Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; complications ; drug therapy ; Atlanto-Axial Joint ; injuries ; Humans ; Joint Dislocations ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Syringomyelia ; diagnosis ; etiology ; physiopathology

Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Precancerous Conditions ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; rho GTP-Binding Proteins ; biosynthesis ; genetics

Nitric oxide (NO) is a short-life free radical that acts as the small biological molecule, and exists in body extensively. Since its discovery over 20 years ago, NO has been found to play an important regulation role in angiogenesis, nerve and immune system. The subsequent studies also showed that NO exerted an important biological action in wound repairing and healing, which involved in the following phases of wound repair, inflammation, cell proliferation, matrix deposition and remodeling. This paper reviews recent findings from in vitro & in vivo studies of NO in wound repair, and the biological function and mechanisms of NO in wound repair.
Animals ; Humans ; Neovascularization, Physiologic ; Nitric Oxide ; metabolism ; physiology ; therapeutic use ; Wound Healing ; drug effects ; physiology

Objective Familial hypertrophic cardiomyopathy (FHCM) is a primary myocardial disease characterized by unexplained ventricular hypertrophy. The application of the techniques of reverse genetics has identified at least five chromosomal loci as the major causes for FHCM in diverse ethnic populations, suggesting substantial genetic heterogeneity for FHCM. Recently, the defective gene loci of two Chinese families with FHCM have been mapped to chromosome 11 and 14q1, respectively. For further understanding of the molecular basis of FHCM in Chinese, we analyzed the linkage between four other Chinese kindreds and DNA markers from chromosome 14q1. Methods Six unrelated Chinese families with FHCM, including two previously reported, were studied. Totally 90 family members were included for analysis. DNA from 80 individuals was extracted and polymerase chain reactions were performed using the primers designed according to the sequences derived from the α and β myosin heavy chain gene. Totally four polymorphisms were studied, including three polymorphic microsatellite sequences and one single strand conformation polymorphism. Genetic linkage analysis were performed using the Linkage program.Results In the six studied families, 39 of the 90 family members were found to be affected diagnosed either by echocardiography or by clinical evaluation. The pattern of inheritance in all six studied families was most consistent with an autosomal dominant trait with a high degree of penetrance. Genetic linkage analysis using polymorphisms on the α and β MHC genes showed a combined maximal lod score of 6.2 for trinucleotide repeat polymorphism AMHC-I 15 at θ=0.00 for three studied families without recombination. Exclusion of linkage to the chromosome 14q1 location was noted in two of three other families with the maximal lod score of -2 or less.Conclusions These results provide further evidence that FHCM in Chinese is genetically heterogeneous. Chromosome 14q1 locus, probably the β myosin heavy chain gene, is important as the molecular basis for FHCM in Chinese.

OBJECTIVETo investigate the promoter methylation status and mRNA expression of APC gene in MCF10 model of breast cancer progression.

METHODSMethylation specific PCR and sodium bisufite genomic sequencing were employed to detect the methylation status of APC promoter 1A in normal breast tissues, conventional breast cancer cell line MCF-7 and MCF10 model cell lines including MCF10A (breast hyperplastic cell line, non-tumorigenic), MCF10AT (pre-malignant cell lines, producing slowly progressing hyperplastic and dysplastic lesions), MCF10DCIS.com (breast ductal carcinoma in-situ cell line, producing ductal carcinoma in-situ), MCF10CA1a, MCF10CA1d, MCF10CA1h cell lines (invasive breast carcinoma cell line, forming aggressive tumors of different morphology and metastatic potential). In addition, mRNA expression of APC was determined by reverse transcriptase PCR and real-time PCR assays.

