description of the alligator (Alligator mississippiensis) kidney and nephron. We present a series of histological, histochemical, and immunohistochemical markers that clearly define the seven regions of the alligator nephron. The alligator kidney is composed of many paired (mirrored) lobules on each kidney (lobe). Single nephrons span the width of lobules three times. The fine structure of glomeruli, lying in rows spanning the height of the lobule, is resolved by periodic acid methionine silver (PAMS) and periodic acid Schiff's (PAS) histochemistry. Glomeruli are connected to the proximal tubule (PT) via a neck segment. The PT is alcian blue-negative, making it distinct from the distal tubule (DT), connecting segment (CS), and collecting duct (CD). The PT is clearly identifiable by a PAS-positive brush border membrane. The PT is connected to the DT via an intermediate segment (IS) that makes a 180 degrees turn to connect these tubules. PAMS-positive material is found in the lumens of the PT, IS, and DT. Also, PAMS-positive granules are found in the DT, CS, and CD. Immunolocalization of the Na(+), K(+)-ATPase to the basolateral membrane of the DT, CS, and CD suggests a role of this enzyme in driving primary and secondary transport processes in these segments, including bicarbonate transport into the lumen of the DT (leading to an alkaline urine). Through the techniques described here, we have identified a series of distinct markers to be used by pathologists, veterinarians, and researchers to easily identify alligator nephron segments. Anat Rec, 2009. (c) 2009 Wiley-Liss, Inc.

  15. Discrete network models of interacting nephrons

    NASA Astrophysics Data System (ADS)

    Moss, Rob; Kazmierczak, Ed; Kirley, Michael; Harris, Peter

    2009-11-01

    The kidney is one of the major organs involved in whole-body homeostasis, and exhibits many of the properties of a complex system. The functional unit of the kidney is the nephron, a complex, segmented tube into which blood plasma is filtered and its composition adjusted. Although the behaviour of individual nephrons can fluctuate widely and even chaotically, the behaviour of the kidney remains stable. In this paper, we investigate how the filtration rate of a multi-nephron system is affected by interactions between nephrons. We introduce a discrete-time multi-nephron network model. The tubular mechanisms that have the greatest effect on filtration rate are the transport of sodium and water, consequently our model attempts to capture these mechanisms. Multi-nephron systems also incorporate two competing coupling mechanisms-vascular and hemodynamic-that enforce in-phase and anti-phase synchronisations respectively. Using a two-nephron model, we demonstrate how changing the strength of the hemodynamic coupling mechanism and changing the arterial blood pressure have equivalent effects on the system. The same two-nephron system is then used to demonstrate the interactions that arise between the two coupling mechanisms. We conclude by arguing that our approach is scalable to large numbers of nephrons, based on the performance characteristics of the model.

  16. Clinicopathological assessment of the nephron number

    PubMed Central

    Tsuboi, Nobuo; Kanzaki, Go; Koike, Kentaro; Kawamura, Tetsuya; Ogura, Makoto; Yokoo, Takashi

    2014-01-01

    Recent studies have demonstrated much larger variability in the total number of nephrons in normal populations than previously suspected. In addition, it has been suggested that individuals with a low nephron number may have an increased lifetime risk of hypertension or renal insufficiency, emphasizing the importance of evaluating the nephron number in each individual. In view of the fact that all previous reports of the nephron number were based on analyses of autopsy kidneys, the identification of surrogate markers detectable in living subjects is needed in order to enhance understanding of the clinical significance of this parameter. In this review, we summarize the clinicopathological factors and findings indicating a reduction in the nephron number, focusing particularly on those found at the time of a preserved renal function. PMID:25852857

  17. Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis.

    PubMed

    Piscione, Tino D; Wu, Megan Y J; Quaggin, Susan E

    2004-10-01

    Hairy/Enhancer of Split (Hes) genes encode transcriptional repressors that function as downstream targets of activated Notch receptors in cell fate decisions during tissue development. During nephrogenesis, multiple Notch pathway genes are co-expressed in multi-potent epithelial progenitors (i.e. pre-tubular aggregates), but demonstrate distinct expression patterns in early nephrons (i.e. S-shaped bodies), suggesting that Notch signaling functions in patterning epithelial cell fate during nephron morphogenesis. To define the spatial activation of the Notch pathway in developing nephrons, we analyzed the expression of Hes1 and Hes5 by mRNA in situ hybridization in cryosections of developing kidneys, and compared their spatiotemporal expression with the expression of other Notch pathway genes in nephron progenitors. Hes1, and to a lesser extent Hes5, were expressed in pre-tubular aggregates and comma-shaped bodies of embryonic day (E) 13.5 and newborn kidneys. In S-shaped bodies, Hes1 expression was detected in the middle part which gives rise to the proximal tubule, but also extended into the lower and upper parts which give rise to the glomerulus and distal tubule, respectively, and was similar to the proximal-distal expression patterns for Notch1 and Jagged1 in these nephrogenic structures. In contrast, strong Hes5 expression was restricted to the middle segment of S-shaped bodies, and resembled Delta-like 1 expression. These data show that Hes1 and Hes5 expression are independently regulated along the proximal-distal axis of the developing nephron. Consequently, the differential, spatial regulation of Hes1 and Hes5 gene expression by the Notch signaling pathway in developing nephrons may be a mechanism for patterning cell fate decisions during nephron morphogenesis. PMID:15465493

  18. Nephron reconstitution from pluripotent stem cells.

    PubMed

    Taguchi, Atsuhiro; Nishinakamura, Ryuichi

    2015-05-01

    It has been a challenge in developmental biology and regenerative medicine to generate nephron progenitors that reconstitute the three-dimensional (3D) nephron structure in vitro. Many studies have tried to induce nephron progenitors from pluripotent stem cells by mimicking the developmental processes in vivo. However, the current developmental model does not precisely address the spatiotemporal origin of nephron progenitors, hampering our understanding of cell fate decisions in the kidney. Here, we present a revised model of early-stage kidney specification, suggesting distinct origins of the two major kidney components: the ureteric bud and metanephric mesenchyme. This model enables the induction of metanephric nephron progenitors from both mouse and human pluripotent stem cells. The induced cells self-organize in the presence of Wnt signaling and reconstitute 3D nephron structures including both nephric tubules with a clear lumina and glomeruli with podocytes. The engrafted kidney tissue develops vascularized glomeruli and nephric tubules, but it does not produce urine, suggesting the requirement for further maturation. Nevertheless, the generation of nephron components from human-induced pluripotent stem cells will be useful for future application in regenerative therapy and modeling of congenital kidney diseases in vitro. This review discusses the possibility of de novo organogenesis of a functional kidney from pluripotent stem cells and the future direction toward clinical applications.

  19. Prorenin receptor is critical for nephron progenitors.

    PubMed

    Song, Renfang; Preston, Graeme; Kidd, Laura; Bushnell, Daniel; Sims-Lucas, Sunder; Bates, Carlton M; Yosypiv, Ihor V

    2016-01-15

    Deficient nephrogenesis is the major factor contributing to renal hypoplasia defined as abnormally small kidneys. Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H(+)-ATPase. Global loss of PRR is lethal in mice and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. To circumvent lethality of the ubiquitous PRR mutation in mice and to determine the potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2(+) nephron progenitors and their epithelial derivatives (Six2(PRR-/-)). Targeted ablation of PRR in Six2(+) nephron progenitors caused a marked decrease in the number of developing nephrons, small cystic kidneys and podocyte foot process effacement at birth, and early postnatal death. Reduced congenital nephron endowment resulted from premature depletion of nephron progenitor cell population due to impaired progenitor cell proliferation and loss of normal molecular inductive response to canonical Wnt/β-catenin signaling within the metanephric mesenchyme. At 2 months of age, heterozygous Six2(PRR+/-) mice exhibited focal glomerulosclerosis, decreased kidney function and massive proteinuria. Collectively, these findings demonstrate a cell-autonomous requirement for the PRR within nephron progenitors for progenitor maintenance, progression of nephrogenesis, normal kidney development and function.

  20. Hepatocyte nuclear factor 1β controls nephron tubular development.

    PubMed

    Massa, Filippo; Garbay, Serge; Bouvier, Raymonde; Sugitani, Yoshinobu; Noda, Tetsuo; Gubler, Marie-Claire; Heidet, Laurence; Pontoglio, Marco; Fischer, Evelyne

    2013-02-01

    Nephron morphogenesis is a complex process that generates blood-filtration units (glomeruli) connected to extremely long and patterned tubular structures. Hepatocyte nuclear factor 1β (HNF1β) is a divergent homeobox transcription factor that is expressed in kidney from the first steps of nephrogenesis. Mutations in HNF1B (OMIM #137920) are frequently found in patients with developmental renal pathologies, the mechanisms of which have not been completely elucidated. Here we show that inactivation of Hnf1b in the murine metanephric mesenchyme leads to a drastic tubular defect characterized by the absence of proximal, distal and Henle's loop segments. Nephrons were eventually characterized by glomeruli, with a dilated urinary space, directly connected to collecting ducts via a primitive and short tubule. In the absence of HNF1β early nephron precursors gave rise to deformed S-shaped bodies characterized by the absence of the typical bulge of epithelial cells at the bend between the mid and lower segments. The lack of this bulge eventually led to the absence of proximal tubules and Henle's loops. The expression of several genes, including Irx1, Osr2 and Pou3f3, was downregulated in the S-shaped bodies. We also observed decreased expression of Dll1 and the consequent defective activation of Notch in the prospective tubular compartment of comma- and S-shaped bodies. Our results reveal a novel hierarchical relationship between HNF1β and key genes involved in renal development. In addition, these studies define a novel structural and functional component of S-shaped bodies at the origin of tubule formation.

  1. Dynamics of nephron-vascular network.

    PubMed

    Postnov, D D; Postnov, D E; Marsh, D J; Holstein-Rathlou, N-H; Sosnovtseva, O V

    2012-12-01

    The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode elimination, and (iii) distantly located areas show asynchronous behavior or, if all nephrons and branches are perfectly identical, an infinitely long transient behavior. These results contribute to the understanding of mechanisms responsible for the highly dynamic and limited synchronization observed among groups of nephrons despite of the fairly strong interaction between the individual units.

  2. The clinical importance of nephron mass.

    PubMed

    Luyckx, Valerie A; Brenner, Barry M

    2010-06-01

    Abundant evidence supports the association between low birth weight (LBW) and renal dysfunction in humans. Anatomic measurements of infants, children, and adults show significant inverse correlation between LBW and nephron number. Nephron numbers are also lower in individuals with hypertension compared with normotension among white and Australian Aboriginal populations. The relationship between nephron number and hypertension among black individuals is still unclear, although the high incidence of LBW predicts low nephron number in this population as well. LBW, a surrogate for low nephron number, also associates with increasing BP from childhood to adulthood and increasing risk for chronic kidney disease in later life. Because nephron numbers can be counted only postmortem, surrogate markers such as birth weight, prematurity, adult height, reduced renal size, and glomerulomegaly are potentially useful for risk stratification, for example, during living-donor assessment. Because early postnatal growth also affects subsequent risk for higher BP or reduced renal function, postnatal nutrition, a potentially modifiable factor, in addition to intrauterine effects, has significant influence on long-term cardiovascular and renal health.

  3. A molecular map of G protein alpha chains in microdissected rat nephron segments.

    PubMed Central

    Senkfor, S I; Johnson, G L; Berl, T

    1993-01-01

    Membrane-associated guanine nucleotide binding proteins regulate many receptor-mediated signals. Heterogeneity of biochemical and functional properties in nephron segments could be due to differences in G protein expression. To ascertain whether such heterogeneity of G proteins is present in various nephron segments, this study examines the distribution and relative abundance of G protein alpha chains in microdissected medullary thick ascending limb, cortical collecting tubules, outer medullary collecting tubules, proximal inner medullary tubules, and distal inner medullary tubules. Reverse transcription and polymerase chain reactions were employed using oligonucleotides encoding highly conserved regions of all known alpha chains. The cDNA was sequenced for alpha chain identification. The alpha i2 versus alpha s distribution was different in the outer medullary collecting tubules, when compared with the medullary thick ascending limb (P < 0.001) or the cortical collecting tubule, the proximal inner medullary tubules, and the distal inner medullary tubules (P < 0.05). These latter four segments did not significantly differ from each other. A similar analysis was applied to the frequently used line of kidney cells, LLC-PK1, whose exact cellular origin remains unclear. Interestingly, we detected both alpha i2 and alpha i3, while only alpha i2 was detected in the rat distal nephron. No alpha o or alpha z reverse transcription PCR products were detected. In contrast alpha 11 and alpha 14 members of the more recently described alpha q family were detected in the outer medullary collecting tubules and the proximal inner medullary tubules, respectively. We conclude that the majority of nephron segments have a relatively constant distribution of G protein alpha chains. Images PMID:8349818

  4. A synthetic niche for nephron progenitor cells.

    PubMed

    Brown, Aaron C; Muthukrishnan, Sree Deepthi; Oxburgh, Leif

    2015-07-27

    FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells. PMID:26190145

  5. Effect of carbonic anhydrase inhibition on superficial and deep nephron bicarbonate reabsorption in the rat.

    PubMed Central

    DuBose, T D; Lucci, M S

    1983-01-01

    The nephron segment responsible for the acetazolamide-insensitive fraction of renal bicarbonate reabsorption has not been clearly delineated. This study compares superficial and deep nephron bicarbonate reabsorption before and after acetazolamide at two dose levels (20 and 50 mg/kg per h) in mutant Munich-Wistar rats employing both cortical and papillary micropuncture and microcalorimetry. Systemic acid-base balance and right whole kidney glomerular filtration rate were similar in all groups examined. The effects of the two doses of acetazolamide were indistinguishable and resulted in a significant increase in whole kidney bicarbonate excretion that compared favorably with the fraction delivered out of the left papillary tip. Acetazolamide inhibited superficial proximal bicarbonate reabsorption by 80.0%, whereas reabsorption up to the deep loop of Henle was decreased by only 52% (P less than 0.001). Bicarbonate reabsorption that was insensitive to acetazolamide occurred in the superficial and deep loop of Henle and between the distal tubule and base collecting duct. Because water reabsorption in these segments could serve to generate transepithelial bicarbonate concentration gradients favorable for reabsorption, we attempted to minimize water abstraction by combined administration of mannitol and acetazolamide. During this condition a significant increase in bicarbonate delivery up to the deep loop of Henle was noted (52 vs. 65%), whereas superficial nephron reabsorption was not altered. Furthermore, an outwardly directed bicarbonate concentration gradient from the deep loop of Henle to vasa recta was demonstrated during acetazolamide (delta tCO2 = 20.9 +/- 3.3 mM), but was abolished during combined mannitol and acetazolamide administration (delta tCO2 = 3.5 +/- 0.9 mM). It is concluded that carbonic anhydrase inhibition results in a disparate effect on nephron bicarbonate reabsorption when juxtamedullary and superficial nephron segments are compared. Our findings

  6. Distal convoluted tubule.

    PubMed

    McCormick, James A; Ellison, David H

    2015-01-01

    The distal convoluted tubule (DCT) is a short nephron segment, interposed between the macula densa and collecting duct. Even though it is short, it plays a key role in regulating extracellular fluid volume and electrolyte homeostasis. DCT cells are rich in mitochondria, and possess the highest density of Na+/K+-ATPase along the nephron, where it is expressed on the highly amplified basolateral membranes. DCT cells are largely water impermeable, and reabsorb sodium and chloride across the apical membrane via electroneurtral pathways. Prominent among this is the thiazide-sensitive sodium chloride cotransporter, target of widely used diuretic drugs. These cells also play a key role in magnesium reabsorption, which occurs predominantly, via a transient receptor potential channel (TRPM6). Human genetic diseases in which DCT function is perturbed have provided critical insights into the physiological role of the DCT, and how transport is regulated. These include Familial Hyperkalemic Hypertension, the salt-wasting diseases Gitelman syndrome and EAST syndrome, and hereditary hypomagnesemias. The DCT is also established as an important target for the hormones angiotensin II and aldosterone; it also appears to respond to sympathetic-nerve stimulation and changes in plasma potassium. Here, we discuss what is currently known about DCT physiology. Early studies that determined transport rates of ions by the DCT are described, as are the channels and transporters expressed along the DCT with the advent of molecular cloning. Regulation of expression and activity of these channels and transporters is also described; particular emphasis is placed on the contribution of genetic forms of DCT dysregulation to our understanding.

  7. Nephron number and its determinants in early life: a primer.

    PubMed

    Charlton, Jennifer R; Springsteen, Caleb H; Carmody, J Bryan

    2014-12-01

    Although there is wide variation, humans possess on average 900,000 nephrons per kidney. So far as is known, nephrons cannot regenerate; therefore, an individual's nephron endowment has profound implications in determining his or her long-term risk of developing chronic kidney disease. Most of the variability in human nephron number is determined early in life. Nephrogenesis is a complex and carefully orchestrated process that occurs during a narrow time window until 36 weeks gestation in humans, and disruption of any part of this sequence may lead to reduced nephron number. In utero, genetic abnormalities, toxic insults, and nutritional deficiencies can each alter final nephron number. Infants born prematurely must continue nephrogenesis in an ex utero environment where there may be multiple threats to successful nephrogenesis. Once the nephron endowment is determined, postnatal factors (such as acute kidney injury or chronic illnesses) can only decrease nephron number. Current techniques for estimating nephron number require an invasive procedure or complete destruction of the tissue, making noninvasive means for counting nephron surgently needed. A better understanding of nephron number and its determinants, particularly during growth and maturation, could allow the development of therapies to support, prolong, or resume nephrogenesis.

  8. Human nephron number: implications for health and disease.

    PubMed

    Bertram, John F; Douglas-Denton, Rebecca N; Diouf, Boucar; Hughson, Michael D; Hoy, Wendy E

    2011-09-01

    Several studies have shown that total nephron (glomerular) number varies widely in normal human kidneys. Whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney, numbers for individual kidneys range from approximately 200,000 to >2.5 million. Several studies have shown loss of glomeruli due to age-related glomerulosclerosis. The rates of loss vary among individuals depending upon blood pressure, diseases affecting the kidney, and other attributes of health, but most of the variation in nephron number is present at birth and is therefore developmentally determined. For example, in a relatively small study of nephron number in 15 children <3 months of age, we found that nephron number ranged from approximately 250,000 to 1.1 million. Given that no new nephrons are formed in human kidneys after approximately 36 weeks' gestation, much interest has focused on renal function and health in individuals born with relatively low nephron endowment. Several studies have reported a direct correlation between birth weight and nephron number and an indirect association between nephron number and blood pressure. Associations between low birth weight and cardiovascular disease, including hypertension, have also been widely reported. This report provides an update on our current knowledge of human nephron number and the associations with adult health and disease.

  9. Single adult kidney stem/progenitor cells reconstitute three-dimensional nephron structures in vitro.

    PubMed

    Kitamura, Shinji; Sakurai, Hiroyuki; Makino, Hirofumi

    2015-03-01

    The kidneys are formed during development from two distinct primordial tissues, the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme develops into the kidney nephron, the minimal functional unit of the kidney. A nephron consists of several segments and regulates water, electrolyte, and acid-base homeostasis in addition to secreting certain hormones. It has been predicted that the kidney will be among the last organs successfully regenerated in vitro due to its complex structure and multiple functions. Here, we show that adult kidney stem/progenitor cells (KS cells), derived from the S3 segment of adult rat kidney nephrons, can reconstitute a three-dimensional kidney-like structure in vitro. Kidney-like structures were formed when a cluster of KS cells was suspended in an extracellular matrix gel and cultured in the presence of several growth factors. Morphological analyses revealed that these kidney-like structures contained every substructure of the kidney, including glomeruli, proximal tubules, the loop of Henle, distal tubules, and collecting ducts, but no vasculature. Our results demonstrate that a cluster of tissue stem/progenitor cells has the ability to reconstitute the minimum unit of its organ of origin by differentiating into specialized cells in the correct location. This process differs from embryonic kidney development, which requires the mutual induction of two different populations of progenitors, metanephric mesenchymal cells and ureteric bud cells.

  10. Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor.

    PubMed

    Kanda, Shoichiro; Tanigawa, Shunsuke; Ohmori, Tomoko; Taguchi, Atsuhiro; Kudo, Kuniko; Suzuki, Yutaka; Sato, Yuki; Hino, Shinjiro; Sander, Maike; Perantoni, Alan O; Sugano, Sumio; Nakao, Mitsuyoshi; Nishinakamura, Ryuichi

    2014-11-01

    The balanced self-renewal and differentiation of nephron progenitors are critical for kidney development and controlled, in part, by the transcription factor Six2, which antagonizes canonical Wnt signaling-mediated differentiation. A nuclear factor, Sall1, is expressed in Six2-positive progenitors as well as differentiating nascent nephrons, and it is essential for kidney formation. However, the molecular functions and targets of Sall1, especially the functions and targets in the nephron progenitors, remain unknown. Here, we report that Sall1 deletion in Six2-positive nephron progenitors results in severe progenitor depletion and apoptosis of the differentiating nephrons in mice. Analysis of mice with an inducible Sall1 deletion revealed that Sall1 activates genes expressed in progenitors while repressing genes expressed in differentiating nephrons. Sall1 and Six2 co-occupied many progenitor-related gene loci, and Sall1 bound to Six2 biochemically. In contrast, Sall1 did not bind to the Wnt4 locus suppressed by Six2. Sall1-mediated repression was also independent of its binding to DNA. Thus, Sall1 maintains nephron progenitors and their derivatives by a unique mechanism, which partly overlaps but is distinct from that of Six2: Sall1 activates progenitor-related genes in Six2-positive nephron progenitors and represses gene expression in Six2-negative differentiating nascent nephrons.

  11. Managing Complications Following Nephron-Sparing Procedures for Renal Masses.

    PubMed

    Gonzalez-Aguirre, Adrian J; Durack, Jeremy C

    2016-09-01

    Small renal malignancies are commonly treated with nephron-sparing procedures including partial nephrectomy and percutaneous ablation. Although these procedures offer faster patient recovery and preserve renal function, a variety of complications can occur. Here, we review vascular and nonvascular complications associated with nephron-sparing renal mass treatments and discuss options for minimally invasive image-guided management. PMID:27641453

  12. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    PubMed

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. PMID:24920757

  13. Nephron blood flow dynamics measured by laser speckle contrast imaging.

    PubMed

    Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga V; Pavlov, Alexey N; Cupples, William A; Sorensen, Charlotte Mehlin; Marsh, Donald J

    2011-02-01

    Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50-100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic techniques for extracting the desired data and for examining them for evidence of nephron synchronization. Synchronized TGF oscillations were detected in pairs or triplets of nephrons. The amplitude and the frequency of the oscillations changed with time, as did the patterns of synchronization. Synchronization may take place among nephrons not immediately adjacent on the surface of the kidney.

  14. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    PubMed

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation.

  15. Synchronization of period-doubling oscillations in vascular coupled nephrons.

    PubMed

    Laugesen, J L; Mosekilde, E; Holstein-Rathlou, N-H

    2011-09-01

    The mechanisms by which the individual functional unit (nephron) of the kidney regulates the incoming blood flow give rise to a number of nonlinear dynamic phenomena, including period-doubling bifurcations and intra-nephron synchronization between two different oscillatory modes. Interaction between the nephrons produces complicated and time-dependent inter-nephron synchronization patterns. In order to understand the processes by which a pair of vascular coupled nephrons synchronize, the paper presents a detailed analysis of the bifurcations that occur at the threshold of synchronization. We show that, besides infinite cascades of saddle-node bifurcations, these transitions involve mutually connected cascades of torus and homoclinic bifurcations. To illustrate the broader range of occurrence of this bifurcation structure for coupled period-doubling systems, we show that a similar structure arises in a system of two coupled, non-identical Rössler oscillators.

  16. Ultrastructure of the nephron in the soft-shelled turtle, Pelodiscus sinensis (Reptilia, Chelonia, Trionychidae).

    PubMed

    Xu, Chun-Sheng; Yang, Ping; Bao, Hui-Jun; Bian, Xun-Guang; Chen, Qiu-Sheng

    2013-01-01

    The structure of the nephron in adult soft-shelled turtles (Pelodiscus sinensis) was studied by light microscopy, transmission and scanning electron microscopy. The kidney contained 5-6 renal lobes. Nephrons of P. sinensis are composed of a renal corpuscle (RC) and of a renal tubule that appears divided morphologically into five distinct segments: neck segment (NS) (This segment is only present in approximately 10% of the nephrons), proximal tubule (PT), intermediate segment (IS), distal tubule (DT), and collecting duct (CD). The RCs and most of the convoluted DTs lie in the central zone, while the PTs and the CDs lie in the peripheral zone of the renal lobe. The renal corpuscle is relatively large with especial processes in podocytes and a thick basement membrane. The podocyte processes covering a large capillary area can be observed by TEM, and the major podocyte processes formed a very specific pattern in SEM. The podocyte processes expand to form a flattened network over the whole capillary loops surface, and only may observe little filtration slits in glomerular area. The neck segment when presentis short and has a relatively narrow lumen, consisting of cuboidal or squamous cells. There is a well-developed endocytic-lysosomal apparatus in the apical cytoplasm of the PT. The proximal tubule and intermediate segment cells show some differences between male and female. It showed that proximal tubule cells of male soft-shelt turtle contain lateral intercellular spaces, into which extensions of the cell membrane protrude, and the basal cell membrane forms a conspicuous labyrinth. Whereas, the basal and lateral cell membranes of the female are smooth, and no later-basal intercellular spaces. The differences between male and female in the middle segment cells is similar to proximal tubule cells. Not previously reported in vertebrate kidneys. The IS is the narrowest nephron segment, formed by multiciliated as well as nonciliated cells. In DT cells, basolateral

  17. Effect of estrogen on calcium and sodium transport by the nephron luminal membranes.

    PubMed

    Brunette, M G; Leclerc, M

    2001-08-01

    Estrogens are widely used for contraception and osteoporosis prevention. The aim of the present study was to investigate the effect of 17 beta-estradiol on calcium (Ca(2+)) transport by the nephron luminal membranes, independently of any other Ca(2+)-regulating hormones. Proximal and distal tubules of rabbit kidneys were incubated with 17 beta-estradiol or the carrier for various periods of time, and the luminal membranes of these tubules were purified and vesiculated. Ca(2+) uptake by membrane vesicles was measured using the Millipore filtration technique. Incubation of proximal tubules with the hormone did not influence Ca(2+) uptake by the luminal membranes. In contrast, incubation of distal tubules with 10(-8) M 17 beta-estradiol for 30 min decreased the initial uptake of 0.5 mM Ca(2+) from 0.34+/-0.04 (s.e.m. ) to 0.17+/-0.04 pmol/microg per 5 s (P<0.05). In the presence of 100 mM Na(+), 0.5 mM Ca(2+) uptake was strongly diminished and the effect of 17 beta-estradiol disappeared (0.17+/-0.01 and 0.21+/-0.07 pmol/microg per 5 s in vesicles from the control and treated tubules). Direct incubation of the membranes with 17 beta-estradiol, however, failed to show any influence of the hormone on Ca(2+) transport. The action of 17 beta-estradiol was dose-dependent, with a half-maximal effect at approximately 10(-9) M. Ca(2+) uptake by the distal tubule membranes presents dual kinetics. 17 beta-Estradiol decreased the V(max) value of the high-affinity component from 0.42+/-0.02 to 0.31+/-0.03 pmol/microg per 10 s (P<0.02). In contrast with the effect of the hormone on Ca(2+) transport, estradiol increased Na(+) uptake by both the proximal and distal tubule luminal membranes. In conclusion, incubation of proximal and distal tubules with estrogen decreases Ca(2+) reabsorption by the high-affinity Ca(2+) channels of the distal luminal membranes, and enhances Na(+) transport by the membranes from proximal and distal nephrons. PMID:11479140

  18. A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

    PubMed Central

    Hobbs, Robert F; Song, Hong; Huso, David L; Sundel, Margaret; Sgouros, George

    2013-01-01

    Objective Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction –based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply the model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. Methods We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin go those used in the Cristy-Eckermann phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured, ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus vs. proximal tubule vs. distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. Results The S-values were calculated for the α-emitters and their descendants between the different nephron compartments

  19. A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

    NASA Astrophysics Data System (ADS)

    Hobbs, Robert F.; Song, Hong; Huso, David L.; Sundel, Margaret H.; Sgouros, George

    2012-07-01

    Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the

  20. Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors.

    PubMed

    Hendry, Caroline E; Vanslambrouck, Jessica M; Ineson, Jessica; Suhaimi, Norseha; Takasato, Minoru; Rae, Fiona; Little, Melissa H

    2013-09-01

    Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions under which adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors. Using a combinatorial screen for lineage-instructive transcription factors, we identified a pool of six genes (SIX1, SIX2, OSR1, EYA1, HOXA11, and SNAI2) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule (HK2) cell line. Consistent with these reprogrammed cells being nephron progenitors, we observed differential contribution of the reprogrammed population into the Six2(+) nephron progenitor fields of an embryonic kidney explant. Dereplication of the pool suggested that SNAI2 can suppress E-CADHERIN, presumably assisting in the epithelial-to-mesenchymal transition (EMT) required to form nephron progenitors. However, neither TGFβ-induced EMT nor SNAI2 overexpression alone was sufficient to create this phenotype, suggesting that additional factors are required. In conclusion, these results suggest that reinitiation of kidney development from a population of adult cells by generating embryonic progenitors may be feasible, opening the way for additional cellular and bioengineering approaches to renal repair and regeneration.

  1. The Fate of Nephrons in Congenital Obstructive Nephropathy: Adult Recovery is Limited by Nephron Number Despite Early Release of Obstruction

    PubMed Central

    Sergio, Maria; Galarreta, Carolina I.; Thornhill, Barbara A.; Forbes, Michael S.; Chevalier, Robert L.

    2015-01-01

    Purpose Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of kidneys and urinary tract. We wished to determine the role of nephron number on the adaptation of remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction (UUO) and followed through adulthood. Materials and Methods Wild-type (WT) and Os/+ mice (with 50% fewer nephrons) were subjected to sham operation or partial UUO in the first 2 days of life. Additional mice underwent release of UUO at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction, and interstitial fibrosis were measured by histomorphometry. Results In the obstructed kidney, UUO caused additional nephron loss in Os/+ but not WT mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral UUO and was not preserved by release in WT or Os/+. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral UUO in all mice. These were attenuated by release of UUO in WT mice, but were not restored in Os/+ mice. UUO increased interstitial collagen in the contralateral kidney; release of UUO enhanced tubular growth and reduced interstitial collagen. Conclusions We conclude that UUO in early postnatal development impairs adaptation to reduced nephron number and induces additional nephron loss despite release of obstruction. Premature and low birth weight infants with congenital obstructive nephropathy are likely at increased risk for progression of chronic kidney disease. PMID:25912494

  2. Prenatal programming of nephron number and blood pressure.

    PubMed

    Schreuder, M F; Nauta, J

    2007-08-01

    A low nephron number has been advocated to explain the association between intrauterine growth restriction (IUGR) and hypertension in later life. IUGR not only leads to a low birth weight but is also hypothesized to reprogram nephrogenesis, which results in a low nephron endowment. Several methods are used to estimate the total glomerular number, but only stereological techniques result in accurate (unbiased) and precise (reproducible) data. Several studies, both in humans and animal models that have used these methods indeed revealed that IUGR leads to a low nephron number. According to the hyperfiltration hypothesis, this reduction in renal mass is supposed to lead to glomerular hyperfiltration and hypertension in remnant nephrons with subsequent glomerular injury with proteinuria, systemic hypertension and glomerulosclerosis. Even though IUGR is associated with both a low nephron endowment and an increased risk of hypertension, only circumstantial evidence is available to support the hyperfiltration hypothesis after prenatal programming. A prerequisite for establishment of this association in long-term, prospective follow-up studies is the ability to estimate glomerular numbers in living human beings, for which a further advancement in radiological techniques is necessary. Only then can the association between nephron endowment and blood pressure in humans be studied more conclusively.

  3. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.

    PubMed

    Diep, Cuong Q; Ma, Dongdong; Deo, Rahul C; Holm, Teresa M; Naylor, Richard W; Arora, Natasha; Wingert, Rebecca A; Bollig, Frank; Djordjevic, Gordana; Lichman, Benjamin; Zhu, Hao; Ikenaga, Takanori; Ono, Fumihito; Englert, Christoph; Cowan, Chad A; Hukriede, Neil A; Handin, Robert I; Davidson, Alan J

    2011-02-01

    Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.

  4. Epigenetic States of nephron progenitors and epithelial differentiation.

    PubMed

    Adli, Mazhar; Parlak, Mahmut; Li, Yuwen; El-Dahr, Samir S

    2015-06-01

    In mammals, formation of new nephrons ends perinatally due to consumption of mesenchymal progenitor cells. Premature depletion of progenitors due to prematurity or postnatal loss of nephrons due to injury causes chronic kidney disease and hypertension. Intensive efforts are currently invested in designing regenerative strategies to form new nephron progenitors from pluripotent cells, which upon further differentiation provide a potential source of new nephrons. To know if reprogramed renal cells can maintain their identity and fate requires knowledge of the epigenetic states of native nephron progenitors and their progeny. In this article, we summarize current knowledge and gaps in the epigenomic landscape of the developing kidney. We now know that Pax2/PTIP/H3K4 methyltransferase activity provides the initial epigenetic specification signal to the metanephric mesenchyme. During nephrogenesis, the cap mesenchyme housing nephron progenitors is enriched in bivalent chromatin marks; as tubulogenesis proceeds, the tubular epithelium acquires H3K79me2. The latter mark is uniquely induced during epithelial differentiation. Analysis of histone landscapes in clonal metanephric mesenchyme cell lines and in Wilms tumor and normal fetal kidney has revealed that promoters of poised nephrogenesis genes carry bivalent histone signatures in progenitors. Differentiation or stimulation of Wnt signaling promotes resolution of bivalency; this does not occur in Wilms tumor cells consistent with their developmental arrest. The use of small cell number ChIP-Seq should facilitate the characterization of the chromatin landscape of the metanephric mesenchyme and various nephron compartments during nephrogenesis. Only then we will know if stem and somatic cell reprogramming into kidney progenitors recapitulates normal development.

  5. The postobstructive kidney. Observations on nephron function after the relief of 24 hr of ureteral ligation in the dog

    PubMed Central

    Bercovitch, D. Danny; Kasen, Leonard; Blann, Laurence; Levitt, Marvin F.

    1971-01-01

    After the relief of 24 hr of complete unilateral ureteral obstruction in the dog, the experimental kidney is characterized by a decrease in filtration rate and an increase in fractional and often absolute excretion of sodium before and after the administration of mannitol. In the hydrated state, the failure to conserve sodium is associated with increases in fractional free water clearance and fractional sodium supply to water-freeing sites signifying that the augmented sodium excretion is derived from a proximal source. In the hydropenic state there is decreased fractional free water reabsorption, and sometimes free water excretion, in the postobstructive kidney. An early plateau in free water reabsorption is associated with an increased fractional excretion of sodium. These findings are attributed to the early development of distal nephron impermeability to water as a result of enhanced distal tubular supply and transport of sodium. There is a decrease in maximal tubular reabsorptive capacity (Tm) of glucose in the post-obstructive kidney which is, however, less marked than the decrease in filtration rate. The fall in filtration rate is to some extent likely due to a dropping out of nephrons from the circulation while the remaining nephrons are hypoperfused. The magnitude of the sodium reabsorptive defect is markedly exaggerated as the concentration of nonreabsorbable solute (mannitol) in the glomerular perfusate is increased. It is concluded that the postobstructive increase in sodium excretion during mannitol administration is in part due to a limit in the capacity to reabsorb sodium against a concentration gradient in the proximal tubule. PMID:5552413

  6. Novel candidate genes for impaired nephron development in a rat model with inherited nephron deficit and albuminuria.

    PubMed

    Herlan, Laura; Schulz, Angela; Schulte, Leonard; Schulz, Herbert; Hübner, Norbert; Kreutz, Reinhold

    2015-10-01

    Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. Here, we performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF rats at embryonic day (E)15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (fold change > +1.5 or < -1.5, respectively). Genes located on rat chromosome (RNO) 6 were of special interest because RNO6 carries genetic loci previously linked to the nephron deficit and renal damage in MWF. Differentially expressed genes located on RNO6 were further investigated by Real-time PCR including the late-stage of fetal kidney development, i.e. E19.0/E19.5, and week 4 of postnatal life when nephrogenesis is completed. Seven genes including Abcg5, Ab1-233, Efcab11, Fntb, Gpx2, Lrrn3, and Rtn1 were assigned on RNO6 and their differential expression was confirmed. Thus, we identified several genes that may act as crucial players in nephron development and are responsible for the nephron deficit in the MWF model.

  7. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice

    PubMed Central

    Hokke, Stacey; Puelles, Victor G.; Armitage, James A.; Fong, Karen; Bertram, John F.; Cullen-McEwen, Luise A.

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20–25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  8. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice.

    PubMed

    Hokke, Stacey; Puelles, Victor G; Armitage, James A; Fong, Karen; Bertram, John F; Cullen-McEwen, Luise A

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20-25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  9. Three-dimensional reconstruction of the rat nephron.

    PubMed

    Christensen, Erik I; Grann, Birgitte; Kristoffersen, Inger B; Skriver, Elisabeth; Thomsen, Jesper S; Andreasen, Arne

    2014-03-15

    This study gives a three-dimensional (3D) structural analysis of rat nephrons and their connections to collecting ducts. Approximately 4,500 2.5-μm-thick serial sections from the renal surface to the papillary tip were obtained from each of 3 kidneys of Wistar rats. Digital images were recorded and aligned into three image stacks and traced from image to image. Short-loop nephrons (SLNs), long-loop nephrons (LLNs), and collecting ducts (CDs) were reconstructed in 3D. We identified a well-defined boundary between the outer stripe and the inner stripe of the outer medulla corresponding to the transition of descending thick limbs to descending thin limbs and between the inner stripe and the inner medulla, i.e., the transition of ascending thin limbs into ascending thick limbs of LLNs. In all nephrons, a mosaic pattern of proximal tubule (PT) cells and descending thin limb (DTL) cells was observed at the transition between the PT and the DTL. The course of the LLNs revealed tortuous proximal "straight" tubules and winding of the DTLs within the outer half of the inner stripe. The localization of loop bends of SLNs in the inner stripe of the outer medulla and the bends of LLNs in the inner medulla reflected the localization of their glomeruli; i.e., the deeper the glomerulus, the deeper the bend. Each CD drained approximately three to six nephrons with a different pattern than previously established in mice. This information will provide a basis for evaluation of structural changes within nephrons as a result of physiological or pharmaceutical intervention.

  10. HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2.

    PubMed

    Heliot, Claire; Desgrange, Audrey; Buisson, Isabelle; Prunskaite-Hyyryläinen, Renata; Shan, Jingdong; Vainio, Seppo; Umbhauer, Muriel; Cereghini, Silvia

    2013-02-01

    The nephron is a highly specialised segmented structure that provides essential filtration and resorption renal functions. It arises by formation of a polarised renal vesicle that differentiates into a comma-shaped body and then a regionalised S-shaped body (SSB), with the main prospective segments mapped to discrete domains. The regulatory circuits involved in initial nephron patterning are poorly understood. We report here that HNF1B, a transcription factor known to be involved in ureteric bud branching and initiation of nephrogenesis, has an additional role in segment fate acquisition. Hnf1b conditional inactivation in murine nephron progenitors results in rudimentary nephrons comprising a glomerulus connected to the collecting system by a short tubule displaying distal fates. Renal vesicles develop and polarise normally but fail to progress to correctly patterned SSBs. Major defects are evident at late SSBs, with altered morphology, reduction of a proximo-medial subdomain and increased apoptosis. This is preceded by strong downregulation of the Notch pathway components Lfng, Dll1 and Jag1 and the Irx1/2 factors, which are potential regulators of proximal and Henle's loop segment fates. Moreover, HNF1B is recruited to the regulatory sequences of most of these genes. Overexpression of a HNF1B dominant-negative construct in Xenopus embryos causes downregulation specifically of proximal and intermediate pronephric segment markers. These results show that HNF1B is required for the acquisition of a proximo-intermediate segment fate in vertebrates, thus uncovering a previously unappreciated function of a novel SSB subcompartment in global nephron segmentation and further differentiation.

  11. Modifications of the genital kidney proximal and distal tubules for sperm transport in Notophthalmus viridescens (Amphibia, Urodela, Salamandridae).

    PubMed

    Nicholson, Abbigail E; Siegel, Dustin S

    2014-08-01

    Male salamanders use nephrons from the genital kidney to transport sperm from the testicular lobules to the Wolffian duct. The microstructure of the epithelia of the genital kidney proximal tubule and distal tubule was studied over 1 year in a population of Notophthalmus viridescens from Crawford and Pike counties in central Missouri. Through ultrastructural analysis, we were able to support the hypothesis that the genital kidney nephrons are modified to aid in the transportation of sperm. A lack of folding of the basal plasma membrane, in both the genital kidney proximal and distal tubules when compared to the pelvic kidney proximal and distal tubules, reduces the surface area and thus likely decreases the efficiency of reabsorption in these nephron regions of the genital kidney. Ciliated epithelial cells are also present along the entire length of the genital kidney proximal tubule, but are lacking in the epithelium of the pelvic kidney proximal tubule. The exact function of these cilia remains unknown, but they may aid in mixing of seminal fluids or the transportation of immature sperm through the genital kidney nephrons. Ultrastructural analysis of proximal and distal tubules of the genital kidney revealed no seasonal variation in cellular activity and no mass production of seminal fluids throughout the reproductive cycle. Thus, we failed to support the hypothesis that the cellular activity of the epithelia lining the genital kidney nephrons is correlated to specific events in the reproductive cycle. The cytoplasmic contents and overall structure of the genital and pelvic kidney epithelial cells were similar to recent observations in Ambystoma maculatum, with the absence of abundant dense bodies apically in the epithelial cells lining the genital kidney distal tubule.

  12. Modifications of the genital kidney proximal and distal tubules for sperm transport in Notophthalmus viridescens (Amphibia, Urodela, Salamandridae).

    PubMed

    Nicholson, Abbigail E; Siegel, Dustin S

    2014-08-01

    Male salamanders use nephrons from the genital kidney to transport sperm from the testicular lobules to the Wolffian duct. The microstructure of the epithelia of the genital kidney proximal tubule and distal tubule was studied over 1 year in a population of Notophthalmus viridescens from Crawford and Pike counties in central Missouri. Through ultrastructural analysis, we were able to support the hypothesis that the genital kidney nephrons are modified to aid in the transportation of sperm. A lack of folding of the basal plasma membrane, in both the genital kidney proximal and distal tubules when compared to the pelvic kidney proximal and distal tubules, reduces the surface area and thus likely decreases the efficiency of reabsorption in these nephron regions of the genital kidney. Ciliated epithelial cells are also present along the entire length of the genital kidney proximal tubule, but are lacking in the epithelium of the pelvic kidney proximal tubule. The exact function of these cilia remains unknown, but they may aid in mixing of seminal fluids or the transportation of immature sperm through the genital kidney nephrons. Ultrastructural analysis of proximal and distal tubules of the genital kidney revealed no seasonal variation in cellular activity and no mass production of seminal fluids throughout the reproductive cycle. Thus, we failed to support the hypothesis that the cellular activity of the epithelia lining the genital kidney nephrons is correlated to specific events in the reproductive cycle. The cytoplasmic contents and overall structure of the genital and pelvic kidney epithelial cells were similar to recent observations in Ambystoma maculatum, with the absence of abundant dense bodies apically in the epithelial cells lining the genital kidney distal tubule. PMID:24643856

  13. Nephron segment identification in the normal canine kidney by using lectin histochemistry.

    PubMed

    Yabuki, Akira; Mitani, Sawane; Mizukami, Keijiro; Yamato, Osamu

    2012-10-01

    Lectin-binding patterns in normal canine kidneys were histochemically investigated using eight lectins. WGA, ConA, and RCA-I showed positive signals in glomerular capillary walls, with signals for RCA-I being detected heterogeneously. In tubular segments, signals for WGA, s-WGA, ConA, and RCA-I were distributed widely from proximal tubules to collecting ducts, whereas those for SBA, PNA, DBA, and UEA-I were localized in thin limbs of the loop of Henle, thick ascending limbs, distal tubules, or collecting ducts. Apart from PNA and UEA-I, lectins showed heterogeneous bindings in collecting ducts with the heterogeneity. UEA-I-positive reactions were restricted to those parts of the distal tubules in close proximity to the glomeruli, and in these parts, signals in the macula densa were markedly stronger than in other regions. Based on the present findings, lectin probes, singly or in combination, could be utilized to identify the affected nephron segment in canine renal pathology.

  14. Inhibition of K+ secretion in the distal nephron in nephrotic syndrome: possible role of albuminuria.

    PubMed

    Fila, Marc; Brideau, Gaëlle; Morla, Luciana; Cheval, Lydie; Deschênes, Georges; Doucet, Alain

    2011-07-15

    Nephrotic syndrome features massive proteinuria and retention of sodium which promotes ascite formation. In the puromycin aminonucleoside-induced rat model of nephrotic syndrome, sodium retention originates from the collecting duct where it generates a driving force for potassium secretion. However, there is no evidence for urinary potassium loss or hypokalaemia in the nephrotic syndrome. We therefore investigated the mechanism preventing urinary potassium loss in the nephrotic rats and, for comparison, in hypovolaemic rats, another model displaying increased sodium reabsorption in collecting ducts. We found that sodium retention is not associated with urinary loss of potassium in either nephrotic or hypovolaemic rats, but that different mechanisms account for potassium conservation in the two models. Collecting ducts from hypovolaemic rats displayed high expression of the potassium-secreting channel ROMK but no driving force for potassium secretion owing to low luminal sodium availability. In contrast, collecting ducts from nephrotic rats displayed a high driving force for potassium secretion but no ROMK. Down-regulation of ROMK in nephrotic rats probably stems from phosphorylation of ERK arising from the presence of proteins in the luminal fluid. In addition, nephrotic rats displayed a blunted capacity to excrete potassium when fed a potassium-rich diet, and developed hyperkalaemia. As nephrotic patients were found to display plasma potassium levels in the normal to high range, we would recommend not only a low sodium diet but also a controlled potassium diet for patients with nephrotic syndrome. PMID:21606114

  15. Development of a Manipulative for Nephron Physiology Education

    ERIC Educational Resources Information Center

    Giffen, Zane C.; Carvalho, Helena

    2015-01-01

    Some physiological concepts, such as physiology of filtration and absorption in the different nephron segments, are so detailed that they can be a challenge to be memorized. This article describes an exercise that solidifies learning as students manipulate, using paper models, "transporters" and "electrolytes" in the…

  16. [Functional and structural characteristics of the nephron segments].

    PubMed

    Rohovyĭ, Iu Ie; Boĭko, O V; Filipova, L O

    2003-01-01

    The review presents a modern view on the functional--morphological peculiarities of 12 segments of the nephron canaliculi possessing some functional, biochemical and histologic distinctions that should be taken into account to study physiology, biochemistry, morphology and pathophysiology of the kidney.

  17. High nephron endowment protects against salt-induced hypertension.

    PubMed

    Walker, Kenneth A; Cai, Xiaochu; Caruana, Georgina; Thomas, Merlin C; Bertram, John F; Kett, Michelle M

    2012-07-15

    While low nephron number is associated with increased risk of developing cardiovascular and renal disease, the functional consequences of a high nephron number are unknown. We tested the hypothesis that a high nephron number provides protection against hypertensive and renal insults. Mean arterial pressure (MAP) and renal function were characterized in male wild-type (WT) and transforming growth factor-β2 heterozygous (Tgfb2(+/-)) mice under basal conditions and following a chronic high-salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. The chronic high-salt diet (5% NaCl for 4 wk followed by 8% NaCl for 4 wk) led to similar step-wise increases in urine volume, Na(+) excretion, and albuminuria in the genotypes. The 5% NaCl diet induced modest and similar increases in MAP (3.5 ± 1.6 and 3.4 ± 0.8 mmHg in WT and Tgfb2(+/-), respectively). After the step up to the 8% NaCl diet, MAP increased further in WT (+15.9 ± 5.1 mmHg), but not Tgfb2(+/-) (-0.1 ± 1.0 mmHg), mice. Nephron number was 30% greater in Tgfb2(+/-) than WT mice and was not affected by the chronic high-salt diet. Mean glomerular volume was lower in Tgfb2(+/-) than WT mice, and the chronic high-salt diet induced significant glomerular hypertrophy. In a separate cohort of mice, an acute, 7-day, 8% NaCl diet induced similar rises in MAP in the genotypes. This is the first study to examine the physiological characteristics of a model of high nephron number, and the findings are consistent with this phenotype providing protection against chronic, but not acute, hypertensive insults.

  18. TGF-mediated dynamics in a system of many coupled nephrons.

    PubMed

    Bayram, Saziye; Stepien, Tracy L; Pitman, E Bruce

    2009-08-01

    This paper presents a mathematical model of a system of many coupled nephrons branching from a common cortical radial artery, and accompanying analysis of that system. This modeling effort is a first step in understanding how coupling magnifies the tendency of nephrons to oscillate owing to tubuloglomerular feedback. Central to the present work is the single nephron integral model (as in Pitman et al., The IMA Volumes in Mathematics and Its Applications, vol. 129, pp. 345-364, 2002 and in Zaritski, Ph.D. Dissertation, 1999) which is a simplification of the single nephron PDE model of Layton et al. (Am. J. Physiol. 261, F904-F919, 1991). A second principal idea used in the present model is a coupling of model nephrons, generalizing the work of Pitman et al. (Bull. Math. Biol. 66, 1463-1492, 2004) who proposed a model of two coupled nephrons. In this study, we couple nephrons through a nearest neighbor interaction.Speaking generally, our results suggest that a series of similar nephrons coupled to their nearest neighbors are more prone to be found in an oscillatory mode, relative to a single nephron with the same properties. More specifically, we show analytically that, for N coupled identical nephrons, the region supporting oscillatory solutions in the time delay-gain parameter plane increases with N. Numerical simulations suggest that, if N nephrons have gains and time delays that do not differ by much, the system is, again, more prone to oscillate, relative to a single nephron, and the oscillations tend to be approximately synchronous and in-phase. We examine the effect of parameters on bifurcation. We also examine alternative models of coupling; this analysis allows us to conclude that the increased propensity of coupled nephrons to oscillate is a robust finding, true for several models of nephron interaction.

  19. Dicer1 activity in the stromal compartment regulates nephron differentiation and vascular patterning during mammalian kidney organogenesis.

    PubMed

    Nakagawa, Naoki; Xin, Cuiyan; Roach, Allie M; Naiman, Natalie; Shankland, Stuart J; Ligresti, Giovanni; Ren, Shuyu; Szak, Suzanne; Gomez, Ivan G; Duffield, Jeremy S

    2015-06-01

    MicroRNAs, activated by the enzyme Dicer1, control post-transcriptional gene expression. Dicer1 has important roles in the epithelium during nephrogenesis, but its function in stromal cells during kidney development is unknown. To study this, we inactivated Dicer1 in renal stromal cells. This resulted in hypoplastic kidneys, abnormal differentiation of the nephron tubule and vasculature, and perinatal mortality. In mutant kidneys, genes involved in stromal cell migration and activation were suppressed as were those involved in epithelial and endothelial differentiation and maturation. Consistently, polarity of the proximal tubule was incorrect, distal tubule differentiation was diminished, and elongation of Henle's loop attenuated resulting in lack of inner medulla and papilla in stroma-specific Dicer1 mutants. Glomerular maturation and capillary loop formation were abnormal, whereas peritubular capillaries, with enhanced branching and increased diameter, formed later. In Dicer1-null renal stromal cells, expression of factors associated with migration, proliferation, and morphogenic functions including α-smooth muscle actin, integrin-α8, -β1, and the WNT pathway transcriptional regulator LEF1 were reduced. Dicer1 mutation in stroma led to loss of expression of distinct microRNAs. Of these, miR-214, -199a-5p, and -199a-3p regulate stromal cell functions ex vivo, including WNT pathway activation, migration, and proliferation. Thus, Dicer1 activity in the renal stromal compartment regulates critical stromal cell functions that, in turn, regulate differentiation of the nephron and vasculature during nephrogenesis. PMID:25651362

  20. Distal splenorenal shunt

    MedlinePlus

    ... shunt procedure; Renal - splenic venous shunt; Warren shunt; Cirrhosis - distal splenorenal; Liver failure - distal splenorenal ... hepatitis Blood clots Certain congenital disorders Primary biliary cirrhosis When blood cannot flow normally through the portal ...

  1. Reduced nephron endowment in the neonates of Indigenous Australian peoples.

    PubMed

    Kandasamy, Y; Smith, R; Wright, I M R; Lumbers, E R

    2014-02-01

    Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.

  2. Cystic gene dosage influences kidney lesions after nephron reduction.

    PubMed

    Le Corre, Stéphanie; Viau, Amandine; Burtin, Martine; El-Karoui, Khalil; Cnops, Yvette; Terryn, Sara; Debaix, Huguette; Bérissi, Sophie; Gubler, Marie-Claire; Devuyst, Olivier; Terzi, Fabiola

    2015-01-01

    Cystic kidney disease is characterized by the progressive development of multiple fluid-filled cysts. Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. The most frequent form of this disease is the inherited polycystic kidney disease (PKD). Experimental models of PKD showed that an increase of cellular proliferation and apoptosis as well as defects in apico-basal and planar cell polarity or cilia play a critical role in cyst development. However, little is known about the mechanisms and the mediators involved in acquired cystic kidney diseases (ACKD). In this study, we used the nephron reduction as a model to study the mechanisms underlying cyst development in ACKD. We found that tubular dilations after nephron reduction recapitulated most of the morphological features of ACKD. The development of tubular dilations was associated with a dramatic increase of cell proliferation. In contrast, the apico-basal polarity and cilia did not seem to be affected. Interestingly, polycystin 1 and fibrocystin were markedly increased and polycystin 2 was decreased in cells lining the dilated tubules, whereas the expression of several other cystic genes did not change. More importantly, Pkd1 haploinsufficiency accelerated the development of tubular dilations after nephron reduction, a phenotype that was associated to a further increase of cell proliferation. These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. In conclusion, our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes involved in PKD is also important in ACKD.

  3. A Shunt Model of the Inner Medullary Nephron with Pre-Bend Transitions

    NASA Astrophysics Data System (ADS)

    Gonzalez, M. T.; Hegarty, A. F.; Thomas, S. R.

    2009-09-01

    Mathematical models of the renal medulla face the problem of representing water and solute transfer among tens of thousands of nephrons and blood vessels of various lengths, arranged in countercurrent fashion. Published models fall into two broad categories with respect to this issue: multi-nephron models, which explicitly represent a large number of individual nephrons, or lumped models with virtual shunts that represent the turning back of nephrons and vessels at varying depths. Shunt models have the advantage of a compact description and relatively rapid execution time but are ill-suited to faithfully represent features such as prebend transitions of epithelial permeabilities in nephrons of different lengths. A new shunt model approach that can accommodate pre-bend transitions of nephrons at all medullary depths is presented in this work together with the results of simulation of predicted flows and concentrations.

  4. Factors associated with a vicious cycle involving a low nephron number, hypertension and chronic kidney disease.

    PubMed

    Kanzaki, Go; Tsuboi, Nobuo; Haruhara, Kotaro; Koike, Kentaro; Ogura, Makoto; Shimizu, Akira; Yokoo, Takashi

    2015-10-01

    It has been reported that there is substantial variation in the nephron number between individuals. Previous studies using autopsy kidneys have demonstrated that a low nephron number, in relation to a low birth weight, may result in hypertension (HTN) and/or chronic kidney disease (CKD). However, recent studies have revealed that the association between a low nephron number and HTN is not a universal finding. This observation indicates that a low nephron number is unlikely to be the sole factor contributing to an elevated blood pressure. In addition to the nephron number, various genetic and congenital factors may contribute to increased susceptibility to HTN and/or CKD in a complex manner. Acquired factors, including aging, obesity and related metabolic abnormalities, and various causes of renal injury, may additionally promote further nephron loss. Such a vicious cycle may induce HTN and/or CKD via the common mechanisms of renal hemodynamic maladaptation.

  5. Factors associated with a vicious cycle involving a low nephron number, hypertension and chronic kidney disease.

    PubMed

    Kanzaki, Go; Tsuboi, Nobuo; Haruhara, Kotaro; Koike, Kentaro; Ogura, Makoto; Shimizu, Akira; Yokoo, Takashi

    2015-10-01

    It has been reported that there is substantial variation in the nephron number between individuals. Previous studies using autopsy kidneys have demonstrated that a low nephron number, in relation to a low birth weight, may result in hypertension (HTN) and/or chronic kidney disease (CKD). However, recent studies have revealed that the association between a low nephron number and HTN is not a universal finding. This observation indicates that a low nephron number is unlikely to be the sole factor contributing to an elevated blood pressure. In addition to the nephron number, various genetic and congenital factors may contribute to increased susceptibility to HTN and/or CKD in a complex manner. Acquired factors, including aging, obesity and related metabolic abnormalities, and various causes of renal injury, may additionally promote further nephron loss. Such a vicious cycle may induce HTN and/or CKD via the common mechanisms of renal hemodynamic maladaptation. PMID:26084263

  6. Upper tract urothelial carcinoma: Paradigm shift towards nephron sparing management

    PubMed Central

    Fiuk, Julia V; Schwartz, Brad F

    2016-01-01

    Upper tract urothelial carcinoma (UTUC) is relatively rare compared to urothelial carcinoma of the lower tract, comprising only 5%-10% of all urothelial cancers. Although both entities share histologic properties, UTUC tends to be more invasive at diagnosis and portend a worse prognosis, with a 5 year overall mortality of 23%. To date, the gold standard management of UTUC has been radical nephroureterectomy (RNU), with nephron sparing techniques reserved for solitary kidneys or cases where the patient could not tolerate radical surgery. Limited data from these series, as well as select series where nephron-sparing endoscopic management has been offered to a broader patient base, suggest that minimally invasive, nephron sparing techniques can offer comparable oncologic and survival outcomes to RNU in appropriately selected patients. We review the current literature on the topic and discuss long term outcomes and sequelae of the gold standard treatment, RNU. We also discuss the oncologic outcomes of minimally invasive, endoscopic management of UTUC. Our goal is to provide the reader a comprehensive overview of the current state of the field in order to inform and guide their treatment decisions. PMID:26981440

  7. Genetics of renal hypoplasia: insights into the mechanisms controlling nephron endowment.

    PubMed

    Cain, Jason E; Di Giovanni, Valeria; Smeeton, Joanna; Rosenblum, Norman D

    2010-08-01

    Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice.

