Identification of oxidative stress-regulated genes in rat aortic smooth muscle cells by suppression subtractive hybridization

AbstractA suppression subtractive hybridization technique was used to identify reactive oxygen species (ROS)-regulated genes in rat vascular smooth muscle cells. Three genes out of 89 clones, identified as fibronectin, p105 coactivator and ECA39, showed increased expression after treatment with H2O2. The mRNA expressions of these three genes were induced in a time- and dose-dependent manner, independent of protein kinase C activation. Immunohistochemical staining showed that the p105 coactivator expression was markedly induced in the neointima of balloon-injured rat carotid arteries. These results suggest that ROS may play an important role in the development of atherosclerosis by regulating the gene expressions we identified in this study

Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes

WSTĘP. Celem badania była ocena wpływu procesu zapalnego o małym nasileniu na wczesną fazę rozwoju zaawansowanej miażdżycy tętnic szyjnych u młodych chorych na cukrzycę typu 1. MATERIAŁ I METODY. U 55 chorych na cukrzycę typu 1 (22 mężczyzn i 33 kobiety, w wieku 22,1 &plusmn; 3,6 lat (&plusmn; SD), z cukrzycą trwającą 14,2 &plusmn; 5,7 lat) oraz u 75 osób bez cukrzycy z tej samej grupy wiekowej (28 mężczyzn i 47 kobiet) wykonano pomiar średniej i maksymalnej grubości kompleksu błony wewnętrznej i środkowej (IMT, intima-media thickness) w tętnicy szyjnej przy użyciu ultrasonograficznej prezentacji B. Stężenie białka C-reaktywnego dużej czułości (hs-CRP, high-sensitive C-reactive protein) oznaczano za pomocą immunonefelometru z zastosowaniem lateksu. WYNIKI. U chorych na cukrzycę typu 1 stężenie hs-CRP (mediana 0,35, zakres 0,05&#8211;1,47 mg/l u chorych na cukrzycę; mediana 0,14, zakres 0,05&#8211;1,44 mg/l u osób bez cukrzycy; p = 0,001) oraz średnia i maksymalna IMT (średnia IMT 0,76 &plusmn; 0,09 vs. 0,72 &plusmn; 0,04 mm, p = 0,003; maksymalna IMT 0,84 &plusmn; 0,11 vs. 0,77 &plusmn; 0,06, p < 0,0001) były wyraźnie większe niż u osób bez cukrzycy. Stężenie hs-CRP wykazywało wyraźną zależność ze średnią i maksymalną IMT u chorych na cukrzycę typu 1 oraz z maksymalną IMT u osób bez cukrzycy. Analiza metodą regresji wielowymiarowej przeprowadzona łącznie dla grupy chorych na cukrzycę oraz osób bez cukrzycy wykazała, że stężenie hs-CRP niezależnie koreluje ze średnią oraz maksymalną IMT (odpowiednio: p = 0,002 i p = 0,023), jak również z rozkurczowym ciśnieniem tętniczym, płcią i czasem trwania cukrzycy. WNIOSKI. Dane uzyskane w badaniu wskazują, że u młodych chorych na cukrzycę typu 1 stężenie hs- -CRP jest podwyższone, co może mieć związek z wczesną fazą rozwoju zaawansowanej miażdżycy tętnic szyjnych.INTRODUCTION. To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes. MATERIAL AND METHODS. The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 &#177; 3.6 years (&#177; SD), duration of diabetes 14.2 &#177; 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer. RESULTS. The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05&#8211;1.47 mg/l vs. median 0.14, range 0.05&#8211;1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 &#177; 0.09 vs. 0.72 &#177; 0.04 mm, P = 0.003; max IMT 0.84 &#177; 0.11 vs. 0.77 &#177; 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes. CONCLUSIONS. Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis

地域を基盤とした老年看護基礎教育における学生の学び : 中山間地域での高齢者の暮らしから

S県立大学Iキャンパス看護学科平成21年度3年次生7名に地域を基盤とした老年看護基礎教育を試み，学びの内容を質的記述的に分析した。学生は健康問題として緊急事態の対応，高塩分・低栄養の食事を捉え，交通手段の不十分さや孤独な環境との関連を学んだ。一方で，高齢者のいつまでもこの地域で暮らしたいというニーズを知り，高齢者がもつ地域に対する愛着心や高齢者のセルフケア能力の向上への支援方法，高齢者を尊重した専門家としての態度を学んだ

Glutamate transporters regulate lesion-induced plasticity in the developing somatosensory cortex.

