Objective To study the locations of P-glycoprotein(P-gp),multi-drug resistanceassociated protein (MRP) and lung resistance.related protein(LRP)in brain tissue of focal cortical dysplasia (FCD) and to compare the quantity of these proteins in different brain tissues in an effort to study the mechanism of refractory epilepsy and to provide theoretical basis for medical treatment in patients with epilepsy.Methods The brain tissues of 16 cases with refractory epilepsy were collected during surgery,including 8 cases of focal cortical dysplasia type Ⅰ(FCD Ⅰ)and 8 cases of focal cortical dysplasia type Ⅱ (FCD Ⅱ) Five cases of glioma without history of epilepsy were included as the control group.Envision method was used to observe the location and intensity of expression of these three proteins.Western-Blot was used to analyze these proteins quantitatively.Results In brain tissue,the locations of P-glycoprotein,multi-drug resistance-associated protein and lung resistance-related protein were difierent.P-gp located mainly in capillary endothelial cells;MRP in neurons components;the location of LRP included capillary endothelial cells,balloon cells and the matrix of lesions.The expressions of three proteins in brain tissue of FCD were significantly higher than in control group(P-gp:0.520 ±0.121,MRP:0.132±0.018,LRP:0.092.±0.018,U=0.000,P<0.01).The expressions of P-gp and LRP in lesions of FCD Ⅱ(3.809 ±0.842 and 0.655±0.303,respectively)were higher than that in surrounding regions(2.636 ±0.622 and 0.290±0.096,U value were 6.000 and 4.500,both P<0.01).Conclusions P-gp,MRP and LRP expressed at different position of focal cortical dysplasia,suggesting that their roles were distinctive.

Objective To investigate the elinieopathologie features of refractory epilepsy. Methods The clinical and pathologic features of refractory epilepsy of 273 cases undergoing surgical treatment in Xuanwu Hospital from January 2005 to December 2007 were reviewed retrospectively. Results The mean age of seizure onset and disease duration were 11.0 years and 11.2 years respectively. The following pathologic subgroups were identified: malformation of cortical development (MCD, 158/273) including focal cortical dysplasia (FCD) type Ⅰ (104, the mean age of seizure onset and disease duration were 11.1 years and 11.2 years respectively), FCD type Ⅱ (30, the mean age of seizure onset and disease duration were 7. 9 years and 12. 7 years respectively) , mild MCD (6) , tuberous sclerosis complex (6) and other types (9) , brain turnouts (26/273, the mean age of seizure onset and disease duration were 14. 5 years and 6. 3 years respectively), ulegyria (63/273), brain infections (13/273), vascular malformation (3/273), cyst (3/273), cholesteatoma (1/273) and other unknown types (6/273). Dual pathology was identified in 31 of 158 MCD cases. Eighty-six of 134 (64. 2%) FCD cases were type Ⅰ B predominantly seen in temporal lobe. Twenty of 26 (76. 9%) brain tumours were mixed neuronal-glial tumours predominantly located in temporal lobe. Cortical dysplasia was often seen in these cases. Conclusions The 3 most common causes of refractory epilepsy are MCD, ulegyria and brain tumours. The predominant subtype of FCD is type Ⅰ B often located in temporal lobe, in which associated hippoeampal sclerosis is often seen. Brain tumors in patients with refractory epilepsy are almost benign neoplasms located in temporal lobe, in which the most frequent type is mixed neuronal-glial tumour.

Objective To investigate the clinicopathologic features of the brain tissue from multilobar resection or hemispherectomy for refractory epilepsy. Methods The clinical and pathologic findings of 46 cases seen at Xuanwu hospital from 2005 to 2009 were reviewed retrospectively. Results The mean age of seizure onset and disease duration were 3.9 years and 10.2 years, respectively. There were 33 cases of hemispherectomy and 13 cases of multilobar resection. Temporal lobe abnormality was seen in all cases. The pathologic subgroups were as follows: ulegyria (31/46), malformation of cortical development (MCD, 7/46 ) and infection (8/46). Microscopic examination of ulegyria showed cortical architectural disturbances, neuronal loss, reactive gliosis and appearance of corpora amylacea. We also noted deposition of hemosiderin (13 cases), calcification (9 cases) and island-like neurons (5 cases). All ulegyria cases were accompanied by varying degree of cortical dysplasia, and hippocampus sclerosis were identified in 7 cases. MCD comprised of 5 cases of focal cortical dysplasia ( FCD), including 3 cases of FCDⅠB, 1 case of FCDⅡA and 1 case of FCDⅠA, 1 case of polymicrogyria and 1 case of porencephaly. Among 8 infection eases, there were 5 cases of Rasmussen encephalitis ( RE), l case of cysticercosis, 1 case of tuberculous meningitis and l case of Cytomegalovirus encephalitis. Conclusions The most common pathological category of specimens from hemispherectomy or multilobar resection is ulegyria with obvious temporal lobe abnormality. This is followed by MCD ( with FCDⅠB as the main type) and central nervous system infection (RE as the most frequent abnormality).