  8. Distal Myopathies: Case Studies.

    PubMed

    Shaibani, Aziz

    2016-08-01

    About 15% of myopathies present with distal weakness. Lack of sensory deficit, and preservation of sensory responses and deep tendon reflexes, favors a myopathic cause for distal weakness. Electromyogram confirms this diagnosis. Profuse spontaneous discharges are common in inflammatory, metabolic, and myofibrillar myopathy (MFM). If the clinical picture indicates a specific disease such as facioscapulohumeral muscular dystrophy (FSHD), genetic testing provides the quickest diagnosis. Otherwise, muscle biopsy can distinguish specific features. The common causes of myopathic distal weakness are FSHD, myotonic dystrophy, and inclusion body myositis. Other causes include MFM, distal muscular dystrophies, metabolic myopathies, and congenital myopathies. PMID:27445241

  9. Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development

    PubMed Central

    Hartwig, Sunny; Ho, Jacqueline; Pandey, Priyanka; MacIsaac, Kenzie; Taglienti, Mary; Xiang, Michael; Alterovitz, Gil; Ramoni, Marco; Fraenkel, Ernest; Kreidberg, Jordan A.

    2010-01-01

    Summary The Wilms' tumor suppressor 1 (WT1) gene encodes a DNA- and RNA-binding protein that plays an essential role in nephron progenitor differentiation during renal development. To identify WT1 target genes that might regulate nephron progenitor differentiation in vivo, we performed chromatin immunoprecipitation (ChIP) coupled to mouse promoter microarray (ChIP-chip) using chromatin prepared from embryonic mouse kidney tissue. We identified 1663 genes bound by WT1, 86% of which contain a previously identified, conserved, high-affinity WT1 binding site. To investigate functional interactions between WT1 and candidate target genes in nephron progenitors, we used a novel, modified WT1 morpholino loss-of-function model in embryonic mouse kidney explants to knock down WT1 expression in nephron progenitors ex vivo. Low doses of WT1 morpholino resulted in reduced WT1 target gene expression specifically in nephron progenitors, whereas high doses of WT1 morpholino arrested kidney explant development and were associated with increased nephron progenitor cell apoptosis, reminiscent of the phenotype observed in Wt1−/− embryos. Collectively, our results provide a comprehensive description of endogenous WT1 target genes in nephron progenitor cells in vivo, as well as insights into the transcriptional signaling networks controlled by WT1 that might direct nephron progenitor fate during renal development. PMID:20215353

  10. Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development.

    PubMed

    Hartwig, Sunny; Ho, Jacqueline; Pandey, Priyanka; Macisaac, Kenzie; Taglienti, Mary; Xiang, Michael; Alterovitz, Gil; Ramoni, Marco; Fraenkel, Ernest; Kreidberg, Jordan A

    2010-04-01

    The Wilms' tumor suppressor 1 (WT1) gene encodes a DNA- and RNA-binding protein that plays an essential role in nephron progenitor differentiation during renal development. To identify WT1 target genes that might regulate nephron progenitor differentiation in vivo, we performed chromatin immunoprecipitation (ChIP) coupled to mouse promoter microarray (ChIP-chip) using chromatin prepared from embryonic mouse kidney tissue. We identified 1663 genes bound by WT1, 86% of which contain a previously identified, conserved, high-affinity WT1 binding site. To investigate functional interactions between WT1 and candidate target genes in nephron progenitors, we used a novel, modified WT1 morpholino loss-of-function model in embryonic mouse kidney explants to knock down WT1 expression in nephron progenitors ex vivo. Low doses of WT1 morpholino resulted in reduced WT1 target gene expression specifically in nephron progenitors, whereas high doses of WT1 morpholino arrested kidney explant development and were associated with increased nephron progenitor cell apoptosis, reminiscent of the phenotype observed in Wt1(-/-) embryos. Collectively, our results provide a comprehensive description of endogenous WT1 target genes in nephron progenitor cells in vivo, as well as insights into the transcriptional signaling networks controlled by WT1 that might direct nephron progenitor fate during renal development.

  11. Prematurity in mice leads to reduction in nephron number, hypertension, and proteinuria.

    PubMed

    Stelloh, Cary; Allen, Kenneth P; Mattson, David L; Lerch-Gaggl, Alexandra; Reddy, Sreenivas; El-Meanawy, Asraf

    2012-02-01

    The nephron number at birth is a quantitative trait that correlates inversely with the risk of hypertension and chronic kidney disease later in life. During kidney development, the nephron number is controlled by multiple factors including genetic, epigenetic, and environmental modifiers. Premature birth, which represents more than 12% of annual live births in the United States, has been linked to low nephron number and the development of hypertension later in life. In this report, we describe the development of a mouse model of prematurity-induced reduction of nephron number. Premature mice, delivered 1 and 2 days early, have 17.4 ± 2.3% (n = 6) and 23.6 ± 2% (n = 10) fewer nephrons, respectively, when compared with full-term animals (12,252 ± 571 nephrons/kidney, n = 10). After 5 weeks of age, the mice delivered 2 days premature show lower real-time glomerular filtration rate (GFR, 283 ± 13 vs 389 ± 26 μL/min). The premature mice also develop hypertension (mean arterial pressure [MAP], 134 ± 18 vs 120 ± 14 mm Hg) and albuminuria (286 ± 83 vs 176 ± 59 μg albumin/mg creatinine). This mouse model provides a proof of concept that prematurity leads to reduced nephron number and hypertension, and this model will be useful in studying the pathophysiology of prematurity-induced nephron number reductions and hypertension.

  12. NEW NEPHRON DEVELOPMENT IN FISH FROM POLLUTED WATERS: A POSSIBLE BIOMARKER

    EPA Science Inventory

    Recent evidence has shown that fish have the ability to develop new nephrons following renal injury. This study evaluated the usefulness of quantifying developing nephrons in mature fish as an ecotoxicological assessment tool. Histological sections of kidney were prepared from At...

  13. NEPHRON-SPARING SURGERY FOR BILATERAL WILMS TUMOR

    PubMed Central

    Kieran, Kathleen; Davidoff, Andrew M.

    2015-01-01

    Synchronous bilateral disease occurs in approximately 5% of children with Wilms tumor (WT), and is independently associated with an increased risk of renal insufficiency. Nephron-sparing surgery (NSS) allows preservation of renal mass and improved renal function. Published oncologic and functional outcomes with NSS to date are generally good, likely reflecting proper patient selection and excellent surgical technique during tumor excision, as well as appropriate use of upfront and adjuvant therapies. Here we highlight important issues regarding the use of NSS in children with bilateral Wilms tumor (BWT). PMID:25633157

  14. The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth.

    PubMed

    Sakaguchi, Masaji; Sharmin, Sazia; Taguchi, Atsuhiro; Ohmori, Tomoko; Fujimura, Sayoko; Abe, Takaya; Kiyonari, Hiroshi; Komatsu, Yoshihiro; Mishina, Yuji; Asashima, Makoto; Araki, Eiichi; Nishinakamura, Ryuichi

    2013-01-01

    Most kidney nephron components, including glomeruli and renal tubules, derive from the metanephric mesenchyme. The overall differentiation into each component finishes at birth, but the molecular events linking the perinatal and adult kidneys remain elusive. Dullard was cloned from Xenopus kidneys, and encodes a phosphatase that negatively regulates BMP signalling. Here we report that Dullard deletion in the murine metanephric mesenchyme leads to failure of nephron maintenance after birth, resulting in lethality before adulthood. The nephron components are lost by massive apoptosis within 3 weeks after birth, leading to formation of a large hollow with a thin-layered cortex and medulla. Phosphorylated Smad1/5/8 is upregulated in the mutant nephrons, probably through cell-autonomous inhibitory effects of Dullard on BMP signalling. Importantly, administration of the BMP receptor kinase inhibitor LDN-193189 partially rescued the defects caused by Dullard deletion. Thus, Dullard keeps BMP signalling at an appropriate level, which is required for nephron maintenance in the postnatal period.

  15. Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport.

    PubMed

    Terker, Andrew S; Yarbrough, Bethzaida; Ferdaus, Mohammed Z; Lazelle, Rebecca A; Erspamer, Kayla J; Meermeier, Nicholas P; Park, Hae J; McCormick, James A; Yang, Chao-Ling; Ellison, David H

    2016-08-01

    Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.

  16. Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport.

    PubMed

    Terker, Andrew S; Yarbrough, Bethzaida; Ferdaus, Mohammed Z; Lazelle, Rebecca A; Erspamer, Kayla J; Meermeier, Nicholas P; Park, Hae J; McCormick, James A; Yang, Chao-Ling; Ellison, David H

    2016-08-01

    Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron. PMID:26712527

  17. Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron

    PubMed Central

    Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira RM; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

    2015-01-01

    The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning. DOI: http://dx.doi.org/10.7554/eLife.04000.001 PMID:25647637

  18. Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep.

    PubMed

    Galinsky, Robert; Moss, Timothy J M; Gubhaju, Lina; Hooper, Stuart B; Black, M Jane; Polglase, Graeme R

    2011-08-01

    Chorioamnionitis is an antecedent of preterm birth. We aimed to determine the effect of experimental chorioamnionitis in fetal sheep during late gestation on 1) nephron number, 2) renal corpuscle volume, and 3) renal inflammation. We hypothesized that exposure to chorioamnionitis would lead to inflammation in fetal kidneys and adversely impact on the development of nephrons, leading to a reduction in nephron number. At ∼121 days of gestation (term ∼147 days), pregnant ewes bearing twin or singleton fetuses received a single intra-amniotic injection of lipopolysaccharide (n = 6; 3 singletons, 3 twins); controls were either untreated or received an intra-amniotic injection of saline (n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At ∼128 days of gestation, fetuses were delivered via Caesarean section. Kidneys were collected and stereologically analyzed to determine nephron number and renal corpuscle volume. Renal inflammation was assessed using immunohistochemistry. Experimental chorioamnionitis did not affect body weight or relative kidney weight. There was a significant reduction in nephron number but no change in renal corpuscle volume in LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18% in singleton and twin LPS-exposed fetuses, respectively. The degree of renal inflammation did not differ between groups. Importantly, this study demonstrates that exposure to experimental chorioamnionitis adversely impacts on nephron number in the developing fetus.

  19. Towards Automated Three-Dimensional Tracking of Nephrons through Stacked Histological Image Sets.

    PubMed

    Bhikha, Charita; Andreasen, Arne; Christensen, Erik I; Letts, Robyn F R; Pantanowitz, Adam; Rubin, David M; Thomsen, Jesper S; Zhai, Xiao-Yue

    2015-01-01

    An automated approach for tracking individual nephrons through three-dimensional histological image sets of mouse and rat kidneys is presented. In a previous study, the available images were tracked manually through the image sets in order to explore renal microarchitecture. The purpose of the current research is to reduce the time and effort required to manually trace nephrons by creating an automated, intelligent system as a standard tool for such datasets. The algorithm is robust enough to isolate closely packed nephrons and track their convoluted paths despite a number of nonideal, interfering conditions such as local image distortions, artefacts, and interstitial tissue interference. The system comprises image preprocessing, feature extraction, and a custom graph-based tracking algorithm, which is validated by a rule base and a machine learning algorithm. A study of a selection of automatically tracked nephrons, when compared with manual tracking, yields a 95% tracking accuracy for structures in the cortex, while those in the medulla have lower accuracy due to narrower diameter and higher density. Limited manual intervention is introduced to improve tracking, enabling full nephron paths to be obtained with an average of 17 manual corrections per mouse nephron and 58 manual corrections per rat nephron.

  20. Maternal nutrition, low nephron number and arterial hypertension in later life.

    PubMed

    Benz, Kerstin; Amann, Kerstin

    2010-12-01

    A potential role of the intrauterine environment in the development of low nephron number and hypertension in later life has been recently recognized in experimental studies and is also postulated in certain conditions in human beings. Nephrogenesis is influenced by genetic as well as by environmental and in particular maternal factors. In man nephrogenesis, i.e. the formation of nephrons during embryogenesis, takes place from weeks 5 to 36 of gestation with the most rapid phase of nephrogenesis occurring from the mid-2nd trimester until 36 weeks. This 16 week period is a very vulnerable phase where genetic and environmental factors such as maternal diet or medication could influence and disturb nephron formation leading to lower nephron number. Given a constant rise in body mass until adulthood lower nephron number may become "nephron underdosing" and result in maladaptive glomerular changes, i.e. glomerular hyperfiltration and glomerular enlargement. These maladaptive changes may then eventually lead to the development of glomerular and systemic hypertension and renal disease in later life. It is the purpose of this review to discuss the currently available experimental and clinical evidence for factors and mechanisms that could interfere with nephrogenesis with particular emphasis on maternal nutrition. In addition, we discuss the emerging concept of low nephron number being a new cardiovascular risk factor in particular for essential hypertension in later life.

  1. Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron.

    PubMed

    Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira R M; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

    2015-02-03

    The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

  2. Role of vitamin A in determining nephron mass and possible relationship to hypertension.

    PubMed

    Bhat, Pangala V; Manolescu, Daniel-Constantin

    2008-08-01

    Vitamin A (retinol) and its analogs (retinoids) are important regulators of cell proliferation, differentiation, immune function, and apoptosis. The kidneys are target organs for vitamin A action. Retinoic acid (RA), a vitamin A metabolite, is involved in embryonic kidney patterning through the control of receptor tyrosine kinase expression, which modulates ureteric bud branching morphogenesis. Vitamin A status of the mother profoundly affects kidney organogenesis of the newborn. In rodents, mild vitamin A deficiency results in a 20% reduction of nephron number. In adult humans, nephron number varies between 0.3 and 1.3 million per kidney, which is accepted as normal. However, recent studies indicate that humans at the low end of nephron number are predisposed to primary hypertension. Because RA regulates nephron mass, its optimal availability during nephrogenesis is critical. RA levels in the embryo are affected by several factors, such as maternal vitamin A nutrition and disturbances in retinol metabolism. Maternal vitamin A deficiency during pregnancy is widespread in developing countries and segments of these populations may be exposed to low vitamin A during fetal life when nephron number is determined. Infants are likely to be born with suboptimal nephrons and may develop primary hypertension later in life. Although maternal vitamin A deficiency is not common in developed countries, congenital nephron number nevertheless varies widely, indicating low fetal RA levels due to common variants of the enzymes that convert retinol to RA. These infants might require heightened surveillance for hypertension later in life. PMID:18641182

  3. Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators.

    PubMed

    O'Brien, Lori L; Guo, Qiuyu; Lee, YoungJin; Tran, Tracy; Benazet, Jean-Denis; Whitney, Peter H; Valouev, Anton; McMahon, Andrew P

    2016-02-15

    Nephron endowment is determined by the self-renewal and induction of a nephron progenitor pool established at the onset of kidney development. In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors. Transient Six1 activity prefigures, and is essential for, active nephrogenesis. By contrast, Six2 maintains later progenitor self-renewal from the onset of nephrogenesis. We compared the regulatory actions of Six2 in mouse and human nephron progenitors by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Surprisingly, SIX1 was identified as a SIX2 target unique to the human nephron progenitors. Furthermore, RNA-seq and immunostaining revealed overlapping SIX1 and SIX2 activity in 16 week human fetal nephron progenitors. Comparative bioinformatic analysis of human SIX1 and SIX2 ChIP-seq showed each factor targeted a similar set of cis-regulatory modules binding an identical target recognition motif. In contrast to the mouse where Six2 binds its own enhancers but does not interact with DNA around Six1, both human SIX1 and SIX2 bind homologous SIX2 enhancers and putative enhancers positioned around SIX1. Transgenic analysis of a putative human SIX1 enhancer in the mouse revealed a transient, mouse-like, pre-nephrogenic, Six1 regulatory pattern. Together, these data demonstrate a divergence in SIX-factor regulation between mouse and human nephron progenitors. In the human, an auto/cross-regulatory loop drives continued SIX1 and SIX2 expression during active nephrogenesis. By contrast, the mouse establishes only an auto-regulatory Six2 loop. These data suggest differential SIX-factor regulation might have contributed to species differences in nephron progenitor programs such as the duration of nephrogenesis and the final nephron count.

  4. Distal biceps brachii.

    PubMed

    Brigido, Monica Kalume; De Maeseneer, Michel; Morag, Yoav

    2013-02-01

    There has been a renewed interest in the recent literature with regard to the normal anatomy of the distal biceps tendon. Cadaveric studies have demonstrated that a large percentage of individuals have two independent muscle bellies, the short and the long head, with two distinct separate tendons attaching at the radial tuberosity. To avoid diagnostic errors that may have an impact on patient management in case of tendon injury, it is important to keep this anatomical variant in mind. Ultrasonography has been shown to be a useful imaging modality in the evaluation of disorders of the distal biceps brachii muscle and tendon. In this article, we review the relevant anatomy of the distal biceps brachii, the ultrasound technique with alternative approaches for optimum visualization of the distal tendon, and the most common pathologies in this region.

  5. Transphyseal Distal Humerus Fracture.

    PubMed

    Abzug, Joshua; Ho, Christine Ann; Ritzman, Todd F; Brighton, Brian

    2016-01-01

    Transphyseal distal humerus fractures typically occur in children younger than 3 years secondary to birth trauma, nonaccidental trauma, or a fall from a small height. Prompt and accurate diagnosis of a transphyseal distal humerus fracture is crucial for a successful outcome. Recognizing that the forearm is not aligned with the humerus on plain radiographs may aid in the diagnosis of a transphyseal distal humerus fracture. Surgical management is most commonly performed with the aid of an arthrogram. Closed reduction and percutaneous pinning techniques similar to those used for supracondylar humerus fractures are employed. Cubitus varus caused by a malunion, osteonecrosis of the medial condyle, or growth arrest is the most common complication encountered in the treatment of transphyseal distal humerus fractures. A corrective lateral closing wedge osteotomy can be performed to restore a nearly normal carrying angle.

  6. Distal humeral epiphyseal separation.

    PubMed

    Moucha, Calin S; Mason, Dan E

    2003-10-01

    Distal humeral epiphyseal separation is an uncommon injury that is often misdiagnosed upon initial presentation. To make a timely, correct diagnosis, the treating physician must have a thorough understanding of basic anatomical relationships and an awareness of the existence of this injury. This is a case of a child who sustained a separation of the distal humeral epiphysis, as well as multiple other bony injuries, secondary to child abuse.

  7. Influence of volume expansion on NaC1 reabsorption in the diluting segments of the nephron: a study using clearance methods.

    PubMed

    Danovitch, G M; Bricker, N S

    1976-09-01

    Whether volume expansion influences NaC1 reabsorption by the diluting segment of the nephron remains a matter of controversy. In the present studies this question has been examined in normal unanesthetized dogs, undergoing maximal water diuresis. Free water clearance (CH2O/GFR) has been used as the index of NaC1 reabsorption in the diluting segment. Three expressions have been employed for "distal delivery" of NaC1: a) V/GFR, designated as the "volume term"; b) (CNa/GFR + CH2O/GFR), the "sodium term;" and c) (CC1/GFR + CH2O/GFR), the "chloride term". The validity of these terms is discussed. Three techniques were used to increase distal delivery: 1) the administration of acetazolamide to dogs in which extracellular fluid (ECF) volume was not expanded (grop 1); 2) "moderate" volume expansion (group 2); and 3) "marked" volume expansion (group 3). CH2O/GFR increased progressively with rising values for "distal delivery" regardless of which term was used to calculate the latter. With all three delivery terms, differences in distal NaC1 reabsorption emerged between the two volume-expanded groups, though only with the "chloride" term did substantial differences also emerge between the nonexpanded group 1 dogs and both volume-expanded groups. In group 1, values for CH2O/GFR increased in close to a linear fashion up to distal delivery values equal to 24% of the volume of glomerular filtrate. However, at high rates of distal delivery the rate of rise of CH2O/GFR was less in group 2 than in group 1 and the depression of values was even greater in group 3. Within the limits of the techniques used, the data suggest that volume expansion inhibits fractional NaC1 reabsorption in the diluting segment of the nephron in a dose-related fashion. The "chloride" term was found to be superior to the "volume" and "sodium" terms in revealing these changes.

  8. Surgical treatment of an aneurysm of a distal branch of the renal artery.

    PubMed

    Abdalla, Solafah; Pierret, Charles; Ba, Bakar; Mlynski, Amélie; de Kerangal, Xavier; Houlgatte, Alain

    2014-01-01

    Aneurysms of the renal artery and its branches are rare, but are associated with significant morbimortality due to the absence of clinical symptoms and hemorrhagic risk in the event of rupture. We report the case of a patient with an aneurysm of a distal branch of the right renal artery that measured 25 mm in diameter. The diagnosis and localization were obtained using selective arteriography. Treatment consisted of resection of the aneurysmal sac associated with closure with a saphenous vein patch rather than an endovascular treatment in order to preserve the nephronic capital. Right renal parenchymatous vascularization was satisfactory on arterial echo-Doppler and angioscanner assessment at 1 year.

  9. Surgical treatment of an aneurysm of a distal branch of the renal artery.

    PubMed

    Abdalla, Solafah; Pierret, Charles; Ba, Bakar; Mlynski, Amélie; de Kerangal, Xavier; Houlgatte, Alain

    2014-01-01

    Aneurysms of the renal artery and its branches are rare, but are associated with significant morbimortality due to the absence of clinical symptoms and hemorrhagic risk in the event of rupture. We report the case of a patient with an aneurysm of a distal branch of the right renal artery that measured 25 mm in diameter. The diagnosis and localization were obtained using selective arteriography. Treatment consisted of resection of the aneurysmal sac associated with closure with a saphenous vein patch rather than an endovascular treatment in order to preserve the nephronic capital. Right renal parenchymatous vascularization was satisfactory on arterial echo-Doppler and angioscanner assessment at 1 year. PMID:24120233

  10. Analysis of nephron composition and function in the adult zebrafish kidney.

    PubMed

    McCampbell, Kristen K; Springer, Kristin N; Wingert, Rebecca A

    2014-08-09

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling.

  11. The relationship between nephron number, kidney size and body weight in two inbred mouse strains.

    PubMed

    Murawski, Inga J; Maina, Rita W; Gupta, Indra R

    2010-01-01

    While some reports in humans have shown that nephron number is positively correlated with height, body weight or kidney weight, other studies have not reproduced these findings. To understand the impact of genetic and environmental variation on these relationships, we examined whether nephron number correlates with body weight, kidney planar surface area, or kidney weight in two inbred mouse strains with contrasting kidney sizes but no overt renal pathology: C3H/HeJ and C57BL/6J. C3H/HeJ mice had smaller kidneys at birth and larger kidneys by adulthood, however there was no significant difference in nephron number between the two strains. We did observe a correlation between kidney size and body weight at birth and at adulthood for both strains. However, there was no relationship between nephron number and body weight or between nephron number and kidney size. From other studies, it appears that a greater than two-fold variation is required in each of these parameters in order to demonstrate these relationships, suggesting they are highly dependent on scale. Our results are therefore not surprising since there was a less than two-fold variation in each of the parameters examined. In summary, the relationship between nephron number and body or kidney size is most likely to be demonstrated when there is greater phenotypic variation either from genetic and/or environmental factors.

  12. Chronic intrauterine exposure to endotoxin does not alter fetal nephron number or glomerular size.

    PubMed

    Ryan, Danica; Atik, Anzari; De Matteo, Robert; Harding, Richard; Black, Mary J

    2013-11-01

    A reduced nephron endowment early in life adversely impacts on long-term functional reserve in the kidney. A recent study has shown that acute exposure to chorioamnionitis during late gestation can adversely impact on nephrogenesis. The present study aimed to examine the effects of chronic, low-dose endotoxin exposure in utero, during the period of nephrogenesis, on nephron number and glomerular size in preterm lambs. Ewes were administered either endotoxin (lipopolysaccharide; 1 mg/day) or saline at 110-133 days of gestation (term approximately 147 days) via surgically implanted osmotic minipumps within the amniotic cavity. The ewes were induced to deliver preterm at 133 days gestation and the kidneys of the lambs were analysed at 8 weeks after term-equivalent age. Nephron number per kidney was determined using a combined optical disector and fractionator stereological approach; renal corpuscle size was also measured stereologically. At 8 weeks after term-equivalent age there was no significant effect of in utero exposure to endotoxin on bodyweight or kidney weight and there were no significant differences in nephron number, nephron density or renal corpuscle volume between groups. We conclude that chronic intrauterine inflammation during the period of nephrogenesis may not adversely impact on the number of nephrons formed within the kidney or on the volume of the renal corpuscle.

  13. Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons.

    PubMed

    Recuenco, Mariam C; Ohmori, Tomoko; Tanigawa, Shunsuke; Taguchi, Atsuhiro; Fujimura, Sayoko; Conti, Mary Anne; Wei, Qize; Kiyonari, Hiroshi; Abe, Takaya; Adelstein, Robert S; Nishinakamura, Ryuichi

    2015-05-01

    The kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud. The mesenchyme transforms into epithelia and forms complicated nephron structures, whereas the ureteric bud extends its pre-existing epithelial ducts. Although the roles are well established for extracellular stimuli, such as Wnt and Notch, it is unclear how the intracellular cytoskeleton regulates these morphogenetic processes. Myh9 and Myh10 encode nonmuscle myosin II heavy chains, and Myh9 mutations in humans are implicated in congenital kidney diseases and focal segmental glomerulosclerosis in adults. Here, we analyzed the roles of Myh9 and Myh10 in the developing kidney. Ureteric bud-specific depletion of Myh9 resulted in no apparent phenotypes, whereas mesenchyme-specific Myh9 deletion caused proximal tubule dilations and renal failure. Mesenchyme-specific Myh9/Myh10 mutant mice died shortly after birth and showed a severe defect in nephron formation. The nascent mutant nephrons failed to form a continuous lumen, which likely resulted from impaired apical constriction of the elongating tubules. In addition, nephron progenitors lacking Myh9/Myh10 or the possible interactor Kif26b were less condensed at midgestation and reduced at birth. Taken together, nonmuscle myosin II regulates the morphogenesis of immature nephrons derived from the metanephric mesenchyme and the maintenance of nephron progenitors. Our data also suggest that Myh9 deletion in mice results in failure to maintain renal tubules but not in glomerulosclerosis.

  14. Fibroblast growth factor receptor–Frs2α signaling is critical for nephron progenitors

    PubMed Central

    Di Giovanni, Valeria; Walker, Kenneth A.; Bushnell, Daniel; Schaefer, Caitlin; Sims-Lucas, Sunder; Puri, Pawan; Bates, Carlton M.

    2015-01-01

    Previous studies using transgenic Pax3cre mice have revealed roles for fibroblast growth factor receptors (Fgfrs) and Fgfr substrate 2α (Frs2α) signaling in early metanephric mesenchyme patterning and in ureteric morphogenesis. The role of Fgfr/Frs2α signaling in nephron progenitors is unknown. Thus, we generated mouse models using BAC transgenic Six2EGFPcre (Six2cre) mediated deletion of Fgfrs and/or Frs2α in nephron progenitors. Six2cre mediated deletion of Fgfr1 or Fgfr2 alone led to no obvious kidney defects. Six2creFgfr1flox/floxFgfr2flox/flox (Fgfr1/2NP−/−) mice generate a discernable kidney; however, they develop nephron progenitor depletion starting at embryonic day 12.5 (E12.5) and later demonstrate severe cystic dysplasia. To determine the role of Frs2α signaling downstream of Fgfr2 in Fgfr1/2NP−/− mice, we generated Six2cre,Fgfr1flox/floxFgfr2LR/LR (Fgfr1NP−/−Fgfr2LR/LR) mice that have point mutations in the Frs2α binding site of Fgfr2. Like Fgfr1/2NP−/− mice, Fgfr1NP−/−Fgfr2LR/LR develop nephron progenitor depletion, but it does not start until E14.5 and older mice have less severe cystic dysplasia than Fgfr1/2NP−/− To determine the role of Frs2α alone in nephron progenitors, we generated Six2creFrs2′Aflox/flox (Frs2aNP−/−) mice. Frs2aNP−/− mice also develop nephron progenitor depletion and renal cysts, although these occurred later and were less severe than in the other Six2cre mutant mice. The nephron progenitor loss in all Six2cre mutant lines was associated with decreased Cited1 expression and increased apoptosis versus controls. FAC-sorted nephron progenitors in Six2cre Frs2′Aflox/flox mice demonstrated evidence of increased Notch activity versus controls, which likely drives the progenitor defects. Thus, Fgfr1 and Fgfr2 have synergistic roles in maintaining nephron progenitors; furthermore, Fgfr signaling in nephron progenitors appears to be mediated predominantly by Frs2α. PMID:25641696

  15. Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.

    PubMed

    Di Giovanni, Valeria; Walker, Kenneth A; Bushnell, Daniel; Schaefer, Caitlin; Sims-Lucas, Sunder; Puri, Pawan; Bates, Carlton M

    2015-04-01

    Previous studies using transgenic Pax3cre mice have revealed roles for fibroblast growth factor receptors (Fgfrs) and Fgfr substrate 2α (Frs2α) signaling in early metanephric mesenchyme patterning and in ureteric morphogenesis. The role of Fgfr/Frs2α signaling in nephron progenitors is unknown. Thus, we generated mouse models using BAC transgenic Six2EGFPcre (Six2cre) mediated deletion of Fgfrs and/or Frs2α in nephron progenitors. Six2cre mediated deletion of Fgfr1 or Fgfr2 alone led to no obvious kidney defects. Six2creFgfr1(flox/flox)Fgfr2(flox/flox) (Fgfr1/2(NP-/-)) mice generate a discernable kidney; however, they develop nephron progenitor depletion starting at embryonic day 12.5 (E12.5) and later demonstrate severe cystic dysplasia. To determine the role of Frs2α signaling downstream of Fgfr2 in Fgfr1/2(NP-/-) mice, we generated Six2cre(,)Fgfr1(flox/flox)Fgfr2(LR/LR) (Fgfr1(NP-/-)Fgfr2(LR/LR)) mice that have point mutations in the Frs2α binding site of Fgfr2. Like Fgfr1/2(NP-/-) mice, Fgfr1(NP-/-)Fgfr2(LR/LR) develop nephron progenitor depletion, but it does not start until E14.5 and older mice have less severe cystic dysplasia than Fgfr1/2(NP-/-) To determine the role of Frs2α alone in nephron progenitors, we generated Six2creFrs2'A(flox/flox) (Frs2a(NP-/-)) mice. Frs2a(NP-/-)mice also develop nephron progenitor depletion and renal cysts, although these occurred later and were less severe than in the other Six2cre mutant mice. The nephron progenitor loss in all Six2cre mutant lines was associated with decreased Cited1 expression and increased apoptosis versus controls. FAC-sorted nephron progenitors in Six2cre Frs2'A(flox/flox) mice demonstrated evidence of increased Notch activity versus controls, which likely drives the progenitor defects. Thus, Fgfr1 and Fgfr2 have synergistic roles in maintaining nephron progenitors; furthermore, Fgfr signaling in nephron progenitors appears to be mediated predominantly by Frs2α.

  16. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

    PubMed

    Kobayashi, Akio; Valerius, M Todd; Mugford, Joshua W; Carroll, Thomas J; Self, Michelle; Oliver, Guillermo; McMahon, Andrew P

    2008-08-01

    Nephrons, the basic functional units of the kidney, are generated repetitively during kidney organogenesis from a mesenchymal progenitor population. Which cells within this pool give rise to nephrons and how multiple nephron lineages form during this protracted developmental process are unclear. We demonstrate that the Six2-expressing cap mesenchyme represents a multipotent nephron progenitor population. Six2-expressing cells give rise to all cell types of the main body of the nephron during all stages of nephrogenesis. Pulse labeling of Six2-expressing nephron progenitors at the onset of kidney development suggests that the Six2-expressing population is maintained by self-renewal. Clonal analysis indicates that at least some Six2-expressing cells are multipotent, contributing to multiple domains of the nephron. Furthermore, Six2 functions cell autonomously to maintain a progenitor cell status, as cap mesenchyme cells lacking Six2 activity contribute to ectopic nephron tubules, a mechanism dependent on a Wnt9b inductive signal. Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population.

  17. Ethnic differences in proximal and distal tubular sodium reabsorption are heritable in black and white populations

    PubMed Central

    Bochud, Murielle; Staessen, Jan A.; Maillard, Marc; Mazeko, Muzi J.; Kuznetsova, Tatiana; Woodiwiss, Angela; Richart, Tom; Norton, Gavin; Thijs, Lutgarde; Elston, Robert; Burnier, Michel

    2013-01-01

    Background Segmental handling of sodium along the proximal and distal nephron might be heritable and different between black and white participants. Methods We randomly recruited 95 nuclear families of black South African ancestry and 103 nuclear families of white Belgian ancestry. We measured the (FENa) and estimated the fractional renal sodium reabsorption in the proximal (RNaprox) and distal (RNadist) tubules from the clearances of endogenous lithium and creatinine. In multivariable analyses, we studied the relation of RNaprox and RNadist with FENa and estimated the heritability (h2) of RNaprox and RNadist. Results Independent of urinary sodium excretion, South Africans (n =240) had higher RNaprox (unadjusted median, 93.9% vs. 81.0%; P < 0.001) than Belgians (n =737), but lower RNadist (91.2% vs. 95.1%; P < 0.001). The slope of RNaprox on FENa was steeper in Belgians than in South Africans (−5.40 ±0.58 vs. −0.78 ±0.58 units; P < 0.001), whereas the opposite was true for the slope of RNadist on FENa (−3.84 ± 0.19 vs. −13.71 ± 1.30 units; P < 0.001). h2 of RNaprox and RNadist was high and significant (P < 0.001) in both countries. h2 was higher in South Africans than in Belgians for RNaprox (0.82 vs. 0.56; P < 0.001), but was similar for RNadist (0.68 vs. 0.50; P = 0.17). Of the filtered sodium load, black participants reabsorb more than white participants in the proximal nephron and less postproximally. Conclusion Segmental sodium reabsorption along the nephron is highly heritable, but the capacity for regulation in the proximal and postproximal tubules differs between whites and blacks. PMID:19262228

  18. Link between reduced nephron number and hypertension: studies in a mutant mouse model.

    PubMed

    Poladia, Deepali Pitre; Kish, Kayle; Kutay, Benjamin; Bauer, John; Baum, Michel; Bates, Carlton M

    2006-04-01

    Low birth weight (LBW) infants with reduced nephron numbers have significantly increased risk for hypertension later in life, which is a devastating health problem. The risk from a reduction in nephron number alone is not clear. Recently, using conditional knock-out approach, we have developed a mutant mouse with reduced nephron number in utero and no change in birth weight, by deleting fibroblast growth factor receptor 2 (fgfr2) in the ureteric bud. Our purpose was to investigate the role of in utero reduced nephron number alone in absence of LBW as a risk for developing hypertension in adulthood. Using tail cuff blood pressure measurements we observed significant increases in systolic blood pressure in one year old mutant mice versus controls. We also detected cardiac end-organ injury from hypertension as shown by significant increases in normalized heart weights, left ventricular (LV) wall thickness, and LV tissue area. Two-dimensional echocardiography revealed no changes in cardiac output and therefore significant increases in systemic vascular resistance in mutants versus controls. We also observed increases in serum blood urea nitrogen (BUN) levels and histologic evidence of glomerular and renal tubular injury in mutant mice versus controls. Thus, these studies suggest that our mutant mice may serve as a relevant model to study the link between reduction of nephron number in utero and the risk of hypertension and chronic renal failure in adulthood.

  19. Glomerulotubular balance in a mathematical model of the proximal nephron.

    PubMed

    Weinstein, A M

    1990-03-01

    A nonelectrolyte model of proximal tubule epithelium has been extended by the inclusion of a compliant tight junction. Here "compliance" signifies that both the junctional salt and water permeability increase and the salt reflection coefficient decreases in response to small pressure differences from lateral interspace to tubule lumen. In previous models of rat proximal tubule, there has been virtually no sensitivity of isotonic salt transport to changes in peritubular oncotic force. With the inclusion of junctional compliance, decreases in peritubular protein can open the junction and produce a secretory salt flux. Thus the model can represent the "backflux hypothesis," as it was originally put forth (J. E. Lewy and E. E. Windhager, Am. J. Physiol. 214: 943-954, 1968). Additional calculations, simulating a tight junction with negligible water permeability, reveal that the quantitative impact of peritubular protein can be realized whether or not there is substantial junctional water flux. The epithelial model of proximal tubule has also been incorporated into a model of the proximal nephron, complete with glomerulus, peritubular capillary, and interstitium. The interstitial compartment is well mixed and interstitial pressure and osmolality are determined iteratively to achieve balance between tubule reabsorption and capillary uptake. For this model, two domains of operation are identified. When interstitial pressures are low, junctions are closed, and filtration fraction has no effect on proximal reabsorption. When interstitial pressures are relatively elevated, epithelial junctions are open, and proximal salt reabsorption changes in proportion to changes in filtration fraction. In neither domain, however, does the model tubule augment salt flux with isolated increases in luminal flow rate (at constant filtration fraction). The absence of a separate effect of tubule fluid flow on salt transport precludes perfect glomerulotubular balance.

  20. Sall1 in renal stromal progenitors non-cell autonomously restricts the excessive expansion of nephron progenitors.

    PubMed

    Ohmori, Tomoko; Tanigawa, Shunsuke; Kaku, Yusuke; Fujimura, Sayoko; Nishinakamura, Ryuichi

    2015-10-29

    The mammalian kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud, the former of which contains nephron progenitors. The third lineage, the stroma, fills up the interstitial space and is derived from distinct progenitors that express the transcription factor Foxd1. We showed previously that deletion of the nuclear factor Sall1 in nephron progenitors leads to their depletion in mice. However, Sall1 is expressed not only in nephron progenitors but also in stromal progenitors. Here we report that specific Sall1 deletion in stromal progenitors leads to aberrant expansion of nephron progenitors, which is in sharp contrast with a nephron progenitor-specific deletion. The mutant mice also exhibited cystic kidneys after birth and died before adulthood. We found that Decorin, which inhibits Bmp-mediated nephron differentiation, was upregulated in the mutant stroma. In contrast, the expression of Fat4, which restricts nephron progenitor expansion, was reduced mildly. Furthermore, the Sall1 protein binds to many stroma-related gene loci, including Decorin and Fat4. Thus, the expression of Sall1 in stromal progenitors restricts the excessive expansion of nephron progenitors in a non-cell autonomous manner, and Sall1-mediated regulation of Decorin and Fat4 might at least partially underlie the pathogenesis.

  1. Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth.

    PubMed

    Tomita, Mayumi; Asada, Misako; Asada, Nariaki; Nakamura, Jin; Oguchi, Akiko; Higashi, Atsuko Y; Endo, Shuichiro; Robertson, Elizabeth; Kimura, Takeshi; Kita, Toru; Economides, Aris N; Kreidberg, Jordan; Yanagita, Motoko

    2013-01-01

    The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.

  2. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development

    PubMed Central

    Costantini, Frank; Kopan, Raphael

    2010-01-01

    Summary The two major components of the kidney, the collecting system and the nephron, have different developmental histories. The collecting system arises by the reiterated branching of a simple epithelial tube, while the nephron forms from a cloud of mesenchymal cells that coalesces into epithelial vesicles. Each develops into a morphologically complex and highly differentiated structure, and together they provide essential filtration and resorption functions. In this review we will consider their embryological origin, and the genes controlling their morphogenesis, patterning and differentiation, focusing on recent advances in several areas. PMID:20493806

  3. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development.

    PubMed

    Costantini, Frank; Kopan, Raphael

    2010-05-18

    The two major components of the kidney, the collecting system and the nephron, have different developmental histories. The collecting system arises by the reiterated branching of a simple epithelial tube, while the nephron forms from a cloud of mesenchymal cells that coalesce into epithelial vesicles. Each develops into a morphologically complex and highly differentiated structure, and together they provide essential filtration and resorption functions. In this review, we will consider their embryological origin and the genes controlling their morphogenesis, patterning, and differentiation, with a focus on recent advances in several areas.

  4. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    PubMed

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M; Raza, Sarah; O'Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population. PMID:27144443

  5. Single-nephron filtration rate and proximal reabsorption in aging rats.

    PubMed

    Corman, B; Roinel, N

    1991-01-01

    Age-related changes in the function of individual nephrons were investigated by micropuncture experiments measuring single-nephron filtration rates (SNGFR) and proximal reabsorptions in 10-, 20-, and 30-mo-old rats. The animals were female WAG/Rij rats with low incidence of chronic progressive nephropathy, no loss of nephrons, and renal hypertrophy of both kidneys in the oldest animals. Mean SNGFR values per gram kidney weight were 41.4 +/- 1.1, 37.1 +/- 1.5, and 32.2 +/- 1.1 nl.min-1.g kidney wt-1 (n = 41) in the 10-, 20-, and 30-mo-old animals, respectively. This age-related decrease in filtration was no longer apparent when SNGFR values were expressed per nephron (means 24.3 +/- 0.7, 23.7 +/- 0.9, and 24.4 +/- 0.9 nl/min. Individual filtered loads of sodium, potassium, calcium, and magnesium and their absolute reabsorption by the proximal tubule were not different in the three age groups; however, absolute and fractional reabsorptions of phosphate decreased significantly in the 30-mo-old rats. These results indicate that, with the exception of phosphate, individual filtrations and proximal reabsorptions are well maintained in aging rats free of disease. This may be related to the observed renal hypertrophy. PMID:1992782

  6. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney

    PubMed Central

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M.; Raza, Sarah; O’Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population. PMID:27144443

  7. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    PubMed

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M; Raza, Sarah; O'Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

  8. Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming.

    PubMed

    Bagby, Susan P

    2007-04-01

    A large body of epidemiologic literature supports an inverse relation between birth weight and both systolic blood pressure and prevalence of hypertension, but mechanisms through which lower birth weight increases risk for hypertension are not established. This article advances the view that 1) permanently reduced nephron number is essential but not alone sufficient to mediate nutritionally induced hypertension; and 2) fetally programmed propensity for increased appetite and accelerated postnatal growth, thus generating inappropriately increased body mass, is a necessary "second hit" to actualize hypertension vulnerability. Based on decades of nephrologic research, this increased ratio of body mass (excretory load) to nephron number (excretory capacity) induces intrarenal compensations (tubular and glomerular hypertrophy with single-nephron hyperfiltration and intrarenal renin-angiotensin II activation), which maintain normal glomerular filtration rate at the expense of systemic and glomerular hypertension and at the risk of progressive renal disease. The vigor of the intrarenal compensatory responses is markedly greater in the immature than in the mature kidney, potentially explaining the greater risk of nephron deficits being present early in life as compared with the minimal risk in adult kidney donors. Effective interventions have not yet been defined. Suboptimal maternal nutrition, pervasive in both developed and developing countries, offers a window of opportunity to enhance the cardiovascular and renal health of future generations.

  9. An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

    ERIC Educational Resources Information Center

    Dirks-Naylor, Amie J.

    2016-01-01

    Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

  10. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis

    PubMed Central

    Xu, Jingyue; Liu, Han; Park, Joo-Seop; Lan, Yu; Jiang, Rulang

    2014-01-01

    Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-directed commitment is not well understood, however. We report here that Six2 is required to maintain expression of Osr1, a homolog of the Drosophila odd-skipped zinc-finger transcription factor, in the undifferentiated cap mesenchyme. Tissue-specific inactivation of Osr1 in the cap mesenchyme caused premature depletion of nephron progenitor cells and severe renal hypoplasia. We show that Osr1 and Six2 act synergistically to prevent premature differentiation of the cap mesenchyme. Furthermore, although both Six2 and Osr1 could form protein interaction complexes with TCF proteins, Osr1, but not Six2, enhances TCF interaction with the Groucho family transcriptional co-repressors. Moreover, we demonstrate that loss of Osr1 results in β-catenin/TCF-mediated ectopic activation of Wnt4 enhancer-driven reporter gene expression in the undifferentiated nephron progenitor cells in vivo. Together, these data indicate that Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by stabilizing TCF-Groucho transcriptional repressor complexes to antagonize Wnt-directed nephrogenic differentiation. PMID:24598167

  11. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis.

    PubMed

    Xu, Jingyue; Liu, Han; Park, Joo-Seop; Lan, Yu; Jiang, Rulang

    2014-04-01

    Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-directed commitment is not well understood, however. We report here that Six2 is required to maintain expression of Osr1, a homolog of the Drosophila odd-skipped zinc-finger transcription factor, in the undifferentiated cap mesenchyme. Tissue-specific inactivation of Osr1 in the cap mesenchyme caused premature depletion of nephron progenitor cells and severe renal hypoplasia. We show that Osr1 and Six2 act synergistically to prevent premature differentiation of the cap mesenchyme. Furthermore, although both Six2 and Osr1 could form protein interaction complexes with TCF proteins, Osr1, but not Six2, enhances TCF interaction with the Groucho family transcriptional co-repressors. Moreover, we demonstrate that loss of Osr1 results in β-catenin/TCF-mediated ectopic activation of Wnt4 enhancer-driven reporter gene expression in the undifferentiated nephron progenitor cells in vivo. Together, these data indicate that Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by stabilizing TCF-Groucho transcriptional repressor complexes to antagonize Wnt-directed nephrogenic differentiation.

  12. Microarrays and RNA-Seq identify molecular mechanisms driving the end of nephron production

    PubMed Central

    2011-01-01

    Background The production of nephrons suddenly ends in mice shortly after birth when the remaining cells of the multi-potent progenitor mesenchyme begin to differentiate into nephrons. We exploited this terminal wave of nephron production using both microarrays and RNA-Seq to serially evaluate gene transcript levels in the progenitors. This strategy allowed us to define the changing gene expression states following induction and the onset of differentiation after birth. Results Microarray and RNA-Seq studies of the progenitors detected a change in the expression profiles of several classes of genes early after birth. One functional class, a class of genes associated with cellular proliferation, was activated. Analysis of proliferation with a nucleotide analog demonstrated in vivo that entry into the S-phase of the cell cycle preceded increases in transcript levels of genetic markers of differentiation. Microarrays and RNA-Seq also detected the onset of expression of markers of differentiation within the population of progenitors prior to detectable Six2 repression. Validation by in situ hybridization demonstrated that the markers were expressed in a subset of Six2 expressing progenitors. Finally, the studies identified a third set of genes that provide indirect evidence of an altered cellular microenvironment of the multi-potential progenitors after birth. Conclusions These results demonstrate that Six2 expression is not sufficient to suppress activation of genes associated with growth and differentiation of nephrons. They also better define the sequence of events after induction and suggest mechanisms contributing to the rapid end of nephron production after birth in mice. PMID:21396121

  13. p53 enables metabolic fitness and self-renewal of nephron progenitor cells

    PubMed Central

    Li, Yuwen; Liu, Jiao; Li, Wencheng; Brown, Aaron; Baddoo, Melody; Li, Marilyn; Carroll, Thomas; Oxburgh, Leif; Feng, Yumei; Saifudeen, Zubaida

    2015-01-01

    Contrary to its classic role in restraining cell proliferation, we demonstrate here a divergent function of p53 in the maintenance of self-renewal of the nephron progenitor pool in the embryonic mouse kidney. Nephron endowment is regulated by progenitor availability and differentiation potential. Conditional deletion of p53 in nephron progenitor cells (Six2Cre+;p53fl/fl) induces progressive depletion of Cited1+/Six2+ self-renewing progenitors and loss of cap mesenchyme (CM) integrity. The Six2(p53-null) CM is disorganized, with interspersed stromal cells and an absence of a distinct CM-epithelia and CM-stroma interface. Impaired cell adhesion and epithelialization are indicated by decreased E-cadherin and NCAM expression and by ineffective differentiation in response to Wnt induction. The Six2Cre+;p53fl/fl cap has 30% fewer Six2(GFP+) cells. Apoptotic index is unchanged, whereas proliferation index is significantly reduced in accordance with cell cycle analysis showing disproportionately fewer Six2Cre+;p53fl/fl cells in the S and G2/M phases compared with Six2Cre+;p53+/+ cells. Mutant kidneys are hypoplastic with fewer generations of nascent nephrons. A significant increase in mean arterial pressure is observed in early adulthood in both germline and conditional Six2(p53-null) mice, linking p53-mediated defects in kidney development to hypertension. RNA-Seq analyses of FACS-isolated wild-type and Six2(GFP+) CM cells revealed that the top downregulated genes in Six2Cre+;p53fl/fl CM belong to glucose metabolism and adhesion and/or migration pathways. Mutant cells exhibit a ∼50% decrease in ATP levels and a 30% decrease in levels of reactive oxygen species, indicating energy metabolism dysfunction. In summary, our data indicate a novel role for p53 in enabling the metabolic fitness and self-renewal of nephron progenitors. PMID:25804735

  14. FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney.

    PubMed

    Fetting, Jennifer L; Guay, Justin A; Karolak, Michele J; Iozzo, Renato V; Adams, Derek C; Maridas, David E; Brown, Aaron C; Oxburgh, Leif

    2014-01-01

    Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1(-/-) tissue. We found that although nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we screened for target genes by comparison of Foxd1 null and wild-type tissues. We found that the gene encoding the small leucine-rich proteoglycan decorin (DCN) is repressed by FOXD1 in cortical interstitial cells, and we show that compound genetic inactivation of Dcn partially rescues the failure of progenitor cell differentiation in the Foxd1 null. We demonstrate that DCN antagonizes BMP/SMAD signaling, which is required for the transition of CITED1-expressing nephron progenitor cells to a state that is primed for WNT-induced epithelial differentiation. On the basis of these studies, we propose a mechanism for progenitor cell retention in the Foxd1 null in which misexpressed DCN produced by prematurely differentiated interstitial cells accumulates in the extracellular matrix, inhibiting BMP7-mediated transition of nephron progenitor cells to a compartment in which they can respond to epithelial induction signals.

  15. p53 Enables metabolic fitness and self-renewal of nephron progenitor cells.

    PubMed

    Li, Yuwen; Liu, Jiao; Li, Wencheng; Brown, Aaron; Baddoo, Melody; Li, Marilyn; Carroll, Thomas; Oxburgh, Leif; Feng, Yumei; Saifudeen, Zubaida

    2015-04-01

    Contrary to its classic role in restraining cell proliferation, we demonstrate here a divergent function of p53 in the maintenance of self-renewal of the nephron progenitor pool in the embryonic mouse kidney. Nephron endowment is regulated by progenitor availability and differentiation potential. Conditional deletion of p53 in nephron progenitor cells (Six2Cre(+);p53(fl/fl)) induces progressive depletion of Cited1(+)/Six2(+) self-renewing progenitors and loss of cap mesenchyme (CM) integrity. The Six2(p53-null) CM is disorganized, with interspersed stromal cells and an absence of a distinct CM-epithelia and CM-stroma interface. Impaired cell adhesion and epithelialization are indicated by decreased E-cadherin and NCAM expression and by ineffective differentiation in response to Wnt induction. The Six2Cre(+);p53(fl/fl) cap has 30% fewer Six2(GFP(+)) cells. Apoptotic index is unchanged, whereas proliferation index is significantly reduced in accordance with cell cycle analysis showing disproportionately fewer Six2Cre(+);p53(fl/fl) cells in the S and G2/M phases compared with Six2Cre(+);p53(+/+) cells. Mutant kidneys are hypoplastic with fewer generations of nascent nephrons. A significant increase in mean arterial pressure is observed in early adulthood in both germline and conditional Six2(p53-null) mice, linking p53-mediated defects in kidney development to hypertension. RNA-Seq analyses of FACS-isolated wild-type and Six2(GFP(+)) CM cells revealed that the top downregulated genes in Six2Cre(+);p53(fl/fl) CM belong to glucose metabolism and adhesion and/or migration pathways. Mutant cells exhibit a ∼ 50% decrease in ATP levels and a 30% decrease in levels of reactive oxygen species, indicating energy metabolism dysfunction. In summary, our data indicate a novel role for p53 in enabling the metabolic fitness and self-renewal of nephron progenitors.

  16. Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development.

    PubMed

    Ahn, Sun-Young; Kim, Yeawon; Kim, Sung Tae; Swat, Wojciech; Miner, Jeffrey H

    2013-06-01

    DLG1 (discs-large homolog 1) and CASK (calcium/calmodulin-dependent serine protein kinase) interact at membrane-cytoskeleton interfaces and function as scaffolding proteins that link signaling molecules, receptors, and other scaffolding proteins at intercellular and synaptic junctions. Dlg1-null mice exhibit hydronephrosis, hydroureter, and occasionally hypoplastic kidneys, whereas Cask-null mice do not. To investigate whether DLG1 and CASK cooperate in the developing urogenital system, we generated mice deficient in both DLG1 and CASK either 1) globally, 2) in metanephric mesenchyme, or 3) in nephron progenitors. With each approach, Dlg1;Cask double-knockout (DKO) kidneys were severely hypoplastic and dysplastic and demonstrated rapid, premature depletion of nephron progenitors/stem cells. Several cellular and molecular defects were observed in the DKO kidneys, including reduced proliferation and increased apoptosis of cells in the nephrogenic zone and a progressive decrease in the number of cells expressing SIX2, a transcription factor essential for maintaining nephron progenitors. Fgf8 expression was reduced in early-stage DKO metanephric mesenchyme, accompanied by reduced levels of components of the Ras pathway, which is activated by fibroblast growth factor (FGF) signaling. Moreover, Dlg1(+/-);Cask(-/-) (het/null) kidneys were moderately hypoplastic and demonstrated impaired aggregation of SIX2-positive cells around the ureteric bud tips. Nephron progenitor-specific het/null mice survived with small kidneys but developed glomerulocystic kidney disease and renal failure. Taken together, these results suggest that DLG1 and CASK play critical cooperative roles in maintaining the nephron progenitor population, potentially via a mechanism involving effects on FGF signaling.

  17. Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron.

    PubMed

    Breljak, Davorka; Ljubojević, Marija; Hagos, Yohannes; Micek, Vedran; Balen Eror, Daniela; Vrhovac Madunić, Ivana; Brzica, Hrvoje; Karaica, Dean; Radović, Nikola; Kraus, Ognjen; Anzai, Naohiko; Koepsell, Hermann; Burckhardt, Gerhard; Burckhardt, Birgitta C; Sabolić, Ivan

    2016-07-01

    The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na(+)-K(+)-ATPase (EC 3.6.3.9), secondary active Na(+)-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs. Na(+)-K(+)-ATPase was immunolocalized to the BLM along the entire human nephron. NaDC3-related immunostaining was detected in the BLM of proximal tubules and in the BLM and/or luminal membrane of principal cells in connecting segments and collecting ducts. The thin and thick ascending limbs, macula densa, and distal tubules exhibited no reactivity with the anti-NaDC3 antibody. OAT1-OAT3-related immunostaining in human kidneys was detected only in the BLM of cortical proximal tubules; all three OATs were stained more intensely in S1/S2 segments compared with S3 segment in medullary rays, whereas the S3 segment in the outer stripe remained unstained. Expression of NaDC3, OAT1, OAT2, and OAT3 proteins exhibited considerable interindividual variability in both male and female kidneys, and sex differences in their expression could not be detected. Our experiments provide a side-by-side comparison of basolateral transporters cooperating in renal OA secretion in the human kidney. PMID:27053689

  18. Use of dual section mRNA in situ hybridisation/immunohistochemistry to clarify gene expression patterns during the early stages of nephron development in the embryo and in the mature nephron of the adult mouse kidney.

    PubMed

    Georgas, Kylie; Rumballe, Bree; Wilkinson, Lorine; Chiu, Han Sheng; Lesieur, Emmanuelle; Gilbert, Thierry; Little, Melissa H

    2008-11-01

    The kidney is the most complex organ within the urogenital system. The adult mouse kidney contains in excess of 8,000 mature nephrons, each of which can be subdivided into a renal corpuscle and 14 distinct tubular segments. The histological complexity of this organ can make the clarification of the site of gene expression by in situ hybridisation difficult. We have defined a panel of seven antibodies capable of identifying the six stages of early nephron development, the tubular nephron segments and the components of the renal corpuscle within the embryonic and adult mouse kidney. We have analysed in detail the protein expression of Wt1, Calb1 Aqp1, Aqp2 and Umod using these antibodies. We have then coupled immunohistochemistry with RNA in situ hybridisation in order to precisely identify the expression pattern of different genes, including Wnt4, Umod and Spp1. This technique will be invaluable for examining at high resolution, the structure of both the developing and mature nephron where standard in situ hybridisation and histological techniques are insufficient. The use of this technique will enhance the expression analyses of genes which may be involved in nephron formation and the function of the mature nephron in the mouse.

  19. Genetics Home Reference: distal arthrogryposis type 1

    MedlinePlus

    ... Conditions distal arthrogryposis type 1 distal arthrogryposis type 1 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Distal arthrogryposis type 1 is a disorder characterized by joint deformities (contractures) ...

  20. Dramatic reduction in tumor burden with neoadjuvant sunitinib prior to bilateral nephron-sparing surgery.

    PubMed

    Gorin, Michael A; Ekwenna, Obi; Soloway, Mark S; Ciancio, Gaetano

    2012-02-01

    Neoadjuvant sunitinib has recently been described for the management of renal cell carcinoma. We present the pre and posttreatment images of a 49-year-old male with bilateral biopsy-proven clear cell renal cell carcinoma who underwent treatment with sunitinib prior to nephron-sparing surgery. After four four-week cycles of daily 50 mg sunitinib, the patient demonstrated a dramatic reduction in tumor burden allowing for successful bilateral partial nephrectomy.

  1. Effect of the antiglucocorticoid RU-486 on glomerular hemodynamics in remnant nephrons.

    PubMed

    Cardoso, L R; Oliveira, A V; Santos, O F; Boim, M A; Razvickas, C V; Ajzen, H; Schor, N

    1997-01-01

    Endogenous glucocorticoid (GC) has been proposed to play a role in the adaptive functions of remnant nephron and participates in the progression of renal disease. The effect of GC blockade by RU-486 (20 mg/kg), an anti-GC agent, on the progression of chronic renal failure (CRF) was evaluated in Munich-Wistar rats. CRF was induced by 5/6 nephrectomy. Global renal function, glomerular hemodynamics, proteinuria and renal histopathology studies were performed after 60 days of CRF induction. RU administration in control or CRF groups did not induce significant changes in total renal function, mean arterial or intraglomerular hydraulic pressures, 24-hour proteinuria or sclerosis index. However, RU induced a significant reduction in single-nephron glomerular filtration rate in the superficial nephrons in both groups' control (decreases 20%) and CRF (decreases 57%), without changing total glomerular filtration rate, when compared with vehicle administration. These reductions were due to a decline in glomerular plasma flow rate (QA) and in glomerular ultrafiltration coefficient (Kf). These data suggest that GC played a role in the adaptive hyperfiltration associated with the compensatory mechanism but did not participate in the genesis of proteinuria or glomerulosclerosis in this experimental model. PMID:9208281

  2. No juvenile arterial hypertension in sheep multiples despite reduced nephron numbers.

    PubMed

    Mühle, Anja; Mühle, Christiane; Amann, Kerstin; Dötsch, Jörg; Nüsken, Kai-Dietrich; Boltze, Johannes; Schneider, Holm

    2010-09-01

    Low birth weight is associated with an increased risk of metabolic dysfunction and arterial hypertension in later life. Because of their reduced birth weight twins have been used repeatedly as a natural model to investigate prenatal programming of hypertension. To reveal an early impact of lower nephron endowment on blood pressure, we performed a longitudinal study on lambs from single, twin and triplet pregnancies. The lambs were studied from birth until adulthood, including regular blood analyses, measurements of body weight and blood pressure and post-mortem estimation of glomerular numbers. Relative weight differences between multiples and singletons at birth were -28% for twins and -44% for triplets, respectively. Some lambs showed rapid catch-up growth. Total nephron number of twins and triplets was reduced by 21 and 37% with respect to that of singletons (p < 0.01). However, multiples did not show increased blood pressure within the time frame of this study. No gender-specific effect was observed. Plasma concentrations of creatinine, urea, electrolytes or osmolality also did not differ. Our data indicate that the previously reported postnatal blood pressure differences between sheep multiples and singletons are a time-limited phenomenon. During infancy and adolescence, a reduced nephron number in sheep multiples is neither associated with increased blood pressure nor reflected by plasma parameters.

