Objective To explore the role of sialic acid-binding immunoglobulin-like lectin-one (Siglec-1) in the process of atherosclerotic inflammation induced by oxidized low-density hpepmtein (ox-LDL). Methods Ox-LDL was synthesized by oxidization of native LDL and different concentration of ox-LDL was added to the culture medium of RAW264.7. Forty-eight hours later, cells and supernatants were collected separately. The expression of Siglec-1 protein and mRNA were measured by flow cytometry(FCM) and real-time quantitative RT-PCR, respectively. The levels of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α(MIP-1α) and IL-8 in supernatants were determined by ELISA. Re-sults By the stimulation of ox-LDL, Siglec-1 protein and mRNA on RAW264.7 cells were significantly in-creased, meanwhile, the cytokines levels in culture supematants were significantly higher than that in the control group. And both Siglec-1 expression and cytokine secretion were ox-LDL dose-dependent. Conclu-sion Ox-LDL can increase Siglec-1 protein and mRNA expression and some inflammatory cytokines secre-tion on RAW264.7 cells in a dose-dependent manner. Manifested by enhanced Siglec-1 expression, the acti-vated macmphages may take a part in the development and progression of atherosclerosis.

Objective To study the clinical characteristics,muscle pathological features,diagnosis and prognosis of TK2-related mitochondrial DNA depletion syndrome(MDS).Methods Clinical and laboratory data of 2 cases of TK2-related myopathic MDS were reported.And data of previously reported 58 TK2-related MDS cases were reviewed.Results Total 60 patients consisted of 35 male and 25 female.The age of onset ranged from the birth to the age of 74 years old,and 54 of the patients were attacked at the age younger than 3 years old.Muscle weakness and hypotonia were detected in all patients,with 40 patients(including the newly diagnosed 2 cases) manifested as pure myopathic form,and 20 patients with other multiple organs involvement.Serum creatine kinase was mildly increased (211-6 500 IU/L) in 53 patients.Elevated serum lactic acid level (2.3-12.0 mmol/L)was observed in 24 patients.Muscle biopsy was available from 55 patients,and ragged red fibers and/or cytochrome C oxidase (COX)-negative fibers were detected in 48 out of them.Nine out of 11 patients received electronic microscope study showed proliferation of abnormal mitochondria.Respiratory chain enzymatic activities in skeletal muscle were reduced in 31 out of 33 patients.Marked mtDNA content reduction was observed in 36 out of 41 patients (4％-25％ of age-and tissue-matched controls).A total of 42 TK2 mutations were found in 60 patients,including 2 novel mutations c.923A ＞ G and c.619-2A ＞ T in this study.Conclusions The most common clinical manifestations of TK2-related MDS are severely,rapidly progressing myopathy with infantile or early childhood onset.As the detection rate of characteristic pathologic features in muscle is high,muscle biopsy is important for the diagnosis of TK2-related MDS.

OBJECTIVETo study the effect of anti-CD25 monoclonal antibody (mAb) combined with antithymocytic globulin (ATG) in the treatment of severe steroid-resistant acute graft-versus-host disease (aGVHD) after unrelated donor hematopoietic stem cell transplantation (UD-HSCT).

METHODSTen leukemic patients who developed severe steroid-resistant aGVHD during UD-HSCT received a standard dose of anti-CD25 mAb and a medium or low dose of ATG. The effect on aGVHD control, patients' survival, infection and relapse after the therapy were analyzed.

RESULTSEight of the 10 patients had complete remission and 2 had partial remission after the combined therapy. In the 8 patients with complete remission, 2 developed third degree aGVHD 3-3.5 months after the transplantation, and were managed with a second combined therapy to successfully achieve complete remission. In the total of 12 combined treatments, the median time of therapeutic effect was 5 days (3-10 days); the median complete relief time was 12 days (8-30 days) in the 10 cases. Among the 8 patients who survived for more than 3 months, 7 were diagnosed to have chronic GVHD including 4 with extensive chronic GVHD. No relapse of leukemia was found in these patients. Five patients survived the 2-year-long follow-up after the transplantation with survival time over 2 years; of the 5 patients who died within 2 years after the transplantation, 1 survived for more than one year, and 4 for less than 6 months. Two patients died from invasive fungal infection, two from aGVHD and one from cGVHD-induced multiple organ failure.

CONCLUSIONAnti-CD25 mAb combined with ATG has good therapeutic effect on steroid-resistant sever aGVHD and may help achieve high complete remission rate and long-term survival in leukemic patients after UD-HSCT.

Acute Disease ; Adult ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Drug Resistance ; Drug Therapy, Combination ; Female ; Graft vs Host Disease ; drug therapy ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; Male ; Prednisone ; therapeutic use ; Young Adult

Dendritic Cells ; immunology ; Granzymes ; Humans ; Immune Tolerance ; Killer Cells, Natural ; immunology ; Multivariate Analysis ; S100 Proteins ; analysis ; Serine Endopeptidases ; analysis ; Stomach Neoplasms ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology

OBJECTIVELysosomal storage diseases are a group of inherited disorders caused by deficiency of lysosomal enzymes or structural components. The manifestations of lysosomal storage diseases are complicated due to different enzyme deficiency. It has been reported that a range of metabolic diseases resulting in abnormal accumulation of metabolic byproducts may exhibit abnormal cytoplasmic vacuolation of lymphocytes. The aim of this study was to elicit the usefulness of vacuolated peripheral lymphocytes detection in screening and diagnosis of lysosomal storage diseases.

