Enhanced Goblet Cell Hyperplasia in HDC Knockout Mice with Allergic Airway Inflammation

BackgroundHistamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified.ObjectiveThis study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation.MethodsWild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively.ResultsThe number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-α in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice.ConclusionsThese results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.     

Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance

Objectives  To describe the results from two years of Japanese encephalitis (JE) sentinel surveillance in Cambodia.
Methods  Sentinel site surveillance for JE in children aged 15 years and under was implemented in Cambodia in mid-2006. It was integrated into the routine meningoencephalitis surveillance system. Six hospitals were selected as sentinel sites. Epidemiological information and diagnostic specimens were collected from each patient presenting with meningoencephalitis. Cerebrospinal fluid and sera were tested for presence of immunoglobulin M antibodies against JE and dengue viruses by an ELISA. Surveillance data from 2006 to 2008 were analysed.
Results  Of 586 patients presenting with meningoencephalitis, 110 (19%) were confirmed to have JE. The percentage of confirmed JE cases at individual sentinel sites ranged from 13% to 35% of all meningoencephalitis cases. Mean age was 6.2 years, with 95% of JE cases in children aged 12 years and under. Cases occurred year-round in both 12-month reporting periods.
Conclusions  JE is an important cause of meningoencephalitis in Cambodian children. As JE is a vaccine-preventable disease, an immunization programme could result in a considerable reduction in morbidity and mortality from JE among children in Cambodia.     

Dynamic imbalance in gait ataxia. Characteristics of plantar pressure measurements

The present study was designed to evaluate the interaction between disequilibrium and irregular stepping components of ataxic gait. For this purpose, we compared the walking patterns of patients with cerebellar dominant multiple system atrophy (MSAc, n = 8), spinocerebellar ataxia type 6 (SCA6, n = 4) and 16q-linked autosomal dominant cortical cerebellar atrophy (16q-linked ADCA, n = 6), and 6 normal subjects, by measuring toe and heel plantar pressures. In healthy subjects, the heel contacted the floor at step-in followed by an immediate shift of the center of pressure (COP) to the contacted leg. In ataxic gait, however, both the heel and toes simultaneously contacted the floor and the disappearance of the immediate shift of the COP was noted. These changes appeared to be nonspecific compensations for the instability. Examination of two parameters of ataxia-specific changes showed that prolongation of the double support period was associated with proportionate increase in the coefficients of variance of the plantar pressures and the step lengths on walking of patients with SCA6, but not those with MSAc and 16q-linked ADCA. Our results suggest that disequilibrium and irregularity are two separate and independent components of cerebellar ataxic gait.     

The Anorexigenic Action of the Octadecaneuropeptide (ODN) in Goldfish is Mediated Through the MC4R- and Subsequently the CRH Receptor-Signaling Pathways

Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte-stimulating hormone (α-MSH), corticotropin-releasing hormone (CRH), and CRH-related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of α-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through α-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist α-helical CRH_(9–41) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways.     

Use of 2-octylcyanoacrylate tissue glue for skin closure in radical retropubic prostatectomy

2-Octylcyanoacrylate tissue adhesive (2-OCA ; Dermabond? , Ethicon, Inc., Sommerville, New Jersey) is a synthetic tissue adhesive recently used for skin closure in the treatment of minor lacerations and minor surgical incisions. We have been using this adhesive for wound closure in radical retropubic prostatectomy (RRP) since August 2006. Before that we used a skin stapler. We assessed the effectiveness of the adhesive as a sole dressing after open radical prostatectomy and compared the economic outcomes of 2-OCA and stapled repair. We retrospectively evaluated patients undergoing RRP for whom 2-OCA (101 patients) and a skin stapler (133 patients) were used at our institution. Superficial surgical site infection (SSI) was seen in 3 patients in the glue group and 3 patients in the staple group (p=0.99). Wound dehiscence without SSI was seen in 1 patient in the glue group. The cost of surgery with 2-OCA was much lower than that with the skin stapler. Wound closure using 2-OCA following RRP is acceptable and has benefits in terms of surgical costs.     

Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology domain-interacting protein, down-regulates PI3K/Akt signaling and suppresses tumor growth in vivo

The serine/threonine kinase Akt plays a central role in cell survival and proliferation. Its activation is linked to tumorigenesis in several human cancers. Although many Akt substrates have been elucidated, the Akt-binding proteins that regulate Akt function remain unclear. We report herein having identified casein kinase 2-interacting protein-1 (CKIP-1) as an Akt pleckstrin homology (PH) domain-binding protein with Akt inhibitory function. CKIP-1 formed a complex with each Akt isoform (Akt1, Akt2, and Akt3) via its NH2 terminus. Dimerization of CKIP-1 via its leucine zipper (LZ) motif at the COOH terminus was found to be associated with Akt inactivation because deletion of the LZ motif eliminated Akt inhibitory function, although it could still bind to Akt. Expression of the NH2 terminus-deleted CKIP-1 mutant containing the LZ motif, but lacking Akt-binding ability, induced Akt phosphorylation and activation by sequestering the ability of endogenous CKIP-1 to bind to Akt. Stable CKIP-1 expression caused Akt inactivation and cell growth inhibition in vitro. In addition, the growth of stable CKIP-1 transfectants xenografted into nude mice was slower than that of mock transfectants. These results indicate that CKIP-1, a novel Akt PH domain-interacting protein, would be a candidate of tumor suppressor with an Akt inhibitory function.     

Allocation of attention and effect of practice on persons with and without mental retardation

Persons with mild and moderate mental retardation and CA-matched persons without mental retardation performed a dual-task, "pencil-and-paper task" (Baddeley, Della Sala, Gray, Papagno, & Spinnler (1997). Testing central executive functioning with a pencil-and-paper test. In Rabbit (Ed.), Methodology of Frontal and Executive Function (pp. 61-80). Hove, East Sussex, UK: Psychology Press), which includes a memory span task and a tracking task. The memory span task loads onto phonological working memory and the tracking task loads onto visuo-spatial working memory. By comparing performance between single and dual-task, we assessed the characteristics of executive function, which allocates attentional resources between two tasks. Results indicate that there was no difference in the characteristics between the two groups, and there was no improvement in the characteristics with practice. Thus, we suggest that when persons with mental retardation perform a dual-task that have no interference in the sub-storage of working memory, their function of attentional allocation can work without impairment.     

Reduced frontopolar activation during verbal fluency task in schizophrenia: a multi-channel near-infrared spectroscopy study

Functional neuroimaging studies to date have shown prefrontal dysfunction during executive tasks in schizophrenia. However, relationships between hemodynamic response in prefrontal sub-regions and clinical characteristics have been unclear. The objective of this study is to evaluate prefrontal hemodynamic response related to an executive task in schizophrenia and to assess the relationship between activation in the prefrontal sub-regions and clinical status. Fifty-five subjects with schizophrenia and age- and gender-matched 70 healthy subjects were recruited for this case-control study in a medical school affiliated hospital in the Tokyo metropolitan area, Japan. We measured hemoglobin concentration changes in the prefrontal (dorsolateral, ventrolateral, and frontopolar regions) and superior temporal cortical surface area during verbal fluency test using 52-channel near-infrared spectroscopy, which enables real-time monitoring of cerebral blood volumes in the cortical surface area under a more restraint-free environment than positron emission tomography or functional magnetic resonance imaging. The two groups showed distinct spatiotemporal pattern of oxy-hemoglobin concentration change during verbal fluency test. Schizophrenia patients were associated with slower and reduced increase in prefrontal activation than healthy controls. In particular, reduced activations of the frontopolar region, rather than lateral prefrontal or superior temporal regions, showed significant positive correlations with lower global assessment of functioning scores in the patient group, although task performance was not significantly associated with the scores. These results suggest that reduced frontopolar cortical activation is associated with functional impairment in patients with schizophrenia and that near-infrared spectroscopy may be an efficient clinical tool for monitoring these characteristics.