  3. An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats.

    PubMed Central

    Levine, D Z

    1985-01-01

    For many years it has been thought that distal nephron hydrogen ion secretion can be importantly modulated by factors such as sodium delivery, sodium avidity, and potassium stores. Free flow micropuncture studies have also indicated that the rate of bicarbonate delivery may also alter the rate of bicarbonate reabsorption. The present studies were undertaken to examine possible luminal influences on total CO2 reabsorption in microperfused distal tubules in the rat in vivo. Tubules from normal and acidotic rats were perfused with five solutions in a manner that induced changes in bicarbonate load, sodium and potassium fluxes (JNa, JK), and luminal sulfate concentration. in each collected perfusate, simultaneous analyses were undertaken to determine water reabsorption, Na, and K concentrations using graphite furnace atomic absorption spectroscopy and total CO2 by microcalorimetry. Using factorial analysis of covariance to account for confounding effects on total CO2 flux (JtCO2) such as water reabsorption, distal tubules of acidotic rats reabsorbed CO2 in the range of 50-112 pmol X min-1 X mm-1 X These JtCO2 values were not significantly correlated with HCO3 load, JNa, or JK despite changes in the latter from net reabsorption to net secretion. Distal tubules of rats with normal acid-base status had JtCO2 values which were neither significantly different from zero nor correlated with changes in JK and JNa. Further, doubling the load from 250-500 pmol/min (by doubling the perfusion rate of 25-mM HCO3 solutions) did not stimulate JtCO2 in these normal animals. Accordingly, these acute in vivo microperfusion studies indicate for the first time that neither load nor potassium or sodium fluxes are important modulators of distal tubule bicarbonate reabsorption. PMID:2982915

  4. [Distal humerus fractures in children].

    PubMed

    Schneidmueller, D; Boettger, M; Laurer, H; Gutsfeld, P; Bühren, V

    2013-11-01

    Fractures of the distal humerus belong to the most common injuries of the upper arm in childhood. Most frequently occurring is the supracondylar fracture of the distal humerus. In these cases and in the second most common epicondylar fractures, the metaphysis is affected and these fractures are therefore extra-articular. They have to be distinguished from articular fractures regarding therapy and prognosis. The growth potential of the distal epiphysis is very limited as is the possibility of spontaneous correction so that major dislocations should not be left uncorrected. Unstable and especially dislocated articular fractures must be anatomically reconstructed employing various osteosynthetic techniques, mostly combined with immobilization. Insufficient reconstruction, growth disturbance and non-union can result in axial deformities, such as cubitus valgus and varus, restriction of motion, pain and nerve palsy.

  5. Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease

    PubMed Central

    Harari-Steinberg, Orit; Metsuyanim, Sally; Omer, Dorit; Gnatek, Yehudit; Gershon, Rotem; Pri-Chen, Sara; Ozdemir, Derya D; Lerenthal, Yaniv; Noiman, Tzahi; Ben-Hur, Herzel; Vaknin, Zvi; Schneider, David F; Aronow, Bruce J; Goldstein, Ronald S; Hohenstein, Peter; Dekel, Benjamin

    2013-01-01

    Identification of tissue-specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell-based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum-free defined conditions and prospective isolation of NCAM1+ cells selects for nephron lineage that includes the SIX2-positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells—but not differentiated counterparts—efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell-based therapeutic strategies and modelling of kidney disease. PMID:23996934

  6. Stromal Fat4 acts non-autonomously with Dchs1/2 to restrict the nephron progenitor pool.

    PubMed

    Bagherie-Lachidan, Mazdak; Reginensi, Antoine; Pan, Qun; Zaveri, Hitisha P; Scott, Daryl A; Blencowe, Benjamin J; Helmbacher, Françoise; McNeill, Helen

    2015-08-01

    Regulation of the balance between progenitor self-renewal and differentiation is crucial to development. In the mammalian kidney, reciprocal signalling between three lineages (stromal, mesenchymal and ureteric) ensures correct nephron progenitor self-renewal and differentiation. Loss of either the atypical cadherin FAT4 or its ligand Dachsous 1 (DCHS1) results in expansion of the mesenchymal nephron progenitor pool, called the condensing mesenchyme (CM). This has been proposed to be due to misregulation of the Hippo kinase pathway transcriptional co-activator YAP. Here, we use tissue-specific deletions to prove that FAT4 acts non-autonomously in the renal stroma to control nephron progenitors. We show that loss of Yap from the CM in Fat4-null mice does not reduce the expanded CM, indicating that FAT4 regulates the CM independently of YAP. Analysis of Six2(-/-);Fat4(-/-) double mutants demonstrates that excess progenitors in Fat4 mutants are dependent on Six2, a crucial regulator of nephron progenitor self-renewal. Electron microscopy reveals that cell organisation is disrupted in Fat4 mutants. Gene expression analysis demonstrates that the expression of Notch and FGF pathway components are altered in Fat4 mutants. Finally, we show that Dchs1, and its paralogue Dchs2, function in a partially redundant fashion to regulate the number of nephron progenitors. Our data support a model in which FAT4 in the stroma binds to DCHS1/2 in the mouse CM to restrict progenitor self-renewal.

  7. Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron.

    PubMed

    Layton, Anita T; Vallon, Volker; Edwards, Aurélie

    2016-06-01

    Diabetes increases the reabsorption of Na(+) (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption [Formula: see text] along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising [Formula: see text] by 5-12% in the cortex and medulla. Diabetes increases overall TNa and [Formula: see text] by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers [Formula: see text] in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises [Formula: see text] in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase [Formula: see text] by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces [Formula: see text] by 33% in S3 segments, and raises [Formula: see text] by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical [Formula: see text] and raises medullary [Formula: see text], particularly in S3 segments. PMID:26764207

  8. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

    PubMed

    Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

    2015-07-01

    Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney.

  9. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

    PubMed Central

    Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

    2015-01-01

    Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

  10. The PI3K pathway balances self-renewal and differentiation of nephron progenitor cells through β-catenin signaling.

    PubMed

    Lindström, Nils Olof; Carragher, Neil Oliver; Hohenstein, Peter

    2015-04-14

    Nephron progenitor cells differentiate to form nephrons during embryonic kidney development. In contrast, self-renewal maintains progenitor numbers and premature depletion leads to impaired kidney function. Here we analyze the PI3K pathway as a point of convergence for the multiple pathways that are known to control self-renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers premature differentiation of the progenitors and activates a differentiation program that precedes the mesenchymal-to-epithelial transition through ectopic activation of the β-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.

  11. Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis

    PubMed Central

    Craigie, Eilidh; Homer, Natalie Z. M.; Mullins, John J.; Bailey, Matthew A.

    2014-01-01

    Na+ reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+ excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+ balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na+ channel (ENaC) downstream. This effect might be mediated by changes in distal Na+ delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na+ flux through ENaC, with a concomitant increase in renal K+ excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K+ excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na+ reabsorption was not normally limited by Na+ delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na+ restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na+ reabsorption through ENaC solely by increasing distal Na+ delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments. PMID:24402096

  12. Genetics Home Reference: Laing distal myopathy

    MedlinePlus

    ... for This Page GeneReview: Laing Distal Myopathy Laing NG, Laing BA, Meredith C, Wilton SD, Robbins P, ... T, Bridges LR, Fabian V, Rozemuller A, Laing NG. Laing early onset distal myopathy: slow myosin defect ...

  13. Distal clavicle fractures in children☆

    PubMed Central

    Labronici, Pedro José; da Silva, Ricardo Rodrigues; Franco, Marcos Vinícius Viana; Labronici, Gustavo José; Pires, Robinson Esteves Santos; Franco, José Sergio

    2015-01-01

    Objective To analyze fractures of the distal clavicle region in pediatric patients. Methods Ten patients between the ages of five to eleven years (mean of 7.3 years) were observed. Nine patients were treated conservatively and one surgically. All the fractures were classified using the Nenopoulos classification system. Results All the fractures consolidated without complications. Conservative treatment was used for nine patients, of whom three were in group IIIB, three IIb, two IIa and one IV. The only patient who was treated surgically was a female patient of eleven years of age with a group IV fracture. Conclusion The treatment indication for distal fractures of the clavicle in children should be based on the patient's age and the displacement of the fragments. PMID:26962489

  14. Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons.

    PubMed

    Mah, S P; Saueressig, H; Goulding, M; Kintner, C; Dressler, G R

    2000-07-01

    During nephrogenesis, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues.

  15. Regulatory volume decrease in perfused proximal nephron: evidence for a dumping of cell K+.

    PubMed

    Kirk, K L; DiBona, D R; Schafer, J A

    1987-05-01

    We utilized the microscopic and morphometric procedures described in the preceding paper to examine the role of a swelling-activated dumping of K-salt in the reversal of hyposmotic cell swelling in the perfused proximal nephron. The rate of the regulatory volume decrease that follows cell swelling in dilute solutions was reduced by two maneuvers that attenuate the K+ chemical potential difference across the basolateral membrane; inhibiting the Na+-K+ pump (e.g., with ouabain) and raising the peritubular K+ concentration. The rate of the regulatory volume decrease was also inhibited by peritubular quinine, which blocks K channels and volume regulation for a number of mammalian cells. Additionally, exposure to hyposmotic solutions resulted in a sustained and quinine-sensitive increase in the apparent permeability of the basolateral membrane to K+ salt, which was monitored qualitatively as the rate of cell volume change that was induced by a perturbation in the peritubular K+ concentration. The simplest interpretation of these results is that the reversal of hyposmotic cell swelling in the proximal nephron is referable at least in part to a swelling-activated loss of K-salt and water from the cells. PMID:2437806

  16. Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons.

    PubMed

    Mah, S P; Saueressig, H; Goulding, M; Kintner, C; Dressler, G R

    2000-07-01

    During nephrogenesis, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues. PMID:10864459

  17. WT1 targets Gas1 to maintain nephron progenitor cells by modulating FGF signals.

    PubMed

    Kann, Martin; Bae, Eunnyung; Lenz, Maximilian O; Li, Liangji; Trannguyen, BaoTran; Schumacher, Valerie A; Taglienti, Mary E; Bordeianou, Liliana; Hartwig, Sunny; Rinschen, Markus M; Schermer, Bernhard; Benzing, Thomas; Fan, Chen-Ming; Kreidberg, Jordan A

    2015-04-01

    Development of the metanephric kidney depends on tightly regulated interplay between self-renewal and differentiation of a nephron progenitor cell (NPC) pool. Several key factors required for the survival of NPCs have been identified, including fibroblast growth factor (FGF) signaling and the transcription factor Wilms' tumor suppressor 1 (WT1). Here, we present evidence that WT1 modulates FGF signaling by activating the expression of growth arrest-specific 1 (Gas1), a novel WT1 target gene and novel modulator of FGF signaling. We show that WT1 directly binds to a conserved DNA binding motif within the Gas1 promoter and activates Gas1 mRNA transcription in NPCs. We confirm that WT1 is required for Gas1 expression in kidneys in vivo. Loss of function of GAS1 in vivo results in hypoplastic kidneys with reduced nephron mass due to premature depletion of NPCs. Although kidney development in Gas1 knockout mice progresses normally until E15.5, NPCs show decreased rates of proliferation at this stage and are depleted as of E17.5. Lastly, we show that Gas1 is selectively required for FGF-stimulated AKT signaling in vitro. In summary, our data suggest a model in which WT1 modulates receptor tyrosine kinase signaling in NPCs by directing the expression of Gas1.

  18. Distal esophageal spasm: an update.

    PubMed

    Achem, Sami R; Gerson, Lauren B

    2013-09-01

    Distal esophageal spasm (DES) is an esophageal motility disorder that presents clinically with chest pain and/or dysphagia and is defined manometrically as simultaneous contractions in the distal (smooth muscle) esophagus in ≥20% of wet swallows (and amplitude contraction of ≥30 mmHg) alternating with normal peristalsis. With the introduction of high resolution esophageal pressure topography (EPT) in 2000, the definition of DES was modified. The Chicago classification proposed that the defining criteria for DES using EPT should be the presence of at least two premature contractions (distal latency<4.5 s) in a context of normal EGJ relaxation. The etiology of DES remains insufficiently understood, but evidence links nitric oxide (NO) deficiency as a culprit resulting in a disordered neural inhibition. GERD frequently coexists in DES, and its role in the pathogenesis of symptoms needs further evaluation. There is some evidence from small series that DES can progress to achalasia. Treatment remains challenging due in part to lack of randomized placebo-controlled trials. Current treatment agents include nitrates (both short and long acting), calcium-channel blockers, anticholinergic agents, 5-phosphodiesterase inhibitors, visceral analgesics (tricyclic agents or SSRI), and esophageal dilation. Acid suppression therapy is frequently used, but clinical outcome trials to support this approach are not available. Injection of botulinum toxin in the distal esophagus may be effective, but further data regarding the development of post-injection gastroesophageal reflux need to be assessed. Heller myotomy combined with fundoplication remains an alternative for the rare refractory patient. Preliminary studies suggest that the newly developed endoscopic technique of per oral endoscopic myotomy (POEM) may also be an alternative treatment modality. PMID:23892829

  19. Chondroblastoma of the distal phalanx.

    PubMed

    Gregory, James R; Lehman, Thomas P; White, Jeremy R; Fung, Kar-Ming

    2014-05-01

    Chondroblastoma is a rare, benign primary bone tumor that usually occurs at the epiphysis of long bones. The authors present an example of the diagnosis and successful treatment of this neoplasm in an exceedingly rare location in the distal phalanx. Clinical and radiographic outcomes after 68 months of follow-up are presented. A 15-year-old, right hand-dominant, boy developed painful swelling of the right ring finger. Radiographs revealed a radiolucent lesion of the distal phalanx with expansile remodeling of the bone. An excisional biopsy was performed with curettage and bone grafting of the lesion. The diagnosis of chondroblastoma was made based on pathologic evaluation of the biopsy specimen. Sixty-six months after surgical treatment, the patient was free of recurrence and metastatic disease with excellent clinical and functional outcomes. To the authors' knowledge, this represents only the second reported case of chondroblastoma of the distal phalanx. The diagnosis of chondroblastoma in this rare location was made by pathologic review of the resection specimen. It is imperative to confirm the diagnosis of any resected bone specimen even when the concern for an aggressive or malignant lesion is low. A tumor presenting in an unusual location may require a change in treatment or surveillance.

  20. Chondroblastoma of the distal phalanx.

    PubMed

    Gregory, James R; Lehman, Thomas P; White, Jeremy R; Fung, Kar-Ming

    2014-05-01

    Chondroblastoma is a rare, benign primary bone tumor that usually occurs at the epiphysis of long bones. The authors present an example of the diagnosis and successful treatment of this neoplasm in an exceedingly rare location in the distal phalanx. Clinical and radiographic outcomes after 68 months of follow-up are presented. A 15-year-old, right hand-dominant, boy developed painful swelling of the right ring finger. Radiographs revealed a radiolucent lesion of the distal phalanx with expansile remodeling of the bone. An excisional biopsy was performed with curettage and bone grafting of the lesion. The diagnosis of chondroblastoma was made based on pathologic evaluation of the biopsy specimen. Sixty-six months after surgical treatment, the patient was free of recurrence and metastatic disease with excellent clinical and functional outcomes. To the authors' knowledge, this represents only the second reported case of chondroblastoma of the distal phalanx. The diagnosis of chondroblastoma in this rare location was made by pathologic review of the resection specimen. It is imperative to confirm the diagnosis of any resected bone specimen even when the concern for an aggressive or malignant lesion is low. A tumor presenting in an unusual location may require a change in treatment or surveillance. PMID:24810830

  1. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    SciTech Connect

    Machiguchi, Toshihiko Nakamura, Tatsuo

    2013-06-07

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues.

  2. The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

    PubMed

    Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

    2016-10-01

    The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule.

  3. Tubuloglomerular and connecting tubuloglomerular feedback during inhibition of various Na transporters in the nephron.

    PubMed

    Wang, Hong; D'Ambrosio, Martin A; Ren, YiLin; Monu, Sumit R; Leung, Pablo; Kutskill, Kristopher; Garvin, Jeffrey L; Janic, Branislava; Peterson, Edward L; Carretero, Oscar A

    2015-05-01

    Afferent (Af-Art) and efferent arterioles resistance regulate glomerular capillary pressure. The nephron regulates Af-Art resistance via: 1) vasoconstrictor tubuloglomerular feedback (TGF), initiated in the macula densa via Na-K-2Cl cotransporters (NKCC2) and 2) vasodilator connecting tubuloglomerular feedback (CTGF), initiated in connecting tubules via epithelial Na channels (ENaC). Furosemide inhibits NKCC2 and TGF. Benzamil inhibits ENaC and CTGF. In vitro, CTGF dilates preconstricted Af-Arts. In vivo, benzamil decreases stop-flow pressure (PSF), suggesting that CTGF antagonizes TGF; however, even when TGF is blocked, CTGF does not increase PSF, suggesting there is another mechanism antagonizing CTGF. We hypothesize that in addition to NKCC2, activation of Na/H exchanger (NHE) antagonizes CTGF, and when both are blocked CTGF dilates Af-Arts and this effect is blocked by a CTGF inhibitor benzamil. Using micropuncture, we studied the effects of transport inhibitors on TGF responses by measuring PSF while increasing nephron perfusion from 0 to 40 nl/min. Control TGF response (-7.9 ± 0.2 mmHg) was blocked by furosemide (-0.4 ± 0.2 mmHg; P < 0.001). Benzamil restored TGF in the presence of furosemide (furosemide: -0.2 ± 0.1 vs. furosemide+benzamil: -4.3 ± 0.3 mmHg; P < 0.001). With furosemide and NHE inhibitor, dimethylamiloride (DMA), increase in tubular flow increased PSF (furosemide+DMA: 2.7 ± 0.5 mmHg, n = 6), and benzamil blocked this (furosemide+DMA+benzamil: -1.1 ± 0.2 mmHg; P < 0.01, n = 6). We conclude that NHE in the nephron decreases PSF (Af-Art constriction) when NKCC2 and ENaC are inhibited, suggesting that in the absence of NKCC2, NHE causes a TGF response and that CTGF dilates the Af-Art when TGF is blocked with NKCC2 and NHE inhibitors. PMID:25715987

  4. Immunolocalization of hyperpolarization-activated cationic HCN1 and HCN3 channels in the rat nephron: regulation of HCN3 by potassium diets.

    PubMed

    López-González, Zinaeli; Ayala-Aguilera, Cosete; Martinez-Morales, Flavio; Galicia-Cruz, Othir; Salvador-Hernández, Carolina; Pedraza-Chaverri, José; Medeiros, Mara; Hernández, Ana Maria; Escobar, Laura I

    2016-01-01

    Hyperpolarization-activated cationic and cyclic nucleotide-gated channels (HCN) comprise four homologous subunits (HCN1-HCN4). HCN channels are found in excitable and non-excitable tissues in mammals. We have previously shown that HCN2 may transport ammonium (NH4 (+)), besides sodium (Na(+)), in the rat distal nephron. In the present work, we identified HCN1 and HCN3 in the proximal tubule (PT) and HCN3 in the thick ascending limb of Henle (TALH) of the rat kidney. Immunoblot assays detected HCN1 (130 kDa) and HCN3 (90 KDa) and their truncated proteins C-terminal HCN1 (93 KDa) and N-terminal HCN3 (65 KDa) in enriched plasma membranes from cortex (CX) and outer medulla (OM), as well as in brush-border membrane vesicles. Immunofluorescence assays confirmed apical localization of HCN1 and HCN3 in the PT. HCN3 was also found at the basolateral membrane of TALH. We evaluated chronic changes in mineral dietary on HCN3 protein abundance. Animals were fed with three different diets: sodium-deficient (SD) diet, potassium-deficient (KD) diet, and high-potassium (HK) diet. Up-regulation of HCN3 was observed in OM by KD and in CX and OM by HK; the opposite effect occurred with the N-terminal truncated HCN3 in CX (KD) and OM (HK). SD diet did not produce any change. Since HCN channels activate with membrane hyperpolarization, our results suggest that HCN channels may play a role in the Na(+)-K(+)-ATPase activity, contributing to Na(+), K(+), and acid-base homeostasis in the rat kidney.

  5. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis. PMID:26460946

  6. Homeostasis, the Milieu Intérieur, and the Wisdom of the Nephron

    PubMed Central

    Zeidel, Mark L.

    2014-01-01

    The concept of homeostasis has been inextricably linked to the function of the kidneys for more than a century when it was recognized that the kidneys had the ability to maintain the “internal milieu” and allow organisms the “physiologic freedom” to move into varying environments and take in varying diets and fluids. Early ingenious, albeit rudimentary, experiments unlocked a wealth of secrets on the mechanisms involved in the formation of urine and renal handling of the gamut of electrolytes, as well as that of water, acid, and protein. Recent scientific advances have confirmed these prescient postulates such that the modern clinician is the beneficiary of a rich understanding of the nephron and the kidney’s critical role in homeostasis down to the molecular level. This review summarizes those early achievements and provides a framework and introduction for the new CJASN series on renal physiology. PMID:24789550

  7. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis.

  8. Dynamics of NAD in cortical nephron segments: Effect of nicotinamide and of dietary phosphate intake

    SciTech Connect

    Yusufi, A.N.K.; Kiebzak, G.M.; Kusano, E.; Werness, J.L.; Homma, S.; Dousa, T.P. )

    1987-08-01

    NAD content and the rate of NAD hydrolysis were determined in proximal convoluted tubules (PCT), proximal straight tubules (PST), and adjacent cortical nephron segments microdissected from kidneys of tyroparathyroidectomized (TPTX) rats. In the basal state, rats fed a normal phosphate diet had an NAD content higher in PCT, PST, and in cortical ascending limb (CAL) than in glomeruli. After intraperitoneal injection of nicotinamide, the NAD content increased significantly in all nephron segments except CAL. In experiments conducted on TPTX rats stabilized on a low-phosphorus diet, NAD content increased in response to a nicotinamide injection in PCT, but did not change significantly in PST. The catabolism of NAD was determined by generation of ({sup 3}H)adenosine, a major metabolite of (adenine-2,8-{sup 3}H)NAD. The rate of ({sup 3}H)adenosine generation from ({sup 3}H)NAD was significantly higher in PST than in PCT. The authors conclude that, in response to nicotinamide administration in vivo, the NAD content increases more in PCT than in PST and that this difference may be, at least partly, due to a lower rate of NAD breakdown in PCT. In a state of dietary phosphate deprivation, NAD also increases significantly in response to intraperitoneal nicotinamide in PCT, but it does not increase significantly in PST. The nicotinamide-elicited increase of NAD content in proximal tubules, mainly in PCT, may be related to inhibition of Na{sup +}-gradient-dependent inorganic phosphate (P{sub i}) reabsorption across the brush-border membrane proximal tubules and to the phosphaturic effect of nicotinamide in rats red normal-P{sub i} diet.

  9. Peripheral nerve blocks for distal extremity surgery.

    PubMed

    Offierski, Chris

    2013-10-01

    Peripheral nerve block is well suited for distal extremity surgery. Blocking the nerves at the distal extremity is easily done. It does not require ultrasound or stimulators to identify the nerve. Blocking nerves in the distal extremity is safe with low risk of toxicity. The effect of the nerve block is limited to the distribution of the nerve. The distal nerves in the lower extremity are sensory branches of the sciatic nerve. This provides a sensory block only. This has the advantage of allowing the patient to actively contract tendons in the foot and ambulate more quickly after surgery. PMID:24093651

  10. Distal metatarsal synostosis: a case report.

    PubMed

    Aspros, Dimitrios; Ananda-Rajan, Ethan; Jnr, Zdenak Klezl; Rajan, Rohan

    2014-09-01

    We report a rare case of distal metatarsal synostosis of the 4th and 5th metatarsals in an 11 year old male. He was referred with forefoot pain. Clinical examination and radiographs have confirmed an osseous connection of the distal 4th and 5th metatarsal. This was treated surgically with bony bridge excision and the patient is now asymptomatic.

  11. Distal symphalangism: a report of two families.

    PubMed

    Poush, J R

    1991-01-01

    This study describes distal symphalangism in 36 individuals in two families, one of which is the largest pedigree of this rare defect yet documented. Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or feet. The findings of this report substantiate the mutation as an autosomal dominant phenotype. Several manifestations of distal symphalangism were observed, including the lack of cutaneous creases over affected joints, brachydactyly, fourth-finger hypophalangism, absent nails, and rudimentary nails. Variability ranged from just toes affected, to a single finger affected, to all fingers and all lesser toes affected. The most common expression of the mutant gene was rigid index fingers. Craniosynostosis, premature closure of the sutures of the skull, was encountered twice in the larger of the two families. It is a possible pleiotropic effect of distal symphalangism. PMID:2061594

  12. Distal symphalangism: a report of two families.

    PubMed

    Poush, J R

    1991-01-01

    This study describes distal symphalangism in 36 individuals in two families, one of which is the largest pedigree of this rare defect yet documented. Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or feet. The findings of this report substantiate the mutation as an autosomal dominant phenotype. Several manifestations of distal symphalangism were observed, including the lack of cutaneous creases over affected joints, brachydactyly, fourth-finger hypophalangism, absent nails, and rudimentary nails. Variability ranged from just toes affected, to a single finger affected, to all fingers and all lesser toes affected. The most common expression of the mutant gene was rigid index fingers. Craniosynostosis, premature closure of the sutures of the skull, was encountered twice in the larger of the two families. It is a possible pleiotropic effect of distal symphalangism.

  13. Robotic distal pancreatectomy: a valid option?

    PubMed

    Jung, M K; Buchs, N C; Azagury, D E; Hagen, M E; Morel, P

    2013-10-01

    Although reported in the literature, conventional laparoscopic approach for distal pancreatectomy is still lacking widespread acceptance. This might be due to two-dimensional vision and decreased range of motion to reach and safely dissect this highly vascularized retroperitoneal organ by laparoscopy. However, interest in minimally invasive access is growing ever since and the robotic system could certainly help overcome limitations of the laparoscopic approach in the challenging domain of pancreatic resection, notably in distal pancreatectomy. Robotic distal pancreatectomy with and without spleen preservation has been reported with encouraging outcomes for benign and borderline malignant disease. As a result of upgraded endowristed manipulation and three-dimensional visualization, improved outcome might be expected with the launch of the robotic system in the procedure of distal pancreatectomy. Our aim was thus to extensively review the current literature of robot-assisted surgery for distal pancreatectomy and to evaluate advantages and possible limitations of the robotic approach.

  14. Eya1 Interacts with Six2 and Myc to Regulate Expansion of the Nephron Progenitor Pool during Nephrogenesis

    PubMed Central

    Xu, Jinshu; Wong, Elaine Y.M.; Cheng, Chunming; Li, Jun; Sharkar, Mohammad T.K.; Xu, Chelsea Y.; Chen, Binglai; Sun, Jianbo; Jing, Dongzhu; Xu, Pin-Xian

    2014-01-01

    SUMMARY Self-renewal and proliferation of nephron progenitor cells and the decision to initiate nephrogenesis are crucial events directing kidney development. Despite recent advancements in defining lineage and regulators for the progenitors, fundamental questions about mechanisms driving expansion of the progenitors remain unanswered. Here we show that Eya1 interacts with Six2 and Myc to control self-renewing cell activity. Cell fate tracing reveals a developmental restriction of the Eya1+ population within the intermediate mesoderm to nephron-forming cell fates and a common origin shared between caudal mesonephric and metanephric nephrons. Conditional inactivation of Eya1 leads to loss of Six2 expression and premature epithelialization of the progenitors. Six2 mediates translocation of Eya1 to the nucleus, where Eya1 uses its threonine phosphatase activity to control Myc phosphorylation/dephosphorylation and function in the progenitor cells. Our results reveal a functional link between Eya1, Six2, and Myc in driving the expansion and maintenance of the multipotent progenitors during nephrogenesis. PMID:25458011

  15. Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells

    PubMed Central

    Pode-Shakked, Naomi; Pleniceanu, Oren; Gershon, Rotem; Shukrun, Rachel; Kanter, Itamar; Bucris, Efrat; Pode-Shakked, Ben; Tam, Gal; Tam, Hadar; Caspi, Revital; Pri-Chen, Sara; Vax, Einav; Katz, Guy; Omer, Dorit; Harari-Steinberg, Orit; Kalisky, Tomer; Dekel, Benjamin

    2016-01-01

    When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms’ tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133− marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2− epithelial progenitors and NCAM1−CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133− marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1−CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. PMID:27020553

  16. AMC: amyoplasia and distal arthrogryposis.

    PubMed

    Kimber, Eva

    2015-12-01

    Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition defined as multiple congenital joint contractures in two or more body areas. The common pathogenesis is impaired fetal movements. Amyoplasia, the most frequent form, is a sporadically occurring condition with hypoplastic muscles and joint contractures. Distal arthrogryposis (DA) syndromes are often hereditary, and joint involvement is predominantly in the hands and feet. In a Swedish study, 131 patients with arthrogryposis were investigated. The most frequent diagnoses were amyoplasia and DA. In amyoplasia, muscle strength was found to be more important than joint range of motion (ROM) for motor function. In DA, muscle weakness was present in 44 % of investigated patients. The clinical findings were found to be highly variable between families and also within families with DA. Fetal myopathy due to sarcomeric protein dysfunction can cause DA. An early multidisciplinary team evaluation of the child with arthrogryposis for specific diagnosis and planning of treatment is recommended. Attention should be directed at the development of muscle strength with early stimulation of active movements. Immobilization should be minimized.

  17. Distal phalanges of Eosimias and Hoanghonius.

    PubMed

    Gebo, Daniel L; Beard, K Christopher; Ni, Xijun; Dagosto, Marian

    2015-09-01

    Seven primate distal phalanges have been identified from two middle Eocene fossil localities (Locality 1 and Nanbaotou) in the Yuanqu Basin, China, providing the first evidence of distal phalangeal morphology in Asian Eocene adapiform and eosimiid primates. The bones are best allocated to the basal anthropoid Eosimias centennicus and to hoanghoniine adapiforms. All distal phalangeal specimens display a morphology consistent with nail-bearing fingers and toes. The hallucal distal phalanx of the basal anthropoid Eosimias is more similar to that of primitive tarsiiforms than to crown group anthropoids. The adapiform distal phalanges from Locality 1 are allocated to Hoanghonius stehlini while those from Nanbaotou are tentatively assigned to an indeterminate hoanghoniine because dental remains of adapiforms have yet to be identified from this site. The distal phalangeal anatomy of hoanghoniines differs slightly from that documented for adapines and notharctines. One distal phalanx from Locality 1 shows a second pedal digit "grooming claw" morphology as noted for notharctines by Maiolino et al. (2012) and cercamoniines by Von Koenigswald et al. (2012).

  18. Transition of permeability properties along the descending limb of long-loop nephron

    SciTech Connect

    Imai, Masashi; Taniguchi, Junichi; Yoshitomi, Koji )

    1988-03-01

    The isolated segments of the hamster descending limb of the long-loop nephron (LDL) were perfused in vitro to demonstrate the axial heterogeneity with respect to permeability properties. When a NaCl gradient from the lumen to bath was present, the lumen-negative diffusion voltage (V{sub D}) was generated in the upper portion (LDL{sub u}). When the V{sub D} was measured stepwise along the axis of tubules, the magnitude of the V{sub D} decreased in the portion within 0.5 mm before the border between the outer and inner medulla in most cases, indicating that a gradual functional transition to the lower position (LDL{sub L}) occurs along the descending limb. The reflection coefficients for NaCl and urea were not different from unity. From these observations, the authors conclude that the functional transition occurs along the LDL from the segment with a high Na{sup +} permeability to that with a low Na{sup +} permeability.

  19. Phenomenological model relating cell shape to water reabsorption in proximal nephron.

    PubMed

    Welling, D J; Welling, L W; Hill, J J

    1978-04-01

    If the complex pattern of intercellular channels in proximal tubule is determined in part by the forces of large transepithelial water flow, the shape of the cells is an indicator of the type and magnitude of the forces required for water movement and the routes of that flow. To test this thesis, morphologic data and volume flow parameters for rabbit proximal tubule are related generally by a mass balance equation. If the intercellular boundaries are assumed to be highly deformable and to respond to changes in hydrostatic pressure, the solution to that equation is a simple relationship between cell shape and the forces required for water movement. The resulting phenomenological model suggests an important new role for peritubular serum proteins and can be used to compute reasonable values for cell wall hydraulic conductivity, intercellular protein diffusion constant, and a channel fluid osmolality not more than 1% greater than that of luminal fluid. It is concluded that quantitative morphologic studies may serve as a powerful means for evaluating and understanding transport phenomena in the nephron.

  20. Nonbridging external fixation of distal radius fractures.

    PubMed

    Eichenbaum, Matthew D; Shin, Eon K

    2010-08-01

    Surgical management of distal radius fractures continues to evolve because of their high incidence in an increasingly active elderly population. Traditional radiocarpal external fixation relies on ligamentotaxis for fracture reduction but has several drawbacks. Nonbridging external fixation has evolved to provide early wrist mobility in the setting of anatomic fracture reduction. Several studies of the nonbridging technique have demonstrated satisfactory results in isolated nonbridging external fixation series and in comparison with traditional spanning external fixation. Nonbridging external fixation for surgical treatment of distal radius fractures can be technically demanding and requires at least 1 cm of intact volar cortex in the distal fracture fragment for successful implementation.

  1. Distal Peripheral Polyneuropathy in a Great Dane

    PubMed Central

    Henricks, Paul M.; Steiss, Jan; Petterson, Joanne D.

    1987-01-01

    A spayed female five year old Great Dane dog was diagnosed as having a chronic, progressive, symmetrical distal polyneuropathy and concurrent hypothyroidism. Axonal degeneration and segmental demyelination were evident in teased nerve fiber preparations. Clinical signs included hindlimb weakness and muscle atrophy of the head and distal limbs. Diagnosis was based on clinical, electrophysiological, and nerve and muscle biopsy findings. Thyroxine supplementation for one month was of no benefit. The etiology of the polyneuropathy was not established but several causes were considered. The extent of demyelination in our case was of greater magnitude than described in a previous report of a similar idiopathic distal symmetrical polyneuropathy in a Great Dane. PMID:17422753

  2. Cell rubidium uptake: a method for studying functional heterogeneity in the nephron

    SciTech Connect

    Beck, F.X.; Doerge, A.B.; Bluemner, E.G.; Giebisch, G.; Thurau, K.

    1988-03-01

    Rubidium uptake into individual tubule cells of rat renal cortex as measured by energy-dispersive X-ray microanalysis on freeze dried cryosections was used as an index of potassium transport. Over a 30 second period following intravenous infusion of rubidium (0.5 mmol/kg body wt) rubidium content increased in all cells. After 30 seconds, rubidium contents were (in mmol/kg dry wt): 225 +/- 8 in distal convoluted tubule cells, 156 +/- 7 in connecting tubule cells, 110 +/- 7 in principal cells, 86 +/- 4 in proximal tubule cells and 24 +/- 2 in intercalated cells (mean +/- SEM). When distal sodium and potassium transport were stimulated by hypertonic saline loading, rubidium uptake was selectively increased into distal convoluted tubule cells by 38%, into connecting tubule cells by 36%, and into principal cells by 52%. However, rubidium uptake into proximal tubule and into intercalated cells remained unchanged. The preferential uptake of rubidium into distal convoluted tubule cells, connecting tubule cells, and principal cells correlates well with the known transport functions of sodium and potassium, whereas intercalated cells are distinguished by low sodium and potassium transport activity.

  3. Regulation of renal potassium secretion: molecular mechanisms.

    PubMed

    Welling, Paul A

    2013-05-01

    A new understanding of renal potassium balance has emerged as the molecular underpinnings of potassium secretion have become illuminated, highlighting the key roles of apical potassium channels, renal outer medullary potassium channel (ROMK) and Big Potassium (BK), in the aldosterone-sensitive distal nephron and collecting duct. These channels act as the final-regulated components of the renal potassium secretory machinery. Their activity, number, and driving forces are precisely modulated to ensure potassium excretion matches dietary potassium intake. Recent identification of the underlying regulatory mechanisms at the molecular level provides a new appreciation of the physiology and reveals a molecular insight to explain the paradoxic actions of aldosterone on potassium secretion. Here, we review the current state of knowledge in the field.

  4. Villous adenoma of the distal appendix.

    PubMed

    Taylor, J V; Thomas, M G; Kelly, S; Sutton, R

    1997-04-01

    Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

  5. Synergistic alpha-1 and alpha-2 adrenergic stimulation of rat proximal nephron Na+/H+ exchange

    SciTech Connect

    Gesek, F.A.; Cragoe, E.J. Jr.; Strandhoy, J.W.

    1989-06-01

    Both alpha-1 and alpha-2 adrenoceptors have been localized to the renal cortex, with the majority of binding sites on the proximal tubule. Because the major regulator of Na+ uptake into the proximal tubule is the Na+/H+ exchanger, and because alpha-1 and alpha-2 adrenoceptors stimulate it in other tissues, we tested the hypothesis that both alpha adrenoceptor subtypes can increase Na+ uptake into the proximal nephron by stimulating the Na+/H+ antiporter. Enhancement of Na+ transport by agonists was studied in isolated rat proximal tubules by determining the uptake of 22Na that was suppressible by the Na+/H+ inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The phorbol ester, phorbol-12-myristate-13-acetate, (0.1 microM), directly stimulated the antiporter through protein kinase C and increased EIPA-suppressible 22Na uptake 250% above control. The alpha-1 adrenoceptor agonists, cirazoline and phenylephrine, in addition to the mixed agonist, norepinephrine, maximally stimulated uptake by 226 to 232% at 1 microM concentrations. alpha-2 agonists produced a range of maximal stimulations at 1 microM from 65% with guanabenz to 251% with B-HT 933. Increases in 22Na uptake by agonists were inhibited by selective adrenergic antagonists and by EIPA. The drugs did not change the EIPA-resistant component of 22Na uptake. Inasmuch as the adrenoceptor subtypes likely stimulated Na+/H+ exchange by differing intracellular pathways impinging upon common transport steps, we examined whether simultaneous stimulation of both pathways was additive. Submaximal concentrations (5 nM each) of alpha-1 and alpha-2 adrenoceptor agonists in combination synergistically enhanced 22Na uptake to a level similar to 1 microM concentrations of adrenoceptor agonists alone or in combination.

  6. Cell-specific regulation of L-WNK1 by dietary K.

    PubMed

    Webb, Tennille N; Carrisoza-Gaytan, Rolando; Montalbetti, Nicolas; Rued, Anna; Roy, Ankita; Socovich, Alexandra M; Subramanya, Arohan R; Satlin, Lisa M; Kleyman, Thomas R; Carattino, Marcelo D

    2016-01-01

    Flow-induced K(+) secretion in the aldosterone-sensitive distal nephron is mediated by high-conductance Ca(2+)-activated K(+) (BK) channels. Familial hyperkalemic hypertension (pseudohypoaldosteronism type II) is an inherited form of hypertension with decreased K(+) secretion and increased Na(+) reabsorption. This disorder is linked to mutations in genes encoding with-no-lysine kinase 1 (WNK1), WNK4, and Kelch-like 3/Cullin 3, two components of an E3 ubiquitin ligase complex that degrades WNKs. We examined whether the full-length (or "long") form of WNK1 (L-WNK1) affected the expression of BK α-subunits in HEK cells. Overexpression of L-WNK1 promoted a significant increase in BK α-subunit whole cell abundance and functional channel expression. BK α-subunit abundance also increased with coexpression of a kinase dead L-WNK1 mutant (K233M) and with kidney-specific WNK1 (KS-WNK1), suggesting that the catalytic activity of L-WNK1 was not required to increase BK expression. We examined whether dietary K(+) intake affected L-WNK1 expression in the aldosterone-sensitive distal nephron. We found a paucity of L-WNK1 labeling in cortical collecting ducts (CCDs) from rabbits on a low-K(+) diet but observed robust staining for L-WNK1 primarily in intercalated cells when rabbits were fed a high-K(+) diet. Our results and previous findings suggest that L-WNK1 exerts different effects on renal K(+) secretory channels, inhibiting renal outer medullary K(+) channels and activating BK channels. A high-K(+) diet induced an increase in L-WNK1 expression selectively in intercalated cells and may contribute to enhanced BK channel expression and K(+) secretion in CCDs.

  7. Archaic and modern human distal humeral morphology.

    PubMed

    Yokley, Todd R; Churchill, Steven E

    2006-12-01

    The morphology of the proximal ulna has been shown to effectively differentiate archaic or premodern humans (such as Homo heidelbergensis and H. neanderthalensis) from modern humans (H. sapiens). Accordingly, the morphology of adjacent, articulating elements should be able to distinguish these two broad groups as well. Here we test the taxonomic utility of another portion of the elbow, the distal humerus, as a discriminator of archaic and modern humans. Principal components analysis was employed on a suite of log-raw and log-shape distal humeral measures to examine differences between Neandertal and modern human distal humeri. In addition, the morphological affinities of Broken Hill (Kabwe) E.898, an archaic human distal humeral fragment from the middle Pleistocene of Zambia, and five Pliocene and early Pleistocene australopith humeri were assessed. The morphometric analyses effectively differentiated the Neandertals from the other groups, while the Broken Hill humerus appears morphologically similar to modern human distal humeri. Thus, an archaic/modern human dichotomy-as previously reported for proximal ulnar morphology-is not supported with respect to distal humeral morphology. Relative to australopiths and modern humans, Neandertal humeri are characterized by large olecranon fossae and small distodorsal medial and lateral pillars. The seeming disparity in morphological affinities of proximal ulnae (in which all archaic human groups appear distinct from modern humans) and distal humeri (in which Neandertals appear distinct from modern humans, but other archaic humans do not) is probably indicative of a highly variable, possibly transitional population of which our knowledge is hampered by sample-size limitations imposed by the scarcity of middle-to-late Pleistocene premodern human fossils outside of Europe.

  8. Management of distal humeral coronal shear fractures

    PubMed Central

    Yari, Shahram S; Bowers, Nathan L; Craig, Miguel A; Reichel, Lee M

    2015-01-01

    Coronal shear fractures of the distal humerus are rare, complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface following distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach (direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails. PMID:25984515

  9. Distal protection for treatment of complete cervical internal carotid occlusion.

    PubMed

    Hungerford, John P; Chaudry, Imran; Turner, Raymond; Turk, Aquilla S

    2012-01-01

    Distal protection devices (DPD) have been advocated for carotid artery stenting to reduce the risk of distal embolization. These devices were designed for deployment in the straight cervical segment of the internal carotid artery. We present a case of total cervical carotid occlusion recanalized with the aid of a distal protection device deployed 'distally' in the intracranial internal carotid artery.

  10. Albuminuria indicates the pressure-associated injury of juxtamedullary nephrons and cerebral strain vessels in spontaneously hypertensive stroke-prone rats.

    PubMed

    Nagasawa, Tasuku; Mori, Takefumi; Ohsaki, Yusuke; Yoneki, Yoshimi; Guo, Qi; Sato, Emiko; Oba, Ikuko; Ito, Sadayoshi

    2012-10-01

    Albuminuria is an indicator of renal injury and is closely linked with cardiovascular disease (CVD). However, the mechanism by which albumin is excreted in the urine remains unclear. As the juxtamedullary region of the kidney is highly susceptible to pressure increase, juxtamedullary injury is observed from an early phase in hypertensive rat models. Anatomical similarities are observed between the pre-glomerular vessels of the juxtamedullary nephron and the cerebral vasculature. We previously named these 'strain vessels' for their high vascular tone and exposure to higher pressures. The current studies were designed to determine whether albuminuria is the result of juxtamedullary nephron injury, indicating the presence of pressure injury to the strain vessels in spontaneously hypertensive stroke-prone rats (SHR-SP) fed a high-salt diet. Albuminuria was associated with juxtamedullary nephron injury, and the enhanced expression of monocyte chemotactic protein-1 (MCP-1) and tumor growth factor-beta (TGF-β) in 12-week-old SHR-SP rats fed a 4% high-salt diet from the age of 6 weeks. The wall thickness of the pre-glomerular vessels of the juxtamedullary nephron was also associated with that of the perforating artery of the middle cerebral artery. Reducing the blood pressure with nifedipine reduced the degree of albuminuria and juxtamedullary nephron injury as well as MCP-1 and TGF-β expression in the SHR-SP rats fed an 8% high-salt diet from the age of 9 weeks. Nifedipine inhibited stroke events in these animals until they were 14 weeks old. These results indicate that albuminuria is a result of juxtamedullary nephron injury and a marker of pressure-induced injury of the strain vessels.

  11. Sextant of Sapphires for Molar Distalization

    PubMed Central

    Palla, Yudistar Venkata; Ganugapanta, Vivek Reddy

    2016-01-01

    Introduction Space analysis quantifies the amount of crowding within the arches estimating the severity of space discrepancy. The space gaining procedures include extraction and non-extraction procedures like expansion, proximal stripping and molar distalization. Aim To identify features seen in molar distalization cases. Materials and Methods The sample size comprised 20 patients in whom molar distalization was decided as the treatment plan. The study models and lateral cephalograms of all the patients were taken. Occlusograms were obtained. Model analysis and cephalometric analysis were performed. Descriptive statistical analysis like mean, standard deviation, standard error and mode were done. Results The parameters in Question gave following results. The Bolton analysis showed anterior mandibular excess with mean value of 1.56mm±1.07. The first order discrepancy between maxillary central and lateral incisors was 5±1.95. The premolar rotation showed mean value of 16.58±5.12. The molar rotation showed the value of 7.66±2.26. The nasolabial angle showed the mean of 101.25±8.7 IMPA of 101.4±5.74. Conclusion The six features studied in molar distalization cases [First order discrepancy between upper central and lateral incisors; Rotation of premolars and molars; Bolton’s discrepancy in anterior dentition; Average to horizontal growth pattern; Proclined lower incisors and Obtuse nasolabial angle] can be taken as patterns seen in molar distalization cases and considered as a valid treatment plan. PMID:27656572

  12. Failure of distal biceps repair by gapping

    PubMed Central

    Copas, David; Watts, Adam C

    2016-01-01

    Background We describe the clinical, radiological and surgical findings of failed distal biceps repair by gapping and report the functional outcomes following revision repair. Methods A retrospective review of five consecutive patients was conducted. Patients presented with radial-sided forearm pain after their distal biceps fixation. All patients had less than 5 cm of retraction of the biceps muscle belly, a palpable tendon although the manoeuvre was painful with weakness on resisted supination. Flexed abducted supinated magnetic resonance imaging (FABS MRI) showed a gap between the distal end of the tendon and the footprint on the radial tuberosity. Results Mean FEA score at presentation was 44/100 (35 to 49). Mean time to re-operation was 18 months (range 4 months to 36 months). At revision, the distal end of the tendon was retracted and not making contact with the bone. All cases were revised to an in-bone endobutton repair. Mean postoperative Functional Elbow Assessment (FEA) scores undertaken at a mean of 14 months (range 5 months to 22 months) after revision improved to 95/100 (90 to 100). Conclusions Patients presenting with persistent radial sided forearm pain and weakness on provocative testing after distal biceps repair with a seemingly intact repair should be investigated with FABS MRI to look for evidence of failure of repair by gapping. Revision repair with an anatomic in-bone technique can lead to good results. PMID:27583018

  13. Fabrication and Evaluation of a Noncompliant Molar Distalizing Appliance: Bonded Molar Distalizer

    PubMed Central

    Sodagar, A.; Ahmad Akhoundi, M. S.; Rafighii, A.; Arab, S.

    2011-01-01

    Objective Attempts to treat class II malocclusions without extraction in non-compliant patients have led to utilization of intraoral molar distalizing appliances. The purpose of this study was to investigate dental and skeletal effects of Bonded Molar Distalizer (BMD) which is a simple molar distalizing appliance. Materials and Methods Sixteen patients (12 girls, four boys) with bilateral half-cusp class II molar relationship, erupted permanent second molars and normal or vertical growth pattern were selected for bilateral distalization of maxillary molars via BMD. The screws were activated every other day, alternately. Lateral cephalograms and study models were obtained before treatment and after 11 weeks activation of the appliance. Results Significant amounts of molar distalization, molar distal tipping and anchorage loss were observed. The mean maxillary first molar distal movement was 1.22±0.936 mm with a distal tipping of 2.97±3.74 degrees in 11 weeks. The rate of distal movement was 0.48 mm per month. Reciprocal mesial movement of the first premolars was 2.26±1.12 mm with a mesial tipping of 4.25±3.12 degrees. Maxillary incisors moved 3.55±1.46 mm and tipped 9.87±5.03 degrees mesially. Lower anterior face height (LAFH) decreased 1.28±1.36 mm. Conclusion BMD is appropriate for distalizing maxillary molars, especially in patients with critical LAFH, although significant amounts of anchorage loss occur using this appliance. PMID:22457837

  14. Treatment Options for Distal Femur Fractures.

    PubMed

    von Keudell, Arvind; Shoji, Kristin; Nasr, Michael; Lucas, Robert; Dolan, Robert; Weaver, Michael J

    2016-08-01

    Despite advances in implant design, the management of distal femur fractures remains challenging. Fracture comminution and intra-articular extension can make it difficult to obtain an adequate reduction while preserving the soft tissue attachments to bone fragments to allow for bone healing. Many implant manufacturers have developed optimal anatomically contoured, distal femoral locking plates with percutaneous guides. This environment allows for the application of lateral locked plates in a biologically friendly manner. Although initial reports had high success rates, more recently a high rate of nonunion has been found, particularly in elderly patients. Limited literature is available for the treatment of patients with osteoporotic bone and associated ipsilateral total knee replacement and hip replacement. We present a patient with a distal femur fracture with significant comminution in the setting of an ipsilateral total hip replacement. PMID:27441931

  15. Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control.

    PubMed

    Moreau, E; Vilar, J; Lelièvre-Pégorier, M; Merlet-Bénichou, C; Gilbert, T

    1998-12-01

    Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all-trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14 (E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-alpha (GDNFR-alpha), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-alpha transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

  16. Phenotyping by magnetic resonance imaging nondestructively measures glomerular number and volume distribution in mice with and without nephron reduction

    PubMed Central

    Baldelomar, Edwin J.; Charlton, Jennifer R.; Beeman, Scott C.; Hann, Bradley D.; Cullen-McEwen, Luise; Pearl, Valeria M.; Bertram, John F.; Wu, Teresa; Zhang, Min; Bennett, Kevin M.

    2015-01-01

    Reduced nephron mass is strongly linked to susceptibility to chronic renal and cardiovascular diseases. There are currently no tools to identify nephropenia in clinical or preclinical diagnostics. Such new methods could uncover novel mechanisms and therapies for chronic kidney disease (CKD) and reveal how variation among traits can affect renal function and morphology. Here we used cationized ferritin (CF) enhanced-MRI (CFE-MRI) to investigate the relationship between glomerular number (Nglom) and volume (Vglom) in kidneys of healthy wild type mice and mice with oligosyndactylism (Os/+), a model of congenital nephron reduction. Mice were injected with cationic ferritin and perfused and the resected kidneys imaged with 7T MRI to detect CF-labeled glomeruli. CFE-MRI was used to measure the intrarenal distribution of individual glomerular volumes and revealed two major populations of glomeruli distinguished by size. Spatial mapping revealed that the largest glomeruli were located in the juxtamedullary region in both wild type and Os/+ mice and the smallest population located in the cortex. Os/+ mice had about a 50% reduction and 35% increase of Nglom and Vglom, respectively, in both glomerular populations compared to wild type, consistent with glomerular hypertrophy in the Os/+ mice. Thus, we provide a foundation for whole-kidney, MRI-based phenotyping of mouse renal glomerular morphology and provide new potential for quantitative human renal diagnostics. PMID:26535998

  17. Distal Humerus Fractures: Open Reduction Internal Fixation.

    PubMed

    Mighell, Mark A; Stephens, Brent; Stone, Geoffrey P; Cottrell, Benjamin J

    2015-11-01

    Distal humerus fractures are challenging injuries for the upper extremity surgeon. However, recent techniques in open reduction internal fixation have been powerful tools in getting positive outcomes. To get such results, the surgeon must be aware of how to properly use these techniques in their respective practices. The method of fixation depends on the fracture, taking the degree of comminution and the restoration of the columns and articular surface into account. This article helps surgeons understand the concepts behind open reduction internal fixation of the distal humerus and makes them aware of pitfalls that may lead to negative results.

  18. Exposure of the forearm and distal radius.

    PubMed

    Klausmeyer, Melissa A; Mudgal, Chaitanya

    2014-11-01

    Approaches to the forearm use internervous planes to allow adequate bone exposure and prevent muscle denervation. The Henry approach utilizes the plane between muscles supplied by the median and radial nerves. The Thompson approach utilizes the plane between muscles supplied by the radial and posterior interosseous nerves. The distal radius may be approached volarly. The extended flexor carpi radialis approach is useful for intraarticular fractures, subacute fractures, and malunions. The distal radius can be approached dorsally by releasing the third dorsal compartment and continuing the dissection subperiosteally. Choice of approach depends on the injury pattern and the need for exposure. PMID:25440071

  19. Comparison of Maxillary Molar Distalization with an Implant-Supported Distal Jet and a Traditional Tooth-Supported Distal Jet Appliance

    PubMed Central

    Cozzani, Mauro; Pasini, Marco; Zallio, Francesco; Ritucci, Robert; Mutinelli, Sabrina; Mazzotta, Laura; Giuca, Maria Rita; Piras, Vincenzo

    2014-01-01

    Aim. To investigate and compare the efficiency of two appliances for molar distalization: the bone-anchored distal screw (DS) and the traditional tooth-supported distal jet (DJ) for molar distalization and anchorage loss. Methods. Tests (18 subjects) were treated with a DS and controls (18 subjects) were treated with a DJ. Lateral cephalograms were obtained before and at the end of molar distalization and were analysed. Shapiro Wilk test, unpaired t-test, and Wilcoxon rank-sum test were applied according to values distribution. The α level was fixed at 0.05. Results. Maxillary first molars were successfully distalized into a Class I relationship in all patients. The mean molar distalization and treatment time were similar in both groups. The DS group exhibited a spontaneous distalization (2.1 ± 0.9 mm) of the first premolar with control of anchorage loss, distal tipping, extrusion, and skeletal changes. Conclusions. The DS is an adequate compliance-free distalizing appliance that can be used safely for the correction of Class II malocclusions. In comparison to the traditional DJ, the DS enables not only a good rate of molar distalization, but also a spontaneous distalization of the first premolars. PMID:25018770

  20. Comparative evaluation of molar distalization therapy using pendulum and distal screw appliances

    PubMed Central

    Cafagna, Alessandra; Fontana, Mattia; Cozzani, Mauro

    2015-01-01

    Objective To compare dentoalveolar and skeletal changes produced by the pendulum appliance (PA) and the distal screw appliance (DS) in Class II patients. Methods Forty-three patients (19 men, 24 women) with Class II malocclusion were retrospectively selected for the study. Twenty-four patients (mean age, 12.2 ± 1.5 years) were treated with the PA, and 19 patients (mean age, 11.3 ± 1.9 years) were treated with the DS. The mean distalization time was 7 months for the PA group and 9 months for the DS group. Lateral cephalograms were obtained at T1, before treatment, and at T2, the end of distalization. A Mann-Whitney U test was used for statistical comparisons of the two groups between T1 and T2. Results PA and DS were equally effective in distalizing maxillary molars (4.7 mm and 4.2 mm, respectively) between T1 and T2; however, the maxillary first molars showed less distal tipping in the DS group than in the PA group (3.2° vs. 9.0°, respectively). Moreover, significant premolar anchorage loss (2.7 mm) and incisor proclination (5.0°) were noted in the PA group, whereas premolar distal movement (1.9 mm) and no significant changes at the incisor (0.1°) were observed in the DS group. No significant sagittal or vertical skeletal changes were detected between the two groups during the distalization phase. Conclusions PA and DS seem to be equally effective in distalizing maxillary molars; however, greater distal molar tipping and premolar anchorage loss can be expected using PA. PMID:26258063

  1. A New Distal Radioulnar Joint Prosthesis

    PubMed Central

    Schuurman, Arnold H.

    2013-01-01

    Pain and instability of the distal radioulnar joint (DRUJ) are common sequelae following a fracture of the distal radius. Many soft tissue procedures have been described, not all of which are successful. Ulnar head replacement prostheses are available but do not always provide stability. We designed a two-part, easy to implant, distal radioulnar prosthesis and implanted it in 19 patients. The first prototype was inserted in 2002 and is still in place. During the study, the design was changed twice, resulting in three groups with four patients in group A, five in group B, and ten in group C. Unfortunately all five prostheses in group B had to be removed because of loosening, while only two prostheses in group C had to be removed, for nonprosthetic reasons. For the 12 patients who retained their prosthesis, forearm function increased while grip strength increased significantly. Pain scores decreased and the Disabilities of the Arm, Shoulder, and Hand (DASH) score improved but remained high. We conclude that the prosthesis offers a new treatment option for ulnar instability following distal ulnar resection. PMID:24436843

  2. Kif3a controls murine nephron number via GLI3 repressor, cell survival, and gene expression in a lineage-specific manner.

    PubMed

    Chi, Lijun; Galtseva, Alevtina; Chen, Lin; Mo, Rong; Hui, Chi-Chung; Rosenblum, Norman D

    2013-01-01

    The primary cilium is required during early embryo patterning, epithelial tubulogenesis, and growth factor-dependent signal transduction. The requirement for primary cilia during renal epithelial-mesenchymal tissue interactions that give rise to nephrons is undefined. Here, we used Cre-mediated recombination to generate mice with Kif3a deficiency targeted to the ureteric and/or metanephric mesenchyme cell lineages in the embryonic kidney. Gradual loss of primary cilia in either lineage leads to a phenotype of reduced nephron number. Remarkably, in addition to cyst formation, loss of primary cilia in the ureteric epithelial cell leads to decreased expression of Wnt11 and Ret and reduced ureteric branching. Constitutive expression of GLI3 repressor (Gli3(Δ699/+) ) rescues these abnormalities. In embryonic metanephric mesenchyme cells, Kif3a deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that Kif3a controls nephron number via distinct cell lineage-specific mechanisms.

