Choristoma ; Humans ; Male ; Middle Aged ; Thyroid Gland ; pathology ; Tracheal Diseases

Adenocarcinoma ; genetics ; metabolism ; Angiomyolipoma ; etiology ; Antibiotics, Antineoplastic ; therapeutic use ; Astrocytoma ; etiology ; Brain Neoplasms ; etiology ; Breast Neoplasms ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Kidney Neoplasms ; etiology ; Lung Neoplasms ; genetics ; metabolism ; Mutation ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Tuberous Sclerosis ; complications ; drug therapy ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

Objective To report a large family with an autosomal dominant dementia associated with mutation in the prion protein gene(PRNP)and the detailed clinical,neuroimaging and pathological manifestations.Methods Two patients from a large family of dementia were admitted to our ward and the data of their medical history,physical examination,video electroenceplialogram,neuroimaging were colleted.A sterotactic biopsy of the right frontal lobe of the proband was done.After the informed consent from the family members obtained,the genomic DNA was extracted from peripheral blood leucocytes of 5 persons followed by in,vitro amplification using polymerase chain reaction(PCR).The PCR products were directly sequenced by Sanger method.PRNP gene sequence was also examined in 150 normal Chinese to exclude single nueleotide polymorphism.Results A missense mutation of PRNP gene in 5 farnily members was detected,resulting in Gll4V mutation in the prion protein,with M/M genotype of eodon 129.This mutation was not detected in 150 normal Chinese.The proband was diagnosed as inherited prion disease by her clinical features,including neuropsychiatrie disturbances and progressive dementia,and manifestations of neuroimaging,EEG,neuropathology and PRNP gene mutation.Conclusion The first autosomal dominant pedigree of family prion disease is found in China with G114V mutation in PRNP gene which may lead to the prion disease directly.

OBJECTIVETo investigate the expression dynamics and significance of matrix metalloproteinase-2 (MMP-2) membrane type-matrix metalloproteinase-2 (MT-MMP-2) in hepatic fibrosis and its reversal counterpart.

METHODSAn experimental CCl4 induced hepatic fibrosis rat model was established by intraperitoneal administration of carbon tetrachloride for 2, 4, 6, 8, 10 weeks, and normal rats were used as a control group. The immunohistochemical methods and in situ hybridization were used to detect MMP-2,MT-MMP-2 mRNA and related antigens in the liver.

RESULTSMMP-2,MT-MMP-2 mRNA and related antigens were expressed in mesenchymal cells and parts of hepatocytes besides active pathological changes, especially in the fibrous septum and portal area. Expression of MMP-2,MT-MMP-2 mRNA and related antigens were increased in hepatic fibrosis and decreased gradually in its reversal counterpart.

CONCLUSIONThis study suggested that mesenchymal cells are the main cellular origins of MMPs. The levels of MMP-2 and MT-MMP-2 antigens and gene expression were closely related to hepatic fibrosis. MMP-2 and MT-MMP-2 may play important roles in hepatic fibrosis and its reversal counterpart.

Animals ; Carbon Tetrachloride Poisoning ; Gene Expression Regulation, Enzymologic ; Hepatocytes ; enzymology ; Liver ; enzymology ; pathology ; Liver Cirrhosis, Experimental ; enzymology ; etiology ; pathology ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinases ; biosynthesis ; genetics ; Matrix Metalloproteinases, Membrane-Associated ; Mesenchymal Stromal Cells ; enzymology ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar

Background:Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas.The p.R132H mutation of IDH1 is the most frequently observed IDH mutation,while IDH2 mutations were relatively rarely studied.The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations.Methods:Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed.The status of IDH1/2 gene mutations,telomerase reverse transcriptase (TERT) promoter mutations,O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation,1p/19q co-deletion and the expressions of IDH1 R132H,alpha-thalassemia X-linked mental retardation,and p53 were evaluated.Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.Results:Totally,71％ (169/238) of patients were positive for IDH mutations,including 12 patients harboring mutations in IDH2.Among the 12 patients with IDH2 mutations,ten patients harbored the R172K mutation,one patient harbored the R172S mutation and one harbored the R172W mutation.Of these,11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma.The proportion of grade Ⅱ tumors was higher than that of grade Ⅲ tumors in IDH2 mutant-gliomas.IDH2 mutations were frequently associated with TERT promoter mutations,1p/19q co-deletion and MGMT promoter methylation.IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P ＜ 0.05).However,the PFS and OS did not differ from that of IDH1 mutant patients (P =0.95 and P =0.60,respectively).Conclusions:IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis.IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas,and therefore may merit routine investigation.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.
Animals ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Dyslipidemias ; metabolism ; Energy Metabolism ; drug effects ; Fatty Liver ; chemically induced ; complications ; Female ; Fibroblast Growth Factors ; administration & dosage ; pharmacology ; therapeutic use ; Insulin Resistance ; Lipolysis ; drug effects ; Liver ; metabolism ; pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Sodium Glutamate

