FRET imaging in nerve growth cones reveals a high level of RhoA activity within the peripheral domain

Rho-family GTPases play a central role in the regulation of neuronal morphogenesis. In growth cones, for example, Rho GTPases transduce extracellular stimuli into structural changes such as filopodia and lamellipodia. Although it is generally accepted that Rac1/Cdc42 and RhoA are positive and negative regulators of neurite outgrowth, respectively, the role of each Rho-family member in neuronal morphogenesis may change according to the cell context. At present, the mechanism underlying this complexity is largely unknown. In growth cones, this is partly due to a lack of information on the distribution of active Rho GTPases. Here, we visualized RhoA/Rac1/Cdc42 activities during laminin-induced growth cone advance of DRG neurons and N1E-115 neuroblastoma cells using probes based on fluorescence/F?rster resonance energy transfer. The Rac1 and Cdc42 activities were high in the peripheral domain (P-domain) of growth cones. Active Rac1 was uniformly detected throughout the P-domain, whereas Cdc42 activity increased gradually toward the growth cone edge. Against a model involving RhoA down-regulation at the periphery of protruding growth cones, we found that the RhoA activity was higher in the P-domain than in the central domain and axon shaft, and that a high level of RhoA activity was maintained in the extending part of growth cones. In lysophosphatidic acid-treated N1E-115 cells, well-developed neurites with growth cones showed RhoA activation, but sustained their extended morphology until they were drawn toward the contracting somata. On the other hand, suppression of RhoA activity by C3 exoenzyme led to loss or deformation of actin bundles in the growth cones. Thus, RhoA activation in the shaft results in neurite retraction, whereas high RhoA activity in the P-domain is necessary to retain the spread morphology of nerve growth cone.     

Renal artery stenosis in a patient with Leriche syndrome: brachial artery access for stent placement

We encountered a patient with Leriche syndrome and general atherosclerotic disease. His renal function had deteriorated, and diabetic nephropathy was suspected. Severe left renal artery stenosis was also found and considered, if untreated, to be an important factor in aggravation of his renal function. Because the infrarenal abdominal aorta was completely occluded, we treated the patient by insertion of a stent into the left renal artery from the brachial approach. The operation was successful, without residual stenosis or complications. Renal blood flow was remarkably improved after stent placement.     

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level 相似文献   

Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation

Human luteal cells have been reported to express human leukocyteantigen-DR and lymphocyte functional antigen-3 on the cell surface,suggesting physiological interaction between luteal cells andT-lymphocytes through the menstrual cycle into early pregnancy.To elucidate the role of peripheral lymphocytes on corpus luteumdifferentiation, the effect of peripheral blood mononuclearcells (PBMC) on steroidogenesis by luteal cells was investigated.The production of Th-2 cytokines such as interleukin (IL)-4and IL-10 by the co-cultured cells was also examined, and theeffects of these cytokines on progesterone production by lutealcells were investigated. Corpora lutea were obtained from eightnon-pregnant women in the luteal phase and five women in earlypregnancy for luteal cell culture. PBMC were isolated from unrelatedwomen in the follicular phase, secretory phase, and early pregnancy.After co-culture with allogenic PBMC for 48 h, progesteroneproduction was significantly enhanced by PBMC from the secretoryphase and early pregnancy in the non-pregnant luteal cell culture.In the pregnant luteal cell culture, a significant increasein progesterone production was also observed by the co-culturewith PBMC from women in early pregnancy, showing that PBMC havea luteotrophic effect. The stimulatory effects of PBMC werealso observed in co-culture conditions which prevented directcell-to-cell interaction with luteal cells, showing the minorinfluence of mixed lymphocyte reaction. By co-culture with PBMC,the production of IL-10, but not IL-4, was significantly augmentedin luteal cell culture derived from non-pregnant women, whereasthe production of both IL-4 and IL-10 was significantly enhancedin the luteal cell culture derived from pregnant women. Moreover,IL-4 and IL-10 promoted progesterone production by culturedluteal cells, especially in the luteal cell culture derivedfrom corpora lutea of early pregnancy. These findings indicatethat PBMC stimulate progesterone production by luteal cellsand suggest the involvement of PBMC in corpus luteum functionand differentiation probably via the Th-2-type lymphocytes.     

A case of ulcerative colitis with preexisting idiopathic thrombocytopenic purpura

A 53-year-old man was diagnosed as having idiopathic thrombocytopenic purpura (ITP). Hematochezia appeared under steroid therapy for ITP after the diagnosis of ITP 18 months. Colonoscopic study demonstrated inflamed rectal mucosa but there was no evidence of infectious colitis. The colonoscopic and pathological findings were compatible with ulcerative colitis (UC). There have been a few reports of patients with UC complicated by ITP, but in all except one report, UC preceded ITP. This is the third case in which ITP preceded UC and the first case in which the proctitis type of UC was complicated by ITP in Japan.     

A case of pancreatic malignant lymphoma diagnosed by EUS-FNA]

A 57-year-old woman was admitted to the hospital because of obstructive jaundice. Abdominal computed tomography and ultrasonography showed a homogeneous mass 7cm in diameter at the head of the pancreas. Gamma-scintigraphy showed uptake in the head of the pancreas. Histological diagnosis was obtained by endoscopic ultrasoundscopy-fine needle aspiration (EUS-FNA). The pathological and immunohistochemical studies showed diffuse lymphoma with large B-cells. We experienced a rare case of pancreatic malignant lymphoma and EUS-FNA was usefull in the diagnosis.     

Surveillance following orchiectomy for stage I testicular seminoma: Long-term outcome

Objectives:   To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan.
Methods:   A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma.
Results:   Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant ( P  = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively.
Conclusions:   The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.     

TAC‐302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats

Aims

To evaluate the ability of TAC‐302, a cyclohexenoic fatty alcohol derivative, to enhance neurite outgrowth in cultured rat dorsal root ganglion (DRG) neurons, and the preventive effects of TAC‐302 on bladder denervation‐related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO).

Methods

Rat DRG neurons were cultured in the presence of TAC‐302. Cell numbers and neurite lengths were quantified after a 24 h culture. BOO was achieved by partial ligature of the proximal urethra in female rats. BOO rats were divided into three groups and orally treated with vehicle of 3 or 30 mg/kg TAC‐302 twice a day for 4 weeks. Cystometry was performed under conscious conditions. Immunohistochemical staining using anti‐PGP9.5 of the bladder muscle layer was performed, and the innervation area was scored.

Results

TAC‐302 significantly and dose‐dependently increased neurite outgrowth in cultured DRG neurons. BOO rats showed a decreased innervation area in the urinary bladder compared to sham‐operated rats. BOO‐induced denervation of the urinary bladder was partially prevented by oral treatment with TAC‐302. TAC‐302 significantly reduced the frequency of non‐voiding contraction (NVC) and residual urine volume (RUV) compared with the BOO vehicle group (P < 0.05). The innervation area score exhibited significant negative correlations with NVC and RUV, indicating that they increased according to the progression of denervation.

Conclusions

Our data indicate that TAC‐302 promotes neurite outgrowth in vitro. In addition, TAC‐302 prevents BOO‐induced bladder dysfunction in rats, and has a protective effect on bladder denervation.