  3. Management of hyperkalaemia.

    PubMed

    Maxwell, A P; Linden, K; O'Donnell, S; Hamilton, P K; McVeigh, G E

    2013-01-01

    Hyperkalaemia, an elevated extracellular fluid potassium concentration, is a common electrolyte disorder and is present in 1-10% of hospitalised patients. Elevated serum potassium concentrations are usually asymptomatic but may be associated with electrocardiogram (ECG) changes. Hyperkalaemia occasionally leads to life-threatening cardiac arrhythmias. Prompt recognition of this disorder, patient risk management and administration of appropriate treatment can prevent serious cardiac complications of hyperkalaemia. Further assessment of the underlying basis for hyperkalaemia usually reveals a problem with renal potassium excretion (rather than transcellular shift of potassium or excess potassium intake). Reduced potassium excretion is typically associated with decreased potassium secretion in the aldosterone-sensitive distal nephron of the kidney. Common causes for hyperkalaemia include kidney failure, limited delivery of sodium and water to the distal nephron and drugs that inhibit the renin-angiotensin-aldosterone system. Treatment of life-threatening hyperkalaemia (particularly those patients with ECG changes) involves administration of intravenous calcium salts to stabilise the resting cardiac membrane potential. The potassium concentration can be lowered by administration of intravenous insulin combined with an infusion of glucose to stimulate intracellular uptake of potassium. Nebulised β-2 adrenoceptor agonists can augment the effects of intravenous insulin and glucose pending more definitive management of the recurrent hyperkalaemia risk. Additional management steps include stopping further potassium intake and careful review of prescribed drugs that may be adversely affecting potassium homeostasis. Changes to prescribing systems and an agreed institutional protocol for management of hyperkalaemia can improve patient safety for this frequently encountered electrolyte disorder.

  4. MicroRNA 802 stimulates ROMK channels by suppressing caveolin-1.

    PubMed

    Lin, Dao-Hong; Yue, Peng; Pan, Chunyang; Sun, Peng; Wang, Wen-Hui

    2011-06-01

    Dietary potassium stimulates the surface expression of ROMK channels in the aldosterone-sensitive distal nephron, but the mechanism by which this occurs is incompletely understood. Here, a high-potassium diet increased the transcription of microRNA (miR) 802 in the cortical collecting duct in mice. In addition, high-potassium intake decreased the expression of caveolin-1, whose 3' untranslated region contains the seed sequence of miR-802. In vitro, expression of miR-802 suppressed the expression of caveolin-1, and conversely, downregulation of endogenous miR-802 increased the expression of caveolin-1. Sucrose-gradient centrifugation suggested that caveolin-1 closely associated with ROMK channels, and immunoprecipitation showed that caveolin-1 interacted with the N terminus of ROMK. Expression of caveolin-1 varied inversely with the expression of ROMK1 in the plasma membrane, and caveolin-1 inhibited ROMK1 channel activity. Removal of the clathrin-dependent endocytosis motif from ROMK1 failed to abolish the effect of caveolin-1 on ROMK1 channel activity. Last, expression of miR-802 increased ROMK1 channel activity, an effect blocked by coexpression of caveolin-1. Taken together, miR-802 mediates the stimulatory effect of a high-potassium diet on ROMK channel activity by suppressing caveolin-1 expression, which leads to increased surface expression of ROMK channels in the distal nephron. PMID:21566059

  5. Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance.

    PubMed

    Rubera, Isabelle; Loffing, Johannes; Palmer, Lawrence G; Frindt, Gustavo; Fowler-Jaeger, Nicole; Sauter, Daniel; Carroll, Tom; McMahon, Andrew; Hummler, Edith; Rossier, Bernard C

    2003-08-01

    Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the alpha subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance. PMID:12925696

  6. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

  7. Genetics Home Reference: distal hereditary motor neuropathy, type V

    MedlinePlus

    ... hereditary motor neuropathy, type V distal hereditary motor neuropathy, type V Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type V is a progressive disorder that affects ...

  8. Nephron sparing endoscopic treatment for primary carcinoma of the renal calyx: A case report and literature review

    PubMed Central

    WANG, QI; OU, TONG-WEN; XU, JIA-WEI; LI, JIN; BORAZJANI, ALI; JIA, CHUN-SONG; WANG, XU; YAN, HAO

    2016-01-01

    Primary carcinoma of the renal calyx is extremely rare. The present study reported nephron sparing endoscopic treatment for primary carcinoma of the renal calyx. An 81-year-old female presented with a 1-year history of intermittent painless gross hematuria. Computed tomography and X-ray of the urinary tract were unable to definitively identify any lesion. Flexible ureteroscopic examination revealed a tumor with epicenter in the lower calyx of the right kidney, with additional involvement around the calyx. Biopsies were obtained and pathology revealed low-grade urothelial carcinoma. Considering additional co-morbidities, the patient elected to undergo endoscopic management with thulium laser. The present report described the feasibility of flexible ureteroscopic thulium laser resection for the treatment of renal calyx carcinoma. PMID:27330785

  9. Extracorporeal shockwave lithotripsy of distal ureteral calculi.

    PubMed

    Miller, K; Bubeck, J R; Hautmann, R

    1986-01-01

    To date, the use of extracorporeal shockwave lithotripsy (ESWL) has been limited to renal calculi and ureteral calculi above the pelvic brim. Modifying the position of the patient on the support of the Dornier lithotripter HM3, we were able to localize and treat distal ureteral calculi. Until April 1986, 43 patients with stones in the lower ureter underwent contact-free lithotripsy. Treatment was successful in 39 patients (90%), 2 of these requiring 2 sessions. In 4 patients treatment failed and stone removal was accomplished using ureteroscopy or open surgery. No complications or adverse side effects were encountered in the whole series. ESWL is now the method of choice for the treatment of distal ureteral calculi in our department.

  10. [Fracture endoprosthesis of distal humerus fractures].

    PubMed

    Müller, L P; Wegmann, K; Burkhart, K J

    2013-08-01

    The treatment of choice for fractures of the distal humerus is double plate osteosynthesis. Due to anatomical preshaped angle stable plates the primary stability and management of soft tissues has been improved. However, osteoporotic comminuted fractures in the elderly are often not amenable to stable osteosynthesis and total elbow arthroplasty has been established as an alternative therapy. Although complication rates have been reduced, complications of total elbow arthroplasty are still much more frequent than in total hip replacement. Furthermore, patients are advised not to exceed a weight bearing of 5 kg. Therefore, the indications for elbow arthroplasty must be evaluated very strictly and should be reserved for comminuted distal humeral fractures in the elderly with poor bone quality that are not amenable to stable osteosynthesis or for simple fractures in cases of preexisting symptomatic osteoarthritis. This article introduces and discusses modern concepts of elbow arthroplasty, such as modular convertible prosthesis systems, hemiarthroplasty and radial head replacement in total elbow arthroplasty.

  11. Nephron filtration rate and proximal tubular fluid reabsorption in the Akita mouse model of type I diabetes mellitus

    PubMed Central

    Schnermann, Jurgen

    2013-01-01

    An increase of glomerular filtration rate (hyperfiltration) is an early functional change associated with type I or type II diabetes mellitus in patients and animal models. The causes underlying glomerular hyperfiltration are not entirely clear. There is evidence from studies in the streptozotocin model of diabetes in rats that an increase of proximal tubular reabsorption results in the withdrawal of a vasoconstrictor input exerted by the tubuloglomerular feedback (TGF) mechanism. In the present study, we have used micropuncture to assess single nephron function in wild type (WT) mice and in two strains of type I diabetic Ins2+/- mice in either a C57Bl/6 (Akita) or an A1AR-/- background (Akita/A1AR-/-) in which TGF is non-functional. Kidney glomerular filtration rate (GFR) of anesthetized mice was increased by 25% in Akita mice and by 52% in Akita/A1AR-/-, but did not differ between genotypes when corrected for kidney weight. Single nephron GFR (SNGFR) measured by end-proximal fluid collections averaged 11.8 ± 1 nl/min (n=17), 13.05 ± 1.1 nl/min (n=23; p=0.27), and 15.4 ± 0.84 nl/min (n=26; p=0.009 compared to WT; p=0.09 compared to Akita) in WT, Akita, and Akita/A1AR-/- mice respectively. Proximal tubular fluid reabsorption was not different between WT and diabetic mice and correlated with SNGFR in all genotypes. We conclude that glomerular hyperfiltration is a primary event in the Akita model of type I diabetes, perhaps driven by an increased filtering surface area, and that it is ameliorated by TGF to the extent that this regulatory system is functional. PMID:24358878

  12. Expression of TLR4 protein is reduced in chronic renal failure: evidence from an experimental model of nephron reduction.

    PubMed

    Kacsó, Ina Maria; Borza, Gabriel Mircea; Ciuce, Cătălin C; Bîrsan, Andrei; Apostu, Raluca Cristina; Dindelegan, George Călin; Bondor, Cosmina Ioana; Potra, Alina Ramona; Netea, Mihai G; Cătoi, Cornel

    2015-01-01

    Toll-like receptor 4 (TLR4) signaling is involved in various acute and chronic renal lesions and contributes to inflammation and fibrosis in several organs; the latter are important determinants to the progression of chronic kidney disease (CKD). We aimed to assess TLR4 expression in progressive CKD and relate it to severity of kidney damage, using an experimental nephron reduction model. Male Wistar rats were subjected to subtotal nephrectomy using the ligation technique, after 12 weeks of observation, serum creatinine and proteinuria were determined, animals were sacrificed, glomerulosclerosis and interstitial scarring were quantified histologically, and TLR4 expression was assessed by immunohistochemistry. Sham-operated rats served as controls. Case animals had significantly higher creatinine, proteinuria, glomerulosclerosis and tubulointerstitial involvement. TLR4 expression was prominent in proximal tubes, less staining was observed on infiltrating inflammatory cells. Percentage of TLR4-positive tubes was reduced in the subtotal nephrectomy animals, when compared to controls (0.67±0.09 versus 0.79±0.07, p=0.003). Percentage of TLR4-positive tubes correlated inversely to markers of kidney damage: to proteinuria (r=-0.55, p=0.02), serum creatinine (r=-0.53, p=0.01); percentage of glomeruli with glomerulosclerosis (r=-0.54, p=0.01) and tubulointerstitial score (r=-0.36, p=0.01). As TLR4 staining appears in tubular casts only in nephrectomy animals, shedding from damaged tubular cells is a very likely explanation for the reduced TLR4 expression in the kidneys of subjects with experimental nephron reduction.

  13. Fracture of distal end clavicle: A review

    PubMed Central

    Sambandam, Balaji; Gupta, Rajat; Kumar, Santosh; Maini, Lalit

    2014-01-01

    Management of fracture distal end clavicle has always puzzled the orthopaedic surgeons. Now-a-days with a relatively active lifestyle, patients want better results both cosmetically and functionally. Despite so much literature available for the management of this common fracture, there is no consensus regarding the gold standard treatment for this fracture. In this article, we reviewed the literature on various techniques of management for this fracture, both conservative as well as surgical, and their merits and demerits. PMID:25983473

  14. Fractures of Distal Radius: An Overview

    PubMed Central

    Meena, Sanjay; Sharma, Pankaj; Sambharia, Abhishek Kumar; Dawar, Ashok

    2014-01-01

    Fractures of distal radius account for up to 20% of all fractures treated in emergency department. Initial assessment includes a history of mechanism of injury, associated injury and appropriate radiological evaluation. Treatment options include conservative management, internal fixation with pins, bridging and non-bridging external fixation, dorsal or volar plating with/without arthroscopy assistance. However, many questions regarding these fractures remain unanswered and good prospective randomized trials are needed. PMID:25657938

  15. Distal Embolic Protection for Renal Arterial Interventions

    SciTech Connect

    Dubel, Gregory J. Murphy, Timothy P.

    2008-01-15

    Distal or embolic protection has intuitive appeal for its potential to prevent embolization of materials generated during interventional procedures. Distal protection devices (DPDs) have been most widely used in the coronary and carotid vascular beds, where they have demonstrated the ability to trap embolic materials and, in some cases, to reduce complications. Given the frequency of chronic kidney disease in patients with renal artery stenosis undergoing stent placement, it is reasonable to propose that these devices may play an important role in limiting distal embolization in the renal vasculature. Careful review of the literature reveals that atheroembolization does occur during renal arterial interventions, although it often goes undetected. Early experience with DPDs in the renal arteries in patients with suitable anatomy suggests retrieval of embolic materials in approximately 71% of cases and renal functional improvement/stabilization in 98% of cases. The combination of platelet inhibition and a DPD may provide even greater benefit. Given the critical importance of renal functional preservation, it follows that everything that can be done to prevent atheroembolism should be undertaken including the use of DPDs when anatomically feasible. The data available at this time support a beneficial role for these devices.

  16. Distal nerve entrapment following nerve repair.

    PubMed

    Schoeller, T; Otto, A; Wechselberger, G; Pommer, B; Papp, C

    1998-04-01

    Failure of nerve repair or poor functional outcome after reconstruction can be influenced by various causes. Besides improper microsurgical technique, fascicular malalignment and unphysiologic tension, we found in our clinical series that a subclinical nerve compression distal to the repair site can seriously impair regeneration. We concluded that the injured nerve, whether from trauma or microsurgical intervention, could be more susceptible to distal entrapment in the regenerative stage because of its disturbed microcirculation, swelling and the increase of regenerating axons followed by increased nerve volume. In two cases we found the regenerating nerve entrapped at pre-existing anatomical sites of narrowing resulting in impaired functional recovery. In both cases the surgical therapy was decompression of the distal entrapped nerve and this was followed by continued regeneration. Thorough clinical and electrophysiologic follow-up is necessary to detect such adverse compression effects and to distinguish between the various causes of failed regeneration. Under certain circumstances primary preventive decompression may be beneficial if performed at the time of nerve coaptation.

  17. Mirrored visual feedback limits distal effect anticipation.

    PubMed

    Sutter, Christine; Ladwig, Stefan

    2012-04-01

    Modern tools in technological environments are often characterized by a spatial separation of hand actions (operating a remote control) and their intended action effects (displayed movements of an unmanned vehicle, a robot, or an avatar on a screen). Often non-corresponding proximal and distal movement effects put high demands on the human information processing system. The present study aimed to investigate how modern technological environments influence processes of planning and controlling actions. Participants performed ipsi- or contralateral movements in response to colored stimuli, while the stimulus location had to be ignored. They did not see the stimuli and hands directly, but received visual feedback (with retained or reversed spatial relations) on a projection screen in front of them. Visual feedback retaining spatial relations led to the usual Simon effect. However, visual feedback reversing spatial relations inverted the Simon effect in ipsilateral responses, and eliminated it in contralateral responses (Exp. 1). Impairing the proximal movement-effect loop so that proprioceptive/tactile information from the moving hand was no longer a reliable source for planning and controlling actions attenuated compatibility effects (Exp. 2). Moreover, distal action effects predominated action control even for opposing body-related effects. It seemed that action control of transformed movements depended on the reliability of proprioceptive/tactile and visual information. When the amount of feature overlap between proprioception and vision was low and proprioceptive (visual) information was no longer reliable, then distal (proximal) action effects stepped forward and became crucial in controlling transformed actions.

  18. Robotic distal pancreatectomy versus conventional laparoscopic distal pancreatectomy: a comparative study for short-term outcomes.

    PubMed

    Lai, Eric C H; Tang, Chung Ngai

    2015-09-01

    Robotic system has been increasingly used in pancreatectomy. However, the effectiveness of this method remains uncertain. This study compared the surgical outcomes between robot-assisted laparoscopic distal pancreatectomy and conventional laparoscopic distal pancreatectomy. During a 15-year period, 35 patients underwent minimally invasive approach of distal pancreatectomy in our center. Seventeen of these patients had robot-assisted laparoscopic approach, and the remaining 18 had conventional laparoscopic approach. Their operative parameters and perioperative outcomes were analyzed retrospectively in a prospective database. The mean operating time in the robotic group (221.4 min) was significantly longer than that in the laparoscopic group (173.6 min) (P = 0.026). Both robotic and conventional laparoscopic groups presented no significant difference in spleen-preservation rate (52.9% vs. 38.9%) (P = 0.505), operative blood loss (100.3 ml vs. 268.3 ml) (P = 0.29), overall morbidity rate (47.1% vs. 38.9%) (P = 0.73), and post-operative hospital stay (11.4 days vs. 14.2 days) (P = 0.46). Both groups also showed no perioperative mortality. Similar outcomes were observed in robotic distal pancreatectomy and conventional laparoscopic approach. However, robotic approach tended to have the advantages of less blood loss and shorter hospital stay. Further studies are necessary to determine the clinical position of robotic distal pancreatectomy.

  19. Complications of Distal Biceps Tendon Repair

    PubMed Central

    Amin, Nirav H.; Volpi, Alex; Lynch, T. Sean; Patel, Ronak M.; Cerynik, Douglas L.; Schickendantz, Mark S.; Jones, Morgan H.

    2016-01-01

    Background: Anatomic reinsertion of the distal biceps is critical for restoring flexion and supination strength. Single- and double-incision surgical techniques have been reported, analyzing complications and outcomes measures. Which technique results in superior clinical outcomes and the lowest associated complications remains unclear. Hypothesis: We hypothesized that rerupture rates would be similar between the 2 techniques, while nerve complications would be higher for the single-incision technique and heterotopic ossification would be more frequent with the double-incision technique. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review was conducted using the PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), SPORTSDiscus, and the Cochrane Central Register of Controlled Trials databases to identify articles reporting distal biceps ruptures up to August 2013. We included English-language articles on adult patients with a minimum of 3 cases reporting single- and double-incision techniques. Frequencies of each complication as a percentage of total cases were calculated. Fisher exact tests were used to test the association between frequencies for each repair method, with P < .05 considered statistically significant. Odds ratios with 95% CIs were also computed. Results: A total of 87 articles met the inclusion criteria. Lateral antebrachial cutaneous nerve neurapraxia was the most common complication in the single-incision group, occurring in 77 of 785 cases (9.8%). Heterotopic ossification was the most common complication in the double-incision group, occurring in 36 of 498 cases (7.2%). Conclusion: The overall frequency of reported complications is higher for single-incision distal biceps repair than for double-incision repair. The frequencies of rerupture and nerve complications are both higher for single-incision repairs while the frequency of heterotopic ossification is higher for

  20. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    NASA Astrophysics Data System (ADS)

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  1. Aqueous outflow: Segmental and distal flow

    PubMed Central

    Swaminathan, Swarup S.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.

    2014-01-01

    A prominent risk factor of primary open-angle glaucoma is ocular hypertension, a pathologic state caused by impaired outflow of aqueous humor through the trabecular meshwork within the iridocorneal angle. The juxtacanalicular region of the trabecular meshwork and the inner wall of Schlemm canal have been identified as the main contributors to aqueous outflow resistance, and both extracellular matrix within the trabecular meshwork and trabecular meshwork cell shape have been shown to affect outflow. Overexpression of multiple ECM proteins in perfused cadaveric human eyes has led to increased outflow resistance and elevated IOP. Pharmacologic agents targeting trabecular meshwork cytoskeletal arrangements have been developed after multiple studies demonstrated the importance of cell shape on outflow. Several groups have shown that aqueous outflow occurs only at certain segments of the trabecular meshwork circumferentially, a concept known as segmental flow. This is based on the theory that aqueous outflow is dependent on the presence of discrete pores within the Schlemm canal. Segmental flow has been described in the eyes of multiple species, including primate, bovine, mouse, and human samples. While the trabecular meshwork appears to be the major source of resistance, trabecular meshwork bypass procedures have been unable to achieve the degree of IOP reduction observed with trabeculectomy, reflecting the potential impact of distal flow, or flow through Schlemm canal and collector channels, on outflow. Multiple studies have demonstrated that outflow occurs preferentially near collector channels, suggesting that these distal structures may be more important to aqueous outflow than previously believed. PMID:25088623

  2. Maxillary molar distalization with first class appliance

    PubMed Central

    Ramesh, Namitha; Palukunnu, Biswas; Ravindran, Nidhi; Nair, Preeti P

    2014-01-01

    Non-extraction treatment has gained popularity for corrections of mild-to-moderate class II malocclusion over the past few decades. The distalization of maxillary molars is of significant value for treatment of cases with minimal arch discrepancy and mild class II molar relation associated with a normal mandibular arch and acceptable profile. This paper describes our experience with a 16-year-old female patient who reported with irregularly placed upper front teeth and unpleasant smile. The patient was diagnosed to have angles class II malocclusion with moderate maxillary anterior crowding, deep bite of 4 mm on a skeletal class II base with an orthognathic maxilla and retrognathic mandible and normal growth pattern. She presented an ideal profile and so molar distalization was planned with the first-class appliance. Molars were distalised by 8 mm on the right and left quadrants and class I molar relation achieved within 4 months. The space gained was utilised effectively to align the arch and establish a class I molar and canine relation. PMID:24577171

  3. Distal metatarsal coalition: A rare case report

    PubMed Central

    Vun, Shen Hwa; Drampalos, Efstathios; Shareef, Sajan; Sinha, Satyajit; Bramley, Diane

    2015-01-01

    Introduction Metatarsal coalition is an extremely rare condition. We report the second documented case of 4th and 5th distal metatarsal coalition in the literature. Presentation of case An eight-year-old girl was referred to an orthopaedic clinic with a four-month history of forefoot pain and swelling on the plantar aspect of the right little toe. Radiograph and clinical examination confirmed distal metatarsal coalition between the 4th and 5th metatarsals. Following a period of conservative treatment, excision was eventually performed due to worsening symptoms. Patient re-attended two years later with a recurrence of the coalition confirmed by computed tomography (CT) scan. The case was discussed at a tertiary paediatric orthopaedic insititution. Decision was made to manage patient conservatively with insole and physiotherapy until skeletal maturity. A year later, patient’s symptoms did not worsen, and her foot displayed no evidence of change in the arch and shape. Discussion The timing of ossification of coalition varies from one anatomical site to another. Surgery when performed before ossification is complete runs the risk of recurrence. Conclusion Our case report illustrates the importance of restoring normal weight bearing dynamics and pain relief when managing metatarsal coalition, or synostosis in skeletally immature patients. We recommend persevering with conservative treatment, with operative treatment reserved only as a later option, and ideally, until skeletal maturity is achieved. PMID:25670408

  4. Distal vacuolar myopathy in nephropathic cystinosis.

    PubMed

    Charnas, L R; Luciano, C A; Dalakas, M; Gilliatt, R W; Bernardini, I; Ishak, K; Cwik, V A; Fraker, D; Brushart, T A; Gahl, W A

    1994-02-01

    Nephropathic cystinosis is a lysosomal storage disorder leading to renal failure by age 10 years. Prolonged patient survival following renal transplantation has allowed the development of previously unknown long-term complications. Muscle involvement has been reported in a single posttransplant cystinosis patient, but the range of clinical, electrophysiologic, and histologic features has not been fully described. Thirteen of 54 post-renal-transplant patients that we examined developed weakness and wasting in the small hand muscles, with or without facial weakness and dysphagia. Tendon reflexes were preserved and sensory examinations were normal. Electrophysiologic studies in 11 affected patients showed normal nerve conduction velocities and preserved sensory action potentials. The voluntary motor units in the affected distal muscles had reduced amplitude and brief duration, confirmed with quantitative electromyography in 4 patients. Biopsy of the severely affected abductor digiti minimi or extensor carpi radialis brevis muscles in 2 patients revealed marked fiber size variability, prominent acid phosphatase-positive vacuoles, and absence of fiber type grouping or inflammatory cells. Crystals of cystine were detected in perimysial cells but not within the muscle cell vacuoles. The muscle cystine content of clinically affected muscles was markedly elevated. We conclude that a distal vacuolar myopathy is a common late complication of untreated nephropathic cystinosis. Although the cause is unclear, the general lysosomal defect in this disease may also affect the lysosomes within muscle fibers.

  5. Distal Communication by Chimpanzees (Pan troglodytes): Evidence for Common Ground?

    PubMed

    Leavens, David A; Reamer, Lisa A; Mareno, Mary Catherine; Russell, Jamie L; Wilson, Daniel; Schapiro, Steven J; Hopkins, William D

    2015-01-01

    van der Goot et al. (2014) proposed that distal, deictic communication indexed the appreciation of the psychological state of a common ground between a signaler and a receiver. In their study, great apes did not signal distally, which they construed as evidence for the human uniqueness of a sense of common ground. This study exposed 166 chimpanzees to food and an experimenter, at an angular displacement, to ask, "Do chimpanzees display distal communication?" Apes were categorized as (a) proximal or (b) distal signalers on each of four trials. The number of chimpanzees who communicated proximally did not statistically differ from the number who signaled distally. Therefore, contrary to the claim by van der Goot et al., apes do communicate distally.

  6. PHILOS humerus plate for a distal tibial fracture.

    PubMed

    Twaij, Haider; Damany, Dev

    2013-01-04

    This report discusses the use of an alternative implant in the emergency fixation of a distal tibial fracture. We planned to fix the shear-type medial malleolar fracture in a closed, tri-malleolar fracture with a locking distal tibial plate. Intra-operatively, it was noted that the required plate was unavailable. A PHILOS humeral plate seemed to fit the contours of the distal tibia. The broad end of the PHILOS, when placed distally, gave options to place locking screws in the medial malleolar fragment. The fracture was stable after fixation. The patient made a full post-operative recovery and follow-up at 4 months was satisfactory. Despite adequate planning, there will be instances where one has to improvise. An understanding of the principles of fracture management can aid in finding solutions. PHILOS humeral plate may be used to stabilize a distal tibial fracture if an appropriate distal tibial locking plate is not available.

  7. Ultrasound-Assisted Distal Radius Fracture Reduction

    PubMed Central

    Socransky, Steve; Skinner, Andrew; Bromley, Mark; Smith, Andrew; Anawati, Alexandre; Middaugh, Jeff; Ross, Peter

    2016-01-01

    Introduction Closed reduction of distal radius fractures (CRDRF) is a commonly performed emergency department (ED) procedure. The use of point-of-care ultrasound (PoCUS) to diagnose fractures and guide reduction has previously been described. The primary objective of this study was to determine if the addition of PoCUS to CRDRF changed the perception of successful initial reduction. This was measured by the rate of further reduction attempts based on PoCUS following the initial clinical determination of achievement of best possible reduction. Methods  We performed a multicenter prospective cohort study, using a convenience sample of adult ED patients presenting with a distal radius fracture to five Canadian EDs. All study physicians underwent standardized PoCUS training for fractures. Standard clinically-guided best possible fracture reduction was initially performed. PoCUS was then used to assess the reduction adequacy. Repeat reduction was performed if deemed indicated. A post-reduction radiograph was then performed. Clinician impression of reduction adequacy was scored on a 5 point Likert scale following the initial clinically-guided reduction and following each PoCUS scan and the post-reduction radiograph. Results  There were 131 patients with 132 distal radius fractures. Twelve cases were excluded prior to analysis. There was no significant difference in the assessment of the initial reduction status by PoCUS as compared to the clinical exam (mean score: 3.8 vs. 3.9; p = 0.370; OR 0.89; 95% CI 0.46 to 1.72; p = 0.87). Significantly fewer cases fell into the uncertain category with PoCUS than with clinical assessment (2 vs 12; p = 0.008). Repeat reduction was performed in 49 patients (41.2%). Repeat reduction led to a significant improvement (p < 0.001) in the PoCUS determined adequacy of reduction (mean score: 4.3 vs 3.1; p < 0.001). In this group, the odds ratio for adequate vs. uncertain or inadequate reduction assessment using PoCUS was 12.5 (95% CI 3

  8. Ultrasound-Assisted Distal Radius Fracture Reduction.

    PubMed

    Socransky, Steve; Skinner, Andrew; Bromley, Mark; Smith, Andrew; Anawati, Alexandre; Middaugh, Jeff; Ross, Peter; Atkinson, Paul

    2016-01-01

    Introduction Closed reduction of distal radius fractures (CRDRF) is a commonly performed emergency department (ED) procedure. The use of point-of-care ultrasound (PoCUS) to diagnose fractures and guide reduction has previously been described. The primary objective of this study was to determine if the addition of PoCUS to CRDRF changed the perception of successful initial reduction. This was measured by the rate of further reduction attempts based on PoCUS following the initial clinical determination of achievement of best possible reduction. Methods  We performed a multicenter prospective cohort study, using a convenience sample of adult ED patients presenting with a distal radius fracture to five Canadian EDs. All study physicians underwent standardized PoCUS training for fractures. Standard clinically-guided best possible fracture reduction was initially performed. PoCUS was then used to assess the reduction adequacy. Repeat reduction was performed if deemed indicated. A post-reduction radiograph was then performed. Clinician impression of reduction adequacy was scored on a 5 point Likert scale following the initial clinically-guided reduction and following each PoCUS scan and the post-reduction radiograph. Results  There were 131 patients with 132 distal radius fractures. Twelve cases were excluded prior to analysis. There was no significant difference in the assessment of the initial reduction status by PoCUS as compared to the clinical exam (mean score: 3.8 vs. 3.9; p = 0.370; OR 0.89; 95% CI 0.46 to 1.72; p = 0.87). Significantly fewer cases fell into the uncertain category with PoCUS than with clinical assessment (2 vs 12; p = 0.008). Repeat reduction was performed in 49 patients (41.2%). Repeat reduction led to a significant improvement (p < 0.001) in the PoCUS determined adequacy of reduction (mean score: 4.3 vs 3.1; p < 0.001). In this group, the odds ratio for adequate vs. uncertain or inadequate reduction assessment using PoCUS was 12.5 (95% CI 3

  9. Distal Xq duplication and functional Xq disomy

    PubMed Central

    Sanlaville, Damien; Schluth-Bolard, Caroline; Turleau, Catherine

    2009-01-01

    Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia), major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X). The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by cytogenetic testing

  10. Preferential Propagation of Competent SIX2+ Nephronic Progenitors by LIF/ROCKi Treatment of the Metanephric Mesenchyme

    PubMed Central

    Tanigawa, Shunsuke; Sharma, Nirmala; Hall, Michael D.; Nishinakamura, Ryuichi; Perantoni, Alan O.

    2015-01-01

    Summary Understanding the mechanisms responsible for nephrogenic stem cell preservation and commitment is fundamental to harnessing the potential of the metanephric mesenchyme (MM) for nephron regeneration. Accordingly, we established a culture model that preferentially expands the MM SIX2+ progenitor pool using leukemia inhibitory factor (LIF), a Rho kinase inhibitor (ROCKi), and extracellular matrix. Passaged MM cells express the key stem cell regulators Six2 and Pax2 and remain competent to respond to WNT4 induction and form mature tubular epithelia and glomeruli. Mechanistically, LIF activates STAT, which binds to a Stat consensus sequence in the Six2 proximal promoter and sustains SIX2 levels. ROCKi, on the other hand, attenuates the LIF-induced differentiation activity of JNK. Concomitantly, the combination of LIF/ROCKi upregulates Slug expression and activates YAP, which maintains SIX2, PAX2, and SALL1. Using this novel model, our study underscores the pivotal roles of SIX2 and YAP in MM stem cell stability. PMID:26321142

  11. Charles Edward Isaacs (1811-1860): exploring the details of nephron structure and function in the post-Bowman period.

    PubMed

    Fine, Leon G

    2003-01-01

    Charles Edward Isaacs (1811-1860), an anatomist working in New York, undertook a series of studies which attempted to define the microscopic structure of the nephrons in a variety of species. Given that he published his findings 15 years after William Bowman's seminal paper on the subject, he was able to add only a few of the finer details to the picture. He observed the continuity of the epithelium of the glomerular capsule with that of the proximal tubule and he demonstrated that the glomerular tuft is covered by a layer of epithelial cells. In a series of studies on human renal function he erroneously concluded that the glomerulus must have an excretory function in addition to its filtration function and that diuretics act primarily on the glomerlus. The latter conclusion was based upon observations of substances not currently categorized as being diuretic agents. The absence of a major conceptual advance in the writings of Isaacs probably accounts for that fact that his contribution has been largely forgotten.

  12. Improved radiographic visualization of calculus in distal ureter.

    PubMed

    Amar, A D

    1979-10-01

    Roentgenographic visualization of a calculus in the distal ureter is often made difficult by gas or bowel contents in the region of the pelvis. Filling the bladder with sterile water raises the bladder dome and displaces the bowel upward. Any calculus in the lower 4 to 5 cm. of the distal ureter is then clearly demonstrated on roentgenograms taken against the water-filled bladder instead of against the bowel filled with gas and feces. This maneuver also aids in differentiation of a calculus in the distal ureter from a phlebolith in the bladder wall, and has improved visualization of distal ureteral calculus in 50 patients during the last six years. PMID:494477

  13. Distal myopathy with rimmed vacuoles and cerebellar atrophy.

    PubMed

    Merkli, Hajnalka; Pál, Endre; Gáti, István; Czopf, József

    2006-01-01

    Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.

  14. Implant arthroplasty for the distal radioulnar joint.

    PubMed

    Scheker, Luis R

    2008-11-01

    The distal radioulnar joint (DRUJ) is a weight-bearing joint; the ulnar head is frequently excised either totally or partially and in some cases is fused because of degenerative, rheumatoid, or posttraumatic arthritis and treated with a "salvage procedure." The result of these procedures is the inability of those patients to lift even minor weight. Articles about these procedures report the ability to pronate and supinate, but they rarely discuss grip strength or lifting capacity. We present an alternative to the salvage procedures that allows full range of motions as well as the ability to grip and lift weights encountered in daily living, such as a gallon of milk. The Aptis total DRUJ replacement prosthesis (Aptis Medical, Louisville, KY), a bipolar self-stabilizing DRUJ endoprosthesis, restores the forearm function. The technique of implantation is presented here.

  15. [Distal radius fractures: conservative or surgical treatment?].

    PubMed

    Mark, G; Ryf, C

    1993-07-01

    The "classical" Colles fracture of the distal radius is the most common fracture in the adult. In order to reduce the still rather high rate of permanent disability, this fracture involving a functionally important joint requires accurate reduction. The AO-fracture classification introduced by Müller not only defines the severity of an injury, but also allows for decision-making as to the most adequate treatment. Besides the purely conservative management by closed reduction and plaster cast for the type-A fractures, we have a number of other treatment modalities for the more complex-B and C-type fractures, such as closed reduction and percutaneous K-wire application or the use of the small external fixator as well as open reduction and internal fixation by plates and screws for a few selected indications. PMID:8211844

  16. Young Children's Sibling Relationship Quality: Distal and Proximal Correlates

    ERIC Educational Resources Information Center

    Kretschmer, Tina; Pike, Alison

    2009-01-01

    Background: Relationships within families are interdependent and related to distal environmental factors. Low socioeconomic status (SES) and high household chaos (distal factors) have been linked to less positive marital and parent-child relationships, but have not yet been examined with regard to young children's sibling relationships. The…

  17. Conservative Treatment Is Sufficient for Acute Distal Radioulnar Joint Instability With Distal Radius Fracture.

    PubMed

    Lee, Sang Ki; Kim, Kap Jung; Cha, Yong Han; Choy, Won Sik

    2016-09-01

    Treatments for acute distal radioulnar joint (DRUJ) instability with distal radius fracture vary from conservative to operative treatment, although it seems to be no consensus regarding which treatment is optimal. This prospective randomized study was designed to compare the clinical outcomes for operative and conservative treatment of acute DRUJ instability with distal radius fracture, according to the presence or absence and type of ulnar styloid process fracture and the degree of its displacement. Between July 2008 and February 2013, we enrolled 157 patients who exhibited an unstable DRUJ during intraoperative manual stress testing (via the ballottement test) after fixation of the distal radius. Patients were classified according to the type of the ulnar styloid process fracture, using preoperative wrist radiography, and each group was divided into subgroups, according to their treatment method. We then compared the clinical outcomes between the conservative and operative treatments, using their range of motion; Disabilities of the Arm, Shoulder, and Hand score; modified Mayo wrist score; and grip strength. At 3 months after surgery, among patients without ulnar styloid process fracture, the flexion-extension range was 79 ± 15° after supination sugar-tong splinting (group A-1), 91 ± 14° after DRUJ transfixation (group A-2), and 89 ± 10° after arthroscopic triangular fibrocartilage complex repair (group A-3); the operative treatments provided greater joint motion ranges than conservative treatment. The groups with ulnar styloid process fractures at the tip (group B) or base (group C) also exhibited better clinical outcomes after the operative treatments, compared with after the conservative treatment. However, at the final follow-up, groups A-1, A-2, and A-3 exhibited similar flexion-extension ranges (122 ± 25°, 119° ± 18°, and 120° ± 16°, respectively) and modified Mayo wrist scores (87 ± 7, 89 ± 8, and 85 ± 9). Thus, the conservative and

  18. Osteoarticular Allograft Reconstruction for an Angiosarcoma of the Distal Radius.

    PubMed

    Mavrogenis, Andreas F; Galanopoulos, John; Vottis, Christos; Megaloikonomos, Panayiotis D; Palmerini, Emanuela; Kokkalis, Zinon T

    2016-01-01

    Angiosarcoma of bone is a rare high-grade malignant vascular tumor accounting for <1% of malignant bone tumors. Tumor location in the distal radius is very rare. Complete surgical resection with limb salvage surgery or amputation is essential for the outcome of the patient. However, the literature is vague regarding the best surgical approach for resection of the distal radius and the optimal reconstruction option after a bone tumor resection. Several reconstruction techniques have been described, varying from arthrodesis to arthroplasties. In this article, we present a report of a patient with angiosarcoma of the distal radius treated with complete resection and reconstruction with a distal radius osteoarticular allograft. We discuss the advantages and the limitations of this surgical technique for the distal radius. PMID:27649764

  19. Giant serpentine aneurysm of the distal anterior cerebral artery.

    PubMed

    Senbokuya, Nobuo; Kanemaru, Kazuya; Kinouchi, Hiroyuki; Horikoshi, Toru

    2012-11-01

    We report a case of a 38-year-old man with a giant serpentine aneurysm arising from the distal anterior cerebral artery. This aneurysm grew from a fusiform aneurysm to a huge aneurysm within 5 months before manifesting as a mass lesion. The aneurysm was largely filled with thrombus, and 4 distal branches arose from the aneurysm dome. Selective balloon test occlusion of the distal anterior cerebral artery using an intravascular technique was performed to confirm the tolerance of the brain tissue. The balloon test occlusion elicited adequate leptomeningeal collateral circulation and no neurologic symptoms; thus, the aneurysm was treated with trapping and resection. The patient had no ischemic complications after the surgery and returned to his job 1 month later. No ischemia developed in the 2 years after surgery. Selective balloon test occlusion of the distal cerebral artery using an intravascular technique can be a very useful tool in planning the therapeutic strategy for a complicated distal cerebral aneurysm.

  20. Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg(2+) handling.

    PubMed

    de Baaij, Jeroen H F; Groot Koerkamp, Marian J; Lavrijsen, Marla; van Zeeland, Femke; Meijer, Hans; Holstege, Frank C P; Bindels, René J M; Hoenderop, Joost G J

    2013-12-01

    The kidney plays a key role in the maintenance of Mg(2+) homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg(2+) handling. In recent years, hereditary Mg(2+) transport disorders have helped to identify important players in DCT Mg(2+) homeostasis. Nevertheless, several proteins involved in DCT-mediated Mg(2+) reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new Mg(2+)-related genes. Here, we report Mg(2+)-sensitive expression of the DCT transcriptome. To this end, transgenic mice expressing enhanced green fluorescent protein under a DCT-specific parvalbumin promoter were subjected to Mg(2+)-deficient or Mg(2+)-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter allowed, for the first time, isolation of enhanced green fluorescent protein-positive DCT cells. RNA extracts thereof were analyzed by DNA microarrays comparing high versus low Mg(2+) to identify Mg(2+) regulatory genes. Based on statistical significance and a fold change of at least 2, 46 genes showed differential expression. Several known magnesiotropic genes, such as transient receptor potential cation channel, subfamily M, member 6 (Trpm6), and Parvalbumin, were upregulated under low dietary Mg(2+). Moreover, new genes were identified that are potentially involved in renal Mg(2+) handling. To confirm that the selected candidate genes were regulated by dietary Mg(2+) availability, the expression levels of solute carrier family 41, member 3 (Slc41a3), pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (Pcbd1), TBC1 domain family, member 4 (Tbc1d4), and uromodulin (Umod) were determined by RT-PCR analysis. Indeed, all four genes show significant upregulation in the DCT of mice fed a Mg(2+)-deficient diet. By elucidating the Mg(2+)-sensitive DCT transcriptome, new candidate genes in renal Mg(2

  1. A 3-Dimensional Anatomic Study of the Distal Biceps Tendon

    PubMed Central

    Walton, Christine; Li, Zhi; Pennings, Amanda; Agur, Anne; Elmaraghy, Amr

    2015-01-01

    Background Complete rupture of the distal biceps tendon from its osseous attachment is most often treated with operative intervention. Knowledge of the overall tendon morphology as well as the orientation of the collagenous fibers throughout the musculotendinous junction are key to intraoperative decision making and surgical technique in both the acute and chronic setting. Unfortunately, there is little information available in the literature. Purpose To comprehensively describe the morphology of the distal biceps tendon. Study Design Descriptive laboratory study. Methods The distal biceps terminal musculature, musculotendinous junction, and tendon were digitized in 10 cadaveric specimens and data reconstructed using 3-dimensional modeling. Results The average length, width, and thickness of the external distal biceps tendon were found to be 63.0, 6.0, and 3.0 mm, respectively. A unique expansion of the tendon fibers within the distal muscle was characterized, creating a thick collagenous network along the central component between the long and short heads. Conclusion This study documents the morphologic parameters of the native distal biceps tendon. Reconstruction may be necessary, especially in chronic distal biceps tendon ruptures, if the remaining tendon morphology is significantly compromised compared with the native distal biceps tendon. Knowledge of normal anatomical distal biceps tendon parameters may also guide the selection of a substitute graft with similar morphological characteristics. Clinical Relevance A thorough description of distal biceps tendon morphology is important to guide intraoperative decision making between primary repair and reconstruction and to better select the most appropriate graft. The detailed description of the tendinous expansion into the muscle may provide insight into better graft-weaving and suture-grasping techniques to maximize proximal graft incorporation. PMID:26665092

  2. Functional and oncologic outcomes after nephron-sparing surgery in a solitary kidney: 10 years of experience

    PubMed Central

    Costabel, José Ignacio; Marchiñena, Patricio García; Tirapegui, Federico; Dantur, Augusto; Jurado, Alberto; Gueglio, Guillermo

    2016-01-01

    ABSTRACT Objectives: To evaluate functional and oncologic outcomes of partial nephrectomy (PN) in patients with a solitary kidney. Materials and Methods: A retrospective analysis of patients with a solitary kidney undergoing nephron-sparing surgery between March 2003 and March 2013 was performed. GFR was recorded before the procedure and 3 months after surgery, thus establishing a change (cGFR). Several variables that may influence cGFR were analyzed. Complications are herein described, namely bleeding, fistula, acute renal failure and end-stage renal disease (ESRD). Local recurrence and margin status are also described. Survival rates were calculated using the Kaplan Meier method (2 patients with metastasis at the time of surgery were excluded from the analysis). Results: Forty-five patients were available for analysis. Median follow-up was 27.56 months (r 3-96). Mean cGFR was-7.12mL/min (SD 2.1). Variables significantly related with lower GFR after surgery were loss of renal mass (p=0.01)) and male gender (p=0.03). Four patients (8.8%) experienced hemorrhage. Nine patients (20%) developed a urinary fistula. Only one patient with bleeding required open surgery. Two patients (4.4%) needed transient dialysis. Three patients (6.6%) developed ESRD. Four patients (8.8%) had positive surgical margins (PSMs) and four patients (88%) had local recurrence (2 of these had PSMs). Five patients (11.1%) died during follow-up. Four patients (8.8%) died because of renal cancer. Estimated 2-year overall survival, disease-free survival and cancer specific survival rates were 88.4% (CI 95% 70.5-96); 87.7% (CI 95% 68.1-96) and 92.4% (CI 95% 75-98), respectively. Conclusion: Loss of renal mass and male gender were associated with lower postoperative GFR. Our outcomes were comparable with those in the World literature. PMID:27256179

  3. Effect of coffee on distal colon function.

    PubMed Central

    Brown, S R; Cann, P A; Read, N W

    1990-01-01

    Ninety nine healthy young volunteers (58 men, 34 women, aged 17-27 years) answered a questionnaire concerning their bowel habit with particular reference to the effects of beverages. Twenty nine per cent (63% women) claimed that coffee induced a desire to defecate. The rectosigmoid motor responses to black, unsweetened coffee were then investigated by multiport manometry in 14 healthy-subjects (12 men, two women, eight of whom claimed coffee caused a desire to defecate (responders). Results revealed an increase in motility index within four minutes after ingestion of both regular and decaffeinated coffee (p less than 0.05) in the eight responders, but not in the six non-responders. The increase in rectosigmoid motility induced by coffee lasted at least 30 minutes. There was no increase in the motility index in any subject after a drink of hot water. These results suggest that drinking coffee can stimulate a motor response of the distal colon in some normal people. PMID:2338272

  4. Distal Stressors and Depression among Homeless Men.

    PubMed

    Coohey, Carol; Easton, Scott D

    2016-05-01

    Depression is a common problem among homeless men that may interfere with functional tasks, such as securing stable housing, obtaining employment, and accessing health services. Previous research on depression among homeless men has largely focused on current psychosocial resources, substance abuse, and past victimization. Guided by Ensel and Lin's life course stress process model, the authors examined whether distal stressors, including victimization and exposure to parent problems in childhood, contributed to men's depression above and beyond current (or proximal) stressors, such as substance abuse and health problems, and social resources. The sample consisted of 309 homeless men who had entered a federally funded emergency shelter. Using the Burns Depression Checklist, the authors found that one out of three men met the threshold for moderate to severe depression during the past week. The logistic regression showed that past exposure to parent problems was related to depression after accounting for current stressors and social resources (number of close adult relationships and whether their emotional support needs were met). Past victimization was not related to depression. To address men's depression, workers should concurrently provide services that meet men's basic needs (for example, housing) and address their relationship needs, including their need for emotional support. PMID:27263201

  5. Increased risk of distal ventriculoperitoneal shunt obstruction associated with slit valves or distal slits in the peritoneal catheter.

    PubMed

    Cozzens, J W; Chandler, J P

    1997-11-01

    The authors describe a relationship between the presence of distal shunt catheter side-wall slits and distal catheter obstruction in a single-surgeon series of ventriculoperitoneal (VP) shunt revisions. Between 1985 and 1996, 168 operations for VP shunt revision were performed by the senior author (J.W.C.) in 71 patients. Indications for shunt revision included obstruction in 140 operations; overdrainage or underdrainage requiring a change of valve in 17 operations; inadequate length of distal shunt tubing resulting in the distal end no longer reaching the peritoneum in five operations; the ventricular catheter in the wrong ventricle or space, requiring repositioning in five operations; and a disconnected or broken shunt in one operation. Of the 140 instances of shunt obstruction, the blockage occurred at the ventricular end in 108 instances (77.1%), the peritoneal end in 17 (12.1%), the ventricular and the peritoneal end in 14 (10%), and in the valve mechanism (not including distal slit valves) in one (0.8%). Thus, the peritoneal end was obstructed in 31 (22.1%) of 140 cases of shunt malfunction. In every case in which the peritoneal end was obstructed, some form of distal slit was found: either a distal slit valve in an otherwise closed catheter or slits in the side of an open catheter. No instances were found of distal peritoneal catheter obstruction when the peritoneal catheter was a simple open-ended tube with no accompanying side slits (0 of 55). It is concluded that side slits in the distal peritoneal catheters of VP shunts are associated with a greater incidence of distal shunt obstruction.

  6. Nephron proximal tubule patterning and corpuscles of Stannius formation are regulated by the sim1a transcription factor and retinoic acid in zebrafish

    PubMed Central

    Cheng, Christina N.; Wingert, Rebecca A.

    2014-01-01

    The mechanisms that establish nephron segments are poorly understood. The zebrafish embryonic kidney, or pronephros, is a simplified yet conserved genetic model to study this renal development process because its nephrons contain segments akin to other vertebrates, including the proximal convoluted and straight tubules (PCT, PST). The zebrafish pronephros is also associated with the corpuscles of Stannius (CS), endocrine glands that regulate calcium and phosphate homeostasis, but whose ontogeny from renal progenitors is largely mysterious. Initial patterning of zebrafish renal progenitors in the intermediate mesoderm (IM) involves the formation of rostral and caudal domains, the former being reliant on retinoic acid (RA) signaling, and the latter being repressed by elevated RA levels. Here, using expression profiling to gain new insights into nephrogenesis, we discovered that the gene single minded family bHLH transcription factor 1a (sim1a) is dynamically expressed in the renal progenitors—first marking the caudal domain, then becoming restricted to the proximal segments, and finally exhibiting specific CS expression. In loss of function studies, sim1a knockdown expanded the PCT and abrogated both the PST and CS populations. Conversely, overexpression of sim1a modestly expanded the PST and CS, while it reduced the PCT. These results show that sim1a activity is necessary and partially sufficient to induce PST and CS fates, and suggest that sim1a may inhibit PCT fate and/or negotiate the PCT/PST boundary. Interestingly, the sim1a expression domain in renal progenitors is responsive to altered levels of RA, suggesting that RA regulates sim1a, directly or indirectly, during nephrogenesis. sim1a deficient embryos treated with exogenous RA formed nephrons that were predominantly composed of PCT segments, but lacked the enlarged PST observed in RA treated wild-types, indicating that RA is not sufficient to rescue the PST in the absence of sim1a expression. Alternately

  7. Nephron proximal tubule patterning and corpuscles of Stannius formation are regulated by the sim1a transcription factor and retinoic acid in zebrafish.

    PubMed

    Cheng, Christina N; Wingert, Rebecca A

    2015-03-01

    The mechanisms that establish nephron segments are poorly understood. The zebrafish embryonic kidney, or pronephros, is a simplified yet conserved genetic model to study this renal development process because its nephrons contain segments akin to other vertebrates, including the proximal convoluted and straight tubules (PCT, PST). The zebrafish pronephros is also associated with the corpuscles of Stannius (CS), endocrine glands that regulate calcium and phosphate homeostasis, but whose ontogeny from renal progenitors is largely mysterious. Initial patterning of zebrafish renal progenitors in the intermediate mesoderm (IM) involves the formation of rostral and caudal domains, the former being reliant on retinoic acid (RA) signaling, and the latter being repressed by elevated RA levels. Here, using expression profiling to gain new insights into nephrogenesis, we discovered that the gene single minded family bHLH transcription factor 1a (sim1a) is dynamically expressed in the renal progenitors-first marking the caudal domain, then becoming restricted to the proximal segments, and finally exhibiting specific CS expression. In loss of function studies, sim1a knockdown expanded the PCT and abrogated both the PST and CS populations. Conversely, overexpression of sim1a modestly expanded the PST and CS, while it reduced the PCT. These results show that sim1a activity is necessary and partially sufficient to induce PST and CS fates, and suggest that sim1a may inhibit PCT fate and/or negotiate the PCT/PST boundary. Interestingly, the sim1a expression domain in renal progenitors is responsive to altered levels of RA, suggesting that RA regulates sim1a, directly or indirectly, during nephrogenesis. sim1a deficient embryos treated with exogenous RA formed nephrons that were predominantly composed of PCT segments, but lacked the enlarged PST observed in RA treated wild-types, indicating that RA is not sufficient to rescue the PST in the absence of sim1a expression. Alternately

  8. Distal anastomotic intimal hyperplasia: histopathologic character and biogenesis.

    PubMed

    Sottiurai, V S; Yao, J S; Batson, R C; Sue, S L; Jones, R; Nakamura, Y A

    1989-01-01

    Although thrombogenicity of the prosthetic graft, progression of the atherosclerotic disease and distal anastomotic intimal hyperplasia are known etiologic factors of late graft failure, its occurrence is frequently encountered in the late graft occlusion. Forth-two canine PTFE iliofemoral grafts (all with end-to-side distal anastomosis) were studied. Computer digitization revealed that distal anastomotic intimal hyperplasia occurred exclusively at the heel and the toe of the graft and the floor of the host artery. The distal anastomotic intimal hyperplasia was 80-130 cells thick. Light microscopy and transmission electron microscopy revealed a similar architecture of interlamination of cellular elements and extracellular matrix in the hyperplastic cells. Transmission electron microscopy further defined a gradual cell transformation and orientation from the graft to the lumen. The cells near the graft were characterized by a gradual reduction of rough endoplasmic reticulum with a concomitant acquisition of myofilaments, transforming ovoid mesenchymoid cells to slender myofibroblasts. The orientation of cells in distal anastomotic intimal hyperplasia was embodied by random cell distribution at the periphery to a well-organized interlamination of myofibroblasts and extracellular matrix near the lumen. Distal anastomotic intimal hyperplasia is a biologic entity with active cellular and subcellular events. Its biogenesis appears to be influenced by the hemodynamics of blood flow at the distal anastomosis. PMID:2713229

  9. The distal radioulnar joint. Anatomic and functional considerations.

    PubMed

    Kauer, J M

    1992-02-01

    The distal radioulnar joint is functionally coupled with the proximal radioulnar joint, thus forming a mechanism for the longitudinal rotation of the hand. Distal radioulnar mobility is derived from the geometry of the joint, joint surfaces, and radioulnar connections. There is a structural and functional separation between the distal radioulnar and carpal joints, giving the possibility of pronation and supination in every position of the hand to the forearm. As for the stability of the joints involved, the ulnar articular disk plays an essential role. Being part of both distal radioulnar and carpal joints, the disk has very specific morphologic features that not only are individualized to the function of both joints but also stabilize the joints in their independent movements. Developmental data give the strong impression of an architectural scheme, of which the distal radioulnar joint is only a part. Traumatic lesions at the distal radioulnar joint and disturbances in normal distal radioulnar alignment have to be viewed, therefore, in a wider context. PMID:1735231

  10. Src family protein tyrosine kinase regulates the basolateral K channel in the distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein.

    PubMed

    Zhang, Chengbiao; Wang, Lijun; Thomas, Sherin; Wang, Kemeng; Lin, Dao-Hong; Rinehart, Jesse; Wang, Wen-Hui

    2013-09-01

    The loss of function of the basolateral K channels in the distal nephron causes electrolyte imbalance. The aim of this study is to examine the role of Src family protein tyrosine kinase (SFK) in regulating K channels in the basolateral membrane of the mouse initial distal convoluted tubule (DCT1). Single-channel recordings confirmed that the 40-picosiemen (pS) K channel was the only type of K channel in the basolateral membrane of DCT1. The suppression of SFK reversibly inhibited the basolateral 40-pS K channel activity in cell-attached patches and decreased the Ba(2+)-sensitive whole-cell K currents in DCT1. Inhibition of SFK also shifted the K reversal potential from -65 to -43 mV, suggesting a role of SFK in determining the membrane potential in DCT1. Western blot analysis showed that KCNJ10 (Kir4.1), a key component of the basolateral 40-pS K channel in DCT1, was a tyrosine-phosphorylated protein. LC/MS analysis further confirmed that SFK phosphorylated KCNJ10 at Tyr(8) and Tyr(9). The single-channel recording detected the activity of a 19-pS K channel in KCNJ10-transfected HEK293T cells and a 40-pS K channel in the cells transfected with KCNJ10+KCNJ16 (Kir.5.1) that form a heterotetramer in the basolateral membrane of the DCT. Mutation of Tyr(9) did not alter the channel conductance of the homotetramer and heterotetramer. However, it decreased the whole-cell K currents, the probability of finding K channels, and surface expression of KCNJ10 in comparison to WT KCNJ10. We conclude that SFK stimulates the basolateral K channel activity in DCT1, at least partially, by phosphorylating Tyr(9) on KCNJ10. We speculate that the modulation of tyrosine phosphorylation of KCNJ10 should play a role in regulating membrane transport function in DCT1.

  11. Localization of a Gene for Autosomal Recessive Distal Renal Tubular Acidosis with Normal Hearing (rdRTA2) to 7q33-34

    PubMed Central

    Karet, Fiona E.; Finberg, Karin E.; Nayir, Ahmet; Bakkaloglu, Aysin; Ozen, Seza; Hulton, Sally A.; Sanjad, Sami A.; Al-Sabban, Essam A.; Medina, Juan F.; Lifton, Richard P.

    1999-01-01

    Summary Failure of distal nephrons to excrete excess acid results in the “distal renal tubular acidoses” (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing. PMID:10577919

  12. P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

    PubMed

    Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

    2014-11-01

    Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

  13. Distal Insertions of the Biceps Femoris

    PubMed Central

    Branch, Eric A.; Anz, Adam W.

    2015-01-01

    Background: Avulsion of the biceps femoris from the fibula and proximal tibia is encountered in clinical practice. While the anatomy of the primary posterolateral corner structures has been qualitatively and quantitatively described, a quantitative analysis regarding the insertions of the biceps femoris on the fibula and proximal tibia is lacking. Purpose: To quantitatively assess the insertions of the biceps femoris, fibular collateral ligament (FCL), and anterolateral ligament (ALL) on the fibula and proximal tibia as well as establish relationships among these structures and to pertinent surgical anatomy. Study Design: Descriptive laboratory study. Methods: Dissections were performed on 12 nonpaired, fresh-frozen cadaveric specimens identifying the biceps femoris, FCL, and ALL, and their insertions on the proximal tibia and fibula. The footprint areas, orientations, and distances from relevant osseous landmarks were measured using a 3-dimensional coordinate measurement device. Results: Dissection produced 6 easily identifiable and reproducible anatomic footprints. Tibial footprints included the insertion of the ALL and an insertion of the biceps femoris (TBF). Fibular footprints included the insertion of the FCL, a distal insertion of the biceps femoris (DBF), a medial footprint of the biceps femoris (MBF), and a proximal footprint of the biceps femoris (PBF). The mean area of these footprints (95% CI) was as follows: ALL, 53.0 mm2 (38.4-67.6); TBF, 93.9 mm2 (72.0-115.8); FCL, 86.8 mm2 (72.3-101.2); DBF, 119 mm2 (91.1-146.9); MBF, 46.8 mm2 (29.0-64.5); and PBF, 215 mm2 (192.4-237.5). The mean distance (95% CI) from the Gerdy tubercle to the center of the ALL footprint was 24.3 mm (21.6-27.0) and to the center of the TBF was 22.5 mm (21.0-24.0). The center of the DBF was 8.68 mm (7.0-10.3) from the anterior border of the fibula, the center of the FCL was 14.6 mm (12.5-16.7) from the anterior border of the fibula and 20.7 mm (19.0-22.4) from the tip of the fibular

  14. The learning curve in robotic distal pancreatectomy.

    PubMed

    Napoli, Niccolò; Kauffmann, Emanuele F; Perrone, Vittorio Grazio; Miccoli, Mario; Brozzetti, Stefania; Boggi, Ugo

    2015-09-01

    No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators.

