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At least 181 records · Page 10Linked to original sources
PubMed2006

Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a broad developmental disease characterized by anemia, bone marrow (BM) erythroblastopenia, and an increased incidence of malignancy. Mutations in ribosomal protein gene S19 (RPS19) are found in approximately 25% of DBA patients; however, the role of RPS19 in the pathogenesis of DBA remains unknown. Using global gene expression analysis, we compared highly purified multipotential, erythroid, and myeloid BM progenitors from RPS19 mutated and control individuals. We found several ribosomal protein genes downregulated in all DBA progenitors. Apoptosis genes, such as TNFRSF10B and FAS, transcriptional control genes, including the erythropoietic transcription factor MYB (encoding c-myb), and translational genes were greatly dysregulated, mostly in diseased erythroid cells. Cancer-related genes, including RAS family oncogenes and tumor suppressor genes, were significantly dysregulated in all diseased progenitors. In addition, our results provide evidence that RPS19 mutations lead to codownregulation of multiple ribosomal protein genes, as well as downregulation of genes involved in translation in DBA cells. In conclusion, the altered expression of cancer-related genes suggests a molecular basis for malignancy in DBA. Downregulation of c-myb expression, which causes complete failure of fetal liver erythropoiesis in knockout mice, suggests a link between RPS19 mutations and reduced erythropoiesis in DBA.

Adult↗
PubMed2004

Chiari pelvic osteotomy for advanced osteoarthritis in patients with hip dysplasia.

BACKGROUND: It is not clear whether a Chiari pelvic osteotomy performed for the treatment of advanced osteoarthritis can delay the need for total hip arthroplasty. We present the mid-term results of the Chiari pelvic osteotomy performed for the treatment of Tönnis grade-3 osteoarthritis (large cysts, severe narrowing of the joint space, or severe deformity or necrosis of the head with extensive osteophyte formation), with a particular focus on whether this procedure can delay the need for total hip arthroplasty. METHODS: We followed thirty-two hips in thirty-one patients with Tönnis grade-3 osteoarthritis who had refused total hip arthroplasty and had been treated with a Chiari pelvic osteotomy. The mean age at the time of surgery was 35.2 years. The mean duration of follow-up was 11.2 years, at which time clinical evaluation with the Harris hip score and radiographic evaluation were performed. RESULTS: The average Harris hip score improved from 52 points preoperatively to 77 points at the time of follow-up; the average pain score improved from 20 to 31 points. Three hips with a hip score of <70 points required total hip arthroplasty. With a hip score of <70 points as the end point, the cumulative rate of survival at ten years was 72%. The clinical outcome was significantly influenced by the preoperative center-edge angle (p = 0.004), the preoperative acetabular head index (p = 0.039), achievement of the appropriate osteotomy level (p = 0.011), and superior migration (p = 0.009) and lateral migration (p = 0.026) of the femoral head. CONCLUSIONS: Although the clinical results were inferior to those of total hip arthroplasty, Chiari pelvic osteotomy may be an option for young patients with advanced osteoarthritis who prefer a joint-conserving procedure to total hip arthroplasty and accept a clinical outcome that is predicted to be less optimal than that of total hip arthroplasty. Moderate dysplasia and moderate subluxation without complete obliteration of the joint space and a preoperative center-edge angle of at least -10 degrees are desirable selection criteria.

Adolescent↗
PubMed2006

WebaCGH: an interactive online tool for the analysis and display of array comparative genomic hybridisation data.

UNLABELLED: Gene copy number variations occur both in normal cells and in numerous pathologies including cancer and developmental diseases. Array comparative genomic hybridisation (aCGH) is an emerging technology that allows detection of chromosomal gains and losses in a high-resolution format. When aCGH is performed on cDNA and oligonucleotide microarrays, the impact of DNA copy number on gene transcription profiles may be directly compared. We have created an online software tool, WebaCGH, that functions to (i) upload aCGH and gene transcription results from multiple experiments; (ii) identify significant aberrant regions using a local Z-score threshold in user-selected chromosomal segments subjected to smoothing with moving averages; and (iii) display results in a graphical format with full genome and individual chromosome views. In the individual chromosome display, data can be zoomed in/out in both dimensions (i.e. ratio and physical location) and plotted features can have 'mouse over' linking to outside databases to identify loci of interest. Uploaded data can be stored indefinitely for subsequent retrieval and analysis. WebaCGH was created as a Java-based web application using the open-source database MySQL. AVAILABILITY: WebaCGH is freely accessible at http://129.43.22.27/WebaCGH/welcome.htm CONTACT: Xiaolin Wu (forestwu@mail.nih.gov) or Ulises Urzúa (uurzua@med.uchile.cl).

