Primary enuresis: relative success of three methods of treatment.

A total of 169 children with primary enuresis were treated by one of three methods--use of a special diet, imipramine, or a waking device (the Mozes detector). Of 64 who received the diet 1 (1.6%) was cured; of 62 who were treated with imipramine 13 (20.9%) were cured; and of 43 who used the detector 23 (53.5%) were cured. Results at follow-up remained substantially unchanged for cure. Improvement rate without cure during treatment was higher for the children treated with imipramine than for those treated with the detector, but at follow-up the reverse was true. Parents of children who received the special diet, because they were unimpressed by the rate of improvement, would not permit their children to continue this form of therapy for longer than 1 or 2 months.     

High-frequency High-resolution Echocardiography: First Evidence on Non-invasive Repeated Measure of Myocardial Strain,Contractility, and Mitral Regurgitation in the Ischemia-reperfused Murine Heart

Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in functional parameters of key clinical significance. Two-dimensional movies were acquired at high frame rate (8 kHz) and were utilized to estimate high-quality myocardial strain. Two-dimensional elastograms (strain images), as well as strain profiles, were visualized. Results were powerful in quantitatively assessing IR-induced changes in cardiac events including left-ventricular (LV) contraction, LV relaxation and isovolumetric phases of both pre-IR and post-IR beating hearts in intact mice. In addition, compromised sector-wise wall motion and anatomical deformation in the infarcted myocardium were visualized. The elastograms were uniquely able to provide information on the following parameters in addition to standard physiological indices that are known to be affected by myocardial infarction in the mouse: internal diameters of mitral valve orifice and aorta, effective regurgitant orifice, myocardial strain (circumferential as well as radial), turbulence in blood flow pattern as revealed by the color Doppler movies and velocity profiles, asynchrony in LV sector, and changes in the length and direction of vectors demonstrating slower and asymmetrical wall movement. This work emphasizes on the visual demonstration of how such analyses are performed.     

COP1 Jointly Modulates Cytoskeletal Processes and Electrophysiological Responses Required for Stomatal Closure

Reorganization of the cortical microtubule cytoskeleton is critical for guard cell function. Here, we investigate how environmental and hormonal signals cause these rearrangements and find that COP1, a RING-finger-type ubiquitin E3 ligase, is required for degradation of tubulin, likely by the 26S proteasome. This degradation is required for stomatal closing. In addition to regulating the cytoskeleton, we show that cop1 mutation impaired the activity of S-type anion channels, which are critical for stomatal closure. Thus, COP1 is revealed as a potential coordinator of cytoskeletal and electrophysiological activities required for guard cell function.     

Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy

The KCC2 cotransporter establishes the low neuronal Cl⁻ levels required for GABA_A and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability. However, no mutations in KCC2 have been documented in human disease. Here, we report two non-synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE). These variants reside in conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly impaired Cl⁻-extrusion capacities resulting in less hyperpolarized Gly equilibrium potentials (E_Gly), and impair KCC2 stimulatory phosphorylation at serine 940, a key regulatory site. These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE.     

Rhinosporidiosis in Delhi, North India: Case Series from a Non-endemic Area and Mini-review

We report three cases of rhinosporidiosis from migrant population of Delhi. Three male patients had sino-nasopharyngeal, nasopharyngeal and nasal rhinosporidiosis, respectively. One patient gave a history of bathing in stagnant water. The diagnosis was made by clinical presentation and microscopic observation of characteristic sporangia of Rhinosporidium seebri in mycological and histopathological investigations. All the patients were successfully treated with complete surgical excision of lesions and cauterization of base. There were no recurrences.     