  15. The learning curve in robotic distal pancreatectomy.

    PubMed

    Napoli, Niccolò; Kauffmann, Emanuele F; Perrone, Vittorio Grazio; Miccoli, Mario; Brozzetti, Stefania; Boggi, Ugo

    2015-09-01

    No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators. PMID:25990666

  16. Quantitative shape measurements of distal volcanic ash

    NASA Astrophysics Data System (ADS)

    Riley, Colleen M.; Rose, William I.; Bluth, Gregg J. S.

    2003-10-01

    Large-scale volcanic eruptions produce fine ash (<200 μm) which has a long atmospheric residence time (1 hour or more) and can be transported great distances from the volcanic source, thus, becoming a hazard to aircraft and public health. Ash particles have irregular shapes, so data on particle shape, size, and terminal velocities are needed to understand how the irregular-shaped particles affect transport processes and radiative transfer measurements. In this study, a methodology was developed to characterize particle shapes, sizes, and terminal velocities for three ash samples of different compositions. The shape and size of 2500 particles from (1) distal fallout (˜100 km) of the 14 October 1974 Fuego eruption (basaltic), (2) the secondary maxima (˜250 km) of the 18 August 1992 Spurr eruption (andesitic), and (3) the Miocene Ash Hollow member, Nebraska (rhyolitic) were measured using image analysis techniques. Samples were sorted into 10 to 19 terminal velocity groups (0.6-59.0 cm/s) using an air elutriation device. Grain-size distributions for the samples were measured using laser diffraction. Aspect ratio, feret diameter, and perimeter measurements were found to be the most useful descriptors of how particle shape affects terminal velocity. These measurement values show particle shape differs greatly from a sphere (commonly used in models and algorithms). The diameters of ash particles were 10-120% larger than ideal spheres at the same terminal velocity, indicating that irregular particle shape greatly increases drag. Gas-adsorption derived surface areas are 1 to 2 orders of magnitude higher than calculated surface areas based on measured dimensions and simple geometry, indicating that particle shapes are highly irregular. Correction factors for surface area were derived from the ash sample measurements so that surface areas calculated by assuming spherical particle shapes can be corrected to reflect more realistic values.

  17. An alternative method of osteosynthesis for distal humeral shaft fractures.

    PubMed

    Levy, Jonathan C; Kalandiak, Steven P; Hutson, James J; Zych, Gregory

    2005-01-01

    Treatment of extra-articular distal humerus shaft fractures with plating techniques is often difficult, as traditional centrally located posterior plates often encroach on the olecranon fossa, limiting distal osseous fixation. The use of a modified Synthes Lateral Tibial Head Buttress Plate (Synthes, Paoli, PA) allows for a centrally placed posterior plating of the humeral shaft that angles anatomically along the lateral column to treat far distal humeral shaft fractures. Fifteen patients treated in this manner were followed to radiographic and clinical union. There were no cases of instrumentation failure or loss of reduction.

  18. Two-wave propagation in in vitro swine distal ulna

    NASA Astrophysics Data System (ADS)

    Mano, Isao; Horii, Kaoru; Matsukawa, Mami; Otani, Takahiko

    2015-07-01

    Ultrasonic transmitted waves were obtained in an in vitro swine distal ulna specimen, which mimics a human distal radius, that consists of interconnected cortical bone and cancellous bone. The transmitted waveforms appeared similar to the fast waves, slow waves, and overlapping fast and slow waves measured in the specimen after removing the surface cortical bone (only cancellous bone). In addition, the circumferential waves in the cortical bone and water did not affect the fast and slow waves. This suggests that the fast-and-slow-wave phenomenon can be observed in an in vivo human distal radius.

  19. Hyperammonaemia in a child with distal renal tubular acidosis.

    PubMed

    Seracini, D; Poggi, G M; Pela, I

    2005-11-01

    A 5-month-old girl with distal renal tubular acidosis (RTA) and hyperammonaemia that had lasted for 12 days, despite metabolic acidosis correction, is presented in this report. The patient showed failure to thrive, poor feeding, hypotonia and vomiting crisis in absence of inborn errors of metabolism. Probably, hyperammonaemia was the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal RTA. Our case confirms that hyperammonaemia may be observed in distal RTA, mimicking an inborn error of metabolism, and it underlines that hyperammonaemia may persist several days after metabolic acidosis correction. PMID:16133056

  20. An Asian Perspective on the Management of Distal Radius Fractures

    PubMed Central

    Sebastin, Sandeep J.; Chung, Kevin C.

    2012-01-01

    Synopsis There is little data with regards to the epidemiology, pathology, or management of distal radius fractures from centers in Asia. Asia includes five advanced economies, namely Hong Kong SAR, Japan, Korea, Singapore, and Taiwan and a number of emerging economies prominent among which are China, India, Malaysia, Philippines, and Thailand. This article examines the available epidemiological data from Asia, and compares the management of distal radius fractures in the advanced and emerging Asian economies and how they match up to the current management in the west. It concludes by offering solutions for improving outcomes of distal radius fractures in both the advanced and emerging economies of Asia. PMID:22554658

  1. An Asian perspective on the management of distal radius fractures.

    PubMed

    Sebastin, Sandeep J; Chung, Kevin C

    2012-05-01

    There is limited data regarding the epidemiology, pathology, and management of distal radius fractures from centers in Asia. The advanced economies in Asia include Hong Kong, Japan, Korea, Singapore, and Taiwan, whereas the prominent emerging economies are China, India, Malaysia, Philippines, and Thailand. This article examines the available epidemiological data from Asia, compares the management of distal radius fractures in the advanced and emerging Asian economies and how they compare with the current management in the west. It concludes by offering solutions for improving outcomes of distal radius fractures in Asia.

  2. Distal Triceps Knotless Anatomic Footprint Repair: A New Technique

    PubMed Central

    Paci, James M.; Clark, Jonathan; Rizzi, Angelo

    2014-01-01

    Distal triceps rupture is a rare injury causing significant disability. Several techniques for treating distal triceps ruptures have been described using bone tunnels or suture anchors. More recent techniques have focused on re-creating the anatomic footprint of the distal triceps tendon. However, the increasing numbers of anchors used increase the risk to the articular surface, and all earlier techniques require knot tying and bulky knots beneath the thin posterior elbow soft-tissue envelope. We describe a technique combining the use of bone tunnels and a single suture anchor to create a knotless anatomic footprint repair of the distal triceps. By using this technique, we are able to create a tension-band construct that self-reinforces the anatomic repair and is very low profile while significantly decreasing risk to the articular surface. PMID:25473618

  3. Distal Renal Tubular Acidosis in Infancy: A Bicarbonate Wasting State

    ERIC Educational Resources Information Center

    Rodriguez-Soriano, J.; And Others

    1975-01-01

    Studied were three unrelated infants with distal renal tubular acidosis (a condition characterized by an inability to acidify the urine to minimal pH levels resulting in the loss of bicarbonates). (DB)

  4. A distal airway foreign body removed with electromagnetic navigation bronchoscopy.

    PubMed

    Karpman, Craig; Midthun, David E; Mullon, John J

    2014-04-01

    Distal airway foreign bodies can be challenging to remove with a flexible bronchoscope because of angulation or deep impaction. Thoracic surgery may be required if bronchoscopy is not successful. The use of electromagnetic navigation for pulmonary nodule localization and characterization is well established; however, its use to localize and remove distal foreign bodies has not been described. We report the initial case of electromagnetic navigation-assisted foreign body removal.

  5. Comparison of Chevron and Distal Oblique Osteotomy for Bunion Correction.

    PubMed

    Scharer, Brandon M; DeVries, J George

    2016-01-01

    The chevron osteotomy is a standard procedure by which bunions are corrected. One of us routinely performs a distal oblique osteotomy, which, to the best of our knowledge, has not been described for the correction of bunion deformities. The purpose of the present study was to compare the short- and medium-term results of the distal oblique and chevron osteotomies for bunion correction. We performed a retrospective clinical and radiographic comparison of patients who had undergone a distal oblique or chevron osteotomy for the correction of bunion deformity. In addition, a prospective patient satisfaction survey was undertaken. A total of 55 patients were included in the present study and were treated from January 2012 to November 2014. Of the 55 patients, 27 (49.2%) were in the chevron group and 28 (50.8%) in the distal oblique group. Radiographically, no statistically significant difference was found between the 2 groups with respect to postoperative first intermetatarsal angle (p < .0001) and hallux valgus angle (p < .0001), but a greater change was found in the intermetatarsal angle in the distal oblique group (p = .467). Prospective patient satisfaction scores were available for 33 patients (60%), 16 (29%) in the chevron group and 17 (31%) in the distal oblique group. When converting the satisfaction score to a numerical score, the chevron group scored 3.3 ± 1.1 and the distal oblique group scored 3.2 ± 0.8 (p = .812). We found that the distal oblique osteotomy used in the present study is simple and reliable and showed radiographic correction and patient satisfaction equivalent to those in the chevron osteotomy. PMID:26972755

  6. Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.

    PubMed

    Al-Qusairi, Lama; Basquin, Denis; Roy, Ankita; Stifanelli, Matteo; Rajaram, Renuga Devi; Debonneville, Anne; Nita, Izabela; Maillard, Marc; Loffing, Johannes; Subramanya, Arohan R; Staub, Olivier

    2016-08-01

    The stimulation of postprandial K(+) clearance involves aldosterone-independent and -dependent mechanisms. In this context, serum- and glucocorticoid-induced kinase (SGK)1, a ubiquitously expressed kinase, is one of the primary aldosterone-induced proteins in the aldosterone-sensitive distal nephron. Germline inactivation of SGK1 suggests that this kinase is fundamental for K(+) excretion under conditions of K(+) load, but the specific role of renal SGK1 remains elusive. To avoid compensatory mechanisms that may occur during nephrogenesis, we used inducible, nephron-specific Sgk1(Pax8/LC1) mice to assess the role of renal tubular SGK1 in K(+) regulation. Under a standard diet, these animals exhibited normal K(+) handling. When challenged by a high-K(+) diet, they developed severe hyperkalemia accompanied by a defect in K(+) excretion. Molecular analysis revealed reduced neural precursor cell expressed developmentally downregulated protein (NEDD)4-2 phosphorylation and total expression. γ-Epithelial Na(+) channel (ENaC) expression and α/γENaC proteolytic processing were also decreased in mutant mice. Moreover, with no lysine kinase (WNK)1, which displayed in control mice punctuate staining in the distal convoluted tubule and diffuse distribution in the connecting tubule/cortical colleting duct, was diffused in the distal convoluted tubule and less expressed in the connecting tubule/collecting duct of Sgk(Pax8/LC1) mice. Moreover, Ste20-related proline/alanine-rich kinase phosphorylation, and Na(+)-Cl(-) cotransporter phosphorylation/apical localization were reduced in mutant mice. Consistent with the altered WNK1 expression, increased renal outer medullary K(+) channel apical localization was observed. In conclusion, our data suggest that renal tubular SGK1 is important in the regulation of K(+) excretion via the control of NEDD4-2, WNK1, and ENaC. PMID:27009335

  7. Distal Locking Screws for Intramedullary Nailing of Tibial Fractures.

    PubMed

    Agathangelidis, Filon; Petsatodis, Georgios; Kirkos, John; Papadopoulos, Pericles; Karataglis, Dimitrios; Christodoulou, Anastasios

    2016-01-01

    Recently introduced tibial intramedullary nails allow a number of distal screws to be used to reduce the incidence of malalignment and loss of fixation of distal metaphyseal fractures. However, the number of screws and the type of screw configuration to be used remains obscure. This biomechanical study was performed to address this question. Thirty-six Expert tibial nails (Synthes, Oberdorf, Switzerland) were introduced in composite bone models. The models were divided into 4 groups with different distal locking configurations ranging from 2 to 4 screws. A 7-mm gap osteotomy was performed 72 mm from the tibial plafond to simulate a 42-C3 unstable distal tibial fracture. Each group was divided in 3 subgroups and underwent nondestructive biomechanical testing in axial compression, coronal bending, and axial torsion. The passive construct stiffness was measured and statistically analyzed with one-way analysis of variance. Although some differences were noted between the stiffness of each group, these were not statistically significant in compression (P=.105), bending (P=.801), external rotation (P=.246), and internal rotation (P=.370). This in vitro study showed that, when using the Expert tibial nail for unstable distal tibial fractures, the classic configuration of 2 parallel distal screws could provide the necessary stability under partial weight-bearing conditions. PMID:26840700

  8. [Epidemiology and management of isolated distal deep venous thrombosis].

    PubMed

    Galanaud, J-P; Kahn, S R; Khau Van Kien, A; Laroche, J-P; Quéré, I

    2012-12-01

    Isolated distal deep-vein thromboses (DVT) are infra-popliteal DVT without involvement of proximal veins or pulmonary embolism (PE). They can affect deep calf (tibial anterior, tibial posterior, or peroneal) or muscular (gastrocnemius or soleal) veins. They represent half of all lower limbs DVT. Proximal and distal DVTs differ in terms of risk factor profile, proximal DVT being more frequently associated with chronic risk factors and distal DVT with transient ones. Their natural history (rate of spontaneous proximal extension) is debated leading to uncertainties on the need to diagnose and treat them with anticoagulant drugs. In the long term, the risk of venous thromboembolic recurrence is lower than that of proximal DVT and their absolute risk of post-thrombotic syndrome is unknown. French national guidelines suggest treating with anticoagulants for 6 weeks a first episode of isolated distal DVT provoked by a transient risk factor and treating for at least 3 months unprovoked or recurrent or active cancer-related distal DVT. The use of compression stockings use is suggested in case of deep calf vein thrombosis. Ongoing therapeutic trials should provide important data necessary to establish an evidence-based mode of care, especially about the need to treat distal DVT at low risk of extension with anticoagulants.

  9. Distal antenna and distal antenna related encode nuclear proteins containing pipsqueak motifs involved in antenna development in Drosophila.

    PubMed

    Emerald, B Starling; Curtiss, Jennifer; Mlodzik, Marek; Cohen, Stephen M

    2003-03-01

    Legs and antennae are considered to be homologous appendages. The fundamental patterning mechanisms that organize spatial pattern are conserved, yet appendages with very different morphology develop. A genetic hierarchy for specification of antennal identity has been partly elucidated. We report identification of a novel family of genes with roles in antennal development. The distal antenna (dan) and distal antenna-related (danr) genes encode novel nuclear proteins that are expressed in the presumptive distal antenna, but not in the leg imaginal disc. Ectopic expression of dan or danr causes partial transformation of distal leg structure toward antennal identity. Mutants that remove dan and danr activity cause partial transformation of antenna toward leg identity. Therefore we suggest that dan and danr contribute to differentiation of antenna-specific characteristics. Antenna-specific expression of dan and danr depends on a regulatory hierarchy involving homothorax and Distal-less, as well as cut and spineless. We propose that dan and danr are effector genes that act downstream of these genes to control differentiation of distal antennal structures.

  10. Autoxidation of oxymyoglobin with the distal (E7) glutamine.

    PubMed

    Suzuki, T

    1987-08-01

    We reported previously that the distal(E7) histidine is replaced by glutamine in myoglobin from the shark, Galeorhinus japonicus. The amino-acid sequence of myoglobin from another shark, Heterodontus japonicus, has been determined. The myoglobin is composed of 148 residues, is acetylated at the N-terminus, and contains the distal(E7) histidine at position 59. Although the sequence homologies between G. japonicus, H. japonicus, and sperm-whale myoglobins were about 40-55%, their hydropathy profiles were very similar, indicating that they have a similar geometry in their globin folding. The autoxidation rates of the two shark oxymyoglobins were examined in 0.1 M buffer at 25 degrees C over pH range 4.5-11.5. The pH dependence for the autoxidation of H. japonicus myoglobin was very similar to that of sperm-whale myoglobin, although the rate was about 10-times higher over the pH range examined. In both myoglobins, autoxidation was largely accelerated by H+. On the other hand, the pH dependence of G. japonicus myoglobin, which has the distal glutamine in the place of histidine, was quite different from those of sperm-whale and H. japonicus myoglobins. One of the most remarkable features is the fact that the autoxidation rate is not enhanced with an increase in the concentration of H+ in the acidic range of pH, where the autoxidation of sperm-whale and H. japonicus myoglobins is most accelerated. This finding suggests that the distal(E7) histidine participates in the autoxidation reaction as a catalytic residue facilitating the movement of a catalytic proton.

  11. Robotic-assisted transperitoneal nephron-sparing surgery for small renal masses with associated surgical procedures: surgical technique and preliminary experience.

    PubMed

    Ceccarelli, Graziano; Codacci-Pisanelli, Massimo; Patriti, Alberto; Ceribelli, Cecilia; Biancafarina, Alessia; Casciola, Luciano

    2013-09-01

    Small renal masses (T1a) are commonly diagnosed incidentally and can be treated with nephron-sparing surgery, preserving renal function and obtaining the same oncological results as radical surgery. Bigger lesions (T1b) may be treated in particular situations with a conservative approach too. We present our surgical technique based on robotic assistance for nephron-sparing surgery. We retrospectively analysed our series of 32 consecutive patients (two with 2 tumours and one with 4 bilateral tumours), for a total of 37 robotic nephron-sparing surgery (RNSS) performed between June 2008 and July 2012 by a single surgeon (G.C.). The technique differs depending on tumour site and size. The mean tumour size was 3.6 cm; according to the R.E.N.A.L. Nephrometry Score 9 procedures were considered of low, 14 of moderate and 9 of hight complexity with no conversion in open surgery. Vascular clamping was performed in 22 cases with a mean warm ischemia time of 21.5 min and the mean total procedure time was 149.2 min. Mean estimated blood loss was 187.1 ml. Mean hospital stay was 4.4 days. Histopathological evaluation confirmed 19 cases of clear cell carcinoma (all the multiple tumours were of this nature), 3 chromophobe tumours, 1 collecting duct carcinoma, 5 oncocytomas, 1 leiomyoma, 1 cavernous haemangioma and 2 benign cysts. Associated surgical procedures were performed in 10 cases (4 cholecystectomies, 3 important lyses of peritoneal adhesions, 1 adnexectomy, 1 right hemicolectomy, 1 hepatic resection). The mean follow-up time was 28.1 months ± 12.3 (range 6-54). Intraoperative complications were 3 cases of important bleeding not requiring conversion to open or transfusions. Regarding post-operative complications, there were a bowel occlusion, 1 pleural effusion, 2 pararenal hematoma, 3 asymptomatic DVT (deep vein thrombosis) and 1 transient increase in creatinine level. There was no evidence of tumour recurrence in the follow-up. RNSS is a safe and feasible technique

  12. Whole bone geometry and bone quality in distal forearm fracture.

    PubMed

    Parkinson, Ian H; Fazzalari, Nicola L

    2008-09-01

    Fracture of the distal radius is a sentinel for future increased risk of other "osteoporotic" fractures, in which the peak age for incidence of distal radius fracture is 5 to 10 years before that for spine and hip fractures. Mean bone mineral density (BMD) of the distal radius was lower in patients with osteoporosis compared with age- and sex-matched normal subjects. However, it has been shown that to predict the strength of the distal radius at the site where fractures occur requires more than measurement of bone mineral content (BMC) or BMD. Only moderate correlations have been found between forearm sites, which may be a result of differences in bone composition between sites. Different forearm sites may be used interchangeably for diagnostic purposes, but the prognostic value is not known. Using the distal radius as a screening tool for identifying individuals at risk of "osteoporotic" fracture shows that forearm site selection and accuracy of measurement can be important confounders in group studies.Improving resolution of computed tomography (CT) scanners has enabled quantitation of cortical bone density and cortical thickness. These measurements have enabled the mechanism of bone loss in the distal radius to be elucidated and show that, after menopause, bone loss is primarily through thinning of the cortex. CT imaging allows the precise localization of bone changes in individuals and should be of value in the assessment of the severity of osteoporosis. It also shows that this technology has the potential to determine the efficacy of therapeutic interventions. A concerted effort has been made to elucidate the interrelationships between the amount of bone and the geometry and that clinical imaging of BMC and/or cross-sectional area in the radius would provide improved prediction of an individual's risk of fracture.The technological tools are available, in the clinic, to accurately measure the 3-dimensional (3D) geometry of the distal radius and the amount of

  13. An intrinsic timer specifies distal structures of the vertebrate limb

    PubMed Central

    Saiz-Lopez, Patricia; Chinnaiya, Kavitha; Campa, Victor M.; Delgado, Irene; Ros, Maria A.; Towers, Matthew

    2015-01-01

    How the positional values along the proximo-distal axis (stylopod-zeugopod-autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein-expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb. PMID:26381580

  14. Distal Radius Radiographic Indices and Perilunate Fracture Dislocation

    PubMed Central

    Bagherifard, Abolfazl; Jafari, Davod; Keihan Shokouh, Hassan; Motavallian, Ebrahim; Najd Mazhar, Farid

    2016-01-01

    Background Distal radius radiographic indices may play a role as risk factors in pathogenesis of Kienbock’s disease, scaphoid fracture and nonunion. Perilunate fracture dislocations are devastating wrist injuries, and their relationship and distal radius indices have not been addressed in the literature. Objectives The aim of this study was to evaluate the possible role of distal radius radiographic indices including radial height, radial inclination, ulnar variance and volar tilt as risk factors in the perilunate fracture dislocation injury of the wrist. Patients and Methods We studied distal radius radiographic indices including radial height, radial inclination, ulnar variance and volar tilt in 43 patients with perilunate fracture dislocations and compared them with 44 wrists in the control group. Results The mean values of the radial height, radial inclination, ulnar variance and volar tilt were 12.74 (5 - 18), 24.20 (7 - 35), -0.73 (-5 - 4) and 12.28 (2 - 20) in the patient group. These values were 12.68 (9 - 22), 23.22 (17 - 30), -0.11 (-4 - 3) and 11.05 (-3 - 20), respectively in the control group. There was no statistically significant difference between the two groups. Conclusions This study did not show that distal radius anatomical indices including the radial height, radial inclination, ulnar variance and volar tilt influence perilunate fracture dislocation as risk factors.

  15. Implant Size Availability Affects Reproduction of Distal Femoral Anatomy.

    PubMed

    Morris, William Z; Gebhart, Jeremy J; Goldberg, Victor M; Wera, Glenn D

    2016-07-01

    A total knee arthroplasty system offers more distal femoral implant anterior-posterior (AP) sizes than its predecessor. The purpose of this study is to investigate the impact of increased size availability on an implant system's ability to reproduce the AP dimension of the native distal femur. We measured 200 cadaveric femora with the AP-sizing guides of Zimmer (Warsaw, IN) NexGen (8 sizes) and Zimmer Persona (12 sizes) total knee arthroplasty systems. We defined "size deviation" as the difference in the AP dimension between the anatomic size of the native femur and the closest implant size. We defined satisfactory reproduction of distal femoral dimensions as < 1 mm difference between the implant and native femur size. The NexGen system was associated with a mean 0.46 mm greater implant size deviation than Persona (p < 0.001). When using a 1 mm size deviation as a cutoff for satisfactory replication of the native distal femoral anatomy, 85/200 specimens (42.5%) were a poor fit by NexGen, but a satisfactory fit by Persona. Only 1/200 specimens (0.5%) was a poor fit by Persona, but a satisfactory fit by NexGen (p < 0.001). The novel knee system with 12 versus 8 sizes reproduces the AP dimension of the native distal femur more closely than its predecessor. Further study is needed to determine the clinical impact of these differences.

  16. A New Orthodontic Appliance with a Mini Screw for Upper Molar Distalization

    PubMed Central

    2016-01-01

    The aim of this study is to present a new upper molar distalization appliance called Cise distalizer designed as intraoral device supported with orthodontic mini screw for upper permanent molar distalization. The new appliance consists of eight main components. In order to understand the optimum force level, the appliance under static loading is tested by using strain gage measurement techniques. Results show that one of the open coils produces approximately 300 gr distalization force. Cise distalizer can provide totally 600 gr distalization force. This range of force level is enough for distalization of upper first and second molar teeth. PMID:27528796

  17. Ejecta emplacement: from distal to proximal

    NASA Astrophysics Data System (ADS)

    Artemieva, N.

    2008-09-01

    Introduction Most part of impact ejecta is deposited ballistically at some distance from a crater, defined by ejection velocity V and ejection angle α: d=v2sinα/g. In case of giant impacts, planetary curvature should be taken into account [1]. Combined with ejecta scaling [2], these relations allow to define ejecta thickness as a function of distance. Ejecta from large craters are deposited at velocity high enough to mobilize substrate material and to thicken ejecta deposits [3]. Ballistic approximation is valid for airless bodies (if impact vaporization is not vast) or for proximal ejecta of large impact craters, where ejecta mass per unit area is substantially greater than the mass of involved vapor/atmosphere (M-ratio). Deposition of distal ejecta, in which ejecta mass is negligible compared to the atmosphere, may be also treated in a simplified manner, i.e. as 1) passive motion of ejected particles within an impact plume and 2) later, as sedimentation of particles in undisturbed atmosphere (equilibrium between gravity and drag). In all intermediate M-ratio values, impact ejecta move like a surge, i.e. dilute suspension current in which particles are carried in turbulent flows under the influence of gravity. Surges are well-known for near-surface explosive tests, described in detail for volcanic explosions (Plinian column collapse, phreato-magmatic eruption, lateral blast), and found in ejecta from the Chicxulub [4] and the Ries [5]. Important aspects of surge transport include its ability to deposit ejecta over a larger area than that typical of continuous ballistic ejecta and to create multiple ejecta layers. Numerical model Two-phase hydrodynamics. Surges should be modeled in the frame of two-phase hydrodynamics, i.e. interaction between solid/molten particles and atmospheric gas/impact vapor should be taken into account. There are two techniques of solving equations for dust particle motion in a gas flow. The first one describes solid/molten particles as a

  18. SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner.

    PubMed

    Grimm, P Richard; Taneja, Tarvinder K; Liu, Jie; Coleman, Richard; Chen, Yang-Yi; Delpire, Eric; Wade, James B; Welling, Paul A

    2012-11-01

    STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress-related kinase (OSR1) activate the potassium-dependent sodium-chloride co-transporter, NKCC2, and thiazide-sensitive sodium-chloride cotransporter, NCC, in vitro, and both co-localize with a kinase regulatory molecule, Cab39/MO25α, at the apical membrane of the thick ascending limb (TAL) and distal convoluted tubule (DCT). Yet genetic ablation of SPAK in mice causes a selective loss of NCC function, whereas NKCC2 becomes hyperphosphorylated. Here, we explore the underlying mechanisms in wild-type and SPAK-null mice. Unlike in the DCT, OSR1 remains at the TAL apical membrane of KO mice where it is accompanied by an increase in the active, phosphorylated form of AMP-activated kinase. We found an alterative SPAK isoform (putative SPAK2 form), which modestly inhibits co-transporter activity in vitro, is more abundant in the medulla than the cortex. Thus, enhanced NKCC2 phosphorylation in the SPAK knock-out may be explained by removal of inhibitory SPAK2, sustained activity of OSR1, and activation of other kinases. By contrast, the OSR1/SPAK/M025α signaling apparatus is disrupted in the DCT. OSR1 becomes largely inactive and displaced from M025α and NCC at the apical membrane, and redistributes to dense punctate structures, containing WNK1, within the cytoplasm. These changes are paralleled by a decrease in NCC phosphorylation and a decrease in the mass of the distal convoluted tubule, exclusive to DCT1. As a result of the dependent nature of OSR1 on SPAK in the DCT, NCC is unable to be activated. Consequently, SPAK(-/-) mice are highly sensitive to dietary salt restriction, displaying prolonged negative sodium balance and hypotension.

  19. Septic arthritis of the distal interphalangeal joint in 12 horses.

    PubMed

    Honnas, C M; Welch, R D; Ford, T S; Vacek, J R; Watkins, J P

    1992-01-01

    The medical records of 12 horses with septic arthritis of a distal interphalangeal joint were reviewed to determine clinical features and response to treatment. Sepsis was caused by trauma or an injection that resulted in an open or contaminated distal interphalangeal joint. All horses were severely lame. Treatment included broad-spectrum parenterally administered antimicrobial drugs (ten horses), percutaneous through-and-through joint lavage (eight horses), indwelling drains (three horses), immobilization of the limb in a cast (three horses), intraarticular injection of sodium hyaluronate (one horse), intraarticular injection of antimicrobial drugs (five horses), curettage of the distal phalanx (one horse), and cancellous bone grafting to promote fusion (one horse). Five horses were euthanatized. Ankylosis of the affected joint developed in five horses, four of which are pasture sound. Two horses treated medically are sound although one underwent subsequent palmar digital neurectomy for treatment of navicular syndrome.

  20. Molar distalization with the assistance of Temporary Anchorage Devices.

    PubMed

    Palencar, Adrian J

    2015-01-01

    This article describes efficient techniques for distalization of maxillary and mandibular molars with the assistance of Temporary Anchorage Devices (TADs). There are numerous occasions where the distalization of molars is required in lieu of the odontectomy of bicuspids. In the past, extra-oral force has been used, (i.e. Cervical or Combination Head Gear, or intra-oral force, i.e. Posterior Sagittal Appliance, Modified Greenfield Appliance, Williams DMJ 20001, CD Distalizer, Magill Sagittal, Pendulum Appliance, etc.). All the intra-oral appliances have a common denominator the orthodontic clinician has to deal with, the undesirable expression of the Third Law of Newton. The utilization of TADs allows us to circumvent this shortcoming, establishing an absolute anchorage, and thus completely negate the expression of the Third Law of Newton. PMID:25881377

  1. Reverse wedge osteotomy of the distal radius in Madelung's deformity.

    PubMed

    Mallard, F; Jeudy, J; Rabarin, F; Raimbeau, G; Fouque, P-A; Cesari, B; Bizot, P; Saint-Cast, Y

    2013-06-01

    Madelung's deformity results from a growth defect in the palmar and ulnar region of the distal radius. It presents as an excessively inclined radial joint surface, inducing "spontaneous progressive palmar subluxation of the wrist". The principle of reverse wedge osteotomy (RWO) consists in the reorientation of the radial joint surface by taking a circumferential bone wedge, the base of which is harvested from the excess of the radial and dorsal cortical bone of the distal radius, then turning it over and putting back this reverse wedge into the osteotomy so as to obtain closure on the excess and opening on the deficient cortical bone. RWO corrects the palmar subluxation of the carpus and improves distal radio-ulnar alignment. All five bilaterally operated patients were satisfied, esthetically and functionally. Its corrective power gives RWO a place apart among the surgical techniques currently available in Madelung's deformity.

  2. Dislocation of the distal phalanx epiphysis in toddlers.

    PubMed

    Waters, P M; Benson, L S

    1993-07-01

    Two cases of physeal fracture dislocation of the distal phalanx are reviewed. Each injury occurred in a toddler, was originally undiagnosed, and appeared years later as a dorsal mass in a fore-shortened digit with decreased distal interphalangeal joint motion. In each case x-ray films revealed a dislocated epiphysis, accounting for the enlarging dorsal prominence and the phalangeal growth disturbance. These cases demonstrate that dislocation of the distal phalanx epiphysis can occur with a crush injury and may be difficult to detect before development of the ossification center. Careful physical examination and a high index of suspicion will increase the likelihood of early diagnosis. Early open reduction may prevent the late complications of deformity and stiffness. PMID:8349960

  3. Low birth weight and nephron mass and their role in the progression of chronic kidney disease: a case report on identical twins with Alport disease.

    PubMed

    Rajan, Tasleem; Barbour, Sean J; White, Colin T; Levin, Adeera

    2011-12-01

    We report the outcomes of 47-year-old monozygotic twins with Alport syndrome, who share the same maternal and genetic factors; however, in adulthood have discordant trajectories in the decline of their renal function. The twin with the more rapid progression to renal failure was born with low birth weight (LBW), suggesting congenital nephron deficiency and increased susceptibility to progressive renal disease, despite having the same genetically inherited kidney condition. This 'natural experiment' adds further credence to the hypothesis that LBW contributes to the susceptibility to chronic kidney disease. We suggest further studies and surveillance for this high-risk group of infants in order to gain additional insights into the impact of perinatal factors such as LBW. PMID:21565948

  4. Mitochondrial dysfunction in distal axons contribute to HIV sensory neuropathy

    PubMed Central

    Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Höke, Ahmet

    2010-01-01

    Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

  5. Reverse telescoping in distal skarns at Campiglia Marittima (Italy)

    NASA Astrophysics Data System (ADS)

    Vezzoni, Simone; Dini, Andrea; Rocchi, Sergio

    2014-05-01

    Skarn deposits commonly results from the metasomatic alteration of a rock, usually carbonate-rich, by infiltration of hydrothermal fluids. Most carbonate-hosted skarn deposits show a direct spatial relationship with magmatic intrusions and an intimate relationship with porphyry copper deposits. Their primary mineralogical and geochemical features indicate metasomatism by high-temperature magmatic fluids. Conversely, many distal Pb-Zn-Ag skarns pose an important challenge because there is no apparent association with magmatic intrusions and external, meteoric and/or basinal fluids should become increasingly dominant with increasing distance from the igneous source. Nevertheless recent investigation of distal skarn deposits indicates that ore-forming fluids match the composition of proximal magmatic fluids in granitoid-related mineral deposits. Besides that metal producer (Pb, Zn, Ag, Cu, Fe, W, Sn), skarn deposits can be key to understanding fluid dynamics at the periphery of magmatic-hydrothermal systems, unraveling pathways to hidden ore deposits (e.g porphyry copper). In this scenario, research on distal skarns opens new perspectives for deep mineral exploration and/or modeling of intrusion centered geothermal systems, because they should represent the outer limit of the hydrothermal system dominated by magmatic aqueous fluids. Here we present exceptional evidences from a distal Pb-Zn-Ag skarn deposit in Campiglia Marittima, Italy, where the magma, after having released the metasomatic fluids, fled up chasing its own fluid stream and invading large pockets of the newly formed skarn bodies at shallower level. Detailed underground mapping and petrologic data indicate that, after the formation of a typical distal Pb-Zn-Ag skarn, the intrusion of the parent magma produced prograde reactions in the skarn silicates, mobilization of the Pb-Zn-Ag sulfides and precipitation of a new Cu-Fe sulfide assemblage. This is a very unusual case of reverse telescoping during which

  6. Distal protection devices during percutaneous coronary and carotid interventions.

    PubMed

    Fasseas, Panayotis; Orford, James L; Denktas, Ali E; Berger, Peter B

    2001-01-01

    Distal embolization of particulate matter complicates percutaneous coronary and peripheral interventions more often than had been recognized until recently. A number of distal protection devices are under development. The PercuSurge GuardWiretrade mark is a balloon occlusion thrombectomy device approved by the United States Food and Drug Administration for saphenous vein graft intervention. A number of filter devices utilize an expandable filter mounted on the angioplasty guidewire to facilitate entrapment of particles and safe removal. The Parodi Anti-Emboli Systemtrade mark is an example of a catheter occlusion device that establishes protection by reversing blood flow in the target vessel.

  7. Galeazzi fracture with volar dislocation of the distal radioulnar joint.

    PubMed

    Kim, Suezie; Ward, James P; Rettig, Michael E

    2012-11-01

    Galeazzi fracture dislocations are fractures of the distal one-third of the radial diaphysis with traumatic disruption of the distal radioulnar joint (DRUJ). This injury results in subluxation or dislocation of the ulnar head. We present a case of a Galeazzi fracture with a volar dislocation of the DRUJ. Open reduction of the DRUJ with Kirschner wire fixation in pronation was necessary to reduce the joint and maintain anatomic alignment. Repair of the triangular fibrocartilage complex was also necessary to maintain stability of the DRUJ.

  8. Future treatment and research directions in distal radius fracture.

    PubMed

    Jupiter, Jesse

    2012-05-01

    Whether or not they will have their lives dramatically extended in the next few decades, it is clear that people are living longer, healthier, and more active lives. The two peak incidences of distal radius fractures will remain within the pediatric and geriatric age groups, with the latter experiencing a substantial increase in the coming years. This article attempts to project future developments with regard to epidemiology, risk and prevention, fracture assessment, and treatment of distal radius fractures, and the ever increasing concern for the economic impact of this prevalent injury.

  9. Modified distal shoe appliance--fabrication and clinical performance.

    PubMed

    Gujjar, Kumar Raghav; Indushekar, K R; Amith, H V; Sharma, Shefali Li

    2012-01-01

    When the primary second molar is prematurely lost, mesial movement and migration of the permanent first molar often occurs. This is one of the most difficult problems of the developing dentition confronted by pediatric dentists. Use of a space maintainer that will guide the permanent first molar into its normal position is indicated. In cases with bilateral premature loss of primary molars, the conventional design of distal shoe poses a variety of problems and, therefore, necessitates a customized design for the eruption guidance of permanent first molars. The purpose of this case report is to discuss an innovative design of a distal shoe appliance, which was used with good clinical results.

  10. Conservation of Na+ vs. K+ by the rat cortical collecting duct.

    PubMed

    Frindt, Gustavo; Houde, Véronique; Palmer, Lawrence G

    2011-07-01

    Regulation of transport by principal cells of the distal nephron contributes to maintenance of Na(+) and K(+) homeostasis. To assess which of these ions is given a higher priority by these cells, we investigated the upregulation of epithelial Na(+) channels (ENaC) in the rat cortical collecting duct (CCD) during Na depletion with and without simultaneous K depletion. ENaC activity, assessed as whole cell amiloride-sensitive current in split-open tubules, was 260 ± 40 pA/cell in K-repleted but virtually undetectable (3 ± 1 pA/cell) in K-depleted animals. This difference was confirmed biochemically by the reduced amounts of the cleaved forms of both the α-ENaC and γ-ENaC subunits measured in immunoblots. In contrast, in K-depleted rats, simultaneously reducing Na intake did not affect the activity of ROMK channels, assessed as tertiapin-Q-sensitive whole cell currents, in the CCDs. The lack of Na current in K-depleted animals was the result of reduced levels of aldosterone in plasma, rather than a reduced sensitivity to the hormone. However, rats on a low-Na, low-K diet for 1 wk did not excrete more Na than those on a low-Na, control-K diet for the same period of time. Immunoblot analysis indicated increased levels of the thiazide-sensitive NaCl cotransporter and the apical Na-H exchanger NHE3. This suggests that with reduced K intake, Na balance is maintained despite reduced aldosterone and Na(+) channel activity by upregulation of Na(+) transport in upstream segments. Under these conditions, Na(+) transport by the aldosterone-sensitive distal nephron is reduced, despite the low-Na intake to minimize K(+) secretion and urinary K losses. PMID:21454253

  11. Conservation of Na+ vs. K+ by the rat cortical collecting duct.

    PubMed

    Frindt, Gustavo; Houde, Véronique; Palmer, Lawrence G

    2011-07-01

    Regulation of transport by principal cells of the distal nephron contributes to maintenance of Na(+) and K(+) homeostasis. To assess which of these ions is given a higher priority by these cells, we investigated the upregulation of epithelial Na(+) channels (ENaC) in the rat cortical collecting duct (CCD) during Na depletion with and without simultaneous K depletion. ENaC activity, assessed as whole cell amiloride-sensitive current in split-open tubules, was 260 ± 40 pA/cell in K-repleted but virtually undetectable (3 ± 1 pA/cell) in K-depleted animals. This difference was confirmed biochemically by the reduced amounts of the cleaved forms of both the α-ENaC and γ-ENaC subunits measured in immunoblots. In contrast, in K-depleted rats, simultaneously reducing Na intake did not affect the activity of ROMK channels, assessed as tertiapin-Q-sensitive whole cell currents, in the CCDs. The lack of Na current in K-depleted animals was the result of reduced levels of aldosterone in plasma, rather than a reduced sensitivity to the hormone. However, rats on a low-Na, low-K diet for 1 wk did not excrete more Na than those on a low-Na, control-K diet for the same period of time. Immunoblot analysis indicated increased levels of the thiazide-sensitive NaCl cotransporter and the apical Na-H exchanger NHE3. This suggests that with reduced K intake, Na balance is maintained despite reduced aldosterone and Na(+) channel activity by upregulation of Na(+) transport in upstream segments. Under these conditions, Na(+) transport by the aldosterone-sensitive distal nephron is reduced, despite the low-Na intake to minimize K(+) secretion and urinary K losses.

  12. Blood Pressure and Amiloride-Sensitive Sodium Channels in Vascular and Renal Cells

    PubMed Central

    Warnock, David G.; Kusche-Vihrog, Kristina; Tarjus, Antoine; Sheng, Shaohu; Oberleithner, Hans; Kleyman, Thomas R.; Jaisser, Frederic

    2014-01-01

    This review is focused on the expression and regulation of amiloride-sensitive sodium channels in the epithelial cells of the aldosterone-sensitive distal nephron (ENaC) and amiloride-sensitive sodium channel activity in vascular endothelial and smooth muscle cells. Guyton’s hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. With the study of Mendelian forms of hypertension and their corresponding transgenic mouse models, the main components of the aldosterone- and angiotensin-dependent sodium transporters have been identified over the past 20 years. Proteolytic processing of the ENaC external domain, and inhibition by increased sodium concentrations are important features of the ENaC complexes expressed in the distal nephron. In contrast, amiloride-sensitive sodium channels expressed in the vascular system are activated by increased external sodium concentrations, resulting in changes in the mechanical properties and function of endothelial cells. Mechano-sensitivity and shear stress affect both epithelial and vascular sodium channel activity. The synergistic effects and complementary regulation of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and may reflect sequential evolution of the two systems. The integration of vascular tone, renal perfusion and regulation of renal sodium reabsorption is the central underpinning of the Guytonian model. We summarize the recent evidence in this review that describes the central role of amiloride-sensitive sodium channels in the efferent (e.g., vascular) and afferent (e.g., epithelial) arms of this homeostatic system. PMID:24419567

  13. The role of pendrin in renal physiology.

    PubMed

    Wall, Susan M; Lazo-Fernandez, Yoskaly

    2015-01-01

    Pendrin is a Na(+)-independent Cl(-)/HCO3(-) exchanger that localizes to type B and non-A, non-B intercalated cells, which are expressed within the aldosterone-sensitive region of the nephron, i.e., the distal convoluted tubule, the connecting tubule, and the cortical collecting duct. Type B cells mediate Cl(-) absorption and HCO3(-) secretion primarily through pendrin-mediated Cl(-)/HCO3(-) exchange. At least in some treatment models, pendrin acts in tandem with the Na(+)-dependent Cl(-)/HCO3(-) exchanger (NDCBE) encoded by Slc4a8 to mediate NaCl absorption. The pendrin-mediated Cl(-)/HCO3(-) exchange process is greatly upregulated in models of metabolic alkalosis, such as following aldosterone administration or dietary NaHCO3 loading. It is also upregulated by angiotensin II. In the absence of pendrin [Slc26a4 (-/-) or pendrin null mice], aldosterone-stimulated NaCl absorption is reduced, which lowers the blood pressure response to aldosterone and enhances the alkalosis that follows the administration of this steroid hormone. Pendrin modulates aldosterone-induced Na(+) absorption by changing ENaC abundance and function through a kidney-specific mechanism that does not involve changes in the concentration of a circulating hormone. Instead, pendrin changes ENaC abundance and function at least in part by altering luminal HCO3(-) and ATP concentrations. Thus, aldosterone and angiotensin II also stimulate pendrin expression and function, which likely contributes to the pressor response of these hormones. This review summarizes the contribution of the Cl(-)/HCO3(-) exchanger pendrin in distal nephron function.

  14. Treatment of distal humerus fractures in adults: a historical perspective.

    PubMed

    Kozánek, Michal; Bartoníček, Jan; Chase, Samantha M; Jupiter, Jesse B

    2014-12-01

    Nonsurgical treatment was the mainstay of management of distal humerus fractures for centuries and nonunions and malunions were common. The 19th century featured the recognition of distinct injury patterns. With advances in radiology, anesthesia, antisepsis, and hardware technology, surgical treatment is now generally preferred, yet loss of elbow joint mobility can still be a vexing problem.

  15. Proximal versus Distal Validity Coefficients for Teacher Observational Instruments

    ERIC Educational Resources Information Center

    Marzano, Robert J.

    2014-01-01

    This study examined the use of measures of student learning computed using end-of-year assessments (distal measures) versus measures of student learning associated with a single lesson (proximal measures) as criterion scores for the validity of observations of teachers' pedagogical skills. The validity coefficients computed using distal…

  16. Sural Versus Perforator Flaps for Distal Medial Leg Wounds.

    PubMed

    Schannen, Andrew P; Truchan, Lisa; Goshima, Kaoru; Bentley, Roger; DeSilva, Gregory L

    2015-12-01

    Soft tissue coverage of distal medial ankle wounds is a challenging problem in orthopedic surgery because of the limited local tissues and prominent instrumentation. Traditionally, these wounds required free tissue transfer to achieve suitable coverage and subsequent bony union. To better respect the reconstructive ladder and to avoid the inherent difficulty of free flap coverage, rotational flaps have been used to cover these wounds. Both sural fasciocutaneous flaps and rotational fasciocutaneous perforator (propeller) flaps have been described for distal medial soft tissue coverage. The authors performed a retrospective chart review of patients who underwent distal medial leg coverage with the use of either sural flaps or rotational fasciocutaneous perforator flaps. The authors identified 14 patients by Current Procedural Terminology code who met the study criteria. The average age and degree of medical comorbidities were comparable in the 2 groups. The authors reviewed their medical records to evaluate fracture healing, flap size, complications, and return to normal shoe wear. All 7 sural flaps healed without incident, with underlying fracture healing. Of the 7 perforator flaps, 6 healed without incident, with underlying fracture healing. One perforator-based flap was complicated by superficial tip necrosis and went on to heal with local wound care. All patients returned to normal shoe wear. Both sural artery rotational flaps and posterior tibial artery-based rotational flaps are viable options for coverage of the distal medial leg. Coverage can be achieved reliably without microsurgery, anticoagulation, or monitoring in the intensive care unit. PMID:26652325

  17. Distally Based Iliotibial Band Flap: Anatomic Study with Surgical Considerations.

    PubMed

    Wong, Victor W; Higgins, James P

    2016-09-01

    Background Reconstruction of high-risk fascia, tendon, or ligament defects may benefit from vascularized tissue. The iliotibial band (ITB), a thick fibrous tract of connective tissue, serves as a potential donor site for free tissue transfer but its blood supply has not been thoroughly investigated. The aim of this anatomical study was to investigate the vascular supply to the distal ITB and its role as a free fascial flap. Methods We dissected 16 fresh-frozen cadaveric legs and injected latex into the superolateral geniculate artery (SLGA). A distal ITB fascial flap was designed and measurements were taken for flap dimensions, pedicle length and size, and SLGA perfusion territory. Results The SLGA perfused 11.5 ± 2.3 cm of distal ITB (proximal to the lateral femoral epicondyle) and provided 6.4 ± 0.7cm of pedicle length to the ITB flap. Conclusions Chimeric options to include bone (from the lateral femoral condyle), cartilage (from the lateral femoral trochlea), muscle (from vastus lateralis or biceps femoris), and skin are possible. Surgical harvest techniques are proposed, including preservation of ITB insertions to minimize lateral knee instability. Clinical validation is needed to determine the role of the distal ITB free fascial flap in reconstructive microsurgery.

  18. Genetics Home Reference: CAV3-related distal myopathy

    MedlinePlus

    ... gene causes a peculiar form of distal myopathy. Neurology. 2002 Jan 22;58(2):323-5. Erratum in: Neurology 2002 Mar 12;58(5):839. Itoyoma Y [ ... 3 cause four distinct autosomal dominant muscle diseases. Neurology. 2004 Feb 24;62(4):538-43. Review. ...

  19. Ultrasound-Guided Reduction of Distal Radius Fractures

    PubMed Central

    Sabzghabaei, Anita; Shojaee, Majid; Arhami Dolatabadi, Ali; Manouchehrifar, Mohammad; Asadi, Mahdi

    2016-01-01

    Introduction: Distal radius fractures are a common traumatic injury, particularly in the elderly population. In the present study we examined the effectiveness of ultrasound guidance in the reduction of distal radius fractures in adult patients presenting to emergency department (ED). Methods: In this prospective case control study, eligible patients were adults older than 18 years who presented to the ED with distal radius fractures. 130 consecutive patient consisted of two group of Sixty-Five patients were prospectively enrolled for around 1 years. The first group underwent ultrasound-guided reduction and the second (control group) underwent blind reduction. All procedures were performed by two trained emergency residents under supervision of senior emergency physicians. Results: Baseline characteristics between two groups were similar. The rate of repeat reduction was reduced in the ultrasound group (9.2% vs 24.6%; P = .019). The post reduction radiographic indices were similar between the two groups, although the ultrasound group had improved volar tilt (mean, 7.6° vs 3.7°; P = .000). The operative rate was reduced in the ultrasound groups (10.8% vs 27.7%; P = .014). Conclusion: Ultrasound guidance is effective and recommended for routine use in the reduction of distal radius fractures. PMID:27299141

  20. Autosomal dominant distal myopathy: Linkage to chromosome 14

    SciTech Connect

    Laing, N.G.; Laing, B.A.; Wilton, S.D.; Dorosz, S.; Mastaglia, F.L.; Kakulas, B.A.; Robbins, P.; Meredith, C.; Honeyman, K.; Kozman, H.

    1995-02-01

    We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64 - the family structure precludes a two-point LOD score {ge} 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity. 24 refs., 3 figs., 1 tab.

  1. Management of distal humeral fractures in the elderly.

    PubMed

    Strauss, Eric J; Alaia, Michael; Egol, Kenneth A

    2007-09-01

    Although relatively uncommon, fractures of the distal humerus in the elderly patient population are significant injuries of which optimal management is a subject of debate in orthopaedic literature. The combination of complex anatomy, poor bone quality and extensive comminution often seen with these fractures makes successful treatment difficult. Currently, most surgeons support surgical fixation of distal humeral fractures with the belief that restoration of the patient's native elbow joint provides the best opportunity for a good functional outcome. Others have proposed the use of total elbow arthroplasty as a primary treatment method for geriatric distal humeral fractures based on the difficulties associated with ORIF and the relatively low demands of this patient population. To date, there have been no prospective randomised trials comparing these two treatment alternatives, and a comparison of available outcome data shows good functional outcome for both forms of fracture management. With the aging of the population and an associated increase in the incidence of distal humeral fractures, the debate over the optimal treatment regime will undoubtedly continue. PMID:17723787

  2. Prediction of distal residue participation in enzyme catalysis.

    PubMed

    Brodkin, Heather R; DeLateur, Nicholas A; Somarowthu, Srinivas; Mills, Caitlyn L; Novak, Walter R; Beuning, Penny J; Ringe, Dagmar; Ondrechen, Mary Jo

    2015-05-01

    A scoring method for the prediction of catalytically important residues in enzyme structures is presented and used to examine the participation of distal residues in enzyme catalysis. Scores are based on the Partial Order Optimum Likelihood (POOL) machine learning method, using computed electrostatic properties, surface geometric features, and information obtained from the phylogenetic tree as input features. Predictions of distal residue participation in catalysis are compared with experimental kinetics data from the literature on variants of the featured enzymes; some additional kinetics measurements are reported for variants of Pseudomonas putida nitrile hydratase (ppNH) and for Escherichia coli alkaline phosphatase (AP). The multilayer active sites of P. putida nitrile hydratase and of human phosphoglucose isomerase are predicted by the POOL log ZP scores, as is the single-layer active site of P. putida ketosteroid isomerase. The log ZP score cutoff utilized here results in over-prediction of distal residue involvement in E. coli alkaline phosphatase. While fewer experimental data points are available for P. putida mandelate racemase and for human carbonic anhydrase II, the POOL log ZP scores properly predict the previously reported participation of distal residues.

  3. Non-reducible palmar dislocation of the distal radioulnar joint

    PubMed Central

    Zannou, Rupestre S.; Rezzouk, Joel; Ruijs, Aleid C.J.

    2015-01-01

    Abstract A rare case of an isolated traumatic palmar dislocation of the distal radioulnar joint is presented. Clinically, there is a loss of pronation and supination. The dislocation was treated using an open reduction, reinsertion of the capsule-ligamentous complex and temporary stabilization using K-wires. PMID:26158121

  4. Exposures of the wrist and distal radioulnar joint.

    PubMed

    Bickel, Kyle D

    2014-11-01

    This article reviews the superficial, skeletal, and ligamentous anatomy of the wrist. Standard and alternative exposures of the wrist joint and the distal radioulnar joint are discussed, emphasizing the importance of avoiding nerve injury. Standard exposure of the wrist joint is used in the treatment of carpal ligament injuries, fractures, and dislocations. Case presentations illustrate these techniques.

  5. Distally Based Iliotibial Band Flap: Anatomic Study with Surgical Considerations.

    PubMed

    Wong, Victor W; Higgins, James P

    2016-09-01

    Background Reconstruction of high-risk fascia, tendon, or ligament defects may benefit from vascularized tissue. The iliotibial band (ITB), a thick fibrous tract of connective tissue, serves as a potential donor site for free tissue transfer but its blood supply has not been thoroughly investigated. The aim of this anatomical study was to investigate the vascular supply to the distal ITB and its role as a free fascial flap. Methods We dissected 16 fresh-frozen cadaveric legs and injected latex into the superolateral geniculate artery (SLGA). A distal ITB fascial flap was designed and measurements were taken for flap dimensions, pedicle length and size, and SLGA perfusion territory. Results The SLGA perfused 11.5 ± 2.3 cm of distal ITB (proximal to the lateral femoral epicondyle) and provided 6.4 ± 0.7cm of pedicle length to the ITB flap. Conclusions Chimeric options to include bone (from the lateral femoral condyle), cartilage (from the lateral femoral trochlea), muscle (from vastus lateralis or biceps femoris), and skin are possible. Surgical harvest techniques are proposed, including preservation of ITB insertions to minimize lateral knee instability. Clinical validation is needed to determine the role of the distal ITB free fascial flap in reconstructive microsurgery. PMID:27135145

  6. Haptic Distal Spatial Perception Mediated by Strings: Haptic "Looming"

    ERIC Educational Resources Information Center

    Cabe, Patrick A.

    2011-01-01

    Five experiments tested a haptic analog of optical looming, demonstrating string-mediated haptic distal spatial perception. Horizontally collinear hooks supported a weighted string held taut by a blindfolded participant's finger midway between the hooks. At the finger, the angle between string segments increased as the finger approached…

  7. The distal shoe space maintainer chairside fabrication and clinical performance.

    PubMed

    Brill, Warren A

    2002-01-01

    The chairside-fabricated distal shoe appliance, with a stainless steel crown as the retainer, is an efficacious and cost-effective appliance for guiding the unerupted permanent first molar into position after premature loss or extraction of the second primary molar. The fabrication technique is illustrated in this case report and data is presented on the success rate of the appliance.

  8. [Distalization of the upper second molar: clinical case].

    PubMed

    Castaldo, A; Blasi, S; Vettese, P

    1991-01-01

    The Authors showed a clinical case in which has been put on a distalizing system together with a palatal bar between the first upper molars, a sectional placed between the first and the second molar and a 100 g precalibrated Sentalloy coil. PMID:1784297

  9. Distal Prosodic Context Affects Word Segmentation and Lexical Processing

    ERIC Educational Resources Information Center

    Dilley, Laura C.; McAuley, J. Devin

    2008-01-01

    Three experiments investigated the role of distal (i.e., nonlocal) prosody in word segmentation and lexical processing. In Experiment 1, prosodic characteristics of the initial five syllables of eight-syllable sequences were manipulated; the final portions of these sequences were lexically ambiguous (e.g., "note bookworm", "notebook worm"). Distal…

  10. Distal Radius Isoelastic Resurfacing Prosthesis: A Preliminary Report

    PubMed Central

    Ichihara, Satoshi; Díaz, Juan José Hidalgo; Peterson, Brett; Facca, Sybille; Bodin, Frédéric; Liverneaux, Philippe

    2015-01-01

    Background Here we present a preliminary case series of unicompartmental isoelastic resurfacing prosthesis of the distal radius to treat comminuted articular fractures of osteoporotic elderly patients. Materials and Methods Our study included 12 patients, mean age 76 years, who presented with comminuted osteoporotic distal radius fracture. Because of the severity of injury and poor bone quality; osteosynthesis was not deemed to be a good option. Description of Technique The surgery was performed through a dorsal approach. The subchondral bone of the entire distal radial articular was excised and a unicompartmental prosthesis was applied. Results At an average follow-up of 32 months, the pain was 2.8/10, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) 37.4/100, grip strength in neutral 49.9%, in supination 59.0%, and in pronation 56.2% of the contralateral normal side. The wrist ranges of motion in flexion and extension were 56.1% and 79.3%, in supination and pronation 87.7% and 91.0% of the contralateral normal side. Two patients experienced a complex regional pain syndrome (CRPS) type II; these resolved spontaneously. One patient experienced distal radioulnar joint (DRUJ) stiffness, which improved after an ulna head resection. Finally, one patient required revision surgery after a secondary traumatic fracture. Radiographically; the average volar tilt was 9.8°; the average of radial inclination was 11.6°. Conclusion The concept of a unicompartmental isoelastic resurfacing prosthesis offers a promising option for the treatment of comminuted, osteoporotic distal radius articular fractures of elderly patients. Level of Evidence IV PMID:26261738

  11. Distal Oblique Bundle Reinforcement for Treatment of DRUJ Instability

    PubMed Central

    Brink, Peter R. G.; Hannemann, Pascal F. W.

    2015-01-01

    Background Chronic, dynamic bidirectional instability in the distal radioulnar joint (DRUJ) is diagnosed clinically, based on the patient's complaints and the finding of abnormal laxity in the vicinity of the distal ulna. In cases where malunion is ruled out or treated and there are no signs of osteoarthritis, stabilization of the DRUJ may offer relief. To this end, several different techniques have been investigated over the past 90 years. Materials and Methods In this article we outline the procedure for a new technique using a tendon graft to reinforce the distal edge of the interosseous membrane. Description of Technique A percutaneous technique is used to harvest the palmaris longus tendon and to create a tunnel, just proximal to the sigmoid notch, through the ulna and radius in an oblique direction. By overdrilling the radial cortex, the knotted tendon can be pulled through the radius and ulna and the knot blocked at the second radial cortex, creating a strong connection between the radius and ulna at the site of the distal oblique bundle (DOB). The tendon is fixed in the ulna with a small interference screw in full supination, preventing subluxation of the ulna out of the sigmoid notch during rotation. Results Fourteen patients were treated with this novel technique between 2011 and October 2013. The QuickDASH score at 25 months postoperatively (range 16–38 months) showed an improvement of 32 points. Similarly, an improvement of 33 points (67–34 months) was found on the PRWHE. Only one recurrence of chronic, dynamic bidirectional instability in the DRUJ was observed. Conclusion This simple percutaneous tenodesis technique between radius and ulna at the position of the distal edge of the interosseous membrane shows promise in terms of both restoring stability and relieving complaints related to chronic subluxation in the DRUJ. PMID:26261750

  12. The influence of amlodipine and verapamil on ion and water transport in the nephron, skin and urinary bladder of amphibians.

