A slow transient potassium current expressed in a subset of neurosecretory neurons of the hypothalamic paraventricular nucleus

Type I putative magnocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVN) express a prominent transient outward rectification generated by an A-type potassium current. Described here is a slow transient outward current that alters cell excitability and firing frequency in a subset of type I PVN neurons (38%). Unlike most of the type I neurons (62%), the transient outward current in these cells was composed of two kinetically separable current components, a fast activating, fast inactivating component, resembling an A-type potassium current, and a slowly activating [10-90% rise time: 20.4 +/- 12.8 (SE) ms], slowly inactivating component (time constant of inactivation: tau = 239.0 +/- 66.1 ms). The voltage dependence of activation and inactivation and the sensitivity to block by 4-aminopyridine (5 mM) and tetraethylammonium chloride (10 mM) of the fast and slow components were similar. Compared to the other type I neurons, the neurons that expressed the slow transient outward current were less excitable when hyperpolarized, requiring larger current injections to elicit an action potential (58.5 +/- 13.2 vs. 15.4 +/- 2.4 pA; 250-ms duration; P < 0.01), displaying a longer delay to the first spike (184.9 +/- 15.7 vs. 89.7 +/- 8.8 ms with 250- to 1,000-ms, 50-pA current pulses; P < 0.01), and firing at a lower frequency (18. 7 +/- 4.6 vs. 37.0 +/- 5.5 Hz with 100-pA current injections; P < 0. 05). These data suggest that a distinct subset of type I PVN neurons express a novel slow transient outward current that leads to a lower excitability. Based on double labeling following retrograde transport of systemically administered fluoro-gold and intracellular injection of biocytin, these cells are neurosecretory and are similar morphologically to magnocellular neurosecretory cells, although it remains to be determined whether they are magnocellular neurons.     

Genes involved in the determination of the rate of inversions at short inverted repeats

BACKGROUND: Not all of the enzymatic pathways involved in genetic rearrangements have been elucidated. While some rearrangements occur by recombination at areas of high homology, others are mediated by short, often interrupted homologies. We have previously constructed an Escherichia coli strain that allows us to examine inversions at microhomologies, and have shown that inversions can occur at short inverted repeats in a recB,C-dependent fashion. RESULTS: Here, we report on the use of this strain to define genetic loci involved in limiting rearrangements on an F' plasmid carrying the lac genes. Employing mini-Tn10 derivatives to generate insertions near or into genes of interest, we detected three loci (rmuA,B,C) that, when mutated, increase inversions. We have mapped, cloned and sequenced these mutator loci. In one case, inactivation of the sbcC gene leads to an increase in rearrangements, and in another, insertions near the recE gene lead to an even larger increase. The third gene involved in limiting inversions, rmuC, has been mapped at 86 min on the E. coli chromosome and encodes a protein of unknown function with a limited homology to myosins, and some of the SMC (structural maintenance of chromosomes) proteins. CONCLUSIONS: This work presents the first example of an anti-mutator role of the sbcC,D genes, and defines a new gene (rmuC) involved in DNA recombination.     

Prognosticating survival of pineal parenchymal tumors of intermediate differentiation (PPTID) by grade

Journal of Neuro-Oncology - Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health...     

Long-Term Outcomes of Immunosuppression-Naïve Steroid Responders Following Hospitalization for Ulcerative Colitis

Digestive Diseases and Sciences - Requirement for hospitalization in ulcerative colitis (UC) is a marker of severity of disease. However, the paradigm of when to escalate therapy in such patients...     

Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn’s Disease Is Not Associated with Emergence of Novel Inflammatory Pathways

Digestive Diseases and Sciences - While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohn’s disease (CD), approximately one-third of...     

Superficial topography of wound: A determinant of underlying biological events?

Three-dimensional configuration of wounds varies considerably according to the etiology. Wounding of skin is proceeded by release of dermal pretension. Subsequent disruption of physical equilibrium with resulting development of force vectors alters the primary shape of wound to maintain a new dynamic physical equilibrium. This leads to the development of stress-relaxation and stress-concentration areas throughout the wound milieu. Mechanical strain produces piezoelectric current which is maximal in stress-relaxation regions due to lower tissue stiffness and higher mobility. Early surge in the tissue level of TGF-beta would be exaggerated through synergistic interaction with piezoelectric current in stress-relaxation areas. Subsequently, fibroblasts migrate to these areas due to galvanotaxis. The gradual dissipation of tissue tension, due to irreversible loss of viscous strain, reduces the synergistic action of TGF-beta and piezoelectricity. However, a similar pattern of activity of TGF-beta due to the polarized migration of fibroblasts, which are the main source of TGF-beta during secondary surge, may be continued. It seems that a biological-mechanical continuum exists for wounds so that even the superficial topography of wounds may affect the underlying biological activity and final healing outcome during healing of dermal wounds.     

Ocular anterior chamber dysgenesis in craniosynostosis syndromes with a fibroblast growth factor receptor 2 mutation

Fibroblast growth factor receptor (FGFR) mutations have been found in craniosynostosis syndromes with and without limb and/or dermatologic anomalies. Ocular manifestations of FGFR2 syndromes are reported to include shallow orbits, proptosis, strabismus, and hypertelorism, but no ocular anterior chamber, structural abnormalities have been reported until now. We evaluated three unrelated patients with severe Crouzon or Pfeiffer syndrome. Two of them had ocular findings consistent with Peters anomaly, and the third patient had opaque corneae, thickened irides and ciliary bodies, and shallow anterior chambers with occluded angles. Craniosynostosis with and without cloverleaf skull deformity, large anterior fontanelle, hydrocephalus, proptosis, depressed nasal bridge, choanal stenosis/atresia, midface hypoplasia, and elbow contractures were also present. These patients had airway compromise, seizures, and two died by age 15 months. All three cases were found to have the same FGFR2 Ser351Cys (1231C to G) mutation predicted to form an aberrant disulfide bond(s) and affect ligand binding. Seven patients with isolated Peters anomaly, two patients with Peters plus syndrome, and three cases with typical Antley-Bixler syndrome were screened for this mutation, but none was found. These phenotype/genotype data demonstrate that FGFR2 is involved in the development of the anterior chamber of the eye and that the Ser351Cys mutation is associated with a severe phenotype and clinical course. Am. J. Med. Genet. 85:160–170, 1999. © 1999 Wiley-Liss, Inc.