Biomedical subjects

Gerald S Braun

Publications and source records attributed to Gerald S Braun.

7 recordsLinked to original sources

PubMed2006

Mycoplasma pneumoniae: usual suspect and unsecured diagnosis in the acute setting.

Mycoplasma pneumoniae is one of the most common known bacterial pathogens of the respiratory tract, especially in patients between 5 and 30 years of age. It may be encountered at a relatively high rate in the non-life-threatened fraction of Emergency Department (ED) patients presenting with upper respiratory symptoms or cough. Yet its hallmarks are very non-specific, including a great variety of presentations from mild pharyngitis to potentially life-threatening complications such as the Stevens-Johnson Syndrome. Here, we describe a typical case of pneumonia due to Mycoplasma pneumoniae in a young adult with mild pharyngitis as the leading symptom. Disease presentation, complications, diagnostic means, therapeutic options, and suspicious clinical settings are discussed to provide a review on the clinical aspects of the disease that are important in the ED setting.

Adult↗

PubMed2004

Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization.

Cell migration requires integration of cellular processes resulting in cell polarization and actin dynamics. Previous work using tools of Drosophila genetics suggested that protocadherin fat serves in a pathway necessary for determining cell polarity in the plane of a tissue. Here we identify mammalian FAT1 as a proximal element of a signaling pathway that determines both cellular polarity in the plane of the monolayer and directed actin-dependent cell motility. FAT1 is localized to the leading edge of lamellipodia, filopodia, and microspike tips where FAT1 directly interacts with Ena/VASP proteins that regulate the actin polymerization complex. When targeted to mitochondrial outer leaflets, FAT1 cytoplasmic domain recruits components of the actin polymerization machinery sufficient to induce ectopic actin polymerization. In an epithelial cell wound model, FAT1 knockdown decreased recruitment of endogenous VASP to the leading edge and resulted in impairment of lamellipodial dynamics, failure of polarization, and an attenuation of cell migration. FAT1 may play an integrative role regulating cell migration by participating in Ena/VASP-dependent regulation of cytoskeletal dynamics at the leading edge and by transducing an Ena/VASP-independent polarity cue.

Actins↗

PubMed2003

Kir1.1 expression in embryonic kidney epithelia.

K(+) channels may regulate cell cycling, cell volume, and cell proliferation. We have recently shown a role for an inwardly rectifying K(+) channel, Kir6.1/SUR2(B), in the regulation of cell proliferation during early kidney development. Here, we show that the protein of a further K(+) channel, Kir1.1 (ROMK), is also developmentally expressed in prenatal rat kidney epithelia. In the embryonic stage, Kir1.1 protein was localized to the plasma membrane of ureteric buds and collecting ducts, and of nephron stages up to the comma-shaped body. Experimental increase in cAMP upregulated Kir1.1b (ROMK2) mRNA abundance in ureteric buds. Kir1.1 protein was restricted to the distal nephron during later postnatal development and adulthood, as has been reported. In conclusion, we demonstrate redundancy of Kir channel expression in early embryonic kidney which could suggest that Kir1.1 acts in a similar way as Kir6.1/SUR2(B) to promote cell proliferation or other developmental functions.

Aging↗

PubMed2003

Ankle and hindfoot arthropathy in hereditary hemochromatosis.

Arthropathy is a leading clinical manifestation of hereditary hemochromatosis (HH), but involvement of the ankle and hindfoot joints is rare. We describe 3 male patients who presented with symmetrical pain and swelling of the ankles. Radiographs and magnetic resonance imaging showed severe osteoarthritic degenerative changes with a radiological triad of joint space narrowing, subchondral sclerosis, and cyst formation. In all 3 cases a homozygous C282Y mutation in the HFE gene was detected and liver biopsies confirmed the diagnosis of HH. Other differential diagnoses could be excluded. Severe arthropathy of the ankle and hindfoot in comparatively young men can be a leading presentation of HH.

Ankle Joint↗

PubMed2002

Developmental expression and functional significance of Kir channel subunits in ureteric bud and nephron epithelia.