Biodegradation of Chlorpyrifos in Soil by Enriched Cultures

Three aerobic bacterial consortia, AC, BC, and DC, developed from pesticide-contaminated soils of Punjab were able to degrade chlorpyrifos after 21 days of incubation in basal medium by 54, 46, and 61% and chlorpyrifos (50 mg/L) in soil after 30 days by 50, 56, and 64%. Pseudomonas aeruginosa, Bacillus cereus, Klebsiella sp., and Serratia marscecens obtained from these consortia showed 84, 84, 81, and 80% degradation of chlorpyrifos (50 mg/L) in liquid medium after 20 days and 92, 60, 56, and 37% degradation of chlorpyrifos (50 mg/L) in soil after 30 days. Populations of Bacillus cereus, Klebsiella sp., and Serratia marscecens remained steady in soil experiments except for P. aeruginosa, where the population showed a substantial increase. Formation of 3,5,6-trichloro-2-pyridinol, the major metabolite of chlorpyrifos degradation, was observed during the degradation of chlorpyrifos by P. aeruginosa, which disappeared to negligible amounts.     

Revisiting the seed and soil in cancer metastasis

Metastasis remains the overwhelming cause of death for cancer patients. During metastasis, cancer cells will leave the primary tumor, intravasate into the bloodstream, arrest at a distant organ, and eventually develop into gross lesions at the secondary sites. This intricate process is influenced by innumerable factors and complex cellular interactions described in 1889 by Stephen Paget as the seed and soil hypothesis. In this review, we revisit this seed and soil hypothesis with an emerging understanding of the cancer cell (i.e. seed) and its microenvironment (i.e. soil). We will provide background to suggest that a critical outcome of the seed–soil interaction is resistance of the stresses that would otherwise impede metastasis.     

Simple high-cell density fed-batch technique for high-level recombinant protein production with Pichia pastoris: Application to intracellular production of Hepatitis B surface antigen

Background  

Hepatitis B is a serious global public health concern. Though a safe and efficacious recombinant vaccine is available, its use in several resource-poor countries is limited by cost. We have investigated the production of Hepatitis B virus surface antigen (HBsAg) using the yeast Pichia pastoris GS115 by inserting the HBsAg gene into the alcohol oxidase 1 locus.     

Tumor necrosis factor-α-mediated severity of idiopathic retinal periphlebitis in young adults (Eales’ disease): implication for anti-TNF-α therapy

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic inflammatory cytokine. Tumor necrosis factor-alpha was evaluated in the serum samples of patients with idiopathic retinal periphlebitis in young adults (Eales’ disease). Retinal periphlebitis was graded according to a new grading system based on severity of inflammation (grade 1–4). Quantification of the TNF-α levels was carried out using ELISA kit in the serum samples of young adults with idiopathic retinal periphlebitis (n = 17) and healthy controls (n = 17) of similar age. Tumor necrosis factor-α level was found to be significantly raised in cases with retinal periphlebitis as compared with controls (p < 0.001). Higher levels of TNF-α were found to be associated with increased severity of retinal periphlebitis. Tumor necrosis factor-α represents a novel target for controlling inflammatory activity in idiopathic retinal periphlebitis. Higher levels of TNF-α, in association with the increased severity of retinal periphlebitis, have implications for early anti-TNF-α therapy.     

EDD mediates DNA damage-induced activation of CHK2

EDD, the human orthologue of Drosophila melanogaster "hyperplastic discs," is overexpressed or mutated in a number of common human cancers. Although EDD has been implicated in DNA damage signaling, a definitive role has yet to be demonstrated. Here we report a novel interaction between EDD and the DNA damage checkpoint kinase CHK2. EDD and CHK2 associate through a phospho-dependent interaction involving the CHK2 Forkhead-associated domain and a region of EDD spanning a number of putative Forkhead-associated domain-binding threonines. Using RNA interference, we demonstrate a critical role for EDD upstream of CHK2 in the DNA damage signaling pathway. EDD is necessary for the efficient activating phosphorylation of CHK2 in response to DNA damage following exposure to ionizing radiation or the radiomimetic, phleomycin. Cells depleted of EDD display impaired CHK2 kinase activity and an inability to respond to DNA damage. These results identify EDD as a novel mediator in DNA damage signal transduction via CHK2 and emphasize the potential importance of EDD in cancer.