Objective: To analyze the relationship between thrombin activatable fibrinolysis inhibitor ( TAFI ) and coronary heart disease ( CHD ), and to provide evidence for the prevention of CHD. Methods: The patients with CHD in Fushun Central Hospital in Liaoning Province were selected as the case group, the patients without CHD in the same hospital and period were selected as the control group. The demographic information and clinical examination results ( serum TAFI, lipid, glucose, etc. ) were collected to analyze the association between TAFI and CHD by logistic regression models.The multivariate logistic regression analysis was used to explore the relationship between TAFI and CHD. Results: There were 222 cases, including 100 cases of stable angina, 44 cases of unstable angina and 78 cases of acute myocardial infarction, and 222 controls. The median ages of cases and controls were 62 and 57 years old. The results of multivariate logistic regression analysis showed that serum TAFI>22.88 μg/mL ( P75 of controls ) was associated with the risk of CHD ( OR=1.619, 95%CI: 1.011-2.593 ), unstable angina ( OR=2.917, 95%CI: 1.433-5.939 ) and acute myocardial infarction ( OR=2.626, 95%CI: 1.007-6.847 ). Conclusion The high level of TAFI is related to CHD, unstable angina and acute myocardial infarction.

In order to investigate the relationship between the expression of breast cancer resistance protein (BCRP) gene and drug resistance in patients with acute leukemia (AL), semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of BCRP mRNA in AL patients and 15 normal subjects. Beta(2)-microglobin (beta(2)-MG) was used as positive reference. BCRP/beta(2)-MG ratio >or= 0.5 was defined as BCRP mRNA positive. The results showed that the positive percentage of BCRP gene expression in newly diagnosed group was 37.6%. The first complete remission rate was 79.3% and 31.6% in BCRP mRNA negative and BCRP mRNA positive patients respectively. The difference was significant (P = 0.001). The expression levels of BCRP mRNA in drug resistance group and drug sensitive group were 0.962 +/- 0.426 and 0.315 +/- 0.296 respectively (P = 0.0001). The expression level of BCRP mRNA in relapsed/refractory group was significantly higher than that in newly diagnosed group (P = 0.0025). The expression level of BCRP gene in normal individuals and long-term survival group was very low and correlated with FAB subtypes. It is concluded that high expression of BCRP mRNA leads to clinical drug resistance and is an unfavorable factor for prognosis of AL patients except acute promyelocytic leukemia.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; Acute Disease ; Adolescent ; Adult ; Aged ; Drug Resistance, Neoplasm ; Female ; Humans ; Leukemia ; drug therapy ; genetics ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; RNA, Messenger ; analysis

This study was purposed to investigate the expression of c-fes gene in leukemia patients and its clinical significance. The expression of c-fes mRNA in bone marrow cells from 121 cases of acute and chronic leukemia patients, and the expression of c-fes mRNA in peripheral blood mononuclear cells of 20 normal persons were detected by real time-quantitative reverse transcription polymerase chain reaction (RQ-PCR). The results showed that the level of c-fes mRNA in AML patients was higher than that in normal controls [(48.017 +/- 57.170) x 10(-3) vs (0.152 +/- 0.398) x 10(-3)] (p < 0.0001); but there was no significant differences of level of c-fes mRNA between samples of ALL and normal controls(0.047 +/- 0.068) x 10(-3) vs(0.152 +/- 0.398) x 10(-3) (p>0.05); the level of c-fes mRNA in CML patients was higher than that in normal persons (21.605 +/- 24.818) x 10(-3) vs (0.152 +/- 0.398) x 10(-3) (p < 0.0001). The positive expression rate of c-fes gene in CML-CP patients (80%) was higher than that in CML-AP patients (66.7%) and CML-BP (28.6%) patients. In AML patients, c-fes gene was expressed higher in M(2) (80.77%) and M(3) (92.86%) patients. The remission rate of AML (except M(3))patients who had expression of c-fes gene was 81.08%, which was higher than that of patients with no expression of c-fes gene (40.00%). It is concluded that c-fes gene expression was found in myeloid leukemias, whereas low or no expression in lymphocytic leukemias. The differentiation of myelocytic cells may be related to c-fes gene. All AML (except M(3))patients with high level of c-fes mRNA may get good prognosis.
Adult ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Prognosis ; Proto-Oncogene Proteins c-fes ; genetics ; RNA, Messenger ; genetics