Kir channel subunit expression during development of the rat collecting-duct epithelium was quantified by RT-PCR of primary monolayer cultures. mRNAs of the vascular-type K(ATP) (K(NDP)) channel-forming subunits Kir6.1/SUR2 were highly expressed in early ureteric bud generations (embryonic day E14) and downregulated thereafter, while Kir1.1b (ROMK2) mRNA increased fourfold during cortical collecting duct (CCD) maturation. As assessed by immunohistochemistry, Kir6.1 protein was abundant in the apical and basolateral plasma membranes of early ureteric buds and trunks (E15 to postnatal day P1), downregulated thereafter and not detectable in CCD and outer medullary collecting ducts (OMCD) (P7). During nephron development, Kir6.1 protein was expressed ubiquitously on plasma membranes of early nephron stages from mesenchymal condensations to S-shaped bodies. After fusion of nephron and CCD, Kir6.1 protein was restricted to the apical membrane of proximal tubule. The Kir6/SUR2 channel opener, pinacidil (100 microM/2 days), increased tubulogenesis in organ culture by a factor of 3. Cell proliferation of human embryonic kidney cells (HEK 293) which endogenously express Kir6.1/SUR2 mRNA was stimulated by pinacidil in a dose-dependent manner, an effect that was partially abolished by glibenclamide (3 microM). In summary, Kir6.1/SUR2 channel subunits are highly expressed during early development of ureteric bud and nephron epithelia where Kir6.1/SUR2 activity regulates cell proliferation.

Animals↗

PubMed2002

Development of renal function.

The mammalian metanephric kidney develops following a general principle of organogenesis of epithelial organs, i.e., along the tree-like structure of an arborizing ductal system (the ureteric bud and cortical collecting duct). In parallel, the proximal portions of the uriniferous tubule develop by mesenchymal-to-epithelial transition of the neighbouring mesenchyme. On one hand, vectorial transport systems in nephrogenesis should be functional at the onset of glomerular filtration in any of the newly formed nephron generations to prevent loss of salt, water and metabolites. On the other hand, developing nephron epithelia must serve the needs of organ-formation such as cell proliferation and fluid-secretion for morphogenic purposes. This review intends to summarize current data and concepts on the development of renal epithelial functions with an emphasis on ion channels. Current model systems are introduced, such as ureteric bud cell monolayer culture, in vitro nephron culture, HEK293 cell culture, and the dissection of tubular cells for direct analysis. The current data on the developmental expression and functions of ENaC Na(+) channels, the CFTR, ClC-2 Cl(ndash;) channels, L-type Ca(2+) channels, P2 purinoceptors, and the Kir6.1/SUR2, ROMK (Kir1.1), and Kv K(+) channels are presented.

Journal Article↗

PubMed2002

Ontogeny of purinergic receptor-regulated Ca2+ signaling in mouse cortical collecting duct epithelium.

Changes in ATP-induced increase in [Ca2+](i) during collecting duct ontogeny were studied in primary monolayer cultures of mouse ureteric bud (UB) and cortical collecting duct (CCD) cells by Fura-PE3 fluorescence ratio imaging. In UB (embryonic day E14 and postnatal day P1) the ATP-stimulated increase (EC(50) approximately 1 microM) in fluorescence ratio (DeltaR(ATP)) was independent of extracellular Ca2+ and insensitive to the P2 purinoceptor-antagonist suramin (1 mM). From day P7 onward when CCD morphogenesis had been completed DeltaR(ATP) increased and became dependent on extracellular Ca2+. This ATP-stimulated Ca2+ entry into CCD cells was non-capacitative and suramin (1 mM)-insensitive, but sensitive to nifedipine (30 microM) and enhanced by Bay K8644 (15 microM), a blocker and an agonist of L-type Ca2+ channels, respectively. Quantitative RT-PCR demonstrated similar mRNA expression of L-type Ca2+ channel alpha1-subunit, P2Y(1), P2Y(2), and P2X(4b) purinoceptors in UB and CCD monolayers while the abundance of P2X(4) mRNA increased with CCD morphogenesis. In conclusion, both embryonic and postnatal cells express probably P2Y(2)-stimulated Ca2+ release from intracellular stores. With development, the CCD epithelium acquires ATP-stimulated Ca2+ entry via L-type Ca2+ channels. This pathway might by mediated by the increasing expression of P2X(4)-receptors resulting in an increasing ATP-dependent membrane depolarization and activation of L-type Ca2+ channels.

Adenosine Triphosphate↗