    PubMed

    Natochin YuV; Goncharevskaya, O A; Johns, E J; Monin YuG; Shakhmatova, E I

    1991-01-01

    1. The addition of amlodipine or verapamil into the lumen of the newt distal tubule led to the decrease of reabsorption of Na, Cl, Ca and of fluid. 2. The application of amlodipine to the outside of the frog skin caused large increases in potential difference (PD) and short circuit (SCC) similar to what is seen with Co2+. If both amlodipine and Co2+ were applied simultaneously to the outer surface the increases in PD and SCC were additive. 3. Verapamil added to the outer surface of the skin caused a reduction in PD which could be overcome by subsequent addition of amlodipine. 4. After addition of amlodipine to serosal or mucosal surfaces of the frog urinary bladder, the ability of vasopressin to increase osmotic permeability was markedly attenuated. 5. It is likely that the calcium channel blockers used here not only affect intracellular calcium levels by inhibiting entry through calcium channels, but they may also alter calcium dependent processes within the plasma membranes which modulate sodium transfer across epithelia.

  13. Missense Mutation of POU Domain Class 3 Transcription Factor 3 in Pou3f3L423P Mice Causes Reduced Nephron Number and Impaired Development of the Thick Ascending Limb of the Loop of Henle.

    PubMed

    Rieger, Alexandra; Kemter, Elisabeth; Kumar, Sudhir; Popper, Bastian; Aigner, Bernhard; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-01-01

    During nephrogenesis, POU domain class 3 transcription factor 3 (POU3F3 aka BRN1) is critically involved in development of distinct nephron segments, including the thick ascending limb of the loop of Henle (TAL). Deficiency of POU3F3 in knock-out mice leads to underdevelopment of the TAL, lack of differentiation of TAL cells, and perinatal death due to renal failure. Pou3f3L423P mutant mice, which were established in the Munich ENU Mouse Mutagenesis Project, carry a recessive point mutation in the homeobox domain of POU3F3. Homozygous Pou3f3L423P mutants are viable and fertile. The present study used functional, as well as qualitative and quantitative morphological analyses to characterize the renal phenotype of juvenile (12 days) and aged (60 weeks) homo- and heterozygous Pou3f3L423P mutant mice and age-matched wild-type controls. In both age groups, homozygous mutants vs. control mice displayed significantly smaller kidney volumes, decreased nephron numbers and mean glomerular volumes, smaller TAL volumes, as well as lower volume densities of the TAL in the kidney. No histological or ultrastructural lesions of TAL cells or glomerular cells were observed in homozygous mutant mice. Aged homozygous mutants displayed increased serum urea concentrations and reduced specific urine gravity, but no evidence of glomerular dysfunction. These results confirm the role of POU3F3 in development and function of the TAL and provide new evidence for its involvement in regulation of the nephron number in the kidney. Therefore, Pou3f3L423P mutant mice represent a valuable research model for further analyses of POU3F3 functions, or for nephrological studies examining the role of congenital low nephron numbers. PMID:27420727

  14. Missense Mutation of POU Domain Class 3 Transcription Factor 3 in Pou3f3L423P Mice Causes Reduced Nephron Number and Impaired Development of the Thick Ascending Limb of the Loop of Henle

    PubMed Central

    Rieger, Alexandra; Kemter, Elisabeth; Kumar, Sudhir; Popper, Bastian; Aigner, Bernhard; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-01-01

    During nephrogenesis, POU domain class 3 transcription factor 3 (POU3F3 aka BRN1) is critically involved in development of distinct nephron segments, including the thick ascending limb of the loop of Henle (TAL). Deficiency of POU3F3 in knock-out mice leads to underdevelopment of the TAL, lack of differentiation of TAL cells, and perinatal death due to renal failure. Pou3f3L423P mutant mice, which were established in the Munich ENU Mouse Mutagenesis Project, carry a recessive point mutation in the homeobox domain of POU3F3. Homozygous Pou3f3L423P mutants are viable and fertile. The present study used functional, as well as qualitative and quantitative morphological analyses to characterize the renal phenotype of juvenile (12 days) and aged (60 weeks) homo- and heterozygous Pou3f3L423P mutant mice and age-matched wild-type controls. In both age groups, homozygous mutants vs. control mice displayed significantly smaller kidney volumes, decreased nephron numbers and mean glomerular volumes, smaller TAL volumes, as well as lower volume densities of the TAL in the kidney. No histological or ultrastructural lesions of TAL cells or glomerular cells were observed in homozygous mutant mice. Aged homozygous mutants displayed increased serum urea concentrations and reduced specific urine gravity, but no evidence of glomerular dysfunction. These results confirm the role of POU3F3 in development and function of the TAL and provide new evidence for its involvement in regulation of the nephron number in the kidney. Therefore, Pou3f3L423P mutant mice represent a valuable research model for further analyses of POU3F3 functions, or for nephrological studies examining the role of congenital low nephron numbers. PMID:27420727

  15. Transosseous-Equivalent Repair for Distal Patellar Tendon Avulsion.

    PubMed

    Galos, David K; Konda, Sanjit R; Kaplan, Daniel J; Ryan, William E; Alaia, Michael J

    2016-04-01

    Extensor mechanism disruptions are relatively uncommon injuries involving injury to the quadriceps tendon, patella, or patellar tendon. Patellar tendon avulsions from the tibial tubercle in adults are rare; as such, little technical information has been written regarding surgical management of this injury in the adult. Transosseous-equivalent repairs have been described in the management of several types of tendon ruptures, including rotator cuff and distal triceps tendon ruptures, but not previously in patellar injuries. We present a technique for repairing an avulsion injury of the patellar tendon from the tibial tubercle using suture anchors in a transosseous-equivalent manner. This technique for treating distal patellar tendon avulsion injuries likely increases contact area at the repair site while potentially improving fixation strength. PMID:27462538

  16. [Results following percutaneous intramedullary pin fixation in distal radius fractures].

    PubMed

    Kirchner, R; Hüttl, T; Krüger-Franke, M; Rosemeyer, B

    1994-01-01

    42 distal radius fractures have been submitted to further examination after percutaneous intramedullary pin fixation. The outcome were 95.3% of very good to good anatomic results and 90.5% of satisfying functional results. This showed the close link between the radiological-anatomical and functional results. The success of the treatment was very acceptable, although the Morbus Sudeck as the major complication--with 7.2%--was still relatively frequently observed. It could be seen that particularly fractures at the risk of dislocation with smash zone constituted an indication for the percutaneous intramedullary pin fixation, that is to say all fractures for which a retention is primarily difficult. It constitutes a supplement, as well as an extension to the therapy of the distal radius fractures. PMID:7516105

  17. Pendulum Therapy of Molar Distalization in Mixed Dentition

    PubMed Central

    Prakash, Amit; Agarwal, Anshu

    2016-01-01

    ABSTRACT Early and timely pedo-orthodontic treatment is aimed at eliminating the disturbances of skeletal or dentoalveolar development, to harmonize the stomatognathic system before the full eruption of all permanent teeth. The advantages of pendulum appliance are its minimal dependence on patient’s compliance (child cooperation), ease of fabrication, onetime activation and adjustment of the springs if necessary to correct minor transverse and vertical molar positions. This article reports a successful treatment method of class II malocclusion with pendulum appliance in mixed dentition phase. Distalization of maxillary molar was done, followed by guidance of canine impaction orthodontically and other dental correction using 0.022 MBT appliances. Posttreatment results were stable and remarkable. How to cite this article: Patil RU, Prakash A, Agarwal A. Pendulum Therapy of Molar Distalization in Mixed Dentition. Int J Clin Pediatr Dent 2016;9(1):67-73. PMID:27274159

  18. Pendulum Therapy of Molar Distalization in Mixed Dentition.

    PubMed

    Patil, Raju Umaji; Prakash, Amit; Agarwal, Anshu

    2016-01-01

    Early and timely pedo-orthodontic treatment is aimed at eliminating the disturbances of skeletal or dentoalveolar development, to harmonize the stomatognathic system before the full eruption of all permanent teeth. The advantages of pendulum appliance are its minimal dependence on patient's compliance (child cooperation), ease of fabrication, onetime activation and adjustment of the springs if necessary to correct minor transverse and vertical molar positions. This article reports a successful treatment method of class II malocclusion with pendulum appliance in mixed dentition phase. Distalization of maxillary molar was done, followed by guidance of canine impaction orthodontically and other dental correction using 0.022 MBT appliances. Posttreatment results were stable and remarkable. How to cite this article: Patil RU, Prakash A, Agarwal A. Pendulum Therapy of Molar Distalization in Mixed Dentition. Int J Clin Pediatr Dent 2016;9(1):67-73. PMID:27274159

  19. Pendulum Therapy of Molar Distalization in Mixed Dentition.

    PubMed

    Patil, Raju Umaji; Prakash, Amit; Agarwal, Anshu

    2016-01-01

    Early and timely pedo-orthodontic treatment is aimed at eliminating the disturbances of skeletal or dentoalveolar development, to harmonize the stomatognathic system before the full eruption of all permanent teeth. The advantages of pendulum appliance are its minimal dependence on patient's compliance (child cooperation), ease of fabrication, onetime activation and adjustment of the springs if necessary to correct minor transverse and vertical molar positions. This article reports a successful treatment method of class II malocclusion with pendulum appliance in mixed dentition phase. Distalization of maxillary molar was done, followed by guidance of canine impaction orthodontically and other dental correction using 0.022 MBT appliances. Posttreatment results were stable and remarkable. How to cite this article: Patil RU, Prakash A, Agarwal A. Pendulum Therapy of Molar Distalization in Mixed Dentition. Int J Clin Pediatr Dent 2016;9(1):67-73.

  20. Epithelial cell fate in the nephron tubule is mediated by the ETS transcription factors etv5a and etv4 during zebrafish kidney development.

    PubMed

    Marra, Amanda N; Wingert, Rebecca A

    2016-03-15

    Kidney development requires the differentiation and organization of discrete nephron epithelial lineages, yet the genetic and molecular pathways involved in these events remain poorly understood. The embryonic zebrafish kidney, or pronephros, provides a simple and useful model to study nephrogenesis. The pronephros is primarily comprised of two types of epithelial cells: transportive and multiciliated cells (MCCs). Transportive cells occupy distinct tubule segments and are characterized by the expression of various solute transporters, while MCCs function in fluid propulsion and are dispersed in a "salt-and-pepper" fashion within the tubule. Epithelial cell identity is reliant on interplay between the Notch signaling pathway and retinoic acid (RA) signaling, where RA promotes MCC fate by inhibiting Notch activity in renal progenitors, while Notch acts downstream to trigger transportive cell formation and block adoption of an MCC identity. Previous research has shown that the transcription factor ets variant 5a (etv5a), and its closely related ETS family members, are required for ciliogenesis in other zebrafish tissues. Here, we mapped etv5a expression to renal progenitors that occupy domains where MCCs later emerge. Thus, we hypothesized that etv5a is required for normal development of MCCs in the nephron. etv5a loss of function caused a decline of MCC number as indicated by the reduced frequency of cells that expressed the MCC-specific markers outer dense fiber of sperm tails 3b (odf3b) and centrin 4 (cetn4), where rescue experiments partially restored MCC incidence. Interestingly, deficiency of ets variant 4 (etv4), a related gene that is broadly expressed in the posterior mesoderm during somitogenesis stages, also led to reduced MCC numbers, which were further reduced by dual etv5a/4 deficiency, suggesting that both of these ETS factors are essential for MCC formation and that they also might have redundant activities. In epistatic studies, exogenous RA

  1. Epithelial cell fate in the nephron tubule is mediated by the ETS transcription factors etv5a and etv4 during zebrafish kidney development.

    PubMed

    Marra, Amanda N; Wingert, Rebecca A

    2016-03-15

    Kidney development requires the differentiation and organization of discrete nephron epithelial lineages, yet the genetic and molecular pathways involved in these events remain poorly understood. The embryonic zebrafish kidney, or pronephros, provides a simple and useful model to study nephrogenesis. The pronephros is primarily comprised of two types of epithelial cells: transportive and multiciliated cells (MCCs). Transportive cells occupy distinct tubule segments and are characterized by the expression of various solute transporters, while MCCs function in fluid propulsion and are dispersed in a "salt-and-pepper" fashion within the tubule. Epithelial cell identity is reliant on interplay between the Notch signaling pathway and retinoic acid (RA) signaling, where RA promotes MCC fate by inhibiting Notch activity in renal progenitors, while Notch acts downstream to trigger transportive cell formation and block adoption of an MCC identity. Previous research has shown that the transcription factor ets variant 5a (etv5a), and its closely related ETS family members, are required for ciliogenesis in other zebrafish tissues. Here, we mapped etv5a expression to renal progenitors that occupy domains where MCCs later emerge. Thus, we hypothesized that etv5a is required for normal development of MCCs in the nephron. etv5a loss of function caused a decline of MCC number as indicated by the reduced frequency of cells that expressed the MCC-specific markers outer dense fiber of sperm tails 3b (odf3b) and centrin 4 (cetn4), where rescue experiments partially restored MCC incidence. Interestingly, deficiency of ets variant 4 (etv4), a related gene that is broadly expressed in the posterior mesoderm during somitogenesis stages, also led to reduced MCC numbers, which were further reduced by dual etv5a/4 deficiency, suggesting that both of these ETS factors are essential for MCC formation and that they also might have redundant activities. In epistatic studies, exogenous RA

  2. Medical management of fragility fractures of the distal radius.

    PubMed

    Morgan, Emily N; Crawford, David A; Scully, William F; Noce, Nicholas J

    2014-12-01

    Fragility fractures of the distal radius represent an opportunity to diagnose and treat osteoporosis before further fractures occur. The goal of this study was to determine the prevalence of prescriptions for calcium/vitamin D supplementation and the prevalence of dual-energy x-ray absorptiometry (DEXA) scans in patients who sustained fragility fractures of the distal radius. A further goal was to determine the prevalence of patients who received prescriptions for the treatment of osteoporosis after DEXA scans. The authors performed a retrospective review of all patients 50 years and older who sustained a fragility fracture of the distal radius and were treated by the orthopedic surgery service at the authors' institution from 2004 to 2010. After a fragility fracture of the distal radius, fewer than 25% of previously unidentified at-risk patients received a prescription for vitamin supplementation and underwent a DEXA scan. Women were 7 times more likely than men to receive calcium/vitamin D supplementation, 14 times more likely to undergo a DEXA scan for the evaluation of osteoporosis, and 25 times more likely to receive a prescription for bisphosphonates. Patients who underwent a DEXA scan were 9 times more likely to receive pharmacologic treatment than those who did not undergo this scan. More than half of patients did not receive a prescription for calcium/vitamin D supplementation and did not undergo DEXA scanning as recommended by current National Osteoporosis Foundation guidelines. Most patients who received prescriptions or underwent DEXA scans did so before rather than after fracture, indicating poor compliance with National Osteoporosis Foundation guidelines. PMID:25437080

  3. Epithelioid Hemangioendothelioma of the Distal Radius: A Case Report.

    PubMed

    Duncan, Scott F M; Krochmal, Daniel J; Craft, Randall O; Merritt, Marianne V; Smith, Anthony A

    2007-01-01

    Epithelioid hemangioendothelioma is a rare vascular tumor with cytologic behavior between angiosarcoma and hemangioma. We present the case of a 58-year-old male with primary epithelioid hemangioendothelioma of the distal radius measuring 6.2 × 5 cm with extension into the pronator quadratus and brachioradialis muscles. We discuss our approach to performing a limb-sparing resection combined with reconstruction to preserve upper extremity function. A review of the clinical, radiographic, and pathologic features of epithelioid hemangioendothelioma is also presented.

  4. Medical management of fragility fractures of the distal radius.

    PubMed

    Morgan, Emily N; Crawford, David A; Scully, William F; Noce, Nicholas J

    2014-12-01

    Fragility fractures of the distal radius represent an opportunity to diagnose and treat osteoporosis before further fractures occur. The goal of this study was to determine the prevalence of prescriptions for calcium/vitamin D supplementation and the prevalence of dual-energy x-ray absorptiometry (DEXA) scans in patients who sustained fragility fractures of the distal radius. A further goal was to determine the prevalence of patients who received prescriptions for the treatment of osteoporosis after DEXA scans. The authors performed a retrospective review of all patients 50 years and older who sustained a fragility fracture of the distal radius and were treated by the orthopedic surgery service at the authors' institution from 2004 to 2010. After a fragility fracture of the distal radius, fewer than 25% of previously unidentified at-risk patients received a prescription for vitamin supplementation and underwent a DEXA scan. Women were 7 times more likely than men to receive calcium/vitamin D supplementation, 14 times more likely to undergo a DEXA scan for the evaluation of osteoporosis, and 25 times more likely to receive a prescription for bisphosphonates. Patients who underwent a DEXA scan were 9 times more likely to receive pharmacologic treatment than those who did not undergo this scan. More than half of patients did not receive a prescription for calcium/vitamin D supplementation and did not undergo DEXA scanning as recommended by current National Osteoporosis Foundation guidelines. Most patients who received prescriptions or underwent DEXA scans did so before rather than after fracture, indicating poor compliance with National Osteoporosis Foundation guidelines.

  5. Distal Femoral Complications Following Antegrade Intramedullary Nail Placement

    PubMed Central

    Fantry, Amanda J.; Elia, Gregory; Vopat, Bryan G.; Daniels, Alan H.

    2015-01-01

    While antegrade nailing for proximal and diaphyseal femur fractures is a commonly utilized fixation method with benefits including early mobilization and high rates of fracture union, both intraoperative and postoperative complications may occur. Intraoperative errors include leg length discrepancy, anterior cortical perforation, malreduction of the fracture, and neurovascular injury, and postoperative complications include nonunion, malunion, infection, and hardware failure. This case series reviews complications affecting the distal femur after intramedullary nailing including fracture surrounding a distal femoral interlocking screw (Case #1), nonunion after dynamization with nail penetration into the knee joint (Case #2), and anterior cortical perforation (Case #3). Prevention of intraoperative and postoperative complications surrounding intramedullary nailing requires careful study of the femoral anatomy and nail design specifications (radius of curvature), consideration of the necessity of distal interlocking screws, the need for close radiographic follow-up after nail placement with X-rays of the entire length of the nail, and awareness of possible nail penetration into the knee joint after dynamization. PMID:25874066

  6. Neural pattern in the human pollical distal phalanx.

    PubMed

    Johnson, Richard K; Shrewsbury, Marvin M

    2005-09-01

    A morphological study of the neural pattern in the human ungual region of the pollical distal phalanx was carried out on eight male cadavers. The dissections showed a palmar neural arrangement consisting of four designated ungual nerves, two proximal and two distal, for each of the ulnar and radial palmar digital nerves at the lateral sides of the thumb. This neural configuration was associated with the compartmentalization of its ungual pulp, the difference between the type of sensory receptors within the ungual pulp, the overlapping of the tactile composition at the thumb tip, seen clinically after laceration of one of the palmar digital nerves, and the sensory supply to the nail bed in the dorsal portion of the thumb. The proximal ungual pulp compartment had a single proximal medial ungual nerve, which did not appear, as far as visually possible, to overlap at the midline of the proximal ungual pulp. In contrast, the distal ungual pulp compartment was supplied by a medial and a lateral ungual nerve, both of which did appear to overlap to their contralateral sides in the thumb tip. A single proximal dorsal sensory nerve branched dorsally from each of ulnar and radial palmar digital nerves at the level of the proximal ungual pulp to supply the nail bed on the dorsum of the thumb.

  7. Early Distal Axonopathy of the Visual Pathway in Experimental Diabetes

    PubMed Central

    Fernandez, Diego C.; Pasquini, Laura A.; Dorfman, Damián; Aldana Marcos, Hernán J.; Rosenstein, Ruth E.

    2012-01-01

    Diabetic retinopathy is a leading cause of acquired blindness. Visual function disorders have been observed in diabetic patients with very early retinopathy or even before the onset of retinopathy. The aim of the present work was to analyze the visual pathway in an early stage of experimental diabetes. Diabetes was induced in Wistar rats by an i.p. injection of streptozotocin. A deficit in anterograde transport from the retina to the superior colliculus was observed 6 weeks after streptozotocin injection. At this time point, morphologic studies did not reveal retinal ganglion cell loss or substantial alterations in the superior colliculus. The optic nerve was morphometrically evaluated at intraorbital (unmyelinated and myelinated) and intracranial sections. In animals that had been diabetic for 6 weeks, a large increase in astrocyte reactivity occurred in the distal (but not the intraorbital) portion, which coincided with significant axon loss. Moreover, profound myelin alterations and altered morphologic features of oligodendrocyte lineage were observed at the distal (but not the proximal) optic nerve portion. The present results suggest that axoglial alterations at the distal portion of the optic nerve could be the first structural change in the diabetic visual pathway. PMID:22079928

  8. Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite ornata

    SciTech Connect

    Chen, Zuxu; de Serrano, Vesna; Betts, Laurie; Franzen, Stefan

    2009-01-28

    The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has a globin fold but can function as both a hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states as it reversibly binds oxygen for storage. Here, it is reported that the distal histidine, His55, exhibits conformational flexibility in the deoxy form and is consequently observed in two solvent-exposed conformations more than 9.5 {angstrom} away from the heme. These conformations are analogous to the open conformation of sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and has an out-of-plane displacement of 0.25 {angstrom} from the heme plane. The observation of five-coordinate heme iron with His55 in a remote solvent-exposed conformation is consistent with the hypothesis that His55 interacts with heme iron ligands through hydrogen bonding in the closed conformation. Since His55 is also displaced by the binding of 4-iodophenol in an internal pocket, these results provide new insight into the correlation between heme iron ligation, molecular binding in the distal pocket and the conformation of the distal histidine in DHP.

  9. A novel, new robotic platform for natural orifice distal pancreatectomy.

    PubMed

    Thakkar, Shyam; Awad, Michael; Gurram, Krishna C; Tully, Steven; Wright, Cornell; Sanan, Siddharth; Choset, Howie

    2015-06-01

    Laparoendoscopic technology has revolutionized the practice of surgery; however, surgeons have not widely accepted laparoscopic techniques for pancreatic surgeries due to the complexity of the operation. Natural orifice transluminal endoscopic surgery (NOTES) offers a great new potential for pancreatic procedures, with early data showing benefits of reduced visible scarring and the potential for decreased wound infections, hernias, pain, and postoperative complications. However, there are significant limitations to the currently used flexible endoscopy tools, including a diminished visual field, spatial orientation and tissue manipulation issues, and 2-dimensional visual feedback. We have adopted a novel snake-like robot, the minimally invasive cardiac surgery (MICS) robot, which addresses these issues. In the current pilot study, the MICS robot was evaluated for transrectal distal pancreas exploration and resection in 2 nonsurvival porcine models. Abdominal navigation and accessing the pancreas was investigated in the first pig, and based on its success, pancreas resection was studied in pig 2. The MICS robot was successful in accessing and visualizing the right upper, left upper, and left lower quadrants of the abdomen in pig 1 and was able to perform a successful complex NOTES procedure with distal pancreas resection in pig 2, with only minimal laparoscopic retraction assistance. In conclusion, preliminary results showing the MICS robot in natural orifice distal pancreatectomy are positive. Enhancements to optics and instrumentation will help further increase the usability in pancreatic interventions. Future indications may include transgastric NOTES approaches, endoluminal procedures, and single-port applications.

  10. Corrective Osteotomy for Intra-Articular Distal Humerus Malunion

    PubMed Central

    Kinaci, Ahmet; Buijze, Geert A.; Leeuwen, Diederik H.van; Jupiter, Jesse B.; Marti, Rene K.; Kloen, Peter

    2016-01-01

    Background: An intra-articular distal humerus malunion can be disabling. To improve function, reduce pain and/or prevent further secondary osteoarthritis an intra-articular corrective osteotomy can be considered. Herein we present the indications, practical guidelines for pre- operative planning and surgical technique. Subsequently, we provide long-term results in a small series. Methods: We included six consecutive patients operated for intra-articular distal humerus malunion. Mean follow-up was 88 months. At lastest follow up elbow function was assessed according to standardized questionnaires and classification systems. Results: All six patients healed their osteotomies. Three patients had a postoperative complication which were treated succesfully. Range of motion improved significantly and all patients were satisfied with the outcome. The elbow performance scores were good to excellent in all. Correlation analyses showed that age and level of osteoarthritis are very strong predictors for the long-term elbow function and quality of life. Conclusion: An intra-articular corrective osteotomy for a malunited distal humerus fracture is a worthwhile procedure. Based on our results it should particularly be considered in young patients with minimal osteoarthritis and moderate to severe functional disability and/or pain. PMID:27200396

  11. Distal Radius Attachments of the Radiocarpal Ligaments: An Anatomical Study

    PubMed Central

    Zumstein, M. A.; Hasan, A. P.; McGuire, D. T.; Eng, Kevin; Bain, Gregory Ian

    2013-01-01

    Background Understanding the anatomy of the ligaments of the distal radius aids in the surgical repair of ligamentous injuries and the prediction of intraarticular fracture patterns. Purposes (1) to measure the horizontal and vertical distances of the origins of the radiocarpal ligaments from the most ulnar corner of the sigmoid notch and the joint line, respectively; and (2) to express them as a percentile of the total width of the bony distal radius. Methods We dissected 8 cadaveric specimens and identified the dorsal radiocarpal, radioscaphocapitate, and the long and short radiolunate ligaments. Results The dorsal radiocarpal ligament attached from the 16th to the 52nd percentile of the radial width. The radioscaphocapitate ligament attached around the radial styloid from the 86th percentile volarly to the 87th percentile dorsally. The long radiolunate ligament attached from the 59th to the 85th percentile, and the short radiolunate ligament attached from the 14th to the 41st percentile. Discussion There was a positive correlation between the radial width and the horizontal distance of the ligaments from the sigmoid notch. These findings may aid individualized surgical repair or reconstruction adjusted to patient size and enable further standardized research on distal radial fractures and their relationship with radiocarpal ligaments. PMID:24436840

  12. Slipped Distal Femoral Epiphysis in Congenital Insensitivity to Pain

    PubMed Central

    Shaikh, M Javed; Rex, C; Vignesh, R; Chavan, Madhav

    2016-01-01

    Introduction: Congenital insensitivity to pain (CIP) is a rare disorder, and often presents to an orthopaedic surgeon as recurrent fractures, dislocations, pseudoarthrosis, osteomyelitis etc. Here, we report a case of congenital insensitivity to pain presenting with distal femoral physeal separation in a child. Case Report: A 12-year-old girl child came with complaints of limp while walking and swelling in the left knee for past 5 weeks. Mother gave a history that the girl is a known case of congenital insensitivity to pain with clear history of no pain on intramuscular injection since birth. She was born of consanguineous marriage and had no significant trauma, fever, other joint involvement or any features of rheumatism. On local examination, she had no bony tenderness, mild warmth, and moderate knee effusion with restricted range of movement. Plain radiograph showed epiphysiolysis of distal femur with widening of physis. Examination under anaesthesia demonstrated gross movement indicating lower femoral physeal separation. This unstable distal femoral epiphysis was treated under general anaesthesia with closed reduction, percutaneous cross pinning and above knee plaster cast. Conclusion: Congenital insensitivity to pain (CIP) is a rare disorder to diagnose. Emphasis is given on early diagnosis of orthopaedic problems and prompt treatment, educating parents and prevention of accidents. Physeal separation without significant trauma must prompt an orthopaedic surgeon to think about congenital insensitivity to pain as a differential diagnosis. PMID:27703943

  13. Complications of pediatric distal radius and forearm fractures.

    PubMed

    Chia, Benjamin; Kozin, Scott H; Herman, Martin J; Safier, Shannon; Abzug, Joshua M

    2015-01-01

    Distal radius and forearm fractures represent a large percentage of pediatric fractures. The most common mechanism of injury is a fall onto an outstretched arm, which can lead to substantial rotational displacement. If this rotational displacement is not adequately addressed, there will be resultant loss of forearm motion and subsequent limitations in performing the activities of daily living. Good initial reductions and proper casting techniques are necessary when treating distal radius and forearm fractures nonsurgically; however, maintaining an acceptable reduction is not always possible. Atraumatic reduction of a displaced physeal fracture should occur within 7 days of the injury. If an impending malunion presents at 2 weeks or later after injury, observation is warranted because of concerns about physeal arrest with repeated attempts at manipulation, and it should be followed by a later assessment of functional limitations. Pediatric patients and their parents have higher expectations for recovery, which has contributed to an increase in the surgical management of pediatric distal radius and forearm fractures. In addition, surgical interventions, such as intramedullary nailing, have their own associated complications.

  14. [Distal tibia peri-implant fracture with an intramedullary nail: a case report].

    PubMed

    Reyes-Cabrera, J M; González-Alconada, R; García-Mota, M D

    2013-01-01

    Peri-implant fractures of the distal tibia after intramedullary nailing are rare. We present a case of a fracture of the distal tibia at the site of the distal interlocking screw. We found two cases reported in the world literature. There are no cases reported in the Spanish literature.

  15. Avascular necrosis of the distal phalangeal epiphysis following physeal fracture: a case report.

    PubMed

    Nissenbaum, M

    1999-05-01

    Avascular necrosis of the distal phalangeal epiphysis following an unrecognized angulated Salter II fracture of the distal phalanx treated by open reduction and internal fixation resulted in premature closure of the growth plate and mild shortening. The epiphysis itself revascularized and good function of the distal interphalangeal joint was maintained.

  16. Successful Return to Sport Following Distal Femoral Varus Osteotomy

    PubMed Central

    Voleti, Pramod Babu; Degen, Ryan; Tetreault, Danielle; Krych, Aaron John; Williams, Riley J.

    2016-01-01

    Objectives: Distal femoral varus osteotomy is an effective treatment for unloading valgus knee malalignment; however, there is limited evidence on the ability for patients to return to athletics following this procedure. The purpose of this study is to report the functional outcomes and return to sport for athletic patients that underwent distal femoral varus osteotomy. Methods: A consecutive series of athletic patients that had undergone distal femoral varus osteotomy for symptomatic lateral compartment overload and valgus knee malalignment were prospectively reviewed. All patients had a minimum of 2-year follow-up. Radiographs were assessed to determine pre-operative and post-operative alignment. Details regarding sport of interest, ability to return to sport, and timing of return were obtained from the patients. Prospective institutional registries were utilized to collect pre-operative and post-operative Marx Activity Scale and International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) scores; these values were compared using paired t-tests with p < 0.05 as the threshold for significance. Results: A total of 13 patients with a mean age of 24 years (range: 17-35) and a mean follow-up of 43 months (range: 24-74) were included in the study. Six patients underwent medial closing wedge osteotomy, and seven patients underwent lateral opening wedge osteotomy. The mean alignment correction was 8 degrees (range: 5-13). Nine patients underwent one or more concomitant procedures at the time of the osteotomy: 6 lateral femoral condyle osteochondral allografts, 2 partial lateral meniscectomies, 1 lateral meniscus allograft transplantation, and 1 revision anterior cruciate ligament reconstruction. All patients were able to successfully return to their sport of choice (4 soccer, 2 softball, 2 running, 1 football, 1 basketball, 1 ice hockey, 1 volleyball, 1 rowing) at a mean of 11 months (range: 9-13). Furthermore, all 13 patients demonstrated an

  17. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors.

    PubMed Central

    Nakeeb, A; Pitt, H A; Sohn, T A; Coleman, J; Abrams, R A; Piantadosi, S; Hruban, R H; Lillemoe, K D; Yeo, C J; Cameron, J L

    1996-01-01

    OBJECTIVE: The objective of this article is to introduce a simple method for classifying cholangiocarcinomas and to apply this system to analyze a large number of patients from a single institution. SUMMARY BACKGROUND DATA: For the past 2 decades, most western reports on cholangiocarcinoma have separated intrahepatic from extrahepatic tumors and have subclassified this latter group into proximal, middle, and distal subgroups. However, "middle" lesions are uncommon and are managed most often either with hilar resection or with pancreatoduodenectomy. The spectrum of cholangiocarcinoma, therefore, is best classified into three broad groups: 1) intrahepatic, 2) perihilar, and 3) distal tumors. These categories correlate with anatomic distribution and imply preferred treatment. METHODS: The records of all patients with histologically confirmed cholangiocarcinoma who underwent surgical exploration at The Johns Hopkins Hospital over a 23-year period were reviewed. RESULTS: Of 294 patients with cholangiocarcinoma, 18 (6%) had intrahepatic, 196 (67%) had perihilar, and 80 (27%) had distal tumors. Age, gender, race, and associated diseases were similar among the three groups. Patients with intrahepatic tumors, by definition, were less likely (p < 0.01) to be jaundiced and more likely (p < 0.05) to present with abdominal pain. The resectability rate increased with a more distal location (50% vs. 56% vs. 91%), and resection improved survival at each site. Five-year survival rates for resected intrahepatic, perihilar, and distal tumors were 44%, 11%, and 28%, and median survival rates were 26, 19, and 22 months, respectively. Postoperative radiation therapy did not improve survival. In a multivariate analysis resection (p < 0.001. hazard ratio 2.80), negative microscopic margins (p < 0.01, hazard ratio 1.79), preoperative serum albumin (p < 0.04, hazard ratio 0.82), and postoperative sepsis (p < 0.001, hard ratio 0.27) were the best predictors of outcome. CONCLUSIONS

  18. A 2D model of axial symmetry for proximal tubule of an average human nephron: indicative results of diffusion, convection and absorption processes

    NASA Astrophysics Data System (ADS)

    Insfrán, J. F.; Ubal, S.; Di Paolo, y. J.

    2016-04-01

    A simplified model of a proximal convoluted tubule of an average human nephron is presented. The model considers the 2D axisymmetric flow of the luminal solution exchanging matter with the tubule walls and the peritubular fluid by means of 0D models for the epithelial cells. The tubule radius is considered to vary along the conduit due to the trans-epithelial pressure difference. The fate of more than ten typical solutes is tracked down by the model. The Navier-Stokes and Reaction-Diffusion-Advection equations (considering the electro-neutrality principle) are solved in the lumen, giving a detailed picture of the velocity, pressure and concentration fields, along with trans-membrane fluxes and tubule deformation, via coupling with the 0D model for the tubule wall. The calculations are carried out numerically by means of the finite element method. The results obtained show good agreement with those published by other authors using models that ignore the diffusive transport and disregard a detailed calculation of velocity, pressure and concentrations. This work should be seen as a first approach towards the development of a more comprehensive model of the filtration process taking place in the kidneys, which ultimately helps in devising a device that can mimic/complement the renal function.

  19. Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.

    PubMed

    Lloyd, Louise J; Foster, Thomas; Rhodes, Phillip; Rhind, Stewart M; Gardner, David S

    2012-01-15

    A nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

  20. Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease

    PubMed Central

    2014-01-01

    Background Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. Result We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman’s space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Conclusion Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron. PMID:25030234

  1. Comparison of dual protection and distal filter protection as a distal embolic protection method during carotid artery stenting: a single-center carotid artery stenting experience.

    PubMed

    Kajihara, Yosuke; Sakamoto, Shigeyuki; Kiura, Yoshihiro; Mukada, Kazutoshi; Chaki, Takahiro; Kajihara, Shiro; Kurisu, Kaoru

    2015-10-01

    There are several protection methods used to prevent distal embolism during carotid artery stenting (CAS). The aim of this study was to compare the dual protection method (proximal balloon and distal filter protection) with the distal filter protection during CAS performed at a single center. Between April 2008 and November 2013, 78 consecutive patients with internal carotid artery stenosis were treated with CAS at Istukaichi Memorial Hospital. Twenty-four consecutive patients were treated with CAS using distal filter protection (distal filter protection group), and 54 consecutive patients were treated with CAS using dual protection with a proximal balloon and distal filter protection (dual protection group). We examined the hyperintensity lesions on diffusion-weighted imaging (DWI) and perioperative complications after CAS. All stenotic lesions were successfully dilated. DWI showed hyperintensity lesions among 54.2 % (13/24 patients) in the distal filter protection group and in 27.8 % (15/54 patients) in the dual protection group (p = 0.024). The average number of hyperintensity lesions on DWI was 1.75 (range, 0 to 6) in the distal filter protection group and 0.59 (range, 0 to 5) in the dual protection group (p = 0.0087). Postprocedural persistent ischemic complications occurred in 4.2 % (1/24 patients) in the distal filter protection group and 3.7 % (2/54 patients) in the dual protection group (p = 0.67). In this study, the dual protection method reduced the number of hyperintensity lesions seen on DWI when compared with the distal filter protection method when used for distal embolic protection during CAS.

  2. Enchondroma in the distal phalanx of the finger

    PubMed Central

    Lu, Hui; Chen, Qiang; Yang, Hu; Shen, Hui

    2016-01-01

    Abstract The goal of our study was to report the clinical presentation, treatment, and complications of enchondroma in the distal phalanx of the finger. This was a retrospective study of 34 patients (19 women and 15 men) who underwent surgery between May 2004 and September 2012 for enchondroma in the distal phalanx of the finger. The average age of the patients was 39.38 ± 10.97 years old (range 14–59). The presenting symptoms and imaging features were recorded. The surgical procedure was performed under regional or general anesthesia. The surgical technique involved removal of tumors by opening a cortical window and curetting the cavity. The defects were filled with an injectable calcium phosphate cement. All patients received follow-up in our outpatient clinic every 6 months. Expansion of bone or thinning of the cortex present in the radiological imaging, including anteroposterior and lateral plain radiographs of the fingers, was used to assess for tumor recurrence. The observational end-point was reoperation. All tumors were confirmed as enchondromas by the pathological results. None of the patients had a tumor recurrence. Three patients (9% of cases) developed an infection. After antibiotic treatment, 2 patients were cured, and 1 patient required an amputation. Enchondroma in the distal phalanx of the finger presents with a variety of clinical symptoms. Injectable calcium phosphate cement is adequate for bone grafting. Postoperative infection is more common than tumor recurrence. If patients have an infection or bilateral bone cortex defects, bone grafting is challenging. Level of Evidence: Therapeutic study, Level IV PMID:27661057

  3. Temporary bridging external fixation in distal tibial fracture.

    PubMed

    Lavini, F; Dall'Oca, C; Mezzari, S; Maluta, T; Luminari, E; Perusi, F; Vecchini, E; Magnan, B

    2014-12-01

    Fractures that involve the distal area of the tibia are associated with a high percentage of complications. Soft tissue oedema, swelling, blisters, skin abrasions and open wounds could compromise the outcome of these lesions. The waiting time before surgery with ORIF is mostly due to soft tissue conditions. Early application of a simple joint-spanning external fixator would achieve the initial goal of stability and the respect of soft tissue, thereby decreasing the time necessary for definitive treatment. A total of 40 consecutive patients (22 male and 18 female) with a mean age of 52 years (range 17-82 years) with distal tibial fracture treated between January 2010 and January 2013 were evaluated. Early temporary external fixation was the first treatment step. Twenty patients had pilon fractures, characterised by the intra-articular involvement of the distal tibia with metaphyseal extension, and 20 patients had malleolar fracture-dislocation. Patients were divided into two groups, A and B. Group A comprised 10 patients with ankle fracture-dislocation and bone fragmentation, who were treated with a temporary bridging external fixation that was maintained after ORIF to exploit ligamentotaxis during the first phases of bone healing. In Group B (30 patients), the external fixation was removed after ORIF. The results of the study are in line with the recent literature: temporary external fixation in high-energy trauma and fracture-dislocation of the ankle enables soft tissue to be restored, which facilitates postoperative assessment of bone fragments by CT scan. The complication rate in this study was 5% in patients with malleolar fractures and 20% in patients with pilon fractures. The maintenance of temporary external fixation after ORIF synthesis during the entire first stage of bone healing seems to be a good method of treatment that has a low rate of soft tissue complications.

  4. Octreotide acetate inhibits motility in the rabbit distal colon.

    PubMed

    John, K D; Ballantyne, G H; Modlin, I M

    1997-01-01

    Octreotide, the long-acting somatostatin analogue, has been reported to modulate gastrointestinal motility in both animals and humans. A role in colonic peristalsis and a possible clinical application in common disorders, such as chronic constipation and irritable bowel syndrome, have not been evaluated. It has been previously suggested that octreotide promotes the descending relaxation of the peristaltic reflex arc. We hypothesized that this effect may involve inhibition of the motility index (MI) of the distal colon. To test this proposal, we studied peristalsis in isolated rabbit colons and also in the intact distal colons of anesthetized rabbits undergoing octreotide administration. Left colons of New Zealand white rabbits were harvested, placed in an isolated organ chamber and perfused with Krebs-Ringer bicarbonate solution via the inferior mesenteric artery. In a separate preparation, the colons were left in situ. Motility was quantified with a 6-port continuous infusion manometry catheter. The MI (mm Hg/min) was calculated by integration of the area of the digitalized signal (8/s), which reflected high-pressure peaks of different magnitudes. High-pressure waves were defined as > 20 mm Hg. Octreotide was infused via the inferior mesenteric artery in the isolated specimen or the lateral ear vein in the anesthetized animals in concentrations of 10(-12) to 10(-6) M. Octreotide inhibited high-pressure waves in a dose-dependent manner. These effects resulted in a decreased MI, with the maximum inhibition of 24.6% at 10(-11) M (p < 0.05 by ANOVA). At that concentration, the number of peaks > 20 mm Hg were reduced by 62.2%. The data indicate that octreotide decreases the MI by inhibition of high-pressure waves in the distal rabbit colon. These findings are consistent with the proposal that somatostatin may augment descending relaxation of the peristaltic reflex arc. This effect is independent of neural modulation.

  5. Stabilisation of distal radius fractures: Lessons learned and future directions.

    PubMed

    Horst, Taylor A; Jupiter, Jesse B

    2016-02-01

    Our understanding of the diagnosis and management of distal radius fractures has been a long developed over centuries. There has been a shift in treatment of these very common injuries from closed reduction and casting to internal fixation. The answer to the best method of treatment has yet to be found. Today, we have a multitude of treatment options available with varying degrees of evidence to support their use. This review helps to illustrate the lessons we have learned and future directions for treatment.

  6. [Postoperative Osteomyelitis of a Distal Phalanx Caused by Raoultella ornithinolytica].

    PubMed

    Schmutz, N; Adler, T; Schelhorn, N; Wirz, S; Fricker, R

    2016-06-01

    We report on a case of osteomyelitis of a distal phalanx of the right ring finger of a 62-year-old patient, which occurred 11 months after transosseous-transungual refixation of a closed flexor digitorum profundus tendon avulsion caused by Raoultella ornithinolytica. R. ornithinolytica is an encapsulated Gram-negative aerobic bacillus. In the literature only 13 cases of human infection by R. ornithinolytica are mentioned. To the best of our knowledge, this is the first case of an osteomyelitis caused by R. ornithinolytica.

  7. Renal histology and immunopathology in distal renal tubular acidosis.

    PubMed

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  8. Primary Epiphyseal Aneurysmal Bone Cyst Of Distal Ulna

    PubMed Central

    Kapila, Rajesh; Sharma, Rakesh; Sohal, Yadwinder Singh; Singh, Dhalwinder; Singh, Sukhpal

    2015-01-01

    Introduction: Aneurysmal Bone Cyst (ABC) is a benign expansile cystic blood filled reactive lesion of the bone, most common in the first 2 decades of life. Though it can involve any bone in the body but tibia, humerus, femur and posterior elements of spine are most commonly affected. They most commonly involve metaphysis or metaphysio-diaphyseal part of the bone. Primary involvement of epiphysis is rarely reported. Here we present a case of 6 year old male child with an epiphyseal ABC of distal ulna. Its diagnosis, surgical management, clinical outcome with review of literature is discussed. PMID:27299110

  9. Measurement of ulnar variance and radial inclination on X-rays of healed distal radius fractures. With the axis of the distal radius or ulna?

    PubMed

    Thuysbaert, Gilles; Ringburg, Akkie; Petronilia, Steven; Vanden Berghe, Alex; Hollevoet, Nadine

    2015-06-01

    Ulnar variance and radial inclination are radiological parameters frequently used to evaluate displacement of distal radius fractures. In most studies measurements are based on the long central axis of the distal radius, although the axis of the distal ulna can also be used. The purpose of this study was to determine which axis is more reliable. Four observers performed measurements on standard anteroposterior digital wrist X-rays of 20 patients taken 1 and 2 months after sustaining an extra-articular distal radius fracture. Intraobserver reliability was similar with both methods. No difference was found in interobserver reliability between both methods for ulnar variance, but for radial inclination it was better with the axis through the radius. Measurements on two X-rays of the same wrist taken at a different moment were similar with both methods. It can be concluded that the central axis of the distal radius can remain the basis to determine ulnar variance and radial inclination.

  10. The distally based forearm island flap in hand reconstruction.

    PubMed

    Jeng, S F; Wei, F C

    1998-08-01

    The distally based forearm island flap is vascularized by the perforators of the distal radial artery. The skin flap is along the axis of the radial artery, and the pivot point of its subcutaneous pedicle is about 2 to 4 cm above the radial styloid process. We have treated 12 patients with 12 flaps for soft-tissue defects of the hand. Of these recipient sites, seven were in dorsal hands, two were in thumbs, two were in forearms, and one was in the palmar area. The donor-tissue variants included eight skin flaps, two adipofascial flaps, and two sensate flaps. The sizes of the flaps ranged from 6 x 4 cm to 14 x 6 cm. The donor site wound could be closed primarily in five patients. Two sensate flaps, innervated by the lateral antebrachial cutaneous nerve, could provide sensation for thumb reconstruction. The advantage of this flap is its constant and reliable blood supply without sacrifice of the main radial artery. The elevation of the flap is simple and rapid. There is the potential that this flap can be used as an innervated flap, and there is no need of microsurgical technique.

  11. Interactions between distal speech rate, linguistic knowledge, and speech environment.

    PubMed

    Morrill, Tuuli; Baese-Berk, Melissa; Heffner, Christopher; Dilley, Laura

    2015-10-01

    During lexical access, listeners use both signal-based and knowledge-based cues, and information from the linguistic context can affect the perception of acoustic speech information. Recent findings suggest that the various cues used in lexical access are implemented with flexibility and may be affected by information from the larger speech context. We conducted 2 experiments to examine effects of a signal-based cue (distal speech rate) and a knowledge-based cue (linguistic structure) on lexical perception. In Experiment 1, we manipulated distal speech rate in utterances where an acoustically ambiguous critical word was either obligatory for the utterance to be syntactically well formed (e.g., Conner knew that bread and butter (are) both in the pantry) or optional (e.g., Don must see the harbor (or) boats). In Experiment 2, we examined identical target utterances as in Experiment 1 but changed the distribution of linguistic structures in the fillers. The results of the 2 experiments demonstrate that speech rate and linguistic knowledge about critical word obligatoriness can both influence speech perception. In addition, it is possible to alter the strength of a signal-based cue by changing information in the speech environment. These results provide support for models of word segmentation that include flexible weighting of signal-based and knowledge-based cues.

  12. Functional and mechanistic diversity of distal transcription enhancers

    PubMed Central

    Bulger, Michael; Groudine, Mark

    2013-01-01

    Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

  13. Distal coronary artery perfusion during percutaneous transluminal coronary angioplasty.

    PubMed

    Anderson, H V; Leimgruber, P P; Roubin, G S; Nelson, D L; Gruentzig, A R

    1985-10-01

    Perfusion of the coronary artery distal to an occluding angioplasty balloon was performed in 34 patients undergoing coronary angioplasty (PTCA). A randomized crossover study was employed using two exogenous substances as perfusates: lactated Ringer's solution (LR) and a fluorocarbon emulsion (FL), Fluosol-DA 20%. Both substances are electrolyte solutions, but the FL will dissolve more oxygen than the LR. During two attempted coronary artery occlusions of 90 seconds each, we perfused through the central lumen (guidewire channel) of the PTCA catheter at 60 ml/min. With FL perfusion the mean time to onset of angina after occlusion was delayed (41 +/- 21 vs 33 +/- 16 seconds, mean +/- SD; p less than 0.05), the mean duration of angina was shortened (77 +/- 58 vs 92 +/- 70 seconds, p less than 0.05), and the rise in the ST segment of the ECG was reduced (0.15 +/- 0.24 vs 0.2 +/- 0.23 mV, p less than 0.001) when compared to LR perfusion. Balloon occlusion time was able to be extended with FL perfusion (71 +/- 22 vs 59 +/- 22 seconds p less than 0.001). These results indicate that perfusion of the distal coronary artery is possible during PTCA and can reduce ischemia during a prolonged balloon occlusion time. PMID:2931968

  14. Florid reactive periostitis ossificans of the distal ulna.

    PubMed

    Porcel López, M T; Fernández Gil, M A; Campos de Orellana, A; Quiles Galindo, M

    2008-03-01

    Florid reactive periostitis is the term used to describe a benign disease characterized by aggressive periosteal reaction and benign soft-tissue inflammation. Although it is considered rare, there are numerous reports in the literature that refer to this disease with different names such as parosteal fasciitis, fasciitis ossificans, benign fibro-osseous pseudotumor, pseudomalignant osseous tumor of soft tissue, and bizarre parosteal osteochondromatous proliferation. As a result, the nomenclature is confusing, and some authors have placed florid reactive periostitis ossificans into the heterogeneous group of pseudomalignant osseous tumors of soft tissue or proliferative periosteal processes, whereas other authors place this entity in the myositis ossificans group. In the same manner, florid reactive periostitis has been considered to be a previous stage of bizarre parosteal osteochondromatous proliferations. This article presents a case of florid reactive periostitis ossificans of the distal ulna in a 13-year-old boy. The patient presented with a painful lesion in the distal ulna, and plain radiographs suggested the presence of a quickly growing periosteal lesion with associated calcification and soft tissue mass. Histologically, the appearance was that of reactive periostitis. The clinical, radiological, and histologic features of florid reactive periostitis are described.

  15. Tarui disease and distal glycogenoses: clinical and genetic update.

    PubMed

    Toscano, A; Musumeci, O

    2007-10-01

    Phosphofructokinase deficiency (Tarui disease) was the first disorder recognized to directly affect glycolysis. Since the discovery of the disease, in 1965, a wide range of biochemical, physiological and molecular studies have greatly contributed to our knowledge concerning not only phosphofructokinase function in normal muscle but also on the general control of glycolysis and glycogen metabolism. Studies on phosphofructokinase deficiency vastly enriched the field of glycogen storage diseases, making a relevant improvement also in the molecular genetic area. So far, more than one hundred patients have been described with prominent clinical symptoms characterized by muscle cramps, exercise intolerance, rhabdomyolysis and myoglobinuria, often associated with haemolytic anaemia and hyperuricaemia. The muscle phosphofructokinase gene is located on chromosome 12 and about 20 mutations have been described. Other glycogenoses have been recognised in the distal part of the glycolytic pathway: these are infrequent but some may induce muscle cramps, exercise intolerance and rhabdomyolysis. Phosphoglycerate Kinase, Phosphoglycerate Mutase, Lactate Dehydrogenase, beta-Enolase and Aldolase A deficiencies have been described as distal glycogenoses. From the molecular point of view, the majority of these enzyme deficiencies are sustained by "private" mutations. PMID:18421897

  16. Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

    PubMed Central

    Minuth, Will W.; Denk, Lucia

    2016-01-01

    Abstract Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way. PMID:26862472

  17. Parallel down-regulation of chloride channel CLC-K1 and barttin mRNA in the thin ascending limb of the rat nephron by furosemide.

    PubMed

    Wolf, Konrad; Meier-Meitinger, Martina; Bergler, Tobias; Castrop, Hayo; Vitzthum, Helga; Riegger, Günter A J; Kurtz, Armin; Krämer, Bernhard K

    2003-09-01

    In the past few years the pivotal role of kidney Cl(-)channels (ClC-K) channels in maintaining salt and water homeostasis in the kidney has been established. The aim of the present study was to investigate the influence of the loop diuretic furosemide on the gene expression of the kidney chloride channel ClC-K1 and its recently described functional subunit barttin. Male Sprague Dawley rats received the loop diuretic furosemide (12 mg/kg/day) for 6 days. Rats had free access to 0.9% NaCl, 0.1%KCl solution to prevent volume depletion. Localisation and regulation of ClC-K1 and barttin mRNA was analysed by RNase protection and in situ hybridisation. Nephron-specific regulation was investigated by microdissection and real-time PCR quantification. In furosemide-treated rats ClC-K1 mRNA decreased to half in the inner medulla. In the renal cortex and outer medulla ClC-K1 mRNA levels were weak and did not change. Under furosemide treatment barttin mRNA was regulated in parallel with ClC-K1 mRNA. A significant mRNA decrease occurred after furosemide treatment in inner medulla (0.50 fold), whereas cortical and outer medulla levels remained unaffected. (35)S in situ hybridisation confirmed the regulation and distribution seen in the RNase protection assay experiments. Microdissection of the inner medullary collecting duct and thin limb of Henle's loop followed by real-time PCR revealed that CLC-K1 and barttin mRNA regulation in inner medulla was limited to the thin limb; mRNA levels in collecting ducts were not affected by furosemide treatment. Our findings imply that during furosemide treatment selective down-regulation of ClC-K1 and barttin mRNAs in thin limb plays a role in maintaining salt and water homeostasis. PMID:12759757

  18. Comparison of inhibitory potency by nonpeptide angiotensin II receptor antagonists PD123177 and DuP 753 on proximal nephron and renal transport.

    PubMed

    Cogan, M G; Liu, F Y; Wong, P C; Timmermans, P B

    1991-11-01

    The nonpeptide angiotensin II receptor antagonists, DuP 753 and PD123177, have been recently proposed to efficiently discriminate between two receptor subtypes. Because angiotensin II uses two signaling systems to control transport in the proximal tubule, the hypothesis was entertained that angiotensin-regulated proximal reabsorption might be transduced through two receptor subtypes and, therefore, have two components, sensitive to either DuP 753 or PD123177. Using in vivo microperfusion in the rat, a maximally effective dose of PD123177 (60 or 120 mg/kg, i.v.) had a powerful inhibitory effect on transport in the S1 proximal tubule, significantly (P less than .001) reducing bicarbonate absorption by 50% (360 +/- 4 to 179 +/- 8 peq/mm.min), chloride absorption by 38% (211 +/- 1 to 131 +/- 4 peq/mm.min) and sodium and water absorption by 32% (5.7 +/- 0.1 to 3.9 +/- 0.5 nl/mm.min). These results were only slightly different than previously reported effects on proximal solute and water absorption by DuP 753 (10 mg/kg). The two drugs demonstrated virtually no additivity in their transport inhibitory effects. Although downstream reabsorptive elements compensate for the powerful action of PD123177 in the earliest segment of the nephron, we also showed, using free-flow micropuncture and clearance techniques, that PD123177 induces a substantial diuresis, natriuresis and chloruresis, again similar in magnitude to DuP 753. These results suggest PD123177 has diuretic potency roughly equivalent to that of DuP 753, but do not lend support to the simple thesis that there are two separately acting receptor-signal transduction systems in the proximal tubule for angiotensin II.

  19. Involvement of dachshund and Distal-less in distal pattern formation of the cricket leg during regeneration

    PubMed Central

    Ishimaru, Yoshiyasu; Nakamura, Taro; Bando, Tetsuya; Matsuoka, Yuji; Ohuchi, Hideyo; Noji, Sumihare; Mito, Taro

    2015-01-01

    Cricket nymphs have the remarkable ability to regenerate a functional leg following amputation, indicating that the regenerating blastemal cells contain information for leg morphology. However, the molecular mechanisms that underlie regeneration of leg patterns remain poorly understood. Here, we analyzed phenotypes of the tibia and tarsus (three tarsomeres) obtained by knockdown with regeneration-dependent RNA interference (rdRNAi) against Gryllus dachshund (Gb'dac) and Distal-less (Gb'Dll). We found that depletion of Gb'Dll mRNA results in loss of the tarsal segments, while rdRNAi against Gb'dac shortens the tibia at the two most distal tarsomeres. These results indicate that Gb'Dll expression is indispensable for formation of the tarsus, while Gb'dac expression is necessary for elongation of the tibia and formation of the most proximal tarsomere. These findings demonstrate that mutual transcriptional regulation between the two is indispensable for formation of the tarsomeres, whereas Gb'dac is involved in determination of tibial size through interaction with Gb'ds/Gb'ft. PMID:25669615

  20. [Differential treatment of fractures of the distal radius].

    PubMed

    Oestern, H J; Hüls, E

    1994-01-01

    Treatment of distal fractures of the radius has undergone considerable change during recent years. The cause for this lies primarily in the poor results of conservative treatments. In addition to osseous instability, the fractures of the radius are frequently combined with ligamentary instability as well, thereby exceeding the ability of conservative treatment. Among the many classifications, the AO classification of these fractures has proven to be the best and most widely accepted. This classification allows the recommendation of suitable procedures of treatment. The problem with inadequately healed fractures of the radius lies in the inherent unphysiological loading of the joint in the characteristic dorsal tilted position. This leads to a pathological displacement of the radius of flexion and extension and thereby to an overloading of the dorsal joint cartilage. The shortening of the radius leads to a mechanical impingement of the triangular fibrocartilagenous complex. The Kirschner wire fixation is particularly indicated in type A and type C fractures when combined with an external fixator. Of great importance here is the crossing of the K-wires, best accomplished by inserting an additional wire in a proximal to distal direction to achieve maximal mechanical stability. Biodegradable fixation devices are not yet in widespread use, as high costs and possible foreign body reactions have prevented their acceptance. The plate osteosynthesis has its domain in the treatment of volar luxation fractures (B3) and the partially articular fractures of the radius (B2). The domain of the external fixator, on the other hand, lies in the C2 and C3 fractures in combination with the K-wire osteosynthesis. Changing the mode of treatment to a plate osteosynthesis after two to three weeks allows a functional postoperative treatment. By use of a differentiated treatment regimen, the complication rate can be significantly reduced whose cause frequently lies in repeatedly attempted

  1. [Treatment of distal ureteral calculi with extracorporeal shockwave lithotripsy: experiences with 310 cases].

    PubMed

    Zehntner, C; Lux, O; Casanova, G A; Marth, D; Zingg, E J

    1989-07-01

    Distal ureteral calculi are approached by ureterorenoscopy by most authors. With increasing experience ESWL of distal ureteral calculi gained in importance. The success rate of 96.2% in a large series of 310 consecutive patients treated in this manner, confirmed the results of other authors. Excluding women of child-bearing age and very large calculi (greater than 2 cm) the ESWL is a suitable treatment modality of distal ureteral calculi.