To investigate the expression and significance of X-linked inhibitor of apoptosis protein (XIAP) and XIAP-associated factor 1 (XAF1) in acute leukemia, the expression of XIAP, XAF1, Smac, and HtrA2 mRNA in the bone marrow aspirates from 87 newly diagnosed AL patients, 23 patients in remission, 6 patients in relapse, and 17 normal controls were detected by means of reverse transcriptase polymerase chain reaction (RT-PCR), and their relationship with clinical therapeutic efficiency was analyzed. The results showed that the expression level of XIAP mRNA in newly diagnosed AL patients (0.990 +/- 0.337) was significantly higher than that in normal controls (0.395 +/- 0.148) (P < 0.01); the positive rate and expression level of XAF1 mRNA in newly diagnosed AL patients (56.32%, 0.246 +/- 0.267) were significantly lower than that in normal controls (100%, 0.964 +/- 0.387) (P < 0.01). In 69 out of 87 newly diagnosed AL patients, efficacy remained evaluable. AL patients with high level of XIAP achieved a lower complete remission (CR) rate than patients with low level of XIAP (54.55% and 86.11%, respectively) (P < 0.01). XAF1 positive patients achieved a higher CR rate than XAF1 negative patients (86.84% and 51.61%, respectively) (P < 0.01). It is concluded that the overexpression of XIAP and negativity of XAF1 may be two adverse prognostic factors in AL patients.
Acute Disease ; High-Temperature Requirement A Serine Peptidase 2 ; Humans ; Inhibitor of Apoptosis Proteins ; biosynthesis ; genetics ; Intracellular Signaling Peptides and Proteins ; genetics ; Leukemia ; metabolism ; Mitochondrial Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Serine Endopeptidases ; biosynthesis ; genetics ; X-Linked Inhibitor of Apoptosis Protein ; biosynthesis ; genetics

Adult ; Female ; Humans ; Male ; Sturge-Weber Syndrome ; diagnosis ; pathology ; Young Adult

OBJECTIVETo detect subtelomeric rearrangement in patients with idiopathic mental retardation/developmental delays (MR/DD) and to provide new methods and evidence for the etiologic diagnosis of MR/DD in China.

METHODS1.

INCLUSION CRITERIA(1) Moderate to severe MR/DD; (2) no definite perinatal brain injury; (3) no toxication, hypoxia, infection of central nervous system and cranial trauma; (4) routine karyotyping is normal; (5) no evidence of typical inherited metabolic disorder or specific neurodegenerative disorders from cranial neuro-imaging and blood/urinary metabolic diseases screening; (6) no mutation of FMR1 gene in male patients plus one of the following criteria: (1) positive family history of MR; (2) positive family history of miscarriages and perinatal deaths; (3) abnormal growth; (4) facial and non-facial dysmorphism. 2. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were applied to detect subtelomeric rearrangements in patients and their parents.

RESULTSFour cases were identified from 39 selected cases with subtelomeric rearrangements (10%), including der (2) t (2; 4) (pter; pter), 11qter del, 8pter del, and 15p11.2 del. The first two abnormalities of chromosome subtelomeric regions have not been reported yet. All these cases had some small dysmorphologies, such as microcephaly, hypertelorism, low nasal bridge, and three of them had hypotonia. One case had recurrent seizure and abnormal behavior (laughter not associated with happiness), and another case with dysgenesis of corpus callosum and septum pellucidum. Family and perinatal histories were normal for all cases. All chromosome rearrangements were de novo which were not from the parents with normal phenotype. It indicated that all these abnormal rearrangements should be responsible for the mental retardation phenotype of these patients. The phenotype of case 4 was similar to Angelman syndrome, his deletion was actually a kind of interstitial rearrangements. It will be confirmed by DNA methylation test to determine whether the deleted allele was of maternal origin.