RESULTSHypomethylation of APC promoter 1A was identified in hyperplastic cell line MCF10A, pre-malignant cell line MCF10AT, ductal carcinoma in-situ cell line MCF10DCIS.com, invasive carcinoma cell lines MCF10CA1a, MCF10CA1d, MCF10CA1h and normal breast tissue. MCF-7 showed partial methylation at the promoter. Statistically significant reduction of APC mRNA expression was not found in all MCF10 cell lines and MCF-7, compared with that of normal breast tissue (MCF10AT, MCF10CA1a, MCF10CA1d, MCF10CA1h and MCF10DCIS.com showed reduced mRNA expressions of APC at 0.27, 0.96, 1.78, 2.70, and 2.03 times respectively. MCF10A and MCF-7 even showed an increase of APC mRNA expression at 0.02 and 0.33 times, respectively).

CONCLUSIONThe aberrant promoter methylation of APC is not related to the breast cancer progression, at least in the MCF10 model system.

Adenomatous Polyposis Coli Protein ; biosynthesis ; genetics ; Breast ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Genes, APC ; Humans ; Hyperplasia ; genetics ; metabolism ; pathology ; Precancerous Conditions ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; biosynthesis ; genetics

Idiopathic Normal Pressure Hydrocephalus (NPH) is a debilitating condition of the elderly. The patient is typically "wet, wobbly and wonky", to different degrees of the triad. The diagnosis is supported by the radiologic finding of dilated ventricles, determined by an elevated Evan's Index (EI) without a demonstrable cause. Patients with newly diagnosed NPH typically respond to ventriculo-peritoneal shunting (VPS). NPH-related dementia is possibly the only surgically reversible dementia. An elevated cerebrospinal fluid (CSF) fl ow rate (FR) is associated with a positive response to shunting. However, post-shunting EI and FRs are unpredictable. Of late, intracranial apparent diffusion coefficient (ADC) quantification via Diffusion Weighted Imaging (DWI) has been emerging as a possible marker in NPH diagnosis. A local study, conducted on a national level, to study the relationship of EI, FR and ADC to pre- and post-shunt clinical measurements has just ended. This review seeks to reconcile the current thinking of NPH, magnetic resonance imaging (MRI) quantification and clinical evaluation, and in the process shed some light on major pathophysiological determinants of the disease.
Biomarkers ; cerebrospinal fluid ; Cerebrospinal Fluid ; physiology ; secretion ; Diffusion Magnetic Resonance Imaging ; Humans ; Hydrocephalus, Normal Pressure ; diagnosis ; physiopathology

INTRODUCTIONFetal imaging has improved with the development of faster magnetic resonance imaging (MRI) sequences, obviating the requirement for sedation. It is useful in characterising abnormality of the central nervous system in fetuses with abnormal or equivocal antenatal ultrasound findings. We reviewed all cases of fetal brain and spine MRI performed in our institution.

MATERIALS AND METHODSAll cases of fetal central nervous system MRI imaging from May 2006 to December 2008 were retrospectively reviewed, including fetal MRI, postnatal MRI and autopsy findings.

RESULTSThirty-one fetuses were imaged with MRI for evaluation of the central nervous system of which 3 were specifically for spinal evaluation. On fetal MRI, there were 11 normal fetuses (2 with minor ventricular asymmetry), 4 fetuses with minor ventriculomegaly and 16 fetuses with significant abnormalities. Twenty-three fetuses were delivered and 8 were terminated. Fifteen of 23 babies underwent postnatal imaging, 21 had clinical follow-up and 2 were lost to clinical follow-up. Of the 11 fetuses reported as normal on fetal MRI, 3 had additional postnatal findings. A fetus with a megacisterna magna on fetal MRI was diagnosed with a posterior fossa arachnoid cyst on postnatal MRI. One, who had fetal MRI to assess suspected absent inferior cerebellar vermis, had intracranial calcifications from rubella infection. One was diagnosed with cerebro-occular-facio-skeletal (COFS) syndrome postnatally, 1 was lost to follow-up and the rest were discharged well. Seven out of 16 fetuses with significantly abnormal fetal MRI findings had confirmation of the findings on postnatal imaging. Postnatal MRI detected 2 cases of polymicrogyria which were not seen on fetal MRI. Autopsy was available in 1 abortus confirming intrauterine diagnosis of Dandy Walker malformation. A myelomeningocele was clinically obvious in 1 abortus.