  2. Total distalization of the maxillary arch in a patient with skeletal Class II malocclusion.

    PubMed

    Choi, Yoon Jeong; Lee, Jong-Suk; Cha, Jung-Yul; Park, Young-Chel

    2011-06-01

    In nongrowing patients with skeletal Class II malocclusion, premolar extraction or maxillary molar distalization can be used as camouflage treatment. Orthodontic miniscrew implants are widely used for this purpose because they do not produce undesirable reciprocal effects and do not depend on the patient's cooperation. This article reports on maxillary molar distalization by using miniscrew implants to correct a Class II problem. The main considerations of molar distalization treatment with miniscrew implants are discussed. PMID:21640890

  3. Rupture of Flexor Pollicis Longus Tendon: A Complication of Volar Locking Plating of the Distal Radius.

    PubMed

    Rajeev, Aysha Sethunathan; Sreverthana, Shanaka; Harrison, John

    2010-08-01

    We report an unusual case of complete rupture of the flexor pollicis longus tendon following volar locking plating for a distal radius fracture. We believe that the prominence of a distal locking screw head predisposed to the rupture of the tendon. We highlight that correctly attaching the distal locking screws to the plate is essential for obtaining the correct biomechanics of the device and preventing flexor tendon rupture.

  4. Brodie's abscess of the distal radius: an unusual complication after percutaneous pinning.

    PubMed

    Johnson, Jeff W; Bindra, Randip R

    2008-12-01

    We report a case of Brodie's abscess of the distal radius that presented 4 years after closed reduction and percutaneous pinning for a closed distal radius fracture. This condition has not been previously reported in the adult distal radius and we detail the clinical features and imaging findings. We also present a new way of management of Brodie's abscess using injectable bone substitute along with adjunctive parenteral antibiotic therapy.

  5. Brodie’s Abscess of the Distal Radius: An Unusual Complication after Percutaneous Pinning

    PubMed Central

    Bindra, Randip R.

    2008-01-01

    We report a case of Brodie’s abscess of the distal radius that presented 4 years after closed reduction and percutaneous pinning for a closed distal radius fracture. This condition has not been previously reported in the adult distal radius and we detail the clinical features and imaging findings. We also present a new way of management of Brodie’s abscess using injectable bone substitute along with adjunctive parenteral antibiotic therapy. PMID:18780011

  6. Preventing distal voids during cementation of the femoral component in total hip arthroplasty.

    PubMed

    Berger, R A; Steel, M J; Schleiden, M; Rubash, H E

    1993-06-01

    Cement voids have been noted in close approximation to the unfilled hole in the distal end of the femoral prosthesis. These cement voids result from the displacement of cement by the expansion of air trapped in the distal prosthesis. Voids in the distal cement have been shown to lead to an increased incidence of cement failures. This potentially deleterious situation can easily be avoided by plugging the hole in the distal stem. This may be accomplished three ways: using a centralizer, using the plastic plug supplied with the prosthesis, or filling the hole with cement prior to implanting the prosthesis. PMID:8326315

  7. Morphometric variation in Plio-Pleistocene hominid distal humeri.

    PubMed

    Lague, M R; Jungers, W L

    1996-11-01

    The magnitude and meaning of morphological variation among Plio-Pleistocene hominid distal humeri have been recurrent points of disagreement among paleoanthropologists. Some researchers have found noteworthy differences among fossil humeri that they believe merit taxonomic separation, while others question the possibility of accurately sorting these fossils into different species and/or functional groups. Size and shape differences among fossil distal humeri are evaluated here to determine whether the magnitude and patterns of these differences can be observed within large-bodied, living hominoids. Specimens analyzed in this study have been assigned to various taxa (Australopithecus afarensis, A. africanus, A. anamensis, Paranthropus, and early Homo) and include AL 288-1m, AL 288-1s, AL 137-48a, AL 322-1, Gomboré IB 7594, TM 1517, KNM-ER 739, KNM-ER 1504, KMN-KP 271 (Kanapoi), and Stw 431. Five extant hominoid populations are sampled to provide a standard by which to consider differences found between the fossils, including two modern human groups (Native American and African American), one group of Pan troglodytes, and two subspecies of Gorilla gorilla (G.g. beringei, G.g. gorilla). All possible pairwise d values (average Euclidena distances) are calculated within each of the reference populations using an exact randomization procedure. This is done using both raw linear measurements as well as scale-free shape data created as ratios of each measurement to the geometric mean. Differences between each pair of fossil humeri are evaluated by comparing their d values to the distribution of d values found within each of the reference populations. Principal coordinate analysis and an unweighted pair group method with arithmetic averages (UPGMA) cluster analysis are utilized to further assess similarities and differences among the fossils. Finally, canonical variates analysis and discriminant analysis are employed using all hominoid samples in order to control for

  8. Distal ventriculoperitoneal shunt failure caused by silicone allergy. Case report.

    PubMed

    Hussain, Namath S; Wang, Paul P; James, Carol; Carson, Benjamin S; Avellino, Anthony M

    2005-03-01

    The placement of a ventriculoperitoneal (VP) shunt is the most common form of treatment for hydrocephalus. Although allergic reactions to the silicone in shunt hardware are very rare, the authors describe a case of silicone allergy causing multiple ventricular shunt revisions. A 24-year-old man, who had undergone multiple VP shunt revisions, presented with shunt malfunction caused by allergic reaction of the tissues surrounding the shunt tubing. The patient's existing silicone-based shunt was replaced with a new polyurethane system, including the proximal and distal catheters as well as the valve mechanism. Contrary to recommendations in previous studies of silicone shunt allergies, long-term immunosuppression was not initiated. The patient was followed up for more than 8 years without recurrence of an allergic reaction to the shunt. This outcome indicates that replacing the original silicone-based shunt system with a polyurethane-based system alone is sufficient in the treatment of a silicone shunt allergy.

  9. Sphincter-saving procedures for distal carcinoma of the rectum.

    PubMed Central

    Yeatman, T J; Bland, K I

    1989-01-01

    Methods of sphincter preservation were developed more than a century ago. Combining these techniques with adequate anterior resection has permitted the resurrection of sphincter-saving procedures that are currently being applied in the therapy of cancer at every level of the rectum. Although Miles' abdominoperineal resection still remains the "gold standard" for the treatment of low rectal neoplasms, restorative resection may now be possible with equivalent oncologic disease control and survival. Further, current trends also suggest that the abdominoperineal resection is being used less frequently in the treatment of most rectal cancers and is being replaced with sphincter-preserving techniques that afford excellent functional results. In this review, the pertinent anorectal anatomy, current issues, and sphincter-saving surgical techniques presently available for the treatment of distal cancers of the rectum are presented. PMID:2642688

  10. Laing distal myopathy pathologically resembling inclusion body myositis

    PubMed Central

    Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig; Mammen, Andrew L; Corse, Andrea M; Lloyd, Thomas E

    2014-01-01

    Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a family with a previously reported deletion (c.5186_5188delAGA, p.K1729del). Muscle pathology in one family member was characterized by an inflammatory myopathy with rimmed vacuoles, increased MHC Class I expression, and perivascular and endomysial muscle inflammation comprising CD3+, CD4+, CD8+, and CD68+ inflammatory cells. Interestingly, this biopsy specimen contained TDP-43, p62, and SMI-31-positive protein aggregates typical of inclusion body myositis. These findings should alert physicians to the possibility that patients with MYH7 mutations may have muscle biopsies showing pathologic findings similar to inclusion body myositis. PMID:25574480

  11. Cutaneous Mycobacterium chelonae infection distal to the arteriovenous fistula

    PubMed Central

    Van Ende, Charlotte; Wilmes, Dunja; Lecouvet, Frédéric E.; Labriola, Laura; Cuvelier, René; Van Ingelgem, Grégory; Jadoul, Michel

    2016-01-01

    A few single cases of Mycobacterium chelonae skin infection have been reported in haemodialysis patients. We report three additional cases that share peculiar clinical characteristics, pointing to diagnostic clues. All three cases presented as erythematous nodules developing distally to a proximal arteriovenous fistula (AVF). This presentation was identical to that of two published cases. A survey of all Belgian haemodialysis units during the period 2007–11 yields an estimated incidence of ∼0.9/10 000 patient-years. Although the source of M. chelonae remains unclear, this specific clinical presentation should be added to the listing of potential complications of an AVF and should be recognized, as it is fully treatable if diagnosed by culture and tissue biopsy. PMID:27679721

  12. [Splanchnic circulation after distal splenorenal anastomosis in hepatic cirrhosis].

    PubMed

    Shalimov, A A; Kalita, N Ia; Kotenko, O G; Andreeshchev, S A

    1999-01-01

    While the result estimation of the distal splenorenal anastomosis formation operation, done in 12 patients according to the W. D. Warren method and in another 12 patients--according to the method, modified by K. Inokuchi, it was established that the hepatic portal perfusion loss causes compensational enhancement of blood flow in a. hepatica, including while the standard method application--by 22% and the modified one--by 8%. Doing the splenorenal venous disconnection improves the patients' quality of life due to the incidence rate of portosystemic encephalopathy reduction by 8.3%, and in this circumstances the life span and the hemorrhage recurrency rate do not differ with such while using the standard method.

  13. Cutaneous Mycobacterium chelonae infection distal to the arteriovenous fistula

    PubMed Central

    Van Ende, Charlotte; Wilmes, Dunja; Lecouvet, Frédéric E.; Labriola, Laura; Cuvelier, René; Van Ingelgem, Grégory; Jadoul, Michel

    2016-01-01

    A few single cases of Mycobacterium chelonae skin infection have been reported in haemodialysis patients. We report three additional cases that share peculiar clinical characteristics, pointing to diagnostic clues. All three cases presented as erythematous nodules developing distally to a proximal arteriovenous fistula (AVF). This presentation was identical to that of two published cases. A survey of all Belgian haemodialysis units during the period 2007–11 yields an estimated incidence of ∼0.9/10 000 patient-years. Although the source of M. chelonae remains unclear, this specific clinical presentation should be added to the listing of potential complications of an AVF and should be recognized, as it is fully treatable if diagnosed by culture and tissue biopsy.

  14. The morphology of Oreopithecus bambolii pollical distal phalanx.

    PubMed

    Almécija, Sergio; Shrewsbury, Marvin; Rook, Lorenzo; Moyà-Solà, Salvador

    2014-04-01

    Oreopithecus bambolii is a Late Miocene ape from Italy, first described in the late 19th century. Its interpretation is still highly controversial, especially in reference to its hand proportions and thumb morphology. In this study, the authors provide detailed descriptions of the available Oreopithecus pollical distal phalanx (PDP) specimens, as well as bivariate and multivariate morphometric analyses in comparison with humans, extant apes, selected anthropoid monkeys, and available Miocene PDP specimens. The multivariate results reveal two opposite poles on the hominoid PDP shape spectrum: on one side, a mediolaterally broad and dorsopalmarly short human PDP, and on the other side, the narrow and "conical" PDP of chimpanzees and orangutans. The authors contend that Oreopithecus exhibits intermediate PDP proportions that are largely primitive for hominoids because it shares morphological similarities with Proconsul. Furthermore, Oreopithecus displays a mediolaterally wide tuft for a hominoid, as well as a palmarly elevated attachment for a long tendon of a flexor muscle that is associated at its proximal edge with a proximal fossa and at its distal edge with an ungual fossa. These nonmetrical traits have been associated in humans with their capability to oppose and contact the proximal pads of the thumb and fingers, that is, pad-to-pad precision grasping. These traits reinforce previous studies that indicate a human-like thumb-to-hand length ratio compatible with pad-to-pad precision grasping in Oreopithecus. Although specific hand use is still unresolved in Oreopithecus, the results suggest enhanced manipulative skills (unrelated to stone tool-making) in this taxon relative to other (extant or fossil) hominoids.

  15. Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

    PubMed

    Willing, Ryan; King, Graham J W; Johnson, James A

    2015-11-26

    Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (p<0.001) and -14±2% (p=0.008) using commercially available, bone reverse engineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p<0.006) and -6±1% (p=0.020), and peak contact stresses increased by 75±52% (p>0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics.

  16. Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap.

    PubMed

    Vincentz, Joshua W; Casasnovas, Jose J; Barnes, Ralston M; Que, Jianwen; Clouthier, David E; Wang, Jun; Firulli, Anthony B

    2016-07-01

    Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, subsequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic protein (BMP) signaling and the transcription factor HAND2 (H2) synergistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways direct transcriptional outcomes that pattern the developing jaw.

  17. Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap

    PubMed Central

    Vincentz, Joshua W.; Casasnovas, Jose J.; Barnes, Ralston M.; Que, Jianwen; Clouthier, David E.; Wang, Jun; Firulli, Anthony B.

    2016-01-01

    Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, subsequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic protein (BMP) signaling and the transcription factor HAND2 (H2) synergistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways direct transcriptional outcomes that pattern the developing jaw. PMID:27335460

  18. Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap.

    PubMed

    Vincentz, Joshua W; Casasnovas, Jose J; Barnes, Ralston M; Que, Jianwen; Clouthier, David E; Wang, Jun; Firulli, Anthony B

    2016-07-01

    Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, subsequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic protein (BMP) signaling and the transcription factor HAND2 (H2) synergistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways direct transcriptional outcomes that pattern the developing jaw. PMID:27335460

  19. Congenital dorsally curving deformity of the distal phalanx of the little finger: case report.

    PubMed

    Iwasaki, Norimasa; Terashima, Takashi; Minami, Akio; Kato, Hiroyuki

    2010-09-01

    A deformity of the distal phalanx of the little finger with a curvature in the dorsal direction, referred to as a reverse Kirner's deformity, is extremely rare. We present a case of such a deformity found in a 6-year-old girl. A successful result was obtained after double corrective osteotomy of the distal phalanx at 12 years of age.

  20. Distal and Proximal Vision: A Multi-Perspective Research in Sociology of Education

    ERIC Educational Resources Information Center

    Giancola, Orazio; Viteritti, Assunta

    2014-01-01

    Drawing inspiration from the research conducted in Italian schools involved in the reform process, the article proposes to investigate two visions in the research on Sociology of Education: one distal and the other proximal. The distal vision is offered by quantitative research nowadays supported by extensive public funding and framed as…

  1. Osteoid osteoma of distal phalanx: A rare disorder and review of literature

    PubMed Central

    Andalib, Ali; Sajadie-khajouei, Sahar

    2013-01-01

    Osteoid osteomata are rarely found in the distal phalanges of the hand. The usual presenting features are chronic pain, nail enlargement and increase in size of the terminal part of the digit. Diagnosis is difficult but surgical excision is effective for treating the patients’ pain. We reported this tumor in distal phalanx of the middle finger. PMID:23930128

  2. Combined treatment with headgear and the Frog appliance for maxillary molar distalization: a randomized controlled trial

    PubMed Central

    2013-01-01

    Objective To evaluate the efficiency of the Frog appliance (FA) alone or in combination with headgear for distalizing the maxillary molars. Methods Fifty patients (25 males and 25 females) aged 12.6 - 16.7 years who received treatment for Class II malocclusion at the Orthodontic Clinic of Al-Baath University were selected for this study and randomly divided into 2 equal groups. Maxillary molar distalization was achieved using the FA alone (group 1) or a combination of the FA with high-pull headgear worn at night (group 2). Lateral cephalograms were obtained before and after treatment. Results The maxillary molars moved distally by 5.51 and 5.93 mm in groups 1 and 2, respectively. Distal movements were associated with axial tipping by 4.96° and 1.25°, and with loss of anchorage by mesial movement of the second maxillary premolars by 2.70 and 0.90 mm in groups 1 and 2, respectively. The combined use of the FA and nighttime high-pull headgear decreased the distalization time and improved the ratio of maxillary molar distalization movement relative to the overall opening space between the first maxillary molars and second premolars. Conclusions The FA can effectively distalize the maxillary molars, this distalization associates with some unfavorable changes. Nighttime use of high-pull headgear combined with the FA can reduce these unfavorable changes and improve treatment outcomes. PMID:23671835

  3. Mallet finger injuries-A new method to maintain distal interphalangeal joint extension.

    PubMed

    Mak, Lonita; Aitkens, Lorna D; Novak, Christine B

    2016-01-01

    Ensuring that distal interphalangeal joint extension is maintained is an important but challenging part of the treatment process. These authors describe a simple approach to ensuring distal interphalangeal joint extension for these patients. - VictoriaPriganc, PhD, OTR, CHT, CLT, Practice Forum Editor. PMID:27496991

  4. Latent Class Analysis with Distal Outcomes: A Flexible Model-Based Approach

    ERIC Educational Resources Information Center

    Lanza, Stephanie T.; Tan, Xianming; Bray, Bethany C.

    2013-01-01

    Although prediction of class membership from observed variables in latent class analysis is well understood, predicting an observed distal outcome from latent class membership is more complicated. A flexible model-based approach is proposed to empirically derive and summarize the class-dependent density functions of distal outcomes with…

  5. Biomechanical Study on Distal Filling Effects in Cementless Total Hip Replacement

    NASA Astrophysics Data System (ADS)

    Chae, Soo-Won; Lee, Jun-Hyoung; Choi, Hyung-Yun

    In cementless total hip replacement, initial stability of the femoral component is important in the long term fixation of the femoral stem. Initial stability is closely related to the relative displacement between the prosthesis and the cancellous bone of the proximal femur. After implantation of the prosthesis, the surrounding bone is partially shielded from load carrying and starts to resorb. Stress shielding causes the loss of the proximal bone. The stress distribution of femur must be assessed to predict stress shielding. The initial stability and the stress shielding were investigated for two loading conditions approximating a single leg stance and stair climbing. Two types of stems involving a distal filling and a distal short stem were studied by the finite element method to investigate the biomechanical distal filling effects. The distal short stem produced less stress shielding at the proximal bone than the distal filling stem, while both types of stems seemed to satisfy the initial stability requirement.

  6. Extensor mechanism-sparing paratricipital posterior approach to the distal humerus.

    PubMed

    Schildhauer, Thomas A; Nork, Sean E; Mills, William J; Henley, M Bradford

    2003-05-01

    Adequate exposure of the articular surface of the distal humerus and elbow joint is required for operative stabilization of bicolumnar distal humerus fractures. The transolecranon approach, which provides complete posterior visualization and access to the distal humerus, is commonly used. Nevertheless, an olecranon osteotomy and other extensor mechanism-disrupting approaches have risks and possible complications. Alternative exposures have been described primarily for total elbow arthroplasty, but these involve extensive and potentially devascularizing dissections. In extra-articular (OTA type A) and simple articular distal humeral fractures with simple or multifragmentary metaphyseal involvement (OTA type C1 and C2), extensile approaches may not be necessary. For these fracture patterns, an alternative exposure is the extensor mechanism-sparing paratricipital posterior approach to the distal humerus through a midline posterior incision. This approach avoids an osteotomy and mobilizes the triceps and anconeus muscle off the posterior humerus and the intermuscular septae and provides adequate exposure for open reduction and internal fixation.

  7. Distal pancreatectomy: en-bloc splenectomy vs spleen-preserving pancreatectomy

    PubMed Central

    Orduña, David; Cesar-Borges, Gleydson; Angel López-Boado, Miguel

    2005-01-01

    Distal pancreatectomy with en-bloc splenectomy has been considered the standard technique for management of benign and malignant pancreatic disorders. However, splenic preservation has recently been advocated. The aim of this study was to review the experiences of distal pancreatectomy using the open or the laparoscopic approach and to critically discuss the need to perform splenectomy. Original articles published in the English literature of peer-reviewed medical journals were selected for detailed analysis. In patients with malignant neoplasms in the body-tail of the pancreas, splenectomy has a negative influence on long-term survival after resection. The incidence of diabetes after spleen-preserving distal pancreatectomy for chronic pancreatitis is less than after en-bloc splenectomy. Spleen salvage eliminates the risk of overwhelming infections. Laparoscopic spleen-preserving distal pancreatectomy is feasible and safe. Laparoscopic spleen-preserving distal pancreatectomy may be preferable for the advantages of a minimally invasive approach. PMID:18333170

  8. Unintended Rotational Changes of the Distal Tibia After Biplane Medial Open-Wedge High Tibial Osteotomy.

    PubMed

    Jang, Ki-Mo; Lee, Jong-Hee; Park, Hyung-Jun; Kim, Jeong Lae; Han, Seung-Beom

    2016-01-01

    This study involved 35 knees undergoing biplane medial open-wedge high tibial osteotomy (OWHTO) to assess the axial rotation of the distal tibia. The distal tibiae were internally rotated by 3.0° ± 7.1° after OWHTO. The opening width showed a Pearson correlation coefficient of -0.743 (P < .001), and the tuberosity osteotomy angle showed that of -0.678 (P < .001) with distal tibial rotation. However, changes in hip-knee-ankle angle, medial proximal tibial angle, and posterior tibial slope were not significantly correlated with the change in distal tibial rotation. In conclusion, there was an unintended tendency of increasing internal rotation of the distal tibia after biplane medial OWHTO, and this tendency was positively related to the opening width and tuberosity osteotomy angle.

  9. Hyperammonemia in distal renal tubular acidosis: is it more common than we think?

    PubMed

    Pela, I; Seracini, D

    2007-08-01

    The hyperammonemia in distal renal tubular acidosis, previously only described in two cases, is considered an unusual occurrence. After the report published in 2005, we observed plasma ammonia levels above normal range during metabolic decompensation in two other consecutive pediatric patients suffering from distal renal tubular acidosis. The ammonia plasma levels returned to normal range after treatment with sodium bicarbonate and potassium salt. In distal renal tubular acidosis, hyperammonemia is probably the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal renal tubular acidosis. According to this physiopathological mechanism, our observation shows that hyperammonemia is not an uncommon finding in distal renal tubular acidosis, and should be included among differential diagnosis of hyperammonemia in infants and children. PMID:17722711

  10. Simultaneous distal radial fractures and carpal bones injuries in children: a review article.

    PubMed

    Pretell-Mazzini, Juan; Carrigan, Robert B

    2011-09-01

    Accurate diagnosis is crucial in effectively managing and treating both the radial and carpal fractures. Injuries to the carpal bones are not usually associated with fractures of the distal radius; however, the presence of a distal radius fracture does not preclude an associated carpal injury. The purpose of this review article is to compile cases of past reported distal radius fractures and simultaneous carpal injuries to restate its low prevalence within the pediatric population while still serving as a collective reference for management and treatment. After an electronic literature search was performed, we identified 18 published articles and 28 cases dealing with combined distal radial and carpal bones injuries in the pediatric population. As the mechanism of injury is similar for both fractures, despite the low incidence, orthopedic surgeons need to rule out carpal injury with a distal forearm fracture. Failure to treat both injuries appropriately may result in an unsatisfactory clinical result.

  11. Primary subcutaneous hydatid cyst in the left distal thigh.

    PubMed

    Mahmoudi, Abdelhalim; Rachidi, Charifa Alaoui; Khattala, Khalid; Chater, Lamiae; Bouabdallah, Youssef; Afifi, My Abderrahmane

    2012-11-01

    Human cystic echinococcosis, a zoonotic infection caused by Echinococcus granulosus, remains a largely extended public health problem in endemic regions. Hydatid cyst disease can occur in all viscera and soft tissues, although the liver and the lungs are the most commonly involved organs. Primary hydatid disease of the soft tissue is extremely rare, even in endemic areas, and accounts for 0.5-5.4 % of all hydatid disease cases, with very little data on the incidence of subcutaneous echinococcosis. The paper will be focused on analyzing this extremely rare disease. A 14-year-old girl came to our Department of pediatric Surgery with a painless, round, palpable mass in the subcutaneous tissue of the distal anteromedial side of the left thigh. Based on clinical and laboratory findings and imaging techniques, we suspected a hydatid cyst. She was treated successfully with complete cyst excision. The macroscopic appearance suggested a hydatid cyst. Histopathologic examination of the specimen revealed a hydatid cyst. No other organ involvement has been detected. Hydatid disease should be considered in the differential diagnosis of all cystic masses in all anatomic locations, especially in regions where the disease is endemic.

  12. Current status in remnant gastric cancer after distal gastrectomy

    PubMed Central

    Ohira, Masaichi; Toyokawa, Takahiro; Sakurai, Katsunobu; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Onoda, Naoyoshi; Hirakawa, Kosei

    2016-01-01

    Remnant gastric cancer (RGC) and gastric stump cancer after distal gastrectomy (DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori (H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis. PMID:26937131

  13. Glycinergic feedback enhances synaptic gain in the distal retina

    PubMed Central

    Jiang, Zheng; Yang, Jinnan; Purpura, Lauren A; Liu, Yufei; Ripps, Harris; Shen, Wen

    2014-01-01

    Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole cell recordings, intracellular recordings and specific antibody labelling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the postsynaptic glycine currents from axon-detached bipolar cells while stimulating presynaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors and suppresses the uptake of glutamate by the type 2A excitatory amino acid transporter on photoreceptors. The net effect is a significant increase in synaptic gain between photoreceptors and their second-order neurons. PMID:24421349

  14. Pediatric aneurysmal bone cyst of the distal tibia.

    PubMed

    Goss, L R; Walter, J H

    1997-03-01

    A rare, large pediatric aneurysmal bone cyst with pathologic fracture of the distal tibia of a 4-year-old female was presented. Classic radiographic and magnetic resonance imaging findings have been discussed. In a comprehensive review of the literature, aneurysmal bone cysts are an infrequently reported neoplasm of the foot and ankle bones. Lesions are characteristically seen in patients younger than 20 years of age, but rarely younger than 5 years. The benign cyst has a 2:1 female-to male predilection. In long bones, the lesion is typically metaphyseal in nature. Although the pathogenesis is still unknown, there exists the possibility of two types of aneurysmal bone cysts: a primary type without preexisting lesion and a secondary form associated with some other lesion. The diagnosis of aneurysmal bone cyst can be strongly suspected by correlating the radiographic and magnetic resonance imaging findings. For definitive diagnosis, accurate histologic evaluation is imperative to rule out any confusion or possibility with a malignant tumor. PMID:9086721

  15. In vivo studies of biotin absorption in distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  16. Distribution of distal femoral osteophytes in a human skeletal population

    PubMed Central

    Shepstone, L.; Rogers, J.; Kirwan, J.; Silverman, B.

    2000-01-01

    OBJECTIVES—To examine objectively spatial patterns of osteophytes around the distal end of the femur and to identify distinct subgroups.
METHODS—A sample of 107 human femora from a large skeletal population were selected for study. These femora included subjects with evidence of late stage osteoarthritis (that is, with eburnation present) and those with no such evidence. The location of osteophytes was recorded using a video camera and digitised computer images were extracted. Multidimensional scaling was used to identify clusters of femora based upon osteophyte location.
RESULTS—A distinct subgroup of femora was identified with osteophytes present only within the intercondylar notch region. None of these subjects had any evidence of eburnation.
CONCLUSIONS—This finding adds to an earlier study based on radiographs. Osteophytes located within the intercondylar notch of the femur appear to be a distinct subset, which may occur either as an early stage of knee osteoarthritis or for some independent reason.

 PMID:10873960

  17. Preliminary evaluation of robotic needle distal tip repositioning

    NASA Astrophysics Data System (ADS)

    Walsh, Conor J.; Slocum, Alexander H.; Gupta, Rajiv

    2011-03-01

    Advances in medical imaging now provide detailed images of solid tumors inside the body and miniaturized energy delivery systems enable tumor destruction through local heating powered by a thin electrode. We have developed a robot for accurately repositioning the distal tip of a medical instrument such an ablation probe to adjacent points within tissue. The position accuracy in ballistics gelatin was evaluated in a 2D experimental setup with a digital SLR camera that was fixed to a rig that also contained the gelatin. The robot was mounted to the rig in such a way that the stylet was deployed in a plane parallel the camera's lens. A grid paper attached to the back of the box containing the gelatin provided a stationary reference point for each of the pictures taken and also served as a coordinate system for making measurements. The measurement repeatability error was found by taking a stylet tip position measurement five times for two different pictures and found to be 0.26 mm. For a stylet with a radius of curvature of 31.5 mm and a diameter of 0.838 mm, the targeting accuracy was found to be 2.5 +/- 1.4 mm at points that were approximately 38 mm lateral from the cannula axis.

  18. Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

    PubMed

    Zamir, Mair; Vercnocke, Andrew J; Edwards, Phillip K; Anderson, Jill L; Jorgensen, Steven M; Ritman, Erik L

    2015-11-01

    A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 μm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control.

  19. Delineation of a characteristic phenotype in distal trisomy 2q.

    PubMed

    Kyllerman, M; Wahlström, J; Westerberg, B; Gustavson, K H

    1984-12-01

    A recombinant chromosome change with dup(2)(q34----qter) secondary to a paternal inv(2) (pter----q34) was found in a 19-year-old boy and his 12-year-old sister. Both were born at term with normal birth weight and head circumference. Hypertelorism, irregular nystagmus, broad flat nasal bridge, and short beaked nose with anteverted nostrils were noted neonatally. Both developed microcephaly and brachycephaly. Cardiac, urogenital, retinal, and optic disc anomalies and onset of progressive kyphosis in adolescence were detected. Their facial appearance, with birdlike "Muppet Gonzo" features, was increasingly accentuated with age. Both had mild mental retardation with IQ's around 70. The clinical findings in these siblings were compared with those described in 23 cases with various 2q partial trisomies. The results of the present study and previous studies indicate a characteristic clinical presentation in children and adults. The reluctance to define the specific phenotype for distal 2q trisomy might be due to the fact that the clinical features tend to be considerably more pronounced towards adolescence than neonatally. PMID:6543860

  20. Coronal shear fractures of distal humerus: Diagnostic and treatment protocols

    PubMed Central

    Singh, Ajay Pal; Singh, Arun Pal

    2015-01-01

    Coronal shear fractures of distal humerus involving the capitellum and the trochlea are rare injuries with articular complexity, and are technically challenging for management. With better understanding of the anatomy and imaging advancements, the complex nature of these fractures is well appreciated now. These fractures involve metaphysealcomminution of lateral column and associated intraarticular injuries are common. Previously, closed reduction and excision were the accepted treatment but now preference is for open reduction and internal fixation with an aim to provide stable and congruent joint with early range of motion of joint. Various approaches including extensile lateral, anterolateral and posterior approaches have been described depending on the fracture pattern and complexity. Good to excellent outcome have been reported with internal fixations and poor results are noted in articular comminution with associated articular injuries. Various implants including headleass compression screws, minifragment screws, bioabsorbable implants and column plating are advocated for reconstruction of these complex fractures. Inspite of articular fragments being free of soft tissue attachments the rate of osteonecrosis and osteoarthritis is reported very less after internal fixation. This article summarizes the diagnostic and treatment strategies for these rare fractures and recommendations for management. PMID:26716083

  1. Histology of a Harris line in a human distal tibia.

    PubMed

    Miszkiewicz, Justyna J

    2015-07-01

    Identification and diagnosis of Harris lines (HLs) is usually achieved using radiography. To date, histological methods have been mainly implemented in research exploring the underlying processes of HL deposition using longitudinal sections taken from animal bone. Here, a new insight into HL formation is provided following transverse histological sectioning in a human specimen. A distinct HL was identified macroscopically, and from a radiograph, in a left distal tibia taken from an adult human male. Transverse sections were taken through the HL, and also from trabeculae immediately superior and inferior to the HL. Thin sections were produced following standard histological procedures. Micrographs were captured using a digital microscope camera. Trabeculae immediately superior and inferior to the HL displayed no indication of abnormal growth, exhibiting abundant osteocyte lacunae and a lamellar structure. However, the micro-anatomy of the HL was characterised by the following three main features: (1) non-lamellar appearance, (2) a complete lack of osteocyte lacunae, and (3) presence of irregularly distributed tubular structures. These three histological features indicate a specific process of bone deposition, implying that trapping of osteoblasts may not take place during HL formation. Pictorial and descriptive records of HL histology are provided, aiding current understanding about the nature of HL, its identification from histology, and serving as a reference point for future comparative research. PMID:25762436

  2. Recurrent uranium relocations in distal turbidites emplaced in pelagic conditions

    NASA Astrophysics Data System (ADS)

    Colley, S.; Thomson, J.

    1985-11-01

    The sediments of the Madeira Abyssal Plain, east of Great Meteor Seamount, are dominated by distal turbidite deposition. While the turbidites exhibit a wide compositional range (25-80% CaCO 3), individual examples can be correlated over a wide area and are relatively homogenous. Organic C oxidation, by bottom water oxygen, proceeds from the turbidite tops downwards after emplacement in pelagic conditions, and the progress of this oxidation front is marked by a sharp colour contrast in the sediments ( WILSONet al., 1985). In turbidites with C org ≫ 0.5%, redistribution of authigenic U occurs to form a concentration peak (4-9 ppm U), just below the oxidation front or colour change. Several tens μg U/cm 2 may be mobilised, and in all examples studied ≫60% of the remobilised U is relocated into the peak. Following burial by subsequent turbidites, such U concentration peaks are persistent as relict indicators of their extinct oxidation fronts for at least 2 × 10 5 years. In the case of thin turbidites where labile C org is almost exhausted, the U peaks may be located in underlying sedimentary units because of their relationship to the oxidation front. A redox mechanism for U peak formation is suggested from these data rather than a complexation with organic matter.

  3. Normative data for distal line bisection and baking tray task.

    PubMed

    Facchin, Alessio; Beschin, Nicoletta; Pisano, Alessia; Reverberi, Cristina

    2016-09-01

    Line bisection is one of the tests used to diagnose unilateral spatial neglect (USN). Despite its wide application, no procedure or norms were available for the distal variant when the task was performed at distance with a laser pointer. Furthermore, the baking tray task was an ecological test aimed at diagnosing USN in a more natural context. The aim of this study was to collect normative values for these two tests in an Italian population. We recruited a sample of 191 healthy subjects with ages ranging from 20 to 89 years. They performed line bisection with a laser pointer on three different line lengths (1, 1.5, and 2 m) at a distance of 3 m. After this task, the subjects performed the baking tray task and a second repetition of line bisection to test the reliability of measurement. Multiple regression analysis revealed no significant effects of demographic variables on the performance of both tests. Normative cut-off values for the two tests were developed using non-parametric tolerance intervals. The results formed the basis for clinical use of these two tools for assessing lateralized performance of patients with brain injury and for diagnosing USN.

  4. Indocyanine green alters transepithelial electrical parameters of the distal colon.

    PubMed

    Hameed, Burhan; Smith, David M; Verrechio, Jon J; Schmidt, J David; Gillooley, Leesa E; Valenzano, Mary Carmen; Lewis, Simon A; Mullin, James M

    2004-09-01

    Indocyanine green (ICG) is used as a dye marker of the vascular space in gastroenterology, ophthalmology, neurology, and critical care medicine. It is widely regarded to be inert. We report, however, that ICG demonstrates effects on colonic transepithelial electrical parameters which could form a basis for a growing number of deleterious gastrointestinal and other clinical effects. Short-circuit current (Iscc), transepithelial conductance (gt), and transepithelial paracellular flux of 14C-D-mannitol were monitored across sheets of rat distal colon. Dye was introduced to mucosal or serosal tissue surfaces at a concentration similar to that used in vivo (10 microg/ml). ICG decreased Iscc by over 50% and gt by over 10%. Transepithelial mannitol flux was not altered. Dye was effective only from the serosal surface. Cyclic AMP-induced spiking of Iscc was not affected by ICG. Preincubation with amiloride or furosemide did not affect the action of the dye on gt or Iscc. ICG at in vivo dosages is clearly capable of inhibiting ion transport across colon epithelial tissue. The serosal site of action indicates activity on a basal-lateral transport system or diffusion into the cell only across the basal-lateral membrane followed by inhibition of a transporter from the intracellular side. ICG should not be considered inert in vivo. Leakage of ICG from the vascular space into the interstitial fluid space will likely result in tissue morbidity. PMID:15481307

  5. Haptic distal spatial perception mediated by strings: haptic "looming".

    PubMed

    Cabe, Patrick A

    2011-10-01

    Five experiments tested a haptic analog of optical looming, demonstrating string-mediated haptic distal spatial perception. Horizontally collinear hooks supported a weighted string held taut by a blindfolded participant's finger midway between the hooks. At the finger, the angle between string segments increased as the finger approached collinearity with the hooks, just as the optical angle subtended by an approaching object increases. The vertical force component at the finger is potentially informative for perception, approaching zero at finger-hook collinearity. In Experiment 1, participants judged hook height reasonably accurately. To retain force relationships but eliminate immediate skin contact, Experiment 2 employed a hand-held rod; results replicated those of Experiment 1. Experiment 3 replicated Experiment 2 using a ring instead of a rod. In all three experiments, estimated hook height closely paralleled actual height, r > .9. Experiments 4 and 5 showed that participants could project impending finger-hook collinearity when finger contact with the string was interrupted during its traverse. Perceivers' estimate errors were nearly perfectly predicted by height-force ratio relationships (Rs > .96). Outcomes are related to optical and acoustic looming, dynamic touch, tau theory, and Gibsonian perceptual theory.

  6. Epithelioid hemangioma of the distal humerus with pathologic fracture.

    PubMed

    Kleck, Christopher J; Seidel, Matthew J

    2012-01-16

    Epithelioid hemangioma is a rare tumor that can have bone involvement. Its clinically and radiographically aggressive appearance mimics a malignant neoplasm. Although epitheliod hemangioma has been described as having an aggressive appearance on magnetic resonance imaging (MRI) and plain radiographs, this is the first reported case of pathologic fracture associated with this lesion to our knowledge. This article describes a case of epithelioid hemangioma involving the distal humerus, which initially presented with progressive pain and fracture of the lateral condyle. The aggressive appearance on plain radiographs and MRI suggested a malignant bone tumor. This preliminary diagnosis was confirmed due to the presence of local lymph node spread on positron emission tomography/computed tomography. After a core needle biopsy revealed nondiagnostic tissue, rather than performing a wide resection based on a presumptive malignant diagnosis, we followed the standard diagnostic algorithm and performed an open biopsy with temporary internal stabilization. The tissue sample was adequate and revealed a diagnosis of epithelioid hemangioma. Based on this finding, we were able to proceed with surgical management, including curettage of the lesion, placement of a bone graft, and internal fixation, rather than a wide resection with elbow joint replacement. This article emphasizes the need for careful adherence to the diagnostic algorithm for musculoskeletal tumors. In doing so, a definitive diagnosis was reached, and our patient was able to resume his occupation as a laborer without the restrictions that would have accompanied elbow arthroplasty.

  7. Normative data for distal line bisection and baking tray task.

    PubMed

    Facchin, Alessio; Beschin, Nicoletta; Pisano, Alessia; Reverberi, Cristina

    2016-09-01

    Line bisection is one of the tests used to diagnose unilateral spatial neglect (USN). Despite its wide application, no procedure or norms were available for the distal variant when the task was performed at distance with a laser pointer. Furthermore, the baking tray task was an ecological test aimed at diagnosing USN in a more natural context. The aim of this study was to collect normative values for these two tests in an Italian population. We recruited a sample of 191 healthy subjects with ages ranging from 20 to 89 years. They performed line bisection with a laser pointer on three different line lengths (1, 1.5, and 2 m) at a distance of 3 m. After this task, the subjects performed the baking tray task and a second repetition of line bisection to test the reliability of measurement. Multiple regression analysis revealed no significant effects of demographic variables on the performance of both tests. Normative cut-off values for the two tests were developed using non-parametric tolerance intervals. The results formed the basis for clinical use of these two tools for assessing lateralized performance of patients with brain injury and for diagnosing USN. PMID:27259570

  8. Haptic distal spatial perception mediated by strings: haptic "looming".

    PubMed

    Cabe, Patrick A

    2011-10-01

    Five experiments tested a haptic analog of optical looming, demonstrating string-mediated haptic distal spatial perception. Horizontally collinear hooks supported a weighted string held taut by a blindfolded participant's finger midway between the hooks. At the finger, the angle between string segments increased as the finger approached collinearity with the hooks, just as the optical angle subtended by an approaching object increases. The vertical force component at the finger is potentially informative for perception, approaching zero at finger-hook collinearity. In Experiment 1, participants judged hook height reasonably accurately. To retain force relationships but eliminate immediate skin contact, Experiment 2 employed a hand-held rod; results replicated those of Experiment 1. Experiment 3 replicated Experiment 2 using a ring instead of a rod. In all three experiments, estimated hook height closely paralleled actual height, r > .9. Experiments 4 and 5 showed that participants could project impending finger-hook collinearity when finger contact with the string was interrupted during its traverse. Perceivers' estimate errors were nearly perfectly predicted by height-force ratio relationships (Rs > .96). Outcomes are related to optical and acoustic looming, dynamic touch, tau theory, and Gibsonian perceptual theory. PMID:21688938

  9. Neurofibromatosis Type 2 Presenting with Oculomotor Ophthalmoplegia and Distal Myopathy

    PubMed Central

    Tevaraj, Jessica Mani Penny; Mohd Noor, Raja Azmi; Yaakub, Azhany

    2016-01-01

    Neurofibromatosis type 2 usually presents with bilateral acoustic schwannomas. We highlight the rare presentation of neurofibromatosis initially involving third nerve. A 23-year-old Malay female presented with left eye drooping of the upper lid and limitation of upward movement for 8 years. It was associated with right-sided body weakness, change in voice, and hearing disturbance in the right ear for the past 2 years. On examination, there was mild ptosis and limitation of movement superiorly in the left eye. Both eyes had posterior subcapsular cataract. Fundoscopy showed generalised optic disc swelling in both eyes. She also had palsy of the right vocal cord, as well as the third and eighth nerve. There was wasting of the distal muscles of her right hand, with right-sided decreased muscle power. Pedunculated cutaneous lesions were noted over her body and scalp. MRI revealed bilateral acoustic and trigeminal schwannomas with multiple extra-axial lesions and intradural extramedullary nodules. Patient was diagnosed with neurofibromatosis type 2 and planned for craniotomy and tumour debulking, but she declined treatment. Neurofibromatosis type 2 may uncommonly present with isolated ophthalmoplegia, so a thorough physical examination and a high index of suspicion are required to avoid missing this condition. PMID:27738538

  10. Current status of preoperative drainage for distal biliary obstruction.

    PubMed

    Sugiyama, Harutoshi; Tsuyuguchi, Toshio; Sakai, Yuji; Mikata, Rintaro; Yasui, Shin; Watanabe, Yuto; Sakamoto, Dai; Nakamura, Masato; Sasaki, Reina; Senoo, Jun-Ichi; Kusakabe, Yuko; Hayashi, Masahiro; Yokosuka, Osamu

    2015-08-28

    Preoperative biliary drainage (PBD) was developed to improve obstructive jaundice, which affects a number of organs and physiological mechanisms in patients waiting for surgery. However, its role in patients who will undergo pancreaticoduodenectomy for biliary obstruction remains controversial. This article aims to review the current status of the use of preoperative drainage for distal biliary obstruction. Relevant articles published from 1980 to 2015 were identified by searching MEDLINE and PubMed using the keywords "PBD", "pancreaticoduodenectomy", and "obstructive jaundice". Additional papers were identified by a manual search of the references from key articles. Current studies have demonstrated that PBD should not be routinely performed because of the postoperative complications. PBD should only be considered in carefully selected patients, particularly in cases where surgery had to be delayed. PBD may be needed in patients with severe jaundice, concomitant cholangitis, or severe malnutrition. The optimal method of biliary drainage has yet to be confirmed. PBD should be performed by endoscopic routes rather than by percutaneous routes to avoid metastatic tumor seeding. Endoscopic stenting or nasobiliary drainage can be selected. Although more expensive, the use of metallic stents remains a viable option to achieve effective drainage without cholangitis and reintervention. PMID:26328029

  11. Transcriptionally Regulated Cell Adhesion Network Dictates Distal Tip Cell Directionality

    PubMed Central

    Wong, Ming-Ching; Kennedy, William P.; Schwarzbauer, Jean E.

    2015-01-01

    Background The mechanisms that govern directional changes in cell migration are poorly understood. The migratory paths of two distal tip cells (DTC) determine the U-shape of the C. elegans hermaphroditic gonad. The morphogenesis of this organ provides a model system to identify genes necessary for the DTCs to execute two stereotyped turns. Results Using candidate genes for RNAi knockdown in a DTC-specific strain, we identified two transcriptional regulators required for DTC turning: cbp-1, the CBP/p300 transcriptional coactivator homologue, and let-607, a CREBH transcription factor homologue. Further screening of potential target genes uncovered a network of integrin adhesion-related genes that have roles in turning and are dependent on cbp-1 and let-607 for expression. These genes include src-1/Src kinase, tln-1/talin, pat-2/α integrin and nmy-2, a nonmuscle myosin heavy chain. Conclusions Transcriptional regulation by means of cbp-1 and let-607 is crucial for determining directional changes during DTC migration. These regulators coordinate a gene network that is necessary for integrin-mediated adhesion. Overall, these results suggest that directional changes in cell migration rely on the precise gene regulation of adhesion. PMID:24811939

  12. Internal fixators: a safe option for managing distal femur fractures?

    PubMed Central

    Batista, Bruno Bellaguarda; Salim, Rodrigo; Paccola, Cleber Antonio Jansen; Kfuri, Mauricio

    2014-01-01

    OBJECTIVE: Evaluate safety and reliability of internal fixator for the treatment of intra-articular and periarticular distal femur fractures. METHODS: Retrospective data evaluation of 28 patients with 29 fractures fixed with internal fixator was performed. There was a predominance of male patients (53.5%), with 52% of open wound fractures, 76% of AO33C type fractures, and a mean follow up of 21.3 months. Time of fracture healing, mechanical axis deviation, rate of infection and postoperative complications were registered. RESULTS: Healing rate was 93% in this sample, with an average time of 5.5 months. Twenty-seven percent of patients ended up with mechanical axis deviation, mostly resulting from poor primary intra-operative reduction. There were two cases of implant loosening; two implant breakage, and three patients presented stiff knee. No case of infection was observed. Healing rate in this study was comparable with current literature; there was a high degree of angular deviation, especially in the coronal plane. CONCLUSION: Internal fixators are a breakthrough in the treatment of knee fractures, but its use does not preclude application of principles of anatomical articular reduction and mechanical axis restoration. Level of Evidence II, Retrospective Study. PMID:25061424

  13. What is new in distal femur periprosthetic fracture fixation?

    PubMed

    Tosounidis, Theodoros H; Giannoudis, Peter V

    2015-12-01

    Distal femoral periprosthetic fractures are on the rise. Increased mortality of these injuries is also evident from recent data. Their incidence and risk factors have been extensively reported in the past but new data are being available that merit attention. The increased incidence and the even higher projected incidence should direct the focus of future strategies to the education of surgeons, relevant capacity of hospital and reconfiguration of health care resources. New and potentially modifiable risk factors should be taken into consideration to the informed consent process and new studies should be developed to clarify the causative relationship of the new risk factors such as the peptic ulcer disease and the COPD. The main internal fixation techniques remain the lateral locking plating and the retrograde intramedullary nailing. New techniques in plating are the supplementary medial plate in selected cases and the far cortical locking. Nailing is considered a valid option especially in fractures located well above the anterior flange of the femoral component of the arthroplasty. Results and outcomes from good quality studies are still sparse regarding the comparison between plating and nailing. Interprosthetic fractures constitute an entity that is lately gaining considerable attention. The best method of management of these injuries is still evolving with considerable amount of work being done in the clinical and biomechanical level.

  14. Matched hemiresection interposition arthroplasty of the distal radioulnar joint.

    PubMed

    Bain, G I; Pugh, D M; MacDermid, J C; Roth, J H

    1995-11-01

    Since 1986 the senior author has performed a matched hemiresection with retinacular/capsular interposition for patients with painful disorders of the distal radioulnar joint. A retrospective review of 55 wrists was performed by an independent hand surgeon and hand therapist. Forty-nine of 54 wrists in the surviving patients were clinically and radiographically reviewed with an average follow-up interval of 36 months. Subjective assessment included a visual analog rating of pain improvement and satisfaction with treatment. Objective assessment included examination of range of motion, strength, stability, and standardized functional testing with the Jebsen and Minnesota Rate of Manipulation tests. Thirty-five patients reported pain improvement and 41 patients were satisfied. The range of supination and pronation increased from 54 degrees and 67 degrees, respectively, to 72 degrees and 72 degrees. Functional ability as measured by the Jebsen test was similar to the contralateral wrist. Patients had most difficulty turning large objects. The clinical, objective, functional, and x-ray films results correlated poorly with pain improvement and patient satisfaction. Complications included one infection, one reflex sympathetic dystrophy, one neuroma of the dorsal sensory branch of the ulnar nerve, and four cases of ulnar-carpal impaction. Pain relief was the primary determinant of patient satisfaction and should be considered the indication for surgery.

  15. A drainage operation for injury to the pancreas preserved the distal pancreas, spleen and the residual stomach after distal gastrectomy: a case report.

    PubMed

    Watanabe, Toshihiro; Kimura, Wataru; Yano, Mitsumasa; Hachiya, Osamu; Ma, Jinfeng; Fuse, Akira

    2007-01-01

    We experienced a case in which a drainage operation for injury of the pancreas preserved the distal pancreas, spleen and the residual stomach after distal gastrectomy for complete laceration of the stomach. A 23-year-old male was crushed by a large truck while driving a car without a seat belt. Abdominal computed tomography (CT) scan showed a low-density area in and around the body of the pancreas, which suggested contusion of the pancreatic parenchyma. An emergent operation was indicated due to free air and massive bleeding in the abdominal cavity and liver damage. At the operation, the antrum of the stomach was completely lacerated and distal gastrectomy was performed. Drains were set around the body of the pancreas. Distal pancreatectomy with splenectomy would have led to total gastrectomy because of lack of blood supply to the residual stomach after distal gastrectomy. We limited the drainage operation for pancreatic trauma. As a result, the pancreatic body and tail were preserved, which is thought to be a much better long-term result for this patient. PMID:18251137

  16. A new fluoroscopy-free navigation device for distal interlocking screw placement.

    PubMed

    Lee, M-Y; Kuo, C H; Hung, S-S

    2008-01-01

    During the treatment of tibia fracture with interlocking nails, the most uncomfortable procedure is for an orthopaedic surgeon to find the location for the distal locking screws. In this study, a fluoroscopy-free non-contact navigation device was developed for the placement of distal locking screws in the tibia intramedullary nailing. This device utilizes a 3D digitization arm integrated with spatial coordinate registration module, graphical user interface module and sound-guided navigation module. The 3D digitization arm, a five-DOF passive robotic arm, was used to register the spatial coordinates of proximal and distal landmarks just before placement of the nail. The registered coordinates were then incorporated with the coordinates of the proximal landmarks after nail placement to calculate the coordinate transformation matrix. The transformed spatial coordinates of the distal screw holes were then computed in real time for interlocking nail navigation. A sound-guided navigation module was designed in which a sound with different tones and intermittence frequencies was produced, as the probe of the digitization arm navigates toward the location of distal screw holes. No intra-operative fluoroscopy was required. In vitro assessment was performed successfully with a donor bone, and a clinical case of a young male with tibia fracture was also carried out in the operating theatre. Operation time, distal screw insertion, total radiation time and accuracy of the distal interlocking screw placement were measured. The surgery was conducted under sterile conditions without complication, and the clinical course was smooth with prompt bone healing.

  17. A new model of the distal convoluted tubule.

    PubMed

    Ko, Benjamin; Mistry, Abinash C; Hanson, Lauren; Mallick, Rickta; Cooke, Leslie L; Hack, Bradley K; Cunningham, Patrick; Hoover, Robert S

    2012-09-01

    The Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney is a key determinant of Na(+) balance. Disturbances in NCC function are characterized by disordered volume and blood pressure regulation. However, many details concerning the mechanisms of NCC regulation remain controversial or undefined. This is partially due to the lack of a mammalian cell model of the DCT that is amenable to functional assessment of NCC activity. Previously reported investigations of NCC regulation in mammalian cells have either not attempted measurements of NCC function or have required perturbation of the critical without a lysine kinase (WNK)/STE20/SPS-1-related proline/alanine-rich kinase regulatory pathway before functional assessment. Here, we present a new mammalian model of the DCT, the mouse DCT15 (mDCT15) cell line. These cells display native NCC function as measured by thiazide-sensitive, Cl(-)-dependent (22)Na(+) uptake and allow for the separate assessment of NCC surface expression and activity. Knockdown by short interfering RNA confirmed that this function was dependent on NCC protein. Similar to the mammalian DCT, these cells express many of the known regulators of NCC and display significant baseline activity and dimerization of NCC. As described in previous models, NCC activity is inhibited by appropriate concentrations of thiazides, and phorbol esters strongly suppress function. Importantly, they display release of WNK4 inhibition of NCC by small hairpin RNA knockdown. We feel that this new model represents a critical tool for the study of NCC physiology. The work that can be accomplished in such a system represents a significant step forward toward unraveling the complex regulation of NCC.

  18. Beyond race and place: distal sociological determinants of HIV disparities.

    PubMed

    Buot, Max-Louis G; Docena, Jeffrey P; Ratemo, Brenda K; Bittner, Matthew J; Burlew, Jacob T; Nuritdinov, Aziz R; Robbins, Jennifer R

    2014-01-01

    Informed behavior change as an HIV prevention tool has yielded unequal successes across populations. Despite decades of HIV education, some individuals remain at high risk. The mainstream media often portrays these risk factors as products of race and national borders; however, a rich body of recent literature proposes a host of complex social factors that influence behavior, including, but not limited to: poverty, income inequality, stigmatizing social institutions and health care access. We examined the relationship between numerous social indicators and HIV incidence across eighty large U.S. cities in 1990 and 2000. During this time, major correlating factors included income inequality, poverty, educational attainment, residential segregation and marriage rates. However, these ecological factors were weighted differentially across risk groups (e.g. heterosexual, intravenous drug use, men who have sex with men (MSM)). Heterosexual risk rose significantly with poor economic indicators, while MSM risk depended more heavily on anti-homosexual stigma (as measured by same-sex marriage laws). HIV incidence among black individuals correlated significantly with numerous economic factors but also with segregation and imbalances in the male:female ratio (often an effect of mass incarceration). Our results support an overall model of HIV ecology where poverty, income inequality and social inequality (in the form of institutionalized racism and anti-homosexual stigma) have over time developed into synergistic drivers of disease transmission in the U.S., inhibiting information-based prevention efforts. The relative weights of these distal factors vary over time and by HIV risk group. Our testable model may be more generally applicable within the U.S. and beyond.

  19. Beyond race and place: distal sociological determinants of HIV disparities.

    PubMed

    Buot, Max-Louis G; Docena, Jeffrey P; Ratemo, Brenda K; Bittner, Matthew J; Burlew, Jacob T; Nuritdinov, Aziz R; Robbins, Jennifer R

    2014-01-01

    Informed behavior change as an HIV prevention tool has yielded unequal successes across populations. Despite decades of HIV education, some individuals remain at high risk. The mainstream media often portrays these risk factors as products of race and national borders; however, a rich body of recent literature proposes a host of complex social factors that influence behavior, including, but not limited to: poverty, income inequality, stigmatizing social institutions and health care access. We examined the relationship between numerous social indicators and HIV incidence across eighty large U.S. cities in 1990 and 2000. During this time, major correlating factors included income inequality, poverty, educational attainment, residential segregation and marriage rates. However, these ecological factors were weighted differentially across risk groups (e.g. heterosexual, intravenous drug use, men who have sex with men (MSM)). Heterosexual risk rose significantly with poor economic indicators, while MSM risk depended more heavily on anti-homosexual stigma (as measured by same-sex marriage laws). HIV incidence among black individuals correlated significantly with numerous economic factors but also with segregation and imbalances in the male:female ratio (often an effect of mass incarceration). Our results support an overall model of HIV ecology where poverty, income inequality and social inequality (in the form of institutionalized racism and anti-homosexual stigma) have over time developed into synergistic drivers of disease transmission in the U.S., inhibiting information-based prevention efforts. The relative weights of these distal factors vary over time and by HIV risk group. Our testable model may be more generally applicable within the U.S. and beyond. PMID:24743728

  20. Beyond Race and Place: Distal Sociological Determinants of HIV Disparities

    PubMed Central

    Buot, Max-Louis G.; Bittner, Matthew J.; Burlew, Jacob T.; Nuritdinov, Aziz R.; Robbins, Jennifer R.

    2014-01-01

    Informed behavior change as an HIV prevention tool has yielded unequal successes across populations. Despite decades of HIV education, some individuals remain at high risk. The mainstream media often portrays these risk factors as products of race and national borders; however, a rich body of recent literature proposes a host of complex social factors that influence behavior, including, but not limited to: poverty, income inequality, stigmatizing social institutions and health care access. We examined the relationship between numerous social indicators and HIV incidence across eighty large U.S. cities in 1990 and 2000. During this time, major correlating factors included income inequality, poverty, educational attainment, residential segregation and marriage rates. However, these ecological factors were weighted differentially across risk groups (e.g. heterosexual, intravenous drug use, men who have sex with men (MSM)). Heterosexual risk rose significantly with poor economic indicators, while MSM risk depended more heavily on anti-homosexual stigma (as measured by same-sex marriage laws). HIV incidence among black individuals correlated significantly with numerous economic factors but also with segregation and imbalances in the male:female ratio (often an effect of mass incarceration). Our results support an overall model of HIV ecology where poverty, income inequality and social inequality (in the form of institutionalized racism and anti-homosexual stigma) have over time developed into synergistic drivers of disease transmission in the U.S., inhibiting information-based prevention efforts. The relative weights of these distal factors vary over time and by HIV risk group. Our testable model may be more generally applicable within the U.S. and beyond. PMID:24743728

  1. The Rationale and Results of Gastroplasty/Distal Gastric Bypass.

    PubMed

    Salmon; McArdle

    1992-02-01

    A recent review of the results of gastroplasties done at the University of Alberta Hospital showed that there was a high incidence of late weight loss failure. Therefore a new operation, gastroplasty/distal gastric bypass, has been performed on 263 patients. This operation results In a profound (mean greatest percentage excess weight loss of 87% at approximately 2 years) and lasting weight loss (mean final percentage excess weight loss of 78%) at 4 years, range 2-7.5 years post-operatively. Only 0.9 % of patients failed to maintain at least a 40% excess weight loss. The operation achieves its effect through a moderate restriction that permits patients to eat normal table food from the time of discharge and with a mild metabsorption that is not ordinarily associated with diarrhea or notable deficiencies. Certain patients required debanding of the stoma and others developed staple-line eventration. Neither of these events after long-term follow-up resulted in weight loss failure nor in other serious side-effects. It Is concluded that moderate failure of the gastroplasty stoma and staple line does not necessarily result in weight loss failure, because the malabsorptive portion of the operation remains intact. Low hemoglobin occurred in 16% of cases and deficiency of serum iron In 34%; a much smaller number of patients had chronic or Intermittent deficiencies of these entities. Correction was easily achieved with oral replacement. Deficiencies in albumin, calcium, phosphorus and folate were rarely seen and minimal elevation of serum AST values occurred In just over 1% of patients. Chronic deficiencies or elevations were not seen in these patients. Stomal ulcer occurred in 6% of patients and bleeding associated with stomal ulcer in 1%. Half the patients with ulcer were managed with H&inf2; blockers, the other half with vagotomy. Both forms of treatment when individualized effectively prevent re-ulceration.