Objective To compare the expression and distribution of drug resistance proteins Pglycoprotein (P-gp) and lung resistance protein (LRP) in brain tissues of patients with refractory epilepsy and to investigate the relationship between expression of drug resistance proteins and concentration of antiepileptic drug carbamazepine (CBZ).Methods We included the brain tissues of 26 cases with refractory epilepsy who had in the experiment.They had following pathologic diagnosis: focal cortical dysplasia (FCD) Ⅰb (n =10),FCD Ⅱ a (n =4),FCD Ⅱb (n =2) and brain tumorsincluding ganglioglioma (n =6) and dysembryoplastic neuroepithelial tumor(n =4).Immunohistochemistry staining using EnVision system was used to reveal the expression location of P-gp and LRP,and Western blot in SDS-polyacrylamide gel was used to quantitatively analyze the expression of P-gp and LRP.Fluorescence polarization immunoassay was used to determine concentration of CBZ.Results Both P-gp and LRP performed(μg/ml) prominent overexpression in brain tissues of patients with refractory epilepsy,especially in the lesions of both FCD type Ⅱ (P-gp: 2.593 ±0.829 vs 1.711 ±0.292,t =-2.201,P=0.028;LRP:1.352 ±0.445 vs 1.179 ±0.593, t =-2.516,P =0.028, respectively)and tumor(P-gp:1.567 ±0.092 vs 0.775 ± 0.101, t =2.698, P =0.024; LRP: 1.091 ± 0.239 vs 0.825 ± 0.297, t =3.997, P =0.003respectively).The concentration of CBZ in lesions of brain tumors were lower than which in surrounding regions(0.848 ±0.726 vs 0.948 ±0.785, t =-3.056,P =0.014), while P-gp and LRP were higher than which in surrounding regions in 80％ cases.There was no relationship between expression of drug resistance proteins and concentration of CBZ.Conclusions In processing of drug resistance, P-gp and LRP play important roles.However, there is no correlation between expression of drug resistance proteins and concentration of CBZ, suggesting epilepsy drug resistance to be a complicated mechanism.

Objective: To compare the methods of metabolic balance (MB) and fecal monitoring (FM) for evaluating the dietary zinc (Zn) absorption in Tibetan men. Methods: In 14 d field trial on 16 adult Tibetan men, capsules of carmine were given to mark the feces from D4 to D12, and samples of diet, water, feces and urine were collected during the period. In addition, 4.0 mg zinc tracer (enriched with 67Zn) and 1.0 mg recovery indicator ytterbium (Yb) were orally administrated to the subjects in the evening meal of the D5. The ratio of 67Zn/68Zn in fecal samples was determined by inductively coupled plasma mass spectrometry, and then the zinc absorption was calculated based on the principle of isotope dilution. Results: The dietary zinc absorption in Tibetan men was (23.8?3.9) % evaluated by MB and (21.4?4.3) % by FM with significant difference (by paired-samples t test) and linear correlation (Pearson). The unabsorbed zinc tracer and Yb had the similar behavior through the digestive tract, mostly excreted within5 d following the intake. Conclusion: In the 14d metabolic period, the dietary zinc absorption from MB was a little higher than that from FM. Using FM, the metabolic period can be shortened to 4-5 days according to excretion of Yb. Both methods suggested that the dietary zinc absorption in the adult Tibetan men was good.

OBJECTIVETo investigate the immunohistochemical expression of isocitrate dehydrogenase 1 gene (IDH1) R132H in glioma and its diagnostic utility.

