Renal Damages in Deoxycorticosterone Acetate-Salt Hypertensive Rats: Assessment with Diffusion Tensor Imaging and T2-mapping.

PURPOSE: This study aimed to investigate the feasibility of diffusion tensor imaging (DTI) and T2-mapping to assess temporal renal damage in deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats and compare the results with histopathologic and immunohistochemical findings. PROCEDURES: After baseline renal magnetic resonance imaging (MRI), 24 out of 30 uninephrectomized Sprague-Dawley rats with DOCA-salt-induced hypertension were divided equally into four groups. Group 1 had renal MRI at weeks 2, 4, 6, and 8, and groups 2, 3, and 4 had MRI at weeks 2, 4, and 6, respectively. The remaining 6 rats were used as sham controls. The renal cortex and outer and inner stripes of the outer medulla were examined over time using fractional anisotropy (FA), apparent diffusion coefficient (ADC), and T2-mapping, and the results were compared with baseline values. The degree of glomerular and tubular injury, endothelial cell thickening, hyaline arteriolosclerosis, macrophage infiltration, microcyst formation, and fibrosis in different zones at different time points in the DOCA-salt rats were compared with controls. RESULTS: Compared with baseline values, DOCA-salt rats demonstrated a significant decrease in renal cortical FA from week 4 to week 8 (0.244 ± 0.015 vs 0.172 ± 0.014-0.150 ± 0.016, P = 0.018-0.002), corresponding to significantly more glomerular damage, arteriolosclerosis, macrophage infiltration, and fibrosis. The DOCA-salt rats had significantly increased cortical ADC and T2 values at weeks 6 and 8 (1.778 ± 0.051 × 10-3 mm2/s vs 1.872 ± 0.058-1.917 ± 0.066 × 10-3 mm2/s; 93.7 ± 4.9 ms vs 98.0 ± 2.9-100.7 ± 4.0 ms, respectively, all P < 0.05), consistent with excessively fluid-filled microcysts (aquaporin-2+). Despite DOCA-salt rats harbored markedly increased fibrosis in outer and inner stripes of the outer medulla at weeks 6 and 8, only nonsignificant decreases in FA were observed in comparison with the controls suggesting that only limited microstructural changes were present. CONCLUSIONS: Renal cortical FA is useful for the early detection and monitoring of renal damage in DOCA-salt hypertensive rats.

Severe bilateral ischemic-reperfusion renal injury: hyperacute and acute changes in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical correlations.

The aim of this study was to investigate the hyperacute and acute changes in apparent diffusion coefficient (ADC), T1, and T2 mapping in rat kidneys after severe bilateral renal ischemic-reperfusion injury (IRI). After baseline MRI, 24 Spraque-Dawley rats with renal IRI were divided equally as group 1 (post-IRI MRI at 6 hours, days 1, 3, and 7) and groups 2, 3, and 4 (post-IRI MRI at 6 hours; 6 hours and day 1; 6 hours, days 1 and 3, respectively), while six other rats without IRI (group 5) were used as sham control. ADC, T1, and T2 values of the cortex and outer and inner stripes of outer medulla (OSOM and ISOM), and immunohistochemical studies assessing monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and collagen deposition in three zones at different time points were evaluated. Significantly reduced ADCs in OSOM and ISOM are noninvasive biomarkers denoting hyperacute damages after IRI. Linear regression analysis revealed a significant inverse correlation between 6-hour/baseline ADC ratios and MCP-1 staining (P < 0.001, r2 = 0.738). ADC, T1, and T2 values are useful for assessing variable IRI changes in different layers depending on underlying microstructural and histopathological changes at different time points.

Dynamin-Related Protein 1 Promotes Mitochondrial Fission and Contributes to The Hippocampal Neuronal Cell Death Following Experimental Status Epilepticus.