CONCLUSIONSThe subtelomeric rearrangements were found in 10% patients with idiopathic MR. It indicated that subtelomeric rearrangements should be one of major reasons of MR/DD related to genetic factors. Two novel subtelomeric rearrangements were identified. These de novo rearrangements are probably disease related, because they are not inherited from their parents with normal phenotype. The detection should be carried out for all the patients with idiopathic MR/DD with unknown origin, because one cannot figure out the specific signs for subtelomeric rearrangements. Sequentially use of MLPA and FISH is a more efficient and economic method to detect the subtelomeric rearrangements.

Adolescent ; Child ; Child, Preschool ; Chromosome Structures ; DNA Probes ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; genetics ; Male ; Mutation ; Sequence Deletion ; Telomere ; genetics

OBJECTIVETo modify the structure of psoralidin using in vitro enzymatic glycosylation to improve its water solubility and stability.

METHODSA new psoralidin glucoside (1) was obtained by enzymatic glycosylation using a UDP- glycosyltransferase. The chemical structure of compound 1 was elucidated by HR-ESI-MS and nuclear magnetic resonance (NMR) analysis. The high-performance liquid chromatography (HPLC) peaks were integrated and sample solution concentrations were calculated. MTT assay was used to detect the cytotoxicity of the compounds against 3 cancer cell lines in vitro. Results Based on the spectroscopic data, the new psoralidin glucoside was identified as psoralidin-6',7-di-O-β-D- glucopyranoside (1), whose water solubility was 32.6-fold higher than that of the substrate. Analyses of pH and temperature stability demonstrated that compound 1 was more stable than psoralidin at pH 8.8 and at high temperatures. Only psoralidin exhibited a moderate cytotoxicity against 3 human cancer cell lines. Conclusion In vitro enzymatic glycosylation is a powerful approach for structural modification and improving water solubility and stability of compounds.

Antineoplastic Agents ; metabolism ; Benzofurans ; metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Coumarins ; metabolism ; Glucosides ; biosynthesis ; Glycosylation ; Glycosyltransferases ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Solubility

OBJECTIVETo study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system (CNS-HB).

METHODSHistopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information.

RESULTSTwenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors (endocrine tumor and microcystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB (34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal cells. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin alpha and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices.

CONCLUSIONSVHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB, which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that, regular clinical inspection is recommended in order to check up the development of any new lesions.

Adolescent ; Adult ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Central Nervous System Neoplasms ; metabolism ; pathology ; surgery ; Child ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Hemangioblastoma ; metabolism ; pathology ; surgery ; Humans ; Inhibins ; metabolism ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms ; metabolism ; pathology ; surgery ; Receptor, Epidermal Growth Factor ; metabolism ; Retinal Neoplasms ; metabolism ; pathology ; surgery ; Survival Analysis ; Vimentin ; metabolism ; Young Adult ; von Hippel-Lindau Disease ; metabolism ; pathology ; surgery

OBJECTIVEA new respiratory virus, human metapneumovirus (HMPV) was recently identified by scientists in the Netherlands first and then in a few other countries. To investigate if this newly discovered virus is associated with the acute respiratory infections in pediatric patients in Beijing, tests were developed to detect HPMV gene fragments from nasopharyngeal aspirates collected from infants and young children hospitalized for acute respiratory infections from November 2002 to March 2003.

METHODSThe HMPV was screened by reverse transcription-polymerase chain reaction (RT-PCR). RNAs were extracted by Trizol from 247 specimens which had been determined as negative for conventional respiratory viruses including RSV, influenza A and B, parainfluenza I, II, III and adenovirus by indirect immunofluorescence test as well as virus isolation. The HMPV RNAs were detected by reverse transcription tests using random primer and M-MLV reverse transcriptase followed by PCR using the primers designed from the published sequence of the N protein-encoding gene from the first HMPV identified in the Netherlands. PCR products were visualized by 1.2% agarose gel electrophoresis. Selected positive PCR products were sequenced and the sequences of the nucleotides and deduced amino acids were compared with those in the GenBank.

RESULTSAmong those 247 specimens negative for common respiratory viruses, 74 (30.0%) showed the predicted 213 bp PCR products in agarose gel. Most of clinical diagnoses for these 58 patients were pneumonia (36, 48.6%), bronchiolitis (21, 28.4%), and bronchitis and asthma in some patients. Nearly 90 percent of positive specimens were from patients under 2 years of age. Ten out of 74 amplicons were randomly selected for sequence analysis. When compared with the sequences in the GenBank, the nucleotide sequences of these 10 amplicons shared high homology only with those of HMPVs. The nucleotide sequence identities of these 10 samples with those from the Netherlands and Canada were 87% - 99%. When compared with the nucleotide sequence from the first reported strain by Van den Hoogen (strain HMPV 00-1), the sequence identities of these 10 fragments ranged from 88.7% to 99.1%. Among the 10 amplicons from the specimens, the nucleotide identities were 87.3% - 100%. One of the 10 amplicons (No. 1816) shared lower identity with others (87.3% - 89.7%), whereas the other 9 shared higher identities (95.8% - 100%) with each other. The comparison of amino acids showed that these 10 amplicons showed high homology (95.8% - 100%). Again, amplicon No.1816 shared lower homology (95.8% - 97.2%) with others, whereas the other 9 shared higher homology (98.6% - 100%). The amino acid homology between No.1816 and HMPV 00-1 was 95.8%, whereas that of the other 9 with HMPV 00-1 was 98.6% - 100%.

CONCLUSIONThese data suggested that some of acute respiratory infections in pediatric patients in Beijing area are related to the newly identified human metapneumovirus. The HMPV circulating in Beijing may have different genotypes.

Acute Disease ; Child ; Child, Preschool ; China ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Infant ; Male ; Metapneumovirus ; genetics ; Nucleocapsid Proteins ; genetics ; Paramyxoviridae Infections ; pathology ; virology ; RNA, Viral ; genetics ; Respiratory Tract Infections ; pathology ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

Blood brain barrier (BBB), as barrier between plasma and brain cells formed by brain capillary wall and glial cells and barrier between plasma and cerebrospinal fluid formed by choroid plexus, can prevent some brain tissues (mostly harmful substances), so as to maintain a stable internal environment of brain tissues, while stopping most drugs from the intracranial and causeing difficulties to cerebral diseases. The establishment of experimental model of BBB is a key technique for drug treatment of craniocerebral diseases. Therefore, the establishment of the BBB model and the study of its permeability change will deepen the understanding of the neuro-vascular interaction and provide an important theoretical basis for the diagnosis and treatment of central nervous system diseases. Traditional Chinese medicine(TCM) can affect brain tissue superoxide dismutase (SOD) activity, inhibit myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) content, so as to affect the expression of zonula occluden-1 (ZO-1) or up-regulate the expression of Claudin-5, inhibit BBB permeability under pathological conditions, and play a protective role in BBB. TCM can also promote the changes in BBB permeability by affecting the expressions of cell adhesion factor-1 (CAM-1), ZO-1, filamentous actin(F-actin), P-glycoprotein(P-gp)and 5-hydroxytryptamine (5-HT), or increase drug permeability through co-delivery with other drugs. In this paper, the methods, advantages and disadvantages of the establishment of experimental models of the BBB in recent years, as well as the effects of TCM monomers, effective components and TCM compounds on the permeability of the BBB were summarized, so as to provide important guidance and direction for the future treatment of intracranial diseases by traditional Chinese and western medicine.