CONCLUSIONFetal MRI is a good method of assessing brain and spine abnormalities in utero. However, disorders of neuronal migration remain a challenging diagnostic problem in fetal imaging.

Central Nervous System ; abnormalities ; Fetus ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; diagnosis ; epidemiology ; physiopathology ; Medical Audit ; Retrospective Studies ; Singapore ; epidemiology

Aged ; Dermis ; pathology ; Disease Progression ; Extremities ; Face ; Fatal Outcome ; Humans ; Male ; Sarcoma, Myeloid ; pathology ; Skin ; pathology ; Thorax

OBJECTIVETo provide appropriate guidelines for treatment of tandem ossification of the posterior longitudinal ligament (OPLL) and flaval ligament (OFL). Data sources Published articles about OPLL and OFL were selected using Medline and Embase electronic databases. Study selection An English literature search from January 1980 to December 2006 was conducted. Because many reported cases were incorporated in OFL studies, the key words for search were OFL or OFL and OPLL. The first step revealed 93 studies of which 13 reports of tandem OPLL and OFL (tandem ossification) were selected.

RESULTSAll studies were case series or case report and advocated that the primary therapy for tandem ossification should be operative. The clinical outcomes of surgery were evaluated in most reports, predominantly using the JOA scores. Gender is the only factor which has prognostic value. A higher proportion of women was found in the failure group. A two-stage classification of tandem ossification was developed to relate diagnosis to outcome.

CONCLUSIONSAll patients with suspected ossification of the spinal ligaments should undergo routine MRI screening of the whole spine. The correlation of the classification with surgical treatments needs further studies to validate its usefulness.

Female ; Humans ; Ligamentum Flavum ; pathology ; Male ; Ossification of Posterior Longitudinal Ligament ; classification ; pathology ; Ossification, Heterotopic ; classification ; pathology

OBJECTIVETo investigate the role of WT1 gene in breast carcinogenesis by analyses of the promoter methylation status and mRNA expression of WT1 gene in MCF10 model system of breast cancer progression.

METHODSMethylation specific PCR and sodium bisufite genomic sequencing were employed to detect methylation status of WT1 promoter in normal breast tissue, traditional breast cancer cell line MCF7 and MCF10 model series, including MCF10A (breast hyperplastic cell line, non-tumorigenic), MCF10AT (pre-malignant cell line, forming slowly progressing hyper and dysplastic lesions), MCF10DCIS.com (breast ductal carcinoma in situ cell line, forming ductal carcinoma in situ), and three invasive cell lines with metastatic potential (MCF10CA1a, MCF10CA1d, and MCF10CA1h). Real time reverse transcription PCR assay was used to determine the mRNA expression levels of WT1 in various cell lines.

RESULTSHypermethylation of WT1 promoter was identified in MCF7 and all MCF10 model cell lines (MCF10A, MCF10AT, MCF10DCIS.com, MCF10CA1a, MCF10CA1d, and MCF10CA1h). Unexpectedly, an increased expression of WT1 mRNA was found in all MCF10 cell lines and MCF7 comparing with normal breast tissue [folds of overexpression: 3.23 (MCF10A), 1.94 (MCF10AT), 4.20 (MCF10CA1a), 1.53 (MCF10CA1d), 4.20 (MCF10CA1h), 4.35 (MCF10DCIS) and 28.69 (MCF7)].

CONCLUSIONSPromoter methylation does not silence the mRNA expression of WT1 during the development of breast cancer. Overexpression of WT1 occurs in the early stages of breast cancer development, suggesting its role as an oncogene rather than a tumor suppressor gene.

Base Sequence ; Breast ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; DNA Methylation ; DNA, Neoplasm ; genetics ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; genetics ; metabolism ; pathology ; Molecular Sequence Data ; Precancerous Conditions ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; RNA, Messenger ; metabolism ; WT1 Proteins ; genetics ; metabolism