AIMS: Prolonged seizure activity may result in mitochondrial dysfunction and lead to cell death in the hippocampus. Mitochondrial fission may occur in an early stage of neuronal cell death. This study examined the role of the mitochondrial fission protein dynamin-related protein 1 (Drp1) in the hippocampus following status epilepticus. METHODS: Kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 area in Sprague Dawley rats to induce prolonged seizure activity. Biochemical analysis, electron microscopy, and immunofluorescence staining were performed to evaluate the subsequent molecular and cellular events. The effects of pretreatment with a mitochondrial fission protein inhibitor, Mdivi-1 (2 nmol), were also evaluated. RESULTS: Phosphorylation of Drp1 at serine 616 (p-Drp1(Ser616)) was elevated from 1 to 24 h after the elicited seizure activity. Pretreatment with Mdivi-1 decreased the Drp1 phosphorylation at Ser616 and limited the mitochondrial fission. Mdivi-1 rescued the Complex I dysfunction, decreased the levels of oxidized proteins, decreased the activation of cytochrome c/caspase-3 signaling, and blunted cell death in CA3 neurons. CONCLUSION: Our findings suggest that activation of p-Drp1(Ser616) is related to seizure-induced neuronal damage. Modulation of p-Drp1(Ser616) expression is accompanied by decreases in mitochondrial fission, mitochondrial dysfunction, and oxidation, providing a neuroprotective effect against seizure-induced hippocampal neuronal damage.

Acute Epididymo-orchitis-Related Global Testicular Infarction: Clinical and Ultrasound Findings With an Emphasis on the Juxta-epididymal String-of-Bead Sign.

Acute epididymo-orchitis (AEO)-related global testicular infarction (GTI) is rare. We report herein the clinical and ultrasound findings of 6 patients with AEO-related GTI. Seventeen patients with torsion-related GTI were also reviewed and compared. The echotexture of AEO-related GTI ranged from mildly inhomogeneous to diffuse heteroechoic, depending on the severity of testicular necrotic changes. All of the patients showed a juxta-epididymal string-of-bead pattern on color Doppler ultrasound, which was ascribed to patent arteries (5/6, 87%) and collateral vessels (1/6, 13%) in the tunica albuginea. There were no significant differences in age, laterality, leukocyte count, testicular volume ratio (infarcted/normal), frequencies of heteroechoic testicular parenchyma, scrotal skin thickening, and hydrocele between the 2 groups. However, the left testis was predominantly affected in both groups. Compared with torsion-related GTI, patients with AEO-related GTI had significantly longer duration from scrotal pain onset to surgery (13.5 ± 5.2 vs 2.6 ± 2.0 days, P < 0.001), a higher level of serum C-reactive protein (110.0 ± 82.0 vs 41.2 ± 35.9 mg/dL, P = 0.013), a higher frequency of the juxta-epididymal string-of-bead sign (100% vs 12%, P < 0.001), and a lower frequency of the whirlpool/knot sign (0% vs 88%, P = 0.002). Although the testis in AEO-related GTI may appear variable from mildly to extensively heteroechoic on gray-scale ultrasound, this unusual disease can be characterized by an avascular testis with a juxta-epididymal string-of-bead sign on color Doppler ultrasound.

Cancer Patient-Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies.

PURPOSE: This study aimed to test the hypothesis that lung cancer patient-derived circulating microparticles (LCC-MPs) enhance metastatic lung tumors in a rat model. PROCEDURES: The controls (n = 6) and LCC-MP-treated rats (n = 6) with N1S1-induced pulmonary metastatic hepatocellular carcinoma (HCC) underwent dual-source CT (DSCT) on days 10, 15, and 20. Cellular and molecular studies were performed subsequently. RESULTS: DSCT revealed slow progression of metastatic lung tumors in the controls. Compared with the controls, the LCC-MP-treated rats exhibited significantly more and larger metastatic tumors on days 15 and 20 on DSCT, enhanced angiogenesis with higher microvessel count (CD34+), more CXCR4+ and VEGF+ cells in immunohistofluorescence studies, and higher protein expression levels of eNOS, angiopoietin, vascular endothelial growth factor, and CD31 on western blotting (Mann-Whitney test, all P < 0.05). CONCLUSIONS: LCC-MPs can elicit oncogenic stimulation and accelerate metastatic HCC growth in rat lung as demonstrated on DSCT and enhanced tumoral angiogenesis as confirmed in cellular and molecular studies.