Glutamate transporters are involved in neural differentiation, neuronal survival, and synaptic transmission. In the present study, we examined glutamate transporter 1 (GLT1) expression in the neonatal somatosensory cortex of C57BL/6 mice, and pursued its role in somatosensory development by comparing barrel development between GLT1 knock-out and control mice. During the first few neonatal days, a critical period for barrels, GLT1 expression is strikingly upregulated in cortical astrocytes, whereas it was downregulated in neuronal elements to below the detection threshold. GLT1 knock-out neonates developed normally in terms of body growth, cortical histoarchitecture, barrel formation, and critical period termination. However, when row C whiskers were lesioned during the critical period, reduction of lesioned row C barrels and reciprocal expansion of intact row B/D barrels were both milder in GLT1 knock-out mice than in control littermates. Accordingly, the map plasticity index, calculated as (B + D)/2C, was significantly lowered in GLT1 knock-out mice. We also found that extracellular glutamate levels in the neonatal somatosensory cortex were significantly elevated in GLT1 knock-out mice. Diminished lesion-induced plasticity was further found in mutant mice lacking glutamate-aspartate transporter (GLAST), an astrocyte-specific glutamate transporter throughout development. Therefore, glutamate transporters regulate critical period plasticity by enhancing expansion of active barrels and shrinkage of inactive barrels. Because cortical contents of glutamate receptors and GLAST were unaltered in GLT1 knock-out mice, this action appears to be mediated, at least partly, by keeping the ambient glutamate level low. Considering an essential role of glutamate receptors in the formation of whisker-related thalamocortical synapse patterning, glutamate transporters thus facilitate their activity-dependent remodeling

Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation

Development of correct topographical connections between peripheral receptors and central somatosensory stations requires activity-dependent synapse refinement, in which the NMDA type of glutamate receptors plays a key role. Here we compared functional roles of GluN2B (GluR epsilon 2 or NR2B) and GluN2D (GluR epsilon 4 or NR2D), two major regulatory subunits of neonatal NMDA receptors, in development of whisker-related patterning at trigeminal relay stations. Compared with control littermates, both the appearance of whisker-related patterning and the termination of the critical period, as assessed by unilateral infraorbital nerve transection, were delayed by nearly a day in the somatosensory cortex of GluN2B(+/-) mice but advanced by nearly a day in GluN2D(-/-) mice. Similar temporal shifts were found at subcortical relay stations in the thalamus and brainstem of GluN2B(+/-) and GluN2D(-/-) mice. In comparison, the magnitude of lesion-induced critical period plasticity in the somatosensory cortex, as assessed following row-C whisker removal, was normal in both mutants. Thus, GluN2B and GluN2D play counteractive roles in temporal development and maturation of somatosensory maps without affecting the magnitude of critical period plasticity. To understand the opposing action, we then examined neuronal and synaptic expressions of the two subunits along the trigeminal pathway. At each trigeminal station, GluN2B was predominant at asymmetrical synapses of non-GABAergic neurons, whereas GluN2D was selective to asymmetrical synapses of GABAergic neurons. Together, our findings suggest that GluN2B expressed at glutamatergic synapses on glutamatergic projection neurons facilitates refinement of ascending pathway synapses directly, whereas GluN2D expressed at glutamatergic synapses on GABAergic interneurons delays it indirectly

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary

Abstract Background Pagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse. Case presentation A 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer. Conclusions To detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient’s lifetime is recommended