Aldosterone requires vasopressin V1a receptors on intercalated cells to mediate acid-base homeostasis

Both aldosterone and luminal vasopressin may contribute to the maintenance of acid-base homeostasis, but the functional relationship between these hormones is not well understood. The effects of luminal vasopressin likely result from its interaction with V1a receptors on the luminal membranes of intercalated cells in the collecting duct. Here, we found that mice lacking the V1a receptor exhibit type 4 renal tubular acidosis. The administration of the mineralocorticoid agonist fludrocortisone ameliorated the acidosis by restoring excretion of urinary ammonium via increased expression of Rhcg and H-K-ATPase and decreased expression of H-ATPase. In a cell line of intercalated cells established from transgenic rats expressing the mineralocorticoid and V1a receptors, but not V2 receptors, knockdown of the V1a receptor gene abrogated the effects of aldosterone on H-K-ATPase, Rhcg, and H-ATPase expression. These data suggest that defects in the vasopressin V1a receptor in intercalated cells can cause type 4 renal tubular acidosis and that the tubular effects of aldosterone depend on a functional V1a receptor in the intercalated cells.     

The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles

The cell type and localization of vascular endothelial growth factor (VEGF)-producing cells in human radiation necrosis (RN) are investigated from a histopathological and immunohistochemical standpoint using clinical specimens. Eighteen surgical specimens of symptomatic RN in the brain were retrospectively reviewed. These cases included different original histological tumor types and were treated with different radiation modalities. Histological analyses were performed using hematoxylin and eosin (H&E) staining, and anti-VEGF and anti-hypoxia-inducible factor (HIF)-1α immunohistochemistry. H&E staining showed marked angiogenesis and reactive astrocytosis at the perinecrotic area. The most prominent vasculature in this area was identified as telangiectasis. Immunohistochemistry indicated that HIF-1α was expressed predominantly in the perinecrotic area and that a large majority of VEGF-expressing cells were reactive astrocytes intensively distributed in this area. VEGF produced by the reactive astrocytes localized mainly in the perinecrotic area might be a major cause of both angiogenesis and the subsequent perilesional edema typically found in RN of the brain. The benefits of anti-VEGF antibody (bevacizumab) treatment in RN may be that VEGF secretion from the perinecrotic tissue is inhibited and that surgery would remove this tissue; both of these benefits result in effective reduction of edema associated with RN.     

Contribution of bone marrow‐derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury

Spinal cord injury causes initial mechanical damage, followed by ischemia‐induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow‐derived EPCs by EPC colony‐forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild‐type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow‐derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow‐derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury. © 2012 Wiley Periodicals, Inc.     

Neuropsychological and functional correlates of clock‐drawing test in elderly institutionalized patients with schizophrenia

Background: There has been a growing need for a cognitive assessment tool that can be used for older adults with schizophrenia in clinical settings. The clock‐drawing test (CDT) is a brief cognitive test that covers a wide range of cognitive function. Although it is widely used to assess patients with dementia, limited data are available on its usefulness in older patients with schizophrenia. Thus, we investigated the psychometric properties of the CDT and their relationship with life functions to examine the test's usefulness for assessing cognitive function in older adults with schizophrenia. Methods: Seventy‐three older adults with chronic schizophrenia who had been hospitalized for over 1 year participated in the study. We adopted the executive clock‐drawing task for administration and scoring of the CDT, which consists of free‐drawn and copy conditions. The Mini‐Mental State Examination and the Brief Assessment of Cognition in Schizophrenia were administered. Symptom severity and life functions were assessed with the Positive and Negative Syndrome Scale and the Life Skills Profile, respectively. Results: Both free‐drawn and copy scores significantly correlated with the Mini‐Mental State Examination score and the Brief Assessment of Cognition in Schizophrenia composite score. These scores also significantly correlated with symptom severity and length of current hospitalization. Stepwise regression analysis showed that only the copy score, together with symptom severity, predicted the Life Skills Profile score. Conclusions: The CDT can assess cognitive function in older adults with schizophrenia. Moreover, CDT performance is associated with life functions independent from other clinical variables. These results suggest that the CDT is a useful cognitive assessment tool for this population.     

Identification of Fabry's disease by the screening of alpha-galactosidase A activity in male and female hemodialysis patients

BACKGROUND: Although previous studies reported that the prevalence of Fabry's disease was 0.16 - 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (alpha-Gal A) activity, few reports detected female patients by the screening for alpha-Gal A. Here we determined the prevalence of Fabry's disease not only in male but also in female HD patients by measuring alpha-Gal A. METHODS: Plasma alpha-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma alpha-Gal A were examined for leukocyte alpha-Gal A, and patients with low leukocyte alpha-Gal A underwent alpha-Gal A gene sequence analysis for possible mutations, and family survey. RESULTS: Among 15 patients with low plasma alpha-Gal A activity, 4 male patients with low leukocyte alpha-Gal A and 1 female patient revealing low plasma alpha-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry's disease. The other 2 patients were newly diagnosed as Fabry's disease, and did not have typical manifestations of Fabry's disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an alpha-Gal missense mutation, previously identified (E66Q, M2961). CONCLUSION: Fabry's disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by alpha-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry's disease.     

Characterization of labeled neural progenitor cells for magnetic targeting

For many diseases and injuries of the central nervous system, transplantation of neural progenitor cells is being evaluated as a possible treatment option. Although local, intravenous and subarachnoid injections have been reported as administration methods of neural progenitor cells, each of these methods has limitations. More effective and minimally invasive cell delivery systems are necessary for transplanting neural progenitor cells. In this study, we have developed a technique to form magnetically labeled neural progenitor cells for a magnetic targeting system. We demonstrated that neural progenitor cells can couple with magnetic beads, and that the labeled neural progenitor cells preserve the characteristics of non-labeled neural progenitor cells, and that they can be localized by magnetic force in vitro. Labeled neural progenitor cells have the potential to be used in magnetic targeting systems in-vivo models.