Adipose-Derived Mesenchymal Stem Cell Exosomes Suppress Hepatocellular Carcinoma Growth in a Rat Model: Apparent Diffusion Coefficient, Natural Killer T-Cell Responses, and Histopathological Features.

We sought to evaluate the effects of adipose-derived mesenchymal stem cells (ADMSCs) exosomes on hepatocellular carcinoma (HCC) in rats using apparent diffusion coefficient (ADC), natural killer T-cell (NKT-cell) responses, and histopathological features. ADMSC-derived exosomes appeared as nanoparticles (30-90 nm) on electron microscopy and were positive for CD63, tumor susceptibility gene-101, and ß-catenin on western blotting. The control (n = 8) and exosome-treated (n = 8) rats with N1S1-induced HCC underwent baseline and posttreatment day 10 and day 20 magnetic resonance imaging and measurement of ADC. Magnetic resonance imaging showed rapidly enlarged HCCs with low ADCs in the controls. The exosome-treated rats showed partial but nonsignificant tumor reduction, and significant ADC and ADC ratio increases on day 10. On day 20, the exosome-treated rats harbored significantly smaller tumors and volume ratios, higher ADC and ADC ratios, more circulating and intratumoral NKT-cells, and low-grade HCC (P < 0.05 for all comparisons) compared to the controls. The ADC and volume ratios exhibited significant inverse correlations (P < 0.001, R (2) = 0.679). ADMSC-derived exosomes promoted NKT-cell antitumor responses in rats, thereby facilitating HCC suppression, early ADC increase, and low-grade tumor differentiation. ADC may be an early biomarker of treatment response.

Posterior choroidal leiomyoma: a rare case report and literature review.

We report a literature review and detailed evaluation of a rare case of posterior choroidal leiomyoma to emphasize the importance of differentiating this from other choroidal tumors. A 30-year-old male presented with variable blurred vision in his right eye secondary to a choroidal tumor. Clinical examinations were performed including fundus photography, optical coherence tomography, B scans, fluorescein and indocyanine green angiography, computed tomography, and magnetic resonance imaging. Preoperative examination revealed a suspected choroidal melanoma and enucleation was performed. However, a definitive diagnosis of choroidal leiomyoma was made following postoperative pathological light microscopy and immunohistochemical studies. Published case reports were collected and the common characteristics and distinctive features were compared with the current case. Posterior choroidal leiomyoma was summarized from the literature, and beneficial information for diagnosis and treatment was obtained. In conclusion, posterior choroidal leiomyoma is rare and should be differentiated from amelanotic melanomas. Despite the benign nature, an explanation regarding the rare incidence and difficult diagnosis of posterior choroidal leiomyoma must be provided to patients, prior to enucleation or detrimental treatment.

Imaging features and outcomes in 10 cases of idiopathic azygos vein aneurysm.

BACKGROUND: Idiopathic azygos vein aneurysm (AVA) is rare. This retrospective study evaluated the imaging features and outcomes in 10 cases of idiopathic AVA. METHODS: We retrospectively evaluated 10 patients with surgically proven or typical imaging features of idiopathic AVA encountered in our institution between 1990 and 2012. Chest roentgenography and computed tomography (CT) were performed in all 10 patients, and magnetic resonance imaging (MRI) was performed in 4 of these patients. The clinical features, AVA morphologic characteristics, and outcomes were analyzed. RESULTS: Chest roentgenograms showed a right paratracheal nodule or mediastinal mass in 7 cases. CT and MRI disclosed 4 thrombosed saccular AVAs (short axis, 3-6 cm; mean, 4.7 cm) and 6 fusiform AVAs (short axis, 2.2-3 cm; mean 2.7 cm). Two large saccular AVAs that presented with chest tightness were resected shortly after diagnosis. One saccular AVA manifested as a pulmonary embolism, whereas the remaining AVA was asymptomatic; they showed 25% to 40% short-axis growth in a 3- to 5-year interval before subsequent AVA resection. Conversely, all 6 fusiform AVAs were asymptomatic and found incidentally, remaining rather stable with less than 8% short-axis growth during 3 to 8 years of follow-up. Compared with fusiform AVAs, saccular AVAs were larger and had a greater frequency of AVA-related symptoms, intralesional thromboses, and greater than 20% short-axis growth during the follow-up period. CONCLUSIONS: Saccular AVAs are larger than fusiform aneurysms, presenting with greater frequency of chest symptoms, intralesional thrombosis, considerable lesion growth, and need for surgical intervention. In contrast, fusiform AVAs are asymptomatic and rather stable in long-term follow-up.

The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study.

Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining.

Management and outcome of primary spinal ependymomas: a single center experience from Taiwan.

BACKGROUND: Surgical treatment of spinal ependymomas requires careful consideration of the relative risks of neurological worsening from surgery. Our aim was to determine the risk factors of neurological deterioration after surgery for spinal ependymomas. MATERIAL AND METHODS: This 20-year study included 17 patients (seven men and 10 women; 44.65±13.62 years) with histologically confirmed spinal ependymomas. The basic features were reviewed and the functional status was assessed by using the modified McCormick classification. We subdivided the patient population into two groups according to whether neurological deterioration occurred after primary tumor resection (N=5) or not (N=12), and compared their clinical characteristics. RESULTS: The average duration of presenting symptoms in the 17 patients was 23.53±21.45 months. Three (17.6%) patients underwent subtotal or partial resection and 14 (82.4%) patients underwent gross total resection. The incidence of neurological deterioration after primary resection of spinal ependymomas was 29.4%. There were five (100%) and two (16.7%) male patients in the neurological-deterioration and no-deterioration groups, respectively (p=0.003). The duration of presenting symptoms was 24 months or over in all the patients with neurological deterioration and five of the 12 patients with improved or stabilized function (p=0.044). CONCLUSION: The risk associated with surgical resection of spinal ependymomas should not be overlooked because of the significant incidence of neurological deterioration. The male gender and long-standing symptom (≥24 months) are risk factors of postoperative neurological worsening. Early diagnosis and surgery are therefore critical for successful treatment of spinal ependymomas.

A clinicopathological study of the significance of the proportion of choroid morphology in chordoid meningioma.

Chordoid meningiomas (CM) account for approximately 0.5% to 1.0% of intracranial meningiomas. This tumor has a strong risk of recurrence and aggressive growth (World Health Organization grade II). Histological analysis of CM tumors shows that the tissue is often dominated by chordoid morphology; however, the exact relationship between the percentage of the chordoid component and other clinicopathological features is unknown. We collected 26 surgical specimens from 17 patients who had a histological diagnosis of CM between January 1986 and June 2010. The chordoid elements constituted 30% to 98% of the area of the tumor. In 12 of 17 (70.6%) primary tumors, over 50% of the area displayed the chordoid pattern. Recurrence was noted in nine of these patients and five underwent a second operation. These five patients showed a histopathological progression of aggressive features. The proportion of chordoid elements in each recurrent tumor also increased. Thus, the chordoid proportion in CM is associated with a greater likelihood of recurrence.

The status of MGMT protein expression is a prognostic factor for meningeal hemangiopericytoma: a clinicopathologic and immunohistochemical study of 12 cases at a single institution.