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

BACKGROUNDDevelopmental dyslexia (DD) is a disorder in which children with normal intelligence and sensory abilities show learning deficits in reading. Abnormal eye movements have been found in DD. However, eye-movement abnormalities during visual search among Chinese children with DD remain unknown. We aimed to identify the eyemovement characteristics and search efficiency of Chinese children with DD during visual search for targets of different conceptual categories, under same-category conditions.

METHODSWe compared 32 Chinese dyslexic children and 39 non-dyslexic children in visual search tasks, which were assessed using EyeLink II High-Speed Eye Tracker (SR Research Ltd., Canada). Letters, single Chinese characters, digits, Chinese phrases, figures and facial expressions were used as stimuli. Targets were similar to distractors in meaning, phonology and/or shape.

RESULTSA main effect of task on visual search scores and all eye-movement parameters were found. Search scores, average saccade amplitude and saccade distance were significantly smaller in the DD group than in the controls. An interaction between group and task was found for pupil diameter.

CONCLUSIONSUnlike normal readers, children with DD had a reduction in the visual attention span and search accuracy. Besides, children with DD could not increase their mental workload with increase in task difficulty. The conceptual category of the stimulus materials significantly impacts search speed, accuracy and eye-movement parameters.

Adolescent ; Asian Continental Ancestry Group ; Child ; Dyslexia ; physiopathology ; Eye Movements ; physiology ; Female ; Humans ; Male

To explore the cytogenetics and related clinical characteristics of adult acute leukemia with Philadelphia chromosome positive (Ph(+)AL), MIC classification by morphology, immunology and cytogenetics was used to retrospectively study 79 patients with Ph(+)AL hospitalized in the Institute of Hematology, People Hospital in Beijing from October 1991 to September 2003. The results showed that 6.9% cases were diagnosed as Ph(+)AL and classified into three subtypes: acute lymphoblastic leukemia (Ph(+)ALL) in 56 patients (18%), acute myeloid leukemia (Ph(+)AML) in 10 patients (1.2%) and mixed acute leukemia (Ph(+)MAL) in 13 patients. B-cell antigen expression was found in 52 out of 56 patients with Ph(+)ALL. 54.4% (43/79) patients had additional chromosome abnormalities including chromosome 7, double Ph and plus 8, etc. Complete remission (CR) rate of Ph(+)ALL and Ph(+)MAL was 57.0%, none of Ph(+)AML achieved CR. Median overall survival of Ph(+)ALL, Ph(+)MAL and Ph(+)AML were 10, 10 and 2.5 months respectively. It is concluded that Ph(+)AL has highly heterogeneity involving various differentiated stages of immature leukemic cells. Since the poor prognosis associated with this kind of AL, early diagnosis with MIC classification is a prerequisite to take more effective conditioning regimen and prospectively consideration of allogeneic stem cell transplantation to improve prognosis.
Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Cytogenetic Analysis ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Kaplan-Meier Estimate ; Karyotyping ; Leukemia, Myeloid, Acute ; genetics ; pathology ; therapy ; Male ; Middle Aged ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology ; therapy ; Remission Induction

This study is to observe allergic response to Qingkailing injection in BN rats and to establish a suitable animal model to evaluate allergic response induced by traditional Chinese medicine. BN rats were sensitized by Qingkailing injection, and guinea pigs were similarly sensitized as the control. The symptoms of allergic response were observed, the levels of histamine in serum and tissues were determined by ELISA assay and pathological changes in lung and trachea were observed with HE staining under light microscope. The total incidence of allergic response in BN rats was 52.78%, which was higher than that in guinea pig groups (16.67%). The total degree of allergic response in BN rats was higher than that in guinea pigs. Compared with control groups, the level of histamine in serum, lung and trachea tissues of BN rats and guinea pigs increased significantly. The release rate of histamine in BN rats was higher than that in guinea pigs. The rate and degree of pathological changes in lung and trachea tissues of BN rats were higher than that in guinea pigs. Compared with guinea pig, BN rat is probably a suitable animal model in evaluating allergic response to injection of traditional Chinese medicine.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; adverse effects ; Guinea Pigs ; Histamine ; blood ; Hypersensitivity, Immediate ; chemically induced ; Injections ; Male ; Rats ; Rats, Inbred BN