  2. Unusual cause for ventriculoperitoneal shunt failure: carcinoma breast compressing distal catheter.

    PubMed

    Roka, Yam B; Gupta, R; Bajracharya, A

    2010-01-01

    Insertion of a ventriculoperitoneal (VP) shunt is one of the most common surgical procedures in any neurosurgery unit worldwide. Distal catheter obstruction outside the peritoneum is a rare cause of shunt failure. We report the first case of distal obstruction in a 70-year old female by carcinoma breast engulfing the catheter and causing kinking. Intraoperatively, the catheter was intratumoral with no flow of cerebrospinal fluid distally. She underwent relocation of a new catheter to the opposite side of the abdomen and modified mastectomy with resolution of the hydrocephalus. The postoperative course has been uneventful.

  3. Tibial rotational osteotomy for idiopathic torsion. A comparison of the proximal and distal osteotomy levels.

    PubMed

    Krengel, W F; Staheli, L T

    1992-10-01

    A retrospective analysis was done of 52 rotational tibial osteotomies (RTOs) performed on 35 patients with severe idiopathic tibial torsion. Thirty-nine osteotomies were performed at the proximal or midtibial level. Thirteen were performed at the distal tibial level with a technique previously described by one of the authors. Serious complications occurred in five (13%) of the proximal and in none of the distal RTOs. For severe and persisting idiopathic tibial torsion, the authors recommend correction by RTO at the distal level. Proximal level osteotomy is indicated only when a varus or valgus deformity required concurrent correction.

  4. (99m)Tc-methylene diphosphonate bone scintigraphy findings in posttransplant distal limb syndrome.

    PubMed

    Derlin, Thorsten; Busch, Jasmin D; Bannas, Peter

    2014-07-01

    We report a case of posttransplant distal limb syndrome (PTDLS) representing a rare complication in kidney transplant recipients characterized by a pain syndrome of the distal extremities. A 68-year-old man with a history of kidney transplantation presented with symmetrical and incapacitating pain in the feet and knees and underwent whole-body Tc-methylene diphosphonate (MDP) scintigraphy for further evaluation. Planar scintigraphy demonstrated marked tracer uptake in the distal femoral and tibial epiphyses, and magnetic resonance imaging showed corresponding osteoedema. Tc-MDP scintigraphy is a valuable tool for evaluation of the etiology of musculoskeletal pain and may demonstrate typical findings in case of PTDLS.

  5. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases

    PubMed Central

    Tandra, Varun Sharma; Kotha, Krishna Mohan Reddy; Satyanarayana, Moorthy Gadisetti Venkata; Vadlamani, Kali Varaprasad; Yerravalli, Vyjayanthi

    2015-01-01

    Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge. PMID:26106496

  6. EUS-guided choledochoduodenostomy for malignant distal biliary obstruction palliation: an article review.

    PubMed

    Artifon, Everson L A; Perez-Miranda, Manuel

    2012-04-01

    The EUS-guided biliary drainage is a new tool for the palliation of distal obstructive biliary lesions. The EUS-guided access, which creates a fistulization between the duodenal bulb and distal common biliary duct, is an effective method to relieve jaundice and has low morbidity and mortality, in patients with distal biliary obstruction (pancreatic mass or papillary câncer). This technique is called choledochoduodenostomy and is presented promptly in this article. The EUS-guided biliary drainage should be made within protocol conditions and done by very experienced endosonographers.

  7. Distalization of the mandibular dentition with a ramal plate for skeletal Class III malocclusion correction.

    PubMed

    Kook, Yoon-Ah; Park, Jae Hyun; Bayome, Mohamed; Kim, Sungkon; Han, Eugene; Kim, Chang Hyen

    2016-08-01

    The retromolar fossa is an anatomically suitable skeletal anchorage site. The aim of this report was to introduce a novel appliance for the correction of skeletal Class III malocclusions with mandibular dentition distalization. The placement site and the procedure of the ramal plate are described. The resulting force vectors are parallel to the functional occlusal plane leading to efficient molar distalization. This approach is demonstrated with 2 adult patients who refused a surgical treatment option. This ramal plate may be indicated for total arch distalization for nonextraction and nonsurgical cases. PMID:27476370

  8. Distal myopathy with rimmed vacuoles and inflammation: a genetically proven case.

    PubMed

    Kannan, Meena A; Challa, S; Urtizberea, Andoni J; Krahn, Martin; Jabeen, A S; Borgohain, R

    2012-01-01

    Distal myopathy with rimmed vacuoles (DMRV) is a major entity of distal myopathy. It is an autosomal recessive disorder and is due to mutations in the GNE gene that regulates the synthesis of sialic acid. Although reported predominantly from Japan, cases have been reported from other parts of the world. We report the first genetically proven case of DMRV from India in a 23-year-old male with gradual onset, progressive distal weakness of both lower limbs with features of inflammation in muscle biopsy.

  9. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases.

    PubMed

    Tandra, Varun Sharma; Kotha, Krishna Mohan Reddy; Satyanarayana, Moorthy Gadisetti Venkata; Vadlamani, Kali Varaprasad; Yerravalli, Vyjayanthi

    2015-01-01

    Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge. PMID:26106496

  10. Upper gastrointestinal bleeding caused by a "hypophrenic" diverticulum of the distal esophagus.

    PubMed

    Sam, Albert D; Chaer, Rabih A; Cintron, Jose; Teresi, Miguel; Massad, Malek G

    2005-04-01

    Distal esophageal diverticula are uncommon acquired anomalies of the distal thoracic esophagus. We report a case of an elderly man presenting with a history of upper gastrointestinal bleeding secondary to a distal esophageal diverticulum arising from the intra-abdominal portion of the esophagus. To our knowledge, this is the first report of upper gastrointestinal bleeding from a subdiaphragmatic esophageal diverticulum. We propose the term "hypophrenic diverticulum of the esophagus" for this disease entity, and we would like to bring it to the attention of readers of The American Surgeon. PMID:15943409

  11. The Evolution of Distal Radius Fracture Management – A Historical Treatise

    PubMed Central

    Diaz-Garcia, Rafael J.; Chung, Kevin C.

    2012-01-01

    Distal radius fractures have been a common affliction for millennia, but their treatment is a more recent development as a result of human erudition. While immobilization has served as the only available treatment for most of our history, many advances have been made in the management of distal radius fractures over the last century as the field of orthopedics has grown. Yet, the topic remains hotly contested in the literature, and research continues to focus upon it given the frequency of the injury. In this article, we chronicle the evolution of distal radius fracture treatment in hopes of providing context for the future that lies ahead. PMID:22554653

  12. The Hybrid Hyrax Distalizer, a new all-in-one appliance for rapid palatal expansion, early class III treatment and upper molar distalization.

    PubMed

    Wilmes, Benedict; Ludwig, Björn; Katyal, Vandana; Nienkemper, Manuel; Rein, Anna; Drescher, Dieter

    2014-09-01

    Growing class III patients with maxillary deficiency may be treated with a maxillary protraction facemask. Because the force generated by this appliance is applied to the teeth, the inevitable mesial migration of the dentition can result in anterior crowding, incisor proclination and a possible need for subsequent extraction therapy. The Hybrid Hyrax appliance, anchored on mini-implants in the anterior palate, can be used to overcome these side-effects during the facemask therapy. In some class III cases, there is also a need for subsequent distalization after the orthopaedic treatment. In this paper, clinical application of the Hybrid Hyrax Distalizer is described, facilitating both orthopaedic advancement of the maxilla and simultaneous orthodontic distalization of the maxillary molars.

  13. Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

    PubMed

    Rau, Kristofer K; Petruska, Jeffrey C; Cooper, Brian Y; Johnson, Richard D

    2014-09-15

    Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted.

  14. Subintimal TRAnscatheter Withdrawal (STRAW) of hematomas compressing the distal true lumen: a novel technique to facilitate distal reentry during recanalization of chronic total occlusion (CTO).

    PubMed

    Smith, Elliot J; Di Mario, Carlo; Spratt, James C; Hanratty, Colm G; de Silva, Ranil; Lindsay, Alistair C; Grantham, J Aaron

    2015-01-01

    The development of a large hematoma impairing visualization of the distal true lumen is a recognized complication of antegrade recanalization of chronic total occlusions, often forcing the operator to abort the procedure or switch to a retrograde approach. We describe a novel technique utilizing an over-the-wire balloon inflated in the proximal occluded vessel to block inflow and allow aspiration of the blood from the subintimal space. This decompressed the true lumen, restored distal visualization, and allowed successful reentry using a dedicated technology. Utilization of this novel technique may rescue antegrade recanalization attempts complicated by large subintimal hematomas.

  15. Osteoblast maturation occurs in overlapping proximal-distal compartments during fin regeneration in zebrafish.

    PubMed

    Brown, Andrew M; Fisher, Shannon; Iovine, M Kathryn

    2009-11-01

    During fin regeneration, osteoblasts must continually differentiate for outgrowth of the bony fin rays. Bone maturity increases in a distal-proximal manner, and osteoblast maturation can be detected similarly when following gene expression. We find that early markers for osteoblast differentiation are expressed in a discrete domain at the distal end of the fin, just proximal to the adjacent germinal compartment of dividing cells. Matrix genes, required at later stages developmentally, are expressed in a population of cells proximally to the early genes. A marker for mature osteoblasts is expressed in cells further proximal. These domains of gene expression are partially overlapping, perhaps revealing additional levels of osteoblast maturity. We suggest a model for growth where new cells are continually added to the distal-most osteoblast compartment, while osteoblasts in more proximal locations differentiate, thus translating developmental time to location on the proximal-distal axis. PMID:19842180

  16. The management of nonunion and malunion of the distal humerus--a 30-year experience.

    PubMed

    Jupiter, Jesse B

    2008-01-01

    This personal series of nonunions of the distal humerus reviews unique features of this problem, categorizes them according to unique anatomic features, and presents pitfalls and pearls in the management of these complex reconstructive problems.

  17. Concurrent Minimally Invasive Carpal Tunnel Release Techniques in Distal Radius Open Reduction Internal Fixation.

    PubMed

    Low, O-Wern; Cheah, Andre E J

    2016-02-01

    Carpal tunnel syndrome is a common complication associated with distal radius fractures. Open carpal tunnel release in the same setting as open reduction and internal fixation of distal radius fractures is widely accepted. In this paper, we describe the technical details of a minimally invasive carpal tunnel release in the same setting as the fixation of a distal radius fracture via the same incision. Two options of minimally invasive techniques are described: The Knifelight® (Stryker, Kalamazoo, Michigan, USA) instrument and the single portal carpal tunnel release system (Agee, 3M Healthcare, St Paul, Minnesota, USA). Being well known and accepted techniques of carpal tunnel release, we believe that the techniques described in this paper provide a viable alternative for carpal tunnel release in the setting of distal radius fracture fixation; with the added advantages of the original minimally invasive techniques. PMID:27454517

  18. A Rare Giant Cell Tumor of the Distal Fibula and its Management

    PubMed Central

    Vaishya, Raju; Kapoor, Chirag; Golwala, Paresh; Vijay, Vipul

    2016-01-01

    Giant Cell Tumour (GCT) of the distal fibula is extremely rare and poses challenges in the surgical management. Wide excision or intralesional curettage, along with adjuvant chemical cauterisation can prevent the recurrence of GCT. The excised bone gap needs reconstruction using tricortical iliac autograft and supportive plate fixation. In addition to wide excision, preservation of ankle mortise is advisable in locally aggressive and large lesions of the distal fibula. We report a GCT of the distal fibula in a young female patient. As part of the treatment, en bloc resection, chemical cauterisation with phenol, and distal fibula reconstruction with a tricortical iliac crest bone graft was done. Eighteen months after the treatment, the patient has no recurrence and her ankle is stable with full range of movement. We suggest this method to be worthwhile for the treatment of this uncommon lesion in quantifying recurrence and functional outcome. PMID:27493848

  19. Bicolumnar 90-90 Plating of Low-Energy Distal Humeral Fractures in the Elderly Patient

    PubMed Central

    Leigey, Daniel F.; Farrell, Dana J.; Siska, Peter A.

    2014-01-01

    Fragility fractures of the distal humerus in elderly patients, especially the low transcondylar fracture pattern, can be difficult to optimally manage. Although the fractures are typically low energy resulting in either extra-articular or simple intra-articular patterns, gaining fixation into the distal fragments can be difficult with open reduction internal fixation (ORIF) using traditional 90-90 or parallel plating techniques. Anatomy preserving reconstruction with ORIF is preferred over total elbow arthroplasty (TEA) if possible. In this study, 15 patients were managed with a bicolumnar 90-90 plating construct as a novel method of enhancing distal fixation in these fractures. Fourteen patients went on to radiographic union at an average of 77 days after surgery with an average arc of motion of 105°. One patient was lost to follow-up. Bicolumnar 90-90 plating of distal humerus fractures in elderly patients may represent a viable alternative to traditional ORIF or TEA. PMID:25360342

  20. Bicolumnar 90-90 plating of low-energy distal humeral fractures in the elderly patient.

    PubMed

    Leigey, Daniel F; Farrell, Dana J; Siska, Peter A; Tarkin, Ivan S

    2014-09-01

    Fragility fractures of the distal humerus in elderly patients, especially the low transcondylar fracture pattern, can be difficult to optimally manage. Although the fractures are typically low energy resulting in either extra-articular or simple intra-articular patterns, gaining fixation into the distal fragments can be difficult with open reduction internal fixation (ORIF) using traditional 90-90 or parallel plating techniques. Anatomy preserving reconstruction with ORIF is preferred over total elbow arthroplasty (TEA) if possible. In this study, 15 patients were managed with a bicolumnar 90-90 plating construct as a novel method of enhancing distal fixation in these fractures. Fourteen patients went on to radiographic union at an average of 77 days after surgery with an average arc of motion of 105°. One patient was lost to follow-up. Bicolumnar 90-90 plating of distal humerus fractures in elderly patients may represent a viable alternative to traditional ORIF or TEA.

  1. Medial Closing-Wedge Distal Femoral Osteotomy: Fixation With Proximal Tibial Locking Plate

    PubMed Central

    Tírico, Luís Eduardo Passarelli; Demange, Marco Kawamura; Bonadio, Marcelo Batista; Helito, Camilo Partezani; Gobbi, Riccardo Gomes; Pécora, José Ricardo

    2015-01-01

    Distal femoral varus osteotomy is a well-established procedure for the treatment of lateral compartment cartilage lesions and degenerative disease, correcting limb alignment and decreasing the progression of the pathology. Surgical techniques can be performed with a lateral opening-wedge or medial closing-wedge correction of the deformity. Fixation methods for lateral opening-wedge osteotomies are widely available, and there are various types of implants that can be used for fixation. However, there are currently only a few options of implants for fixation of a medial closing-wedge osteotomy on the market. This report describes a medial, supracondylar, V-shaped, closing-wedge distal femoral osteotomy using a locked anterolateral proximal tibial locking plate that fits anatomically to the medial side of the distal femur. This is a great option as a stable implant for a medial closing-wedge distal femoral osteotomy. PMID:26870647

  2. An in vivo study of the effect of distal femoral resection on passive knee extension.

    PubMed

    Smith, Conrad K; Chen, Justin A; Howell, Stephen M; Hull, Maury L

    2010-10-01

    A previous study showed that 1 mm of distal femoral resection restored knee extension 4.5°. We determined the relationship with a more accurate measurement technique. Twenty-six subjects treated with total knee arthroplasty were studied. Digital photographs of the extended knee with and without 1.5 and 3.0 mm thick augments placed between the femoral component and distal femur were analyzed, and knee extension was measured. One millimeter of distal femoral resection restored 1.8° of extension that is less correction than the previous study reported. Because an attempt to correct a 10° extension deficit by resecting the distal femur could require 5 mm or more of bone removal that moves the joint line too proximal, we recommend exploring other techniques before resecting the femur.

  3. Nemaline myopathy caused by mutations in the nebulin gene may present as a distal myopathy.

    PubMed

    Lehtokari, Vilma-Lotta; Pelin, Katarina; Herczegfalvi, Agnes; Karcagi, Veronika; Pouget, Jean; Franques, Jerôme; Pellissier, Jean François; Figarella-Branger, Dominique; von der Hagen, Maja; Huebner, Angela; Schoser, Benedikt; Lochmüller, Hanns; Wallgren-Pettersson, Carina

    2011-08-01

    Mutations in the nebulin gene are the main cause of autosomal recessive nemaline myopathy, with clinical presentations ranging from mild to severe disease. We have previously reported a nonspecific distal myopathy caused by homozygous missense mutations in the nebulin gene in six Finnish patients from four different families. Here we describe three non-Finnish patients in two unrelated families with distal nemaline myopathy caused by four different compound heterozygous nebulin mutations, only one of which is a missense mutation. One of the mutations has previously been identified in one family with the severe form of nemaline myopathy. We conclude that nemaline myopathy and distal myopathy caused by nebulin mutations form a clinical and histological continuum. Nemaline myopathy should be considered as a differential diagnosis in patients presenting with an early-onset predominantly distal myopathy. PMID:21724397

  4. A Noble, Easy and Conceptual Radiographic Analysis to Assess the Type of Tooth Movement (Molar Distalization)

    PubMed Central

    Prakash, Anaveri Thimmappa; Deepthi; Naik, Atri

    2015-01-01

    Context and Aim Bodily tooth movement is desirable in the field of Orthodontics and so is with molar distalization. Till date there is no such analysis available which could gauge and quantify the molar distalization and the type of tooth movement achieved, therefore one was required. Materials and Methods An OPG and Lateral cephalogram was used taking Inter orbitale plane and FH plane respectively as reference lines and the analysis was devised to measure the amount and type of tooth movement achieved in distalization of molar. Conclusion This analysis is a noble, easy and conceptual analysis to assess the type of tooth movement achieved during molar distalization and other molar movements using Lateral cephalogram and orthopantomogram. PMID:26436040

  5. Bicolumnar 90-90 plating of low-energy distal humeral fractures in the elderly patient.

    PubMed

    Leigey, Daniel F; Farrell, Dana J; Siska, Peter A; Tarkin, Ivan S

    2014-09-01

    Fragility fractures of the distal humerus in elderly patients, especially the low transcondylar fracture pattern, can be difficult to optimally manage. Although the fractures are typically low energy resulting in either extra-articular or simple intra-articular patterns, gaining fixation into the distal fragments can be difficult with open reduction internal fixation (ORIF) using traditional 90-90 or parallel plating techniques. Anatomy preserving reconstruction with ORIF is preferred over total elbow arthroplasty (TEA) if possible. In this study, 15 patients were managed with a bicolumnar 90-90 plating construct as a novel method of enhancing distal fixation in these fractures. Fourteen patients went on to radiographic union at an average of 77 days after surgery with an average arc of motion of 105°. One patient was lost to follow-up. Bicolumnar 90-90 plating of distal humerus fractures in elderly patients may represent a viable alternative to traditional ORIF or TEA. PMID:25360342

  6. Endovascular treatment for ruptured distal anterior inferior cerebellar artery aneurysm -case report-.

    PubMed

    Ishii, Daizo; Takechi, Akihiko; Shinagawa, Katsuhiro; Sogabe, Takashi

    2010-01-01

    A 73-year-old woman presented with subarachnoid hemorrhage caused by a ruptured left distal anterior inferior cerebellar artery (AICA) aneurysm. Computed tomography showed a thin subarachnoid hemorrhage in the ambient cistern, and digital subtraction angiography revealed an aneurysm arising from the lateral branch of the left AICA, which was separate from the meatal loop. Endovascular treatment was performed to achieve parent artery occlusion using two Guglielmi detachable coils. Postoperatively, the patient had no complications except for left hearing disturbance, and she was independent in daily life. Endovascular parent artery occlusion for distal AICA aneurysm, especially distal from the meatal loop, can avoid sacrificing the internal auditory artery if the lateral branch of the AICA could be occluded more distally from the meatal loop. Sufficient collateral circulation prevents major infarction, and this strategy may be the first-line treatment choice. PMID:20505296

  7. A Rare Giant Cell Tumor of the Distal Fibula and its Management.

    PubMed

    Vaishya, Raju; Kapoor, Chirag; Golwala, Paresh; Agarwal, Amit Kumar; Vijay, Vipul

    2016-01-01

    Giant Cell Tumour (GCT) of the distal fibula is extremely rare and poses challenges in the surgical management. Wide excision or intralesional curettage, along with adjuvant chemical cauterisation can prevent the recurrence of GCT. The excised bone gap needs reconstruction using tricortical iliac autograft and supportive plate fixation. In addition to wide excision, preservation of ankle mortise is advisable in locally aggressive and large lesions of the distal fibula. We report a GCT of the distal fibula in a young female patient. As part of the treatment, en bloc resection, chemical cauterisation with phenol, and distal fibula reconstruction with a tricortical iliac crest bone graft was done. Eighteen months after the treatment, the patient has no recurrence and her ankle is stable with full range of movement. We suggest this method to be worthwhile for the treatment of this uncommon lesion in quantifying recurrence and functional outcome. PMID:27493848

  8. Distal ejecta - an efficient tool to study ancient impacts?

    NASA Astrophysics Data System (ADS)

    Artemieva, N.

    2011-12-01

    Ejecta from impact craters received a scientific attention not too many years ago, after the revolutionary discovery of the global K-Pg layer and its Ir-anomaly. Impact ejecta are subjected to quick erosion and, hence, are not widely presented on Earth. However, globally distributed ejecta from the largest terrestial craters may be locally preserved even if the crater itself is totally obliterated. The oldest craters on Earth, Vredefort and Sudbury, are ~1.5 Gyr younger than then oldest Archean spherule layers [1-2]. These ejecta layers potentially allow to extract an important information regarding a projectile type/size, the Earth's crust and ocean. Recent numerical modeling of the K-Pg layer [3] successfully reproduced ejecta distribution around the globe including chemical composition, shock metamorphic features, and pressure-temperature history of deposited materials. It has been shown that the main components of global ejecta are projectile and sediments (the uppermost layer of the target), while materials from the crystalline basement represent the minor component and have been transported non-ballistically by atmospheric flows. These results could serve as a benchmark for the modeling of ancient impacts. As the Archean layers are much thicker and the spherules are larger, we can speculate about much larger and more frequent impacts. A few questions should be addressed via numerical modeling: 1) are these ejecta layers proximal layers of relatively small impacts or distal layers of giant impacts; 2) is there any correlation between layers at different locations;.3) why there are no any shocked minerals within these layers; 3) why the composition of spherules is mainly basaltic? In this paper the modeling results are compared with available observations (mainly on K-Pg boundary) and then are extrapolated to much larger impacts. [1] Lowe D.R., Byerly G. R., Asaro F., Kyte F. T. (1989) Science 245:959-962. [2] Simonson, B. M. and B. P. Glass (2004) Annual

  9. Human anion exchanger1 mutations and distal renal tubular acidosis.

    PubMed

    Yenchitsomanus, Pa-thai

    2003-09-01

    The human anion exchanger 1 (AE1 or SLC4A1) gene encodes anion exchanger 1 (or band 3) protein in erythrocytes and in alpha-intercalated cells of the kidney. Thus, AE1 mutations show pleiotrophic effects resulting in two distinct and seemingly unrelated defects, an erythrocyte abnormality and distal renal tubular acidosis (dRTA). Southeast Asian ovalocytosis (SAO), a well-known red blood cell (RBC) defect, which is widespread in Southeast Asian regions, is caused by AE1 mutation due to a deletion of 27 base pairs in codons 400-408 (delta400-408) leading to an in-frame 9 amino-acid loss in the protein. Co-existence of SAO and dRTA is usually not seen in the same individual. However, the two conditions can co-exist as the result of compound heterozygosities between delta400-408 and other mutations. The reported genotypes include delta400-408/G701D, delta400-408/R602H, delta400-408/deltaV850, and delta400-408/A858D. The presence of dRTA, with or without RBC abnormalities, may occur from homozygous or compound heterozygous conditions of recessive AE1 mutations (eg G701D/G701D, V488M/V488M, deltaV850/deltaV850, deltaV850/A858D, G701D/S773P) or heterozygous dominant AE1 mutations (eg R598H, R589C, R589S, S613F, R901X). Codon 589 of this gene seems to be a 'mutational hot-spot' since repeated mutations at this codon occurring in different ethnic groups and at least two de novo (R589H and R589C) mutations have been observed. Therefore, AE1 mutations can result in both recessive and dominant dRTA, possibly depending on the position of the amino acid change in the protein. As several mutant AE1 proteins still maintain a significant anion transport function but are defective in targeting to the cell surface, impaired intracellular trafficking of the mutant AE1 is an important molecular mechanism involved in the pathogenesis of dRTA associated with AE1 mutations. PMID:15115146

  10. Insufficiency fractures of the distal tibia misdiagnosed as cellulitis in three patients with rheumatoid arthritis

    SciTech Connect

    Straaton, K.V.; Lopez-Mendez, A.; Alarcon, G.S. )

    1991-07-01

    We describe 3 patients with rheumatoid arthritis who presented with diffuse pain, swelling, and erythema of the distal aspect of the lower extremity, suggestive of either cellulitis or thrombophlebitis, but were found to have insufficiency fractures of the distal tibia. The value of technetium-99m diphosphonate bone scintigraphy in the early recognition of these fractures and a possible explanation for the associated inflammatory symptoms are discussed.

  11. Toward endoscopes with no distal optics: video-rate scanning microscopy through a fiber bundle.

    PubMed

    Andresen, Esben Ravn; Bouwmans, Géraud; Monneret, Serge; Rigneault, Hervé

    2013-03-01

    We report a step toward scanning endomicroscopy without distal optics. The focusing of the beam at the distal end of a fiber bundle is achieved by imposing a parabolic phase profile across the exit face with the aid of a spatial light modulator. We achieve video-rate images by galvanometric scanning of the phase tilt at the proximal end. The approach is made possible by the bundle, designed to have very low coupling between cores.

  12. Mononeuropathy of a distal branch of the femoral nerve in a body building champion

    PubMed Central

    Padua, L; D'Aloya, E; LoMonaco, M; Padua, R; Gregori, B; Tonali, P

    1997-01-01

    A unique case of a body building champion with localised atrophy of the distal portion of the vastus lateralis muscle is reported; neurophysiological evaluation suggests a selective lesion of a distal branch of the vastus lateralis nerve (a motor branch of the femoral nerve). A necroscopic study in four cases was performed to better clarify the site and mechanism of nerve lesion. The data suggest that stretching and compression of the nerve has probably occurred during strenous exercise.

 PMID:9408112

  13. Carpal tunnel syndrome: A rare manifestation of distal radius osteoid osteoma.

    PubMed

    Basran, Sukhvinder Singh; Kumar, Sandeep; Jameel, Javed; Sajid, Imran

    2015-09-01

    Osteoid Osteoma is a benign bone tumor that normally affects long bones and rarely affects distal radius. Because of its nonspecific presentation in the wrist, it remains a diagnostic challenge. We report an unusual case of Osteoid Osteoma at distal radius having symptoms resembling that of carpal tunnel syndrome. The diagnosis was confirmed preoperatively with X-rays; bone scintigraphy, CT, and MRI, later histological examination confirmed the diagnoses. Surgical excision lead to a dramatic improvement in the condition of the patient.

  14. Distal myopathy with coexisting heterozygous TIA1 and MYH7 Variants.

    PubMed

    Brand, Patricio; Dyck, P James B; Liu, Jie; Berini, Sarah; Selcen, Duygu; Milone, Margherita

    2016-08-01

    TIA1 mutations cause Welander distal myopathy. MYH7 mutations result in various clinical phenotypes, including Laing distal myopathy and cardiomyopathy. We describe a family with coexisting TIA1 and MYH7 variants. The proband is a 67-year-old woman with easy tripping since childhood and progressive asymmetric distal limb weakness, but no cardiac involvement. Muscle biopsy showed rare rimmed vacuoles, minicore-like structures and congophilic inclusions. Her 66-year-old sister has a mild distal myopathy, supraventricular tachycardia and hypertrophic cardiomyopathy. Both sisters carry the only known pathogenic TIA1 mutation and a heterozygous MYH7 variant (c.5459G > A; p.Arg1820Gln). Another sibling with isolated distal myopathy carries only the TIA1 mutation. MYH7 p.Arg1820Gln involves a highly conserved residue and is predicted to be deleterious. Furthermore, the proband's childhood-onset distal leg weakness and sister's cardiomyopathy suggest that MYH7 p.Arg1820Gln likely affects function, favoring a digenic etiology of the myopathy. PMID:27282841

  15. Chloroperoxidase-Catalyzed Epoxidation of Cis-β-Methylstyrene:Distal Pocket Flexibility Tunes Catalytic Reactivity

    PubMed Central

    Morozov, Alexander N.; Chatfield, David C.

    2012-01-01

    Chloroperoxidase, the most versatile heme protein, has a hybrid active site pocket that shares structural features with peroxidases and cytochrome P450s. The simulation studies presented here show that the enzyme possesses a remarkable ability to efficiently utilize its hybrid structure, assuming structurally different peroxidase-like and P450-like distal pocket faces and thereby enhancing the inherent catalytic capability of the active center. We find that during epoxidation of cis-β-methylstyrene (CBMS), the native peroxidase-like aspect of the distal pocket is diminished as the polar Glu183 side chain is displaced away from the active center and the distal pocket takes on a more hydrophobic, P450-like, aspect. The P450-like distal pocket provides a significant enthalpic stabilization of ~4 kcal/mol of the 14 kcal/mol reaction barrier for gas-phase epoxidation of CMBS by an oxyferryl heme-thiolate species. This stabilization comes from breathing of the distal pocket. As until recently the active site of chloroperoxidase was postulated to be inflexible, these results suggest a new conceptual understanding of the enzyme’s versatility: catalytic reactivity is tuned by flexibility of the distal pocket. PMID:23020548

  16. Pearls and Pitfalls of the Volar Locking Plating for Distal Radius Fractures.

    PubMed

    Im, Jin-Hyung; Lee, Joo-Yup

    2016-06-01

    Volar locking plate fixation has been widely accepted method for the treatment of unstable distal radius fractures. Although the results of volar locking plate fixation are encouraging, it may cause implant-related complications such as flexor or extensor tendon injuries. In depth understanding of anatomy of the distal radius is mandatory in order to obtain adequate fixation of the fracture fragments and to avoid these complications. This article will review the anatomic characteristics of the distal radius because selecting proper implant and positioning of the plate is closely related to the volar surface anatomy of the distal radius. The number and the length of distal locking screws are also important to provide adequate fixation strength to maintain fracture fixation. We will discuss the pros and cons of the variable-angle locking plate, which was introduced in an effort to provide surgeons with more freedom for fixation. Finally, we will discuss about correcting radial length and volar tilt by using eccentric drill holes and distal locking first technique.

  17. Shape Ontogeny of the Distal Femur in the Hominidae with Implications for the Evolution of Bipedality

    PubMed Central

    Tallman, Melissa

    2016-01-01

    Heterochrony has been invoked to explain differences in the morphology of modern humans as compared to other great apes. The distal femur is one area where heterochrony has been hypothesized to explain morphological differentiation among Plio-Pleistocene hominins. This hypothesis is evaluated here using geometric morphometric data to describe the ontogenetic shape trajectories of extant hominine distal femora and place Plio-Pleistocene hominins within that context. Results of multivariate statistical analyses showed that in both Homo and Gorilla, the shape of the distal femur changes significantly over the course of development, whereas that of Pan changes very little. Development of the distal femur of Homo is characterized by an elongation of the condyles, and a greater degree of enlargement of the medial condyle relative to the lateral condyle, whereas Gorilla are characterized by a greater degree of enlargement of the lateral condyle, relative to the medial. Early Homo and Australopithecus africanus fossils fell on the modern human ontogenetic shape trajectory and were most similar to either adult or adolescent modern humans while specimens of Australopithecus afarensis were more similar to Gorilla/Pan. These results indicate that shape differences among the distal femora of Plio-Pleistocene hominins and humans cannot be accounted for by heterochrony alone; heterochrony could explain a transition from the distal femoral shape of early Homo/A. africanus to modern Homo, but not a transition from A. afarensis to Homo. That change could be the result of genetic or epigenetic factors. PMID:26886416

  18. A Pitfall in Fixation of Distal Humeral Fractures with Pre-Contoured Locking Compression Plate

    PubMed Central

    Jayakumar, Prakash; Ring, David

    2015-01-01

    Anatomically precontoured locking plates are intended to facilitate the fixation of articular fractures and particularly those associated with osteoporosis. Fractures of the distal humerus are relatively uncommon injuries where operative intervention can be exceptionally challenging. The distal humeral trochlea provides a very narrow anatomical window through which to pass a fixed-angle locking screw, which must also avoid the olecranon, coronoid, and radial fossae. We describe 3 patients (ages 27, 49, and 73 years) with a bicolumnar fracture of the distal humerus where very short distal locking screws were used. Intra-articular screw placement was avoided but loss of fixation occurred in two patients and a third was treated with a prolonged period of immobilization. We postulate that fixed-angle screw trajectories may make it difficult for the surgeon to place screws of adequate length in this anatomically confined region, and may lead to insufficient distal fixation. Surgical tactics should include placement of as many screws as possible into the distal fragment, as long as possible and that each screw passes through a plate without necessarily locking in. PMID:26110181

  19. Shape Ontogeny of the Distal Femur in the Hominidae with Implications for the Evolution of Bipedality.

    PubMed

    Tallman, Melissa

    2016-01-01

    Heterochrony has been invoked to explain differences in the morphology of modern humans as compared to other great apes. The distal femur is one area where heterochrony has been hypothesized to explain morphological differentiation among Plio-Pleistocene hominins. This hypothesis is evaluated here using geometric morphometric data to describe the ontogenetic shape trajectories of extant hominine distal femora and place Plio-Pleistocene hominins within that context. Results of multivariate statistical analyses showed that in both Homo and Gorilla, the shape of the distal femur changes significantly over the course of development, whereas that of Pan changes very little. Development of the distal femur of Homo is characterized by an elongation of the condyles, and a greater degree of enlargement of the medial condyle relative to the lateral condyle, whereas Gorilla are characterized by a greater degree of enlargement of the lateral condyle, relative to the medial. Early Homo and Australopithecus africanus fossils fell on the modern human ontogenetic shape trajectory and were most similar to either adult or adolescent modern humans while specimens of Australopithecus afarensis were more similar to Gorilla/Pan. These results indicate that shape differences among the distal femora of Plio-Pleistocene hominins and humans cannot be accounted for by heterochrony alone; heterochrony could explain a transition from the distal femoral shape of early Homo/A. africanus to modern Homo, but not a transition from A. afarensis to Homo. That change could be the result of genetic or epigenetic factors.

  20. Treatment effects of mandibular total arch distalization using a ramal plate

    PubMed Central

    Yu, Jonghan; Park, Jae Hyun; Bayome, Mohamed; Kim, Sungkon; Kook, Yoon-Ah; Kim, Yoonji

    2016-01-01

    Objective The purpose of this study was to evaluate treatment effects after distalization of the mandibular dentition using ramal plates through lateral cephalograms. Methods Pre- and post-treatment lateral cephalograms and dental casts of 22 adult patients (11 males and 11 females; mean age, 23.9 ± 5.52 years) who received ramal plates for mandibular molar distalization were analyzed. The treatment effects and amount of distalization of the mandibular molars were calculated and tested for statistical significance. The significance level was set at p < 0.001. Results The mandibular first molar distalization at the crown and root were 2.10 mm (p < 0.001) and 0.81 mm (p = 0.011), respectively. In the evaluation of skeletal variables, there was a significant increase in the Wits appraisal (p < 0.001). In the evaluation of the soft tissue, there was no significant effect on upper lip position, but the lower lips showed a significant retraction of 2.2 mm (p < 0.001). Conclusions The mandibular molars showed a significant amount of distalization accompanied by limited extrusion and mesiobuccal rotation of the crowns. A ramal plate may be a viable device for mandibular total arch distalization in Class III patients who are reluctant to undergo orthognathic surgery. PMID:27478798

  1. Bilateral en-masse distalization of maxillary posterior teeth with skeletal anchorage: a case report

    PubMed Central

    Noorollahian, Saeed; Alavi, Shiva; Shirban, Farinaz

    2016-01-01

    ABSTRACT Objective: The aim of this study was to introduce a new method for bilateral distal movement of the entire maxillary posterior segment. Case report: A 17-year-old girl with Class I skeletal malocclusion (end-to-end molar relationships, deviated midline and space deficiency for left maxillary canine) was referred for orthodontic treatment. She did not accept maxillary first premolars extraction. A modified Hyrax appliance (Dentaurum Ispringen, Germany) was used for bilateral distalization of maxillary posterior teeth simultaneously. Expansion vector was set anteroposteriorly. Posterior legs of Hyrax were welded to first maxillary molar bands. All posterior teeth on each side consolidated with a segment of 0.017 × 0.025-in stainless steel wire from the buccal side. Anterior legs of Hyrax were bent into eyelet form and attached to the anterior palate with two mini-screws (2 × 10 mm) (Jeil Medical Corporation Seoul, South Korea). Hyrax opening rate was 0.8 mm per month. Lateral cephalometric radiographs were used to evaluate the extent of distal movement. 3.5-mm distalization of posterior maxillary teeth was achieved in five months. Results: A nearly bodily distal movement without anchorage loss was obtained. Conclusion: The mini-screw-supported modified Hyrax appliance was found to be helpful for achieving en-masse distal movement of maxillary posterior teeth. PMID:27409657

  2. Prebending of a titanium elastic intramedullary nail in the treatment of distal radius fractures in children.

    PubMed

    Cai, Haoqi; Wang, Zhigang; Cai, Haiqing

    2014-01-01

    The aims of this study were to introduce a method to treat distal radius diaphyseal metaphyseal junction fractures by prebending an elastic intramedullary nail and to evaluate the factors influencing fracture apposition. Fifty-two consecutive patients (4 to 15 years old) with a distal radius diaphyseal metaphyseal junction fracture were included. The nail was inserted and advanced into the proximal radial fragment as normal. After bending the nail distally about 90° at the site predetermined to lie at the distal segment, the elastic intramedullary nail was advanced until the prebent part completely entered the marrow cavity. The fracture angular deformity was fully corrected in anterior-posterior and lateral views. The apposition rate was 90% to 100% in lateral view, >50% in anterior-posterior view. The operation time was 16.73 ± 6.253 minutes. The average time of fracture healing was 5 months (range, 4-7 months). During 12 to 19 months of follow-up, firm fracture healing and good remodeling were observed, and there was no impaired forearm rotation function or secondary fracture. Our study showed the treatment of distal radius diaphyseal metaphyseal junction fractures by prebent intramedullary nail could make up for the deficiency of Kirschner wires and steel plates and keep the fracture stable. Fracture type and the anatomical features of the distal radius were associated with fracture apposition. PMID:24833151

  3. A reliable method for evaluating upper molar distalization: Superimposition of three-dimensional digital models

    PubMed Central

    Nalcaci, Ruhi; Bicakci, Ali Altug; Ozturk, Firat; Babacan, Hasan

    2015-01-01

    Objective The aim of this study was to evaluate the reliability of measurements obtained after the superimposition of three-dimensional (3D) digital models by comparing them with those obtained from lateral cephalometric radiographs and photocopies of plaster models for the evaluation of upper molar distalization. Methods Data were collected from plaster models and lateral cephalometric radiographs of 20 Class II patients whose maxillary first molars were distalized with an intraoral distalizer. The posterior movements of the maxillary first molars were evaluated using lateral cephalometric radiographs (group CP), photocopies of plaster models (group PH), and digitized 3D models (group TD). Additionally, distalization and expansion of the other teeth and the degrees of molar rotation were measured in group PH and group TD and compared between the two groups. Results No significant difference was observed regarding the amount of molar distalization among the three groups. A comparison of the aforementioned parameters between group PH and group TD did not reveal any significant difference. Conclusions 3D digital models are reliable to assess the results of upper molar distalization and can be considered a valid alternative to conventional measurement methods. PMID:25798414

  4. Pearls and Pitfalls of the Volar Locking Plating for Distal Radius Fractures.

    PubMed

    Im, Jin-Hyung; Lee, Joo-Yup

    2016-06-01

    Volar locking plate fixation has been widely accepted method for the treatment of unstable distal radius fractures. Although the results of volar locking plate fixation are encouraging, it may cause implant-related complications such as flexor or extensor tendon injuries. In depth understanding of anatomy of the distal radius is mandatory in order to obtain adequate fixation of the fracture fragments and to avoid these complications. This article will review the anatomic characteristics of the distal radius because selecting proper implant and positioning of the plate is closely related to the volar surface anatomy of the distal radius. The number and the length of distal locking screws are also important to provide adequate fixation strength to maintain fracture fixation. We will discuss the pros and cons of the variable-angle locking plate, which was introduced in an effort to provide surgeons with more freedom for fixation. Finally, we will discuss about correcting radial length and volar tilt by using eccentric drill holes and distal locking first technique. PMID:27454625

  5. Shape Ontogeny of the Distal Femur in the Hominidae with Implications for the Evolution of Bipedality.

    PubMed

    Tallman, Melissa

    2016-01-01

    Heterochrony has been invoked to explain differences in the morphology of modern humans as compared to other great apes. The distal femur is one area where heterochrony has been hypothesized to explain morphological differentiation among Plio-Pleistocene hominins. This hypothesis is evaluated here using geometric morphometric data to describe the ontogenetic shape trajectories of extant hominine distal femora and place Plio-Pleistocene hominins within that context. Results of multivariate statistical analyses showed that in both Homo and Gorilla, the shape of the distal femur changes significantly over the course of development, whereas that of Pan changes very little. Development of the distal femur of Homo is characterized by an elongation of the condyles, and a greater degree of enlargement of the medial condyle relative to the lateral condyle, whereas Gorilla are characterized by a greater degree of enlargement of the lateral condyle, relative to the medial. Early Homo and Australopithecus africanus fossils fell on the modern human ontogenetic shape trajectory and were most similar to either adult or adolescent modern humans while specimens of Australopithecus afarensis were more similar to Gorilla/Pan. These results indicate that shape differences among the distal femora of Plio-Pleistocene hominins and humans cannot be accounted for by heterochrony alone; heterochrony could explain a transition from the distal femoral shape of early Homo/A. africanus to modern Homo, but not a transition from A. afarensis to Homo. That change could be the result of genetic or epigenetic factors. PMID:26886416

  6. A comparison of proximal and distal high-frequency jet ventilation in an experimental animal model.

    PubMed

    Bandy, K P; Donn, S M; Nicks, J J; Naglie, R A

    1986-01-01

    High-frequency jet ventilation using either a proximal or a distal endotracheal injection site through a triple-lumen endotracheal tube was studied in 10 adult cats. The comparative effects on pulmonary gas exchange, tracheal pressure, heart rate, and blood pressure were examined for each injection site at both high (8-12 pounds per square inch [PSI] and low (5-8 PSI) jet-driving pressures in normal and lung-injured cats. Lung injury was created by modification of a surfactant washout technique previously demonstrated in rabbits. Alveolar ventilation (PaCO2) was found to be significantly better with distal than with proximal jet injection under all experimental conditions. At high jet-driving pressures, peak inspiratory pressure was higher in both normal (p = 0.03) and lung-injured cats (p = 0.002) with distal high-frequency jet ventilation. In addition, lung-injured animals were observed to have higher distal mean airway pressures at high jet-driving pressures (p less than 0.01). No differences in oxygenation were found in any circumstances. The results of this animal study suggest that distal high-frequency jet ventilation may be more effective in those situations in which improvement in alveolar ventilation is the major goal and that during proximal high-frequency jet ventilation airway pressures should be monitored as far distally as possible.

  7. Comparison of K-loop Molar Distalization with that of Pendulum Appliance - A Prospective Comparative Study

    PubMed Central

    Shashidhar, Nagam Reddy; Reddy, S.Rama Koteswara

    2016-01-01

    Introduction Molar distalization is the non extraction method of managing Class II malocclusions. Aim The purpose of this study was to evaluate the skeletal and dentoalveolar effects of maxillary molar distalization with K-loop appliance, and to compare these effects with that of pendulum group. Materials and Methods Class I and dental Class II malocclusions were divided into two groups of 15 each: In Group 1 (nine females and six males; mean age, 16.0±2.6 years) patients were treated with K-Loop molar distalization supported palatally by Nance button, while in Group 2 (seven females and eight males; mean age, 15.4±4.7 years), the patients were treated with conventional pendulum appliance. Standardized lateral cephalograms were taken at the beginning of treatment (T0) and at the end of molar distalization (T1) and the changes were statistically analyzed with paired t-test. Results The results showed no statistically significant difference in the amount of molar distalization in either of the appliance groups: the mean amount of molar distal movement of 5.1±0.8 mm and 4.93±1.68 mm was observed in the Group 1 and 2 respectively. The incisors moved mesially by 1.3±0.63 mm in Group 1 and 1.57±0.58 mm in Group 2. Conclusion K-Loop molar distalizing appliance has similar skeletal and dentoalveolar effects as that of pendulum appliance, with the advantages of simple yet efficient to control the moment-force ratio to produce all types of tooth movements and also requires minimal patient co-operation. PMID:27504403

  8. Osteopathology in the Equine Distal Phalanx Associated With the Development and Progression of Laminitis.

    PubMed

    Engiles, J B; Galantino-Homer, H L; Boston, R; McDonald, D; Dishowitz, M; Hankenson, K D

    2015-09-01

    Although the equine distal phalanx and hoof lamellae are biomechanically and physiologically integrated, bony changes in the distal phalanx are poorly described in laminitis. The aims of this study were (1) to establish a laminitis grading scheme that can be applied to the wide spectrum of lesions seen in naturally occurring cases and (2) to measure and describe changes in the distal phalanx associated with laminitis using micro-computed tomography (micro-CT) and histology. Thirty-six laminitic and normal feet from 15 performance and nonperformance horses were evaluated. A laminitis grading scheme based on radiographic, gross, histopathologic, and temporal parameters was developed. Laminitis severity grades generated by this scheme correlated well with clinical severity and coincided with decreased distal phalanx bone volume and density as measured by micro-CT. Laminitic hoof wall changes included progressive ventral rotation and distal displacement of the distal phalanx with increased thickness of the stratum internum-corium tissues with lamellar wedge formation. Histologically, there was epidermal lamellar necrosis with basement membrane separation and dysplastic regeneration, including acanthosis and hyperkeratosis, corresponding to the lamellar wedge. The changes detected by micro-CT corresponded to microscopic findings in the bone, including osteoclastic osteolysis of trabecular and osteonal bone with medullary inflammation and fibrosis. Bone changes were identified in horses with mild/early stages of laminitis as well as severe/chronic stages. The authors conclude that distal phalangeal pathology is a quantifiable and significant component of laminitis pathology and may have important implications for early detection or therapeutic intervention of equine laminitis. PMID:26063172

  9. Does Total Gastrectomy Provide Better Outcomes than Distal Subtotal Gastrectomy for Distal Gastric Cancer? A Systematic Review and Meta-Analysis

    PubMed Central

    Qi, Jin; Zhang, Peng; Wang, Yanan; Chen, Hao; Li, Yumin

    2016-01-01

    Background/Aims Total gastrectomy (TG) has shown to be superior regarding low risk of recurrence and readmission to distal subtotal gastrectomy (DG) for treatment of distal stomach cancer, but the incidence of postoperative morbidity and mortality in TG cannot be ignored. Therefore, we performed a meta-analysis to compare the effectiveness between TG and DG for distal stomach cancer. Methodology A search in PubMed, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Database through January 2016 was performed. Eligible studies in comparing of TG and DG for distal gastric cancer were included in this meta-analysis. Review Manager 5.2 software from the Cochrane Collaboration was used for the performance of meta-analysis and STATA 12.0 software for meta-regression analysis. Results Ten retrospective cohort studies and one randomized control trial involving 5447 patients were included. The meta-analysis showed no significant difference of postoperative mortality (RR = 1.48, 95%CI = 0. 90–2.44,p = 0.12), intraoperative blood loss (MD = 24.34, 95%CI = -3.31–51.99, p = 0.08) and length of hospital stay(MD = 0.76, 95%CI:-0.26–1.79, p = 0.15). TG procedure could retrieve more lymph nodes than DG(MD = 4.33, 95% CI = 2.34–6.31, p<0.0001). According to different postoperative complications, we performed subgroup analysis, subgroup analysis revealed that patients in TG group tended to have a higher rate of postoperative intra-abdominal abscess than DG procedure (RR = 3.41, 95% CI = 1.21–9.63,p<0.05). No statistical differences were found in leakage, intestinal obstruction, postoperative bleeding, anastomotic stricture and wound infection between the two groups (p>0.05). We pooled the data together, the accumulated 5-year Overall Survival rates of TG and DG groups were 49.6% (919/1852) vs.55.9%(721/1290) respectively. Meta-analysis revealed a favoring trend to DG procedure and there was a statistical difference between the two groups (RR = 0.91,95% CI = 0

  10. Ankylosis of the distal interphalangeal joint in a horse after septic arthritis and septic navicular bursitis.

    PubMed

    Honnas, C M; Schumacher, J; Kuesis, B S

    1992-04-01

    A 6-month-old 300-kg Quarter Horse filly was treated for septic arthritis of the distal interphalangeal joint and septic navicular bursitis that developed as a result of a deep puncture to the foot. Initial treatment consisted of establishing ventral drainage for the navicular bursa, lavage of the distal interphalangeal joint, and administration of broad-spectrum antimicrobial drugs and non-steroidal anti-inflammatory drugs. Because of continuing sepsis in the distal interphalangeal joint, subsequent treatment included packing the defect in the bottom of the foot with cancellous bone in an attempt to prevent ascending contamination of the joint, placing the limb in a short limb cast, and inserting a Penrose drain into the joint for passive drainage of septic exudate. The goal of treatment was to encourage ankylosis of the distal interphalangeal joint. Because of the filly's persistent lameness and laxity of the lateral collateral ligament in the contralateral carpus, the palmar nerves of the affected foot were injected with a long-acting local anesthetic at the level of the proximal sesamoid bones to encourage weight-bearing. Ankylosis of the distal interphalangeal joint was complete 9 months after the puncture, but a grade-2 lameness remained and the horse had a varus deformity resulting from ligamentous laxity of the lateral collateral ligament in the contralateral carpus.

  11. The presence of distal and proximal promoters for rat mitochondrial glycerol-3-phosphate acyltransferase

    PubMed Central

    Aneja, Kawalpreet K; Guha, Prajna; Shilpi, Rasheda Y.; Chakraborty, Sanjoy; Schramm, Laura M.; Haldar, Dipak

    2008-01-01

    Sequence analysis using the Promoser program predicted two promoter like regions for rat mtGPAT: a distal promoter ∼30 kb upstream and a proximal promoter near the first translational codon. Rat liver cells transfected with pGL3-basic vector containing the distal and proximal promoter resulted in 10.8 and 4.8 fold increase in the luciferase activity, respectively. Results of electromobility shift assay and chromatin immunoprecipitation suggested binding of transcription factors to the distal and proximal promoter regions. 5′RACE PCR showed two transcripts with different transcriptional start sites. When transfected rat liver cells were starved and refed, there was about 2.7 fold increase in the luciferase activity with cells transfected with the distal promoter while the proximal promoter showed no change. Thus, the two promoters could be functionally distinguished. Taken together, we conclude that there are two promoters for rat mtGPAT gene and that the transcriptional regulation is mediated through the distal promoter. PMID:18021946

  12. New phenotype and pathology features in MYH7-related distal myopathy.

    PubMed

    Tasca, Giorgio; Ricci, Enzo; Penttilä, Sini; Monforte, Mauro; Giglio, Vincenzo; Ottaviani, Pierfrancesco; Camastra, Giovanni; Silvestri, Gabriella; Udd, Bjarne

    2012-07-01

    Laing distal myopathy is an autosomal dominant disease due to mutations in the gene encoding for the human slow-β myosin heavy chain, MYH7. Most reports describe it as a mild, early onset myopathy with involvement usually restricted to foot extensors, hand finger extensors and neck flexors, and unspecific findings on muscle biopsy. We identified the first two Italian families with Laing distal myopathy, harboring two novel mutations in the MYH7 gene and performed clinical, neurophysiological, pathological, muscle MRI and cardiological investigations on affected members from the two families. Subjects from one family presented a moderate-severe phenotype, with proximal together with distal involvement and even loss of ambulation at advanced age. One patient displayed atypical muscle biopsy findings including cytoplasmic bodies and myofibrillar myopathy-like features. Affected members from the second family shared a very mild phenotype, with weakness largely limited to long toe and foot extensors and/or late onset. No patient showed any sign of heart involvement. Our study significantly broadens the clinical and pathological spectrum of Laing distal myopathy. We suggest that MYH7 screening should be considered in undiagnosed late-onset distal myopathy or cytoplasmic body myopathy patients.

  13. Type IIA Monteggia Fracture Dislocation with Ipsilateral Distal Radius Fracture in Adult – A Rare Association

    PubMed Central

    James, Boblee

    2016-01-01

    Monteggia fracture constitutes about 5-10% of the forearm fractures. Monteggia fracture by definition is proximal ulnar fracture with disruption of proximal radioulnar joint. Bado classified Monteggia fracture dislocation into four types and Jupiter subclassified type II Bado’s fractures into four types. The associated injury in the form of distal radial fractures and distal humerus fractures are rare though many cases of distal radial physeal injuries have been reported in paediatric population. Hereby we report a rare association of type IIA Monteggia fracture dislocation with ipsilateral distal radius fracture in an adult patient. This case report also highlights on proper examination and full length radiographs of forearm to avoid missing injury at wrist in cases of elbow injuries. Management of such complex injuries included open reduction and internal fixation of olecronon fracture, distal radius fracture and radial head resection. Functional outcome at six months was good at wrist whereas at elbow, stiffness was a major concern with elbow range of movement from 40°-110°. PMID:27656518

  14. Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

    PubMed Central

    Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

    2013-01-01

    Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

  15. Type IIA Monteggia Fracture Dislocation with Ipsilateral Distal Radius Fracture in Adult - A Rare Association.

    PubMed

    Kembhavi, Raghavendra S; James, Boblee

    2016-08-01

    Monteggia fracture constitutes about 5-10% of the forearm fractures. Monteggia fracture by definition is proximal ulnar fracture with disruption of proximal radioulnar joint. Bado classified Monteggia fracture dislocation into four types and Jupiter subclassified type II Bado's fractures into four types. The associated injury in the form of distal radial fractures and distal humerus fractures are rare though many cases of distal radial physeal injuries have been reported in paediatric population. Hereby we report a rare association of type IIA Monteggia fracture dislocation with ipsilateral distal radius fracture in an adult patient. This case report also highlights on proper examination and full length radiographs of forearm to avoid missing injury at wrist in cases of elbow injuries. Management of such complex injuries included open reduction and internal fixation of olecronon fracture, distal radius fracture and radial head resection. Functional outcome at six months was good at wrist whereas at elbow, stiffness was a major concern with elbow range of movement from 40°-110°. PMID:27656518

  16. Outcome Analysis of Fernandez Osteotomy in Malunited Extra-Articular Fractures of Distal Radius.

    PubMed

    Bhattacharyya, A; Kumar, S

    2016-07-01

    Deformity of wrist is very common after mal union of extra articular fractures over distal end of Radius. It causes limitation of movements too in different directions with or without pain. Deformity may be treated by different types of corrective osteotomy. We treated cases of this type of malunion with Fernandez osteotomy. This study is to observe the amount of correction and recovery of functional status in patients with malunited distal radius fractures treated with Fernandez osteotomy. This is a prospective study. We treated 10 cases of malunited radius with Fernandez osteotomy from February 2013 to October 2014 in the Departments of Orthopaedics, Medical College and Hospital, Kolkata, India. There were six males and four females with mean age of thirty years (with range from twenty to forty years. Indications for surgical intervention include pain and functional deficit severe enough to interfere significantly with daily activities. Radius is exposed through distal dorsal radial incision and radial osteotomy done two and half centimetre proximal to the wrist joint and after achieving correction; gap is filled with iliac bone graft and fixed with contoured distal radius T-plate. Follow up was for an average one year and three months. Results were excellent in one, satisfactory in four cases, good in four cases and bad in one case. Fernandez osteotomy is valuable option for correction of malunited distal radius fracture especially in young demanding patients. PMID:27612904

  17. Bone healing of an unfixed bone fragment of the distal segment in sagittal split ramus osteotomy.

    PubMed

    Park, Won-Jong; Hwang, Soon Jung

    2014-03-01

    In bilateral sagittal split ramus osteotomy for the correction of asymmetry of the mandible, yawing movement of the distal segment can displace the proximal segment. This displacement can be minimized through osteotomy of the posterior part of the distal segment (ie, distal cutting). This free bone fragment is usually removed because of the difficulty of fixation. No previous studies have examined whether union of the bone fragment after distal cutting could join and consequently strengthen the thinned mandibular posterior border. This study used CT imaging to evaluate bone union of the unfixed bone fragment at 3 months postoperatively. The location of the bone fragment and the morphology of bone healing were evaluated in 2D and 3D. The amount of cancellous bone healing between the free bone segment and the proximal segment averaged 63.69%. There was no correlation between the size of the bone gap and the degree of bone union. In most cases, the free bone fragment was located between the distal and proximal segments and tended to dislocate in an anterior-superior direction. Because the postoperative follow-up period was only 3 months, a longer-term study of the changes in bone volume after remodeling is necessary.

  18. Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements▿§

    PubMed Central

    De, Supriyo; Wurster, Andrea L.; Precht, Patricia; Wood, William H.; Becker, Kevin G.; Pazin, Michael J.

    2011-01-01

    T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes. PMID:21262765

  19. Dynamic BRG1 recruitment during T helper differentiation and activation reveals distal regulatory elements.

    PubMed

    De, Supriyo; Wurster, Andrea L; Precht, Patricia; Wood, William H; Becker, Kevin G; Pazin, Michael J

    2011-04-01

    T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes.

  20. Risk factors associated with distal catheter migration following ventriculoperitoneal shunt placement.

    PubMed

    Abode-Iyamah, Kingsley O; Khanna, Ryan; Rasmussen, Zachary D; Flouty, Oliver; Dahdaleh, Nader S; Greenlee, Jeremy; Howard, Matthew A

    2016-03-01

    Ventriculoperitoneal (VP) shunt placement is used to treat hydrocephalus. Shunt migration following VP shunt placement has been reported. The risk factors related to this complication have not been previously evaluated to our knowledge. In this retrospective cohort study, we aimed to determine risk factors leading to distal catheter migration and review the literature on the current methods of management and prevention. Adult patients undergoing VP shunt placement from June 2011 to December 2013 at a single institution were identified using electronic health records. The records were reviewed for demographic and procedural information, and subsequent treatment characteristics. The parameters of patients with distal shunt migration were compared to those undergoing new VP shunt placement for the same time period. We identified 137 patients undergoing 157 new VP shunt procedures with an average age of 57.7 ± standard deviation of 18.4 years old. There were 16 distal shunt migrations. Body mass index >30 kg/m(2) and number of previous shunt procedures were found to be independent risk factors for distal catheter migration. Obesity and number of previous shunt procedures were factors for distal catheter migration. Providers and patients should be aware of these possible risk factors prior to VP shunt placement.