METHODClinical data of 42 patients who underwent microscopic and electron microscopic examination of peripheral blood specimens in our department were retrospectively evaluated between January 2008 and December 2009.

RESULTForty-two patients with the suspected lysosomal storage diseases were included, these patients presented with motor and developmental retardation and/or regression. Seizure occurred in 32 patients. Hepatosplenomegaly were found in 4 patients. Three patients presented with declined visual acuity. Atrophy and/or abnormal signals were detected on cranial CT/MRI images in 24 patients. Blood biochemical tests were normal. Serum levels of ammonia, lactic acid and pyruvate were normal. Serum amino acid profiles and urinary organic acid profiles were normal. Serum fatty acid profiles were normal. Vacuolated lymphocytes were detected on microscopic examination of blood film in 14 patients, and 8 of these patients were confirmed to have lysosomal storage disease. Curvilinear body was found on electronic microscopic examination of peripheral lymphocytes specimens in 4 patients, confirming the diagnosis of neuronal ceroid lipofuscinosis. In 3 of these 4 patients, curvilinear body were also found on electronic microscopic examination of skin and/or muscle specimens. Enzyme analysis confirmed the diagnosis of metachromatic leukodystrophy in one patient and Pompe's disease in another patient. Typical pathological changes were found on the examination of bone marrow in 2 patients with normal acid sphingomyelinase activity. So the patients were diagnosed with Niemann-Pick disease type C. The diagnosis of other 6 patients with vacuolated lymphocytes was unknown.

CONCLUSIONBecause of its usefulness and minimal invasiveness, vacuolated peripheral lymphocytes examination should be a screening test for lysosomal storage disease. As for patients with suspected neuronal ceroid lipofuscinosis, electron microscopic examination of peripheral lymphocyte specimens may provide specific clues to the final diagnosis.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphocytes ; pathology ; Lysosomal Storage Diseases ; blood ; diagnosis ; pathology ; Male ; Microscopy, Electron ; Retrospective Studies ; Vacuoles

Objective To observe the urodynamic change after spinal cord injury at different levels and the relationship with neurogenic dysfunction of bladder and urethra. Methods Eighty female rats were divided into a control group (20 rats) , a suprasacral spinal cord injury group (30 rats) and a sacral spinal cord injury (30 rats). The urodynamic exam was performed with all the rats before and 20 days after the spinal cord injury model was established by surgical operation. Results The maximum bladder volume and compliance in the su- prasacral injury group were significantly less than the sacral spinal cord injury group and the control, the maxi- mum volume and compliance in sacral spinal cord injury group were significantly less than the control. The DLPP in suprasacral injury group was significantly higher than that in the sacral spinal cord injury group and the con- trol, the DLPP in sacral spinal cord injury group was significantly less than that in the control group. Conclu- sion Urodynamic study is very useful for the early diagnosis and individualized treatment of the neurogenic bladder after spinal cord injury.

Objective To investigate the effects of dominant-negative truncation mutant?NTCF4, lacking the N-terminal form of TCF4 gene,on biological characteristics of renal cancer cell line GRC-I and explore the molecular mechanisms.Methods GRC-I cell was transfected with pCDNA3-?NTCF4 eukary- otie expression plasmid,pCDNA3 empty vector to construct the stable cell line GRC-I/?NTCF4 and GRC-I/ Mock respectively.The morphological changes of stable cells were observed and the cells growth curve was detected through light microscope.The cellular proliferation activities were determined using the MTT assay. The protein expression of Wnt pathway downstream target gene C-Myc and Cox-2 was evaluated by immuno- cytoehemieal method and Western Blot analysis.Results After the dominant-negative?NTCF4 gene was permanently expressed,the GRC-I/?NTCF4 stable cells morphologically showed that appearance changed from circular to long-spindle shape,growth rate decreased with less karyosehisis found,malignant pheno- types reversed to normal renal tubular cells.MTT assay revealed that the proliferation activities of GRC-1/?NTCF4 cells were inhibited by 11.2%-35.5% compared with GRC-I cells (P＜0.05),while the GRC- I/Mock cells have no difference with the control cells.Immunocytochemical analysis and Western Blot showed that the C-Myc and Cox-2 protein expression level of GRC-I/?ANTCF4 cells were significantly sup- pressed in comparison with that of GRC-I/Mock and GRC-I cells.Conclusions The dominant-negative truncation mutant?NTCF4 could partially inhibit the growth of renal cancer cells and down-regulate the pro- tein expression of Wnt pathway target gene C-Myc and Cox-2.These findings provide a experimental founda- tion for applying cell signal therapy to renal cell cancer by blocking the Wnt signaling pathway.