Meningeal hemangiopericytoma (HPC) is a clinicopathologically well-characterized malignancy with a high tendency to recur locally and to metastasize outside the central nervous system (CNS). We render clinicopathologic features of 12 cases of this uncommon tumor to further elucidate the relationship between the status of the DNA-repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) and the prognosis. Twenty-five specimens of meningeal HPC belonging to 12 patients were obtained at a single institution from 1992 to 2001. Correlations of histologic parameters, immunohistochemical study and clinical features were assessed. This series included five men and seven women with a median age of 37.5 years at the first surgery. The median post-operative follow-up period was 7.6 years. Six patients (55%) had single or multiple local tumor recurrences. The mean time to recurrence was 6.7 years. Distant metastasis occurred in three patients (27%) at a mean time of 6.5 years after first operation. The most frequent metastatic sites were liver and lung. Histopathologically, eight primary tumors (67%) belonged to WHO grade II, while four primary tumors (33%) belonged to WHO grade III. Immunohistochemically, 18% primary tumors exhibited 3+ to 4+ nuclear staining for MGMT protein, 18% exhibited 2+ staining, and 64% exhibited 0 to 1+ staining. The overall survival rate was 67 and 33% for primary tumors with 0 to 1+ and 2+ to 4+ MGMT staining, respectively (P = 0.018). The study illustrates aggressive behavior of meningeal HPC and the prognostic value of the status of MGMT protein expression.

Rhabdoid papillary meningioma: a clinicopathologic case series study.

World Health Organization (WHO) grade III meningiomas are subclassified on the basis of their architectural pattern into papillary and rhabdoid subtypes. Some meningiomas even combine papillary architecture with rhabdoid cytology. Additionally, they always show malignant histological features, follow an aggressive clinical course and tend to spread through the CSF after frequent local recurrence. We render the first series of rhabdoid papillary meningioma with review of the literature to further elucidate its biological behavior. From six patients (three male, three female), nine specimens of rhabdoid papillary meningioma were obtained between 1994 and 2010. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. The mean age of patients was 44.7 years at their first operation. The mean postoperative follow-up period was 63.2 months. Five patients experienced tumor recurrence, and one of them died from the disease after diffuse leptomeningeal dissemination. The mean time to first recurrence was 28 months. Only one patient was free of tumoral recurrence after an 8-year follow-up. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB-1 labeling indices were higher following tumor recurrence. The present study expands the clinicopathologic horizon of rhabdoid papillary meningioma and suggests that it will behave aggressively based on its histology and concomitant features of atypia or malignancy or high MIB-1 labeling indices. Close follow-up and aggressive treatments of these tumors are warranted.

Clear cell meningioma with frequent chordoid features and aggressive behavior: a clinicopathologic study of ten cases at a single institution.

Clear cell meningioma is an uncommon variant of meningiomas that often occurs in young patients, shows a proclivity for spinal intradural extramedullary and cerebellopontine angle, and follows an aggressive clinical course. We render clinicopathologic features of ten cases of this rare tumor to further elucidate its behavior. Fifteen specimens of clear cell meningioma belonging to ten patients were obtained at a single institution from 2001 to 2009. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. This series included eight men and two women with a mean age of 62.1 years at the first surgery. The mean post-operative follow-up period was 3.9 years. Four patients (40%) had single or multiple local tumor recurrences. The mean time to recurrence was 2.3 years. Seven tumors (46.7%) were combined with chordoid features. There was a wide range of MIB-1 labeling indices (4.4-33.5%, mean 15.8%), which were higher in recurrent tumors, tumors with chordoid features, and tumors with necrosis. There was no correlation between MIB-1 labeling indices and brain invasion. The study illustrates aggressive behavior of clear cell meningioma and frequently combined chordoid features in our cases.

Primary orbital meningioma: a study of six cases at a single institution.

Primary orbital meningioma is a rare tumor of the anterior visual pathway and constitutes approximately 2% of all orbital tumors and 1-2% of all meningiomas. The differentiation from secondary orbital meningioma of intracranial origin is sometimes difficult on image. As the tumor often leads to visual loss if left untreated and surgical intervention inevitably causes morbidity, the timing and modality of treatment are very important. We carried out the study involving six cases (mean age: 42.7 years, male to female ratio: 1:5) of primary orbital meningioma to further elucidate its behavior. The clinical signs and symptoms, diagnosis, treatment strategies, and follow-up information are recorded for all cases. The most frequent initial symptoms were visual complaints (100%) and proptosis (67%). In five cases, the diagnosis was based on pathologic findings and the tumors were all grade I meningiomas. In one case, however, the diagnosis was based on radiographic and clinical findings, lacking histologic confirmation. Five patients were operated on, four underwent tumor removal, and one received eyeball exenteration. One patient was treated with Novalis radiotherapy. The mean follow-up period was 8.8 years (range from 9 months to 15 years). All patients experienced loss of vision during the course without exception. No recurrent tumor was found in five cases during follow-up. In case 5, whose eyeball was exenterated, developed recurrent meningioma 7 years later. She received radiotherapy but the tumor was out of control. She expired 8 years after eyeball exenteration. The primary orbital meningioma is aggressive in behavior despite its benign histopathologic features. Loss of vision is frequently seen even after treatment. The tumor could be fatal if surgery and radiotherapy fail to control its intracranial extension.

The prognostic impact of O6-methylguanine DNA methyltransferase and epidermal growth factor receptor expressions on primary gliosarcoma: a clinicopathologic and immunohistochemical study of seven cases at a single institution.

CONTEXT: Gliosarcoma is an uncommon variant of glioblastoma characterized by a biphasic tissue pattern of glial and mesenchymal differentiation. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients of malignant glioma treated with alkylating agents. Epidermal growth factor receptor (EGFR) is the most frequently amplified gene in glioblastoma and associated with tumor invasiveness, angiogenesis, poor survival, and resistance to radiation therapy. AIMS: To elucidate the relationship between the statuses of the MGMT as well as EGFR proteins and the prognosis. The study was undertaken on samples received at the Department of Pathology from 2003 to 2009. MATERIALS AND METHODS: Clinicopathologic and immunohistochemical study of seven cases was performed. RESULTS: This series included three men and four women with a mean age of 49.3 years at first surgery. The median progression-free survival (PFS) was 22.2 months and 8.6 months for primary tumors with 0 to 1+ and 2+ to 3+ MGMT staining, respectively; the median overall survival (OS) was 27.5 months and 14.2 months for primary tumors with 0 to 1+ and 2+ to 3+ MGMT staining, respectively. The median PFS was 17.2 months and 11.2 months for primary tumors with 0 to 1+ and 2+ to 3+ EGFR staining, respectively; the median OS was 20.4 months and 17.7 months for primary tumors with 0 to 1+ and 2+ to 3+ EGFR staining, respectively. CONCLUSIONS: The series showed that MGMT and EGFR protein expressions were both unfavorable prognostic factors for patients with gliosarcoma.

Activation of calcium/calmodulin-dependent protein kinase IV and peroxisome proliferator-activated receptor γ coactivator-1α signaling pathway protects against neuronal injury and promotes mitochondrial biogenesis in the hippocampal CA1 subfield after transient global ischemia.

Delayed neuronal cell death occurs in the vulnerable CA1 subfield of the hippocampus after transient global ischemia (TGI). We demonstrated previously, based on an experimental model of TGI, that the significantly increased content of oxidized proteins in hippocampal CA1 neuron was observed as early as 30 min after TGI, followed by augmentation of PGC-1α expression at 1 hr, as well as up-regulation of mitochondrial uncoupling protein 2 (UCP2) and superoxide dismutases 2 (SOD2). Using the same animal model, the present study investigated the role of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and PGC-1α in delayed neuronal cell death and mitochondrial biogenesis in the hippocampus. In Sprague-Dawley rats, significantly increased expression of nuclear CaMKIV was noted in the hippocampal CA1 subfield as early as 15 min after TGI. In addition, the index of mitochondrial biogenesis, including a mitochondrial DNA-encoded polypeptide, cytochrome c oxidase subunit 1 (COX1), and mitochondrial number significantly increased in the hippocampal CA1 subfield 4 hr after TGI. Application bilaterally into the hippocampal CA1 subfield of an inhibitor of CaMKIV, KN-93, 30 min before TGI attenuated both CaMKIV and PGC-1α expression, followed by down-regulation of UCP2 and SOD2, decrease of COX1 expression and mitochondrial number, heightened protein oxidation, and enhanced hippocampal CA1 neuronal damage. This study provides correlative evidence for the neuroprotective cascade of CaMKIV/PGC-1α which implicates at least in part the mitochondrial antioxidants UCP2 and SOD2 as well as mitochondrial biogenesis in ischemic brain injury.