METHODSImmunohistochemical study of IDH1R132H expression was performed on formalin-fixed paraffin-embedded tissue samples of 75 gliomas, including 33 cases of grade II, 20 cases of grade III and 22 cases of grade IV tumors. Six cases of pilocytic astrocytoma and 12 cases of gliosis were used as controls.

RESULTSNineteen in 33 cases of grade II (57.6%), 8 in 20 cases of grade III (40.0%), 6 in 22 cases of grade IV (27.3%) showed positive cytoplasmic staining of IDH1R132H. Scattered invasive glioma cells at the tumor periphery also expressed IDH1R132H. Gliomas involving the frontal lobe showed more strong IDH1R132H staining. In contrast, none of the pilocytic astrocytomas and gliosis showed IDH1R132H staining. Moreover, the rate of p53 immunopositivities were 42.4% (14/33) in grade II, 65.0% (13/20) in grade III and 77.3% (17/22) in grade IV gliomas. There were no statistic correlations between expression of IDH1R132H and p53.

CONCLUSIONIDH1R132H tends to express preferentially in low-grade gliomas, and it thus may serve as a valuable marker in distinguishing low grade gliomas from gliosis.

Adolescent ; Adult ; Aged ; Astrocytoma ; metabolism ; pathology ; Brain Neoplasms ; metabolism ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioma ; metabolism ; pathology ; Gliosis ; metabolism ; pathology ; Humans ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Tumor Suppressor Protein p53 ; metabolism ; Young Adult

OBJECTIVETo study the immunohistochemical expression and diagnostic significance of CD34 in brain tumors of patients with refractory epilepsy.

METHODSImmunohistochemical study for CD34 was performed on formalin-fixed paraffin-embedded tissue blocks of 54 cases of brain tumors occurring in patients with refractory epilepsy. The tumor types included ganglioglioma (GG, number = 21), dysembryoplastic neuroepithelial tumor (DNT, number = 8), tumors/lesions which had the transitional features that between glioneuronal hamartia and mixed neuronal-glial tumor (number = 21) and pleomorphic xanthoastrocytoma (PXA, number = 4). Cases of glioblastoma (number = 4) and oligoastrocytoma (number = 5) were used as controls.

RESULTSTwenty of the 21 cases of GG, 1 of the 8 cases of DNT, 16 of the 21 cases of tumors/lesions which had the transitional features and 3 of the 4 cases of PXA showed cytoplasmic and membranous positivity for CD34. The adjoining brain tissues in 9 of the 18 cases of GG, 6 of the 16 cases of tumors/lesions which had the transitional features and 1 of the 3 cases of PXA also expressed CD34. In contrast, only 1 case of glioblastoma showed membranous positivity for CD34.

CONCLUSIONSCD34 preferred to staining for GG and PXA. Which represent a valuable tool for distinguishing GG, PXA and DNT, oligoastrocytoma, glioblastoma.

Antigens, CD34 ; metabolism ; Astrocytoma ; complications ; metabolism ; pathology ; surgery ; Brain Neoplasms ; complications ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Epilepsy ; etiology ; Ganglioglioma ; complications ; metabolism ; pathology ; surgery ; Glioblastoma ; complications ; metabolism ; pathology ; Humans ; Neoplasms, Neuroepithelial ; complications ; metabolism ; pathology ; surgery

OBJECTIVETo investigate the phenotypes and functions of cord blood dendritic cells of fetuses whose mothers are patients with chronic hepatitis B.

METHODSPeripheral blood and cord blood mononuclear cells (PBMC) were isolated from whole blood by density gradient centrifugation with Ficoll-Hypaque. The adherent cells were cultured in AIM-V medium containing recombinant human IL-4, TNF-alpha and GM-CSF. On day 9, mature DCs (mDC) were harvested and used for phenotype analysis. The amounts of IL-12 which dendritic cells produced were measured. The dendritic cells that were studied and compared were from cord blood of fetuses of both CHB positive and negative mothers and from CHC adult peripheral blood.