OBJECTIVEThe congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders with progressive muscle wasting and weakness that begin during neonatal or early infantile period. To study the clinical diagnosis, immunohistochemical feature and follow-up information of CMD, data of 8 cases with CMD were analyzed.

METHODSImmunohistochemical features of biopsied muscle specimens were summarized and analyzed by using anti-laminin alpha2 (merosin), anti alpha-dystroglycan (alpha-DG) and anti beta-dystroglycan (beta-DG) antibodies.

RESULTSThese patients mostly presented at birth or during the first six months of life with muscle weakness, hypotonia, contractures, and feeding difficulty or respiratory dysfunction. Hematoxylin-eosin staining of skeletal muscle specimens from these patients showed typical characteristics of CMD. Differences in fiber size, with predominantly small and round fibers, and dense connective tissue infiltration were seen. Four of the 8 patients were merosin-stain negative, which might be due to primary merosin deficiency. T2-weighted magnetic resonance imaging of the brain shows abnormalities of the white matter. Four cases were merosin-stain positive, and two of them also had hypoglycosylation of alpha-dystroglycan. Two patients had mental retardation. One of them had optic nerve atrophy and abnormal brain structure.

CONCLUSIONSTwo types of CMD were present in our group. Merosin-deficient congenital muscular dystrophy (congenital muscular dystrophy 1A, MDC1A) was more common, accompanied by abnormalities of the white matter. "Alpha-dystroglycanopathy" could be seen in merosin-positive cases.

Female ; Humans ; Infant ; Laminin ; deficiency ; Male ; Muscular Dystrophies ; congenital ; diagnosis ; metabolism

OBJECTIVEMultiple sclerosis is a demyelinating disease frequently showing a relapsing-remitting disease course. Clinical manifestations of 25 inpatients with MS were summarized and analyzed so that the clinical features and therapeutic approaches to childhood multiple sclerosis (MS) were investigated in order to improve its diagnosis and management.

METHODSClinical features and information during following-up of 25 cases with MS from June 1993 to May 2006 were collected and analyzed.

RESULTSAmong the 25 cases, 16 were female and the F:M ratio was 1.78:1. The relapsing-remitting type was seen in 21 cases, the secondary progressive MS in 3 cases and the classification was impossible in one case. The mean age of onset was 6.7 years (2-12) with various initial symptoms including visual loss (11 cases), cortical symptoms (8 cases with seizures, consciousness disturbance, aphasia and apraxia, etc.), myeleterosis (3 cases), symptoms of brainstem (2 cases) and cerebellar ataxia (1 case). Fever was present in 10 cases at the onset. Nine cases were monosymptomatic, while the other 16 had multiple symptoms. Visual loss occurred in 19 cases during the course of MS and 22 were found to have abnormal visual evoked potential (88%). The mean course of disease was 8.5 years (1.2-17.2) and 0-4 times of recurrences (0 means no new clinical attack occurred during following-up period).

CONCLUSIONSMS is increasingly recognized as a disease affecting children though it is uncommon. Childhood MS possesses some manifestations different from those of adults. There was a female predominance. The most common finding at the onset of disease was optic neuritis. Other features include acute onset and shorter course of disease. Atypical demyelinating symptoms were often seen. White matter lesions on MRI are required for the diagnosis. CSF oligoclonal bands could be found less commonly than in adults. Neurological sequelae were less often seen than in adults MS even though optic nerve atrophy and visual loss were relatively common. Steroid and IVIG are effective in acute period treatment.

Age of Onset ; Child ; Child, Preschool ; Demyelinating Diseases ; etiology ; Disease Progression ; Female ; Humans ; Immunoglobulins, Intravenous ; immunology ; Male ; Multiple Sclerosis ; immunology ; physiopathology ; therapy ; Optic Neuritis ; etiology ; immunology ; Secondary Prevention

OBJECTIVETo examine the urinary level of tissue factor (uTF) and its procoagulant activity (PCA) in patients with diabetes mellitus, and explore the relationship between uTF and renal damage in diabetes mellitus.

METHODSEighty-six patients with type 2 diabetes mellitus were divided into 3 groups according to urine albumin excretion (UACR), namely normal albuminuria group, microalbuminuria group and macroalbuminuria group. The levels of uTF, PCA, blood urea nitrogen (BUN), serum creatinine (CRE), serum cystatin C (CYSC), glycohemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured in all the patients and 21 healthy controls.

RESULTSCompared with normal control, the diabetic patients showed significantly increased levels of uTF and PCA. The urinary TF-PCA was positively correlated to BUN, CYSC, CRE, UACR, fasting glucose and hs-CRP, but not to uTF; only hs-CRP, UACR were positively correlated to uTF.

CONCLUSIONuTF is probably implicated in the development and progression of diabetic nephropathy.

Adult ; Albuminuria ; urine ; Blood Coagulation ; Case-Control Studies ; Creatinine ; urine ; Diabetes Mellitus, Type 2 ; physiopathology ; urine ; Female ; Humans ; Male ; Middle Aged ; Thromboplastin ; urine