Clinicopathologic analysis of rhabdoid meningioma.

Rhabdoid meningioma is an uncommon variant of meningioma, and was classified separately for the first time in the 2000 World Health Organization's classification of tumors of the nervous system. Because it often shows malignant histological features and follows an aggressive clinical course, it has been classified as a grade III neoplasm. We describe the clinicopathologic features of 13 patients with this rare tumor. From 13 patients (seven male, six female), 19 specimens of rhabdoid meningioma were obtained between 2001 and 2009. The mean age of patients was 50.4years at their first operation. The mean postoperative follow-up period was 35.7months. Five patients experienced tumor recurrence, and two patients died from the disease. The mean time to first recurrence was 36.1months. The recurrence-free survival rates at 1 and 5years were 62% and 23%, respectively. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB-1 labeling indices were higher following tumor recurrence. Close follow-up and aggressive treatment of these tumors is warranted.

Chordoid meningioma: a clinicopathologic study of 11 cases at a single institution.

Chordoid meningioma is an uncommon variant of meningioma, which histologically bears a great resemblance to chordoma and often follows an aggressive clinical course. We examine clinicopathologic features of 11 cases of this rare tumor to further elucidate its behavior. Thirteen specimens of chordoid meningioma belonging to 11 patients were obtained at a single institution from 1995 to 2009. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. This series included six men and five women with a mean age of 60.8 years at first surgery. Aside from one patient (case 5) who died of disease immediately after the first operation, the mean postoperative follow-up period for the other 10 patients was 41.4 months. Two patients each had a local tumor recurrence. The mean time to recurrence was 10.4 years. No systemic manifestations of Castleman syndrome, such as iron-refractory hypochromic/microcytic anemia and dysgammaglobulinemia, were found. Six tumors (46%) were classified as benign (grade I) and seven tumors (54%) atypical (grade II), if based solely on histologic grading irrespective of chordoid or clear cell components in our cases. Lymphoplasmacytic infiltrate was moderate in one tumor (7%), mild in eight tumors (62%), and absent in four tumors (31%). The inflammatory cells were predominantly T cells (CD3+), with only scarce B cells (CD20+). There was a wide range of MIB-1 labeling indices (0.3-25.8%, mean 7.5%), which increased following tumor recurrence. Our study demonstrates that chordoid meningiomas are not always associated with Castleman's Syndrome, and that this histologic category can be seen in the elderly as opposed to only in younger age groups.

CA125-producing clear cell adenocarcinoma arising from the upper ureter and renal pelvis.

Clear cell adenocarcinomas similar to those found in the female genital organs can arise in the lower urinary tract of both women and men. Clear cell adenocarcinomas occurring in the upper urinary system are exceedingly rare. Here, we present a case of clear cell adenocarcinoma arising from the upper ureter and renal pelvis of a postmenopausal woman with a ureteral stone. The patient had elevated serum levels of cancer antigen (CA) 125 (103.80 U/mL) and CA19-9 (151.96 U/mL). The tumor showed typical features of tubulopapillary structures lined with clear-to-eosinophilic cytoplasm and frequent hobnail configuration. The tumor cells were immunoreactive for cytokeratin 7, cytokeratin 20, carcinoembryonic antigen and CA125, but negative for PAX-2 and alpha-methylacyl coenzyme A racemase. Given the presence of intestinal and squamous metaplasia of the adjacent urothelium, we propose that this clear cell adenocarcinoma developed through a metaplastic process. The tumor behaved so aggressively that the patient developed multiple metastases and died of the disease 5 months after radical nephroureterectomy.