RESULTSThe expression rate of CD80 and CD83 of chronic hepatitis B mother cord blood dendritic cells was low compared with that of the healthy cord blood, healthy adult peripheral blood, and chronic hepatitis B adult peripheral blood, P < 0.05. The amount of IL-12 produced by chronic hepatitis B mother cord blood dendritic cells was lower than that of healthy cord blood, healthy adult peripheral blood, chronic hepatitis B adult peripheral blood (P < 0.05). The T lymphocyte proliferation inducing ability of dendritic cells of healthy adult peripheral blood was higher in inducing cord blood T lymphocytes proliferation, which was greater than that of the healthy adult peripheral blood in inducing adult T lymphocytes and was greater than that of the healthy cord blood dendritic cells in inducing cord blood T lymphocytes, which was greater than that of the healthy cord blood in inducing adult T lymphocytes, which was greater than that of chronic hepatitis B mothers in inducing cord blood T lymphocytes, which was greater than that of chronic hepatitis B mother cord blood in inducing adult T lymphocytes.

CONCLUSIONThe maturation and functioning of CHB mother cord blood dendritic cells were lower than those of healthy cord blood, healthy adult peripheral blood and CHB adult peripheral blood.

Adult ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; Female ; Fetal Blood ; immunology ; Hepatitis B, Chronic ; immunology ; Humans ; Phenotype ; Pregnancy ; Pregnancy Complications, Infectious ; immunology ; T-Lymphocytes ; immunology

OBJECTIVETo study the expression of P-glycoprotein, multi-drug resistance associated protein and major vault protein in pathologic brain specimens, and to investigate their roles in the pathogenesis of refractory epilepsy.

METHODSImmunohistochemical study was performed in pathology specimens from 18 cases of refractory epilepsy (including 5 cases of focal cortical dysplasia, 3 cases of tuberous sclerosis, 5 cases of ganglioglioma and 5 cases of dysembryoplastic neuroepithelial tumor).

RESULTSBoth the P-glycoprotein and major vault protein were localized in microvascular endothelium of the lesions. Major vault protein was also seen in balloon cells and some neuronal cells. On the other hand, multi-drug resistance associated protein was mainly localized in the neuronal component of the lesions. In general, the expression of P-glycoprotein and major vault protein in tumoral tissue was higher than that in non-tumoral tissue. The expression of multi-drug resistance associated protein and major vault protein was also different in the neoplastic glial cells of ganglioglioma and dysembryoplastic neuroepithelial tumor.

CONCLUSIONSP-glycoprotein, multi-drug resistance associated protein and major vault protein contribute to the pathogenesis of refractory epilepsy. They may however have different roles, with different cellular localization.

ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Adolescent ; Adult ; Brain ; metabolism ; Brain Neoplasms ; chemistry ; Child ; Drug Resistance, Multiple ; Epilepsy ; drug therapy ; genetics ; metabolism ; Female ; Ganglioglioma ; genetics ; metabolism ; Humans ; Male ; Malformations of Cortical Development ; genetics ; metabolism ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; pharmacology ; Tuberous Sclerosis ; metabolism ; Young Adult

OBJECTIVETo evaluate the alteration of subunits composition in NMDA receptor and the alterations of the expression and distribution of NMDA receptors and parvalbumin (PV)-positive neurons in focal cortical dysplasia (FCD) cortices.

METHODSTwenty cases of FCD samples (including all four subtypes of FCD) obtained during epilepsy surgery and 4 controls were analysed by immunohistochemical staining for NR1, NR2A/B and PV.

RESULTSIncreased expression of NR1 was detected in the giant neurons and dysmorphic neurons in FCD; while pronounced expression of NR2A/B was detected in immature neurons, giant neurons and dysmorphic neurons of FCD, especially in somata and processes of the immature neurons. Compared with the controls, FCD cortices showed prominent scattered arrangement of PV positive neurons and fibers, dramatically decreased number of PV positive interneurons and PV background staining, especially in foci of FCD II subtype.

CONCLUSIONThere are increased expressions of NR1 and NR2A/B subunits in FCD abnormal neurons, as well as scattered and reduced expressions of PV positive neurons and fibers in FCD cortices.

Adolescent ; Biomarkers, Tumor ; metabolism ; Cerebral Cortex ; metabolism ; pathology ; Child ; Child, Preschool ; Epilepsies, Partial ; pathology ; Female ; Gene Expression Regulation ; Humans ; Infant ; Interneurons ; metabolism ; Male ; Malformations of Cortical Development ; pathology ; Neurons ; metabolism ; Parvalbumins ; analysis ; isolation & purification ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism