Haplotypes of the plasminogen activator gene associated with ischemic stroke

Ischemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to perform a haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p = 0.003). Diplotype analysis also showed a significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32-97.9, p = 0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene is a genetic marker for IS, and that tPA or a neighboring gene is a susceptibility gene for IS.     

Decreased activation of anterior cingulate cortex in the working memory of the elderly

We examined aging effects on activation in the anterior cingulate cortex during a verbal working memory using functional magnetic resonance imaging. Ten young (mean age 25 years) and 10 elderly (mean age 69 years) healthy adults performed the reading span test in which performance reflects individual differences in verbal working memory. We found an age-related difference in executive function in the prefrontal cortex; younger participants showed significant anterior cingulate cortex activation whereas the elderly did not. We found that the anterior cingulate cortex plays a critical role in executive function related to working memory. We found that behavioral deficits in verbal working memory because of aging result from the deterioration of cognitive control owing to decreased activation of the anterior cingulate cortex.     

RE‐EPITHELIALIZATION OF SQUAMOUS EPITHELIUM FOR A RADIATION‐INDUCED RECTAL ULCER WHILE GIVING AN ECABET SODIUM ENEMA

The present patient developed a severe rectal ulcer more than 1 month after having received external beam radiation therapy for prostate cancer. Surveillance endoscopy every 3 months demonstrated healing of this rectal ulcer using a novel therapy. He was given enemas with ecabet sodium, which provides physical protection and promotes healing by increasing prostaglandin E₂, and this process induced squamous metaplasia that halted the progression of the ulcer of radiation proctitis as a late‐phase reaction. Intrapapillary capillary loops were visualized with magnified narrow band imaging at the healing ulcer site as seen via the esophagus and, moreover, demonstrated histologically.     

Differential cell-specific location of Cav-1 and Ca2+-ATPase in terminal Schwann cells and mechanoreceptive Ruffini endings in the periodontal ligament of the rat incisor

Caveolae are involved in clathrin-independent endocytosis, transcytosis, signal transduction, and tumor suppression – all of which depend on their main constituent protein caveolin families. The periodontal Ruffini ending has been reported to develop a caveola-like structure on the cell membrane of both the axon terminals and Schwann sheaths, suggesting the existence of an axon–Schwann cell interaction in the periodontal Ruffini endings. However, little information is available concerning the functional significance of these caveolae. The present study was undertaken to examine the immunolocalization of caveolin-1, -3 (Cav-1, Cav-3) and Ca²⁺-ATPase in the periodontal Ruffini endings of the rat incisor. Decalcified sections of the upper jaws were processed for immunocytochemistry at the levels of light and electron microscopy. Some immunostained sections were treated with histochemistry for nonspecific cholinesterase (nChE) activity. Observations showed the periodontal Ruffini endings were immunopositive for Cav-1, but not Cav-3. Immunoreactive products for Cav-1 were confined to caveola-like structures in the cell membranes of the cytoplasmic extensions and cell bodies of the terminal Schwann cells associated with the periodontal Ruffini endings. However, the axonal membranes of the terminals did not express any Cav-1 immunoreaction. Double staining with Ca²⁺-ATPase and either protein gene product 9.5 (PGP 9.5) or S-100 protein disclosed the co-localization of immunoreactions in the axonal branches of the periodontal Ruffini endings, but not in the terminal Schwann cells. As Ca²⁺ plays an important role in mechanotransduction, these characteristic immunolocalizations show Cav-1/Ca²⁺-ATPase might be involved in the quick elimination of intracellular Ca²⁺ in mechanotransduction.     

Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis

Abscisic acid (ABA) signaling is important for stress responses and developmental processes in plants. A subgroup of protein phosphatase 2C (group A PP2C) or SNF1-related protein kinase 2 (subclass III SnRK2) have been known as major negative or positive regulators of ABA signaling, respectively. Here, we demonstrate the physical and functional linkage between these two major signaling factors. Group A PP2Cs interacted physically with SnRK2s in various combinations, and efficiently inactivated ABA-activated SnRK2s via dephosphorylation of multiple Ser/Thr residues in the activation loop. This step was suppressed by the RCAR/PYR ABA receptors in response to ABA. However the abi1–1 mutated PP2C did not respond to the receptors and constitutively inactivated SnRK2. Our results demonstrate that group A PP2Cs act as ‘gatekeepers’ of subclass III SnRK2s, unraveling an important regulatory mechanism of ABA signaling.     

Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness

Purpose: To assess the efficacy of diazepam suppositories at preventing febrile seizure recurrence during a single febrile illness to determine how to treat children with a febrile seizure on presentation at the hospital. Methods: We studied 203 children with febrile seizures from December 2004 through March 2006. On admission between December 2004 and May 2005, a diazepam suppository was administered to the patients. Patients seen between June 2005 and March 2006 were not treated with antiepileptic drugs on admission. Results: We saw a significant difference in the rate of recurrence of febrile seizures between children treated with diazepam and those who were not. Recurrences were observed in 2 (2.1%) of 95 children treated with diazepam and in 16 (14.8%) of 108 untreated children. For the 108 untreated patients, the median age was 22.8 months in those with recurrences and 30.6 months in those without, confirming that a younger age was related to a recurrence. Conclusions: A diazepam suppository after a febrile seizure will reduce the incidence of recurrent febrile seizures during the same febrile illness. However, a diazepam suppository after a febrile seizure should be used after carefully considering the benefits and potential adverse effects.     

Practice on conflict tasks promotes executive function of working memory in the elderly

Effects of practice on a conflict task in elderly individuals are examined with a focus on its impact on executive function in working memory. During a short-term practice period, healthy elderly participants practiced switching attention using a Stroop task that involved a conflict between a task relevant stimulus and an irrelevant stimulus. To explore neural substrates underlying practice effects, two working memory tasks were used: a focus reading span test (F-RST) and a non-focus reading span test (NF-RST); the NF-RST test demanded greater switching attention due to a conflict between the relevant task stimulus and an irrelevant task stimulus, thus requiring an attention switch from the latter to the former. Following the Stroop task practice, fMRI data showed that participants who had engaged in practice had significant increases in activation in the anterior cingulate cortex (ACC), the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex (DLPFC) and the precuneus regions during the NF-RST. By contrast, a control group, which did not practice, showed no significant increases in these regions. Results suggest that practice on conflict tasks in elderly individuals activated regions related to conflict perceiving and attention switching regions as well as attention-maintenance regions thereby improving performance on tasks requiring a high degree of attention control of working memory.     

Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis.

X-linked juvenile retinoschisis (RS) is a common cause of juvenile macular degeneration in males. RS is characterized by cystic spoke-wheel-like maculopathy, peripheral schisis, and a negative (b-wave more reduced than a-wave) electroretinogram (ERG). These symptoms are due to mutations in the RS1 gene in Xp22.2 leading to loss of functional protein. No medical treatment is currently available. We show here that in an Rs1h-deficient mouse model of human RS, delivery of the human RS1 cDNA with an AAV vector restored expression of retinoschisin to both photoreceptors and the inner retina essentially identical to that seen in wild-type mice. More importantly, unlike an earlier study with a different AAV vector and promoter, this work shows for the first time that therapeutic gene delivery using a highly specific AAV5-opsin promoter vector leads to progressive and significant improvement in both retinal function (ERG) and morphology, with preservation of photoreceptor cells that, without treatment, progressively degenerate.     

Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP

Persistent reduction of renal perfusion pressure induces renovascular hypertension by activating the renin-angiotensin-aldosterone system; however, the sensing mechanism remains elusive. Here we investigated the role of PGI2 in renovascular hypertension in vivo, employing mice lacking the PGI2 receptor (IP-/- mice). In WT mice with a two-kidney, one-clip model of renovascular hypertension, the BP was significantly elevated. The increase in BP in IP-/- mice, however, was significantly lower than that in WT mice. Similarly, the increases in plasma renin activity, renal renin mRNA, and plasma aldosterone in response to renal artery stenosis were all significantly lower in IP-/- mice than in WT mice. All these parameters were measured in mice lacking the four PGE2 receptor subtypes individually, and we found that these mice had similar responses to WT mice. PGI2 is produced by COX-2 and a selective inhibitor of this enzyme, SC-58125, also significantly reduced the increases in plasma renin activity and renin mRNA expression in WT mice with renal artery stenosis, but these effects were absent in IP-/- mice. When the renin-angiotensin-aldosterone system was activated by salt depletion, SC-58125 blunted the response in WT mice but not in IP-/- mice. These results indicate that PGI2 derived from COX-2 plays a critical role in regulating the release of renin and consequently renovascular hypertension in vivo.