Animals↗
PubMed2007

Genetic basis of respiratory distress syndrome.

Respiratory distress syndrome (RDS) is a multifactorial developmental disease caused by lung immaturity and presenting as high-permeability lung edema ("hyaline membrane disease"). It is characterized by a transient deficiency of alveolar surfactant during the first week of life. During the first few days of life, the alveolar surfactant pool size increases up to that in the controls. The allelic variants of the genes encoding the surfactant proteins (SP) SP-A1, SP-A2, SP-B, and SP-C have been associated with RDS. The main SP-A haplotype, interactively with the SP-B Ile131Thr polymorphism and with constitutional and environmental factors, influence the risk. Case reports on mutations with partially functional SP-B have been published. The genetic susceptibility factors depend on the degree of prematurity at birth, consistent with sequential differentiation of the lung and gestation-dependent differences in clinical presentation. The preferentially type 2 cell expressed genes involved in critical functions (such as ATP-binding cassette transporter, ABCA3), those involved in susceptibility to acute lung damage, and those with known susceptibility to other severe lung diseases (such as G protein-coupled receptor for asthma susceptibility, GPR154 alias GPRA) will possibly serve as candidate genes in future studies. RDS associated with near-term and term births may have a different genetic predisposition and pathogenesis compared to RDS after very preterm birth. As we learn more about the molecular consequences of allelic variation, new therapies based on a new generation of surfactant diagnostics and individualized therapies may follow.

ATP-Binding Cassette Transporters↗
PubMed1996

Causes of epilepsy: contributions of the Rochester epidemiology project.

The contributions of the Rochester (Minnesota) Epidemiology Project and Mayo Clinic studies in the evaluation of the causes of epilepsy are summarized. The development of the unique population-based medical records-linkage resource is chronicled, and the measures of occurrence and association used in epidemiologic study designs to assess the causes of epilepsy are presented. The historical cohort design is optimal for the study of the relationship between common central nervous system insults and seizures, and case-control studies are best used for analysis of relatively rare seizure disorders. The major findings about the etiologic roles of traumatic brain injuries, central nervous system infections, cerebrovascular disease, brain tumors, neurodegenerative diseases, developmental disabilities, perinatal insults, and familial factors are discussed. The role of genetic factors in epilepsy has been controversial, perhaps because of the numerous causes of seizures and their episodic nature. Both potential environmental and genetic causes will continue to be assessed.

Epidemiologic Methods↗
PubMedDate not supplied

Unilateral late-onset tibia vara associated with bilateral proximal femoral growth disturbance in monozygotic twins: case report.

Clinical and histopathological similarities and rare association of Blount's disease with various proximal femoral physeal affections (i.e. adolescent coxa vara and slipped capital femoral epiphysis) are well known. Association of tibia vara with another epiphyseal disease of the proximal femur has not been reported previously. In this paper, a monozygotic set of twins with concordant bilateral epiphyseal growth disturbance of the proximal femur and unilateral late-onset tibia vara is presented. Radiological characteristics of the affected knees revealed a wedging in the proximal tibial epiphysis, depression of the medial joint surface and varus deformity of the tibia. Proximal femurs of both cases showed aspheric congruity, coxa magna, shortness of the femoral neck, and subchondral cystic changes. The presented cases support the genetic etiology of tibia vara, and association of the two conditions is unique.

Adolescent↗
PubMed1999

Regulation of gene expression by herbal medicines--a new paradigm of gene therapy for multifocal abnormalities of genes.

Japanese herbal medicine has long been considered as only supplementary therapy to Western medicine. However, we discovered that an herbal mixture, Saiko-keishi-to-ka shakuyaku (SK, TJ-960), showed regulatory function of gene expression such as increased expression of seizure-related gene PTZ-17, proto-oncogene c-fos and heat shock protein HSP 72. These results provide a scientific basis for an important ancient concept and usage of herbal mixtures as a "therapy against diseases which will be suffered in the future". Our results also give an adequate provide break-throughs for therapy and even prevention of intractable epilepsy, Alzheimer's disease, developmental disorders during pregnancy and the postnatal period, and also probably for prevention of metastasis or relapse of various cancers.

Animals↗
PubMed2001

Dome (modified Chiari) pelvic osteotomy: 10- to 18-year followup study.

Ninety-six dome (modified Chiari) pelvic osteotomies in 87 patients with pain and disability because of osteoarthrosis secondary to hip dysplasia were reviewed. The mean age of the patients at the time of surgery was 29 years (range, 16-55 years). The mean followup was 13 years (range, 10-18 years). Forty-one hips were classified into a hip dysplasia stage, 32 hips into an early stage of osteoarthrosis, and 23 hips into an advanced stage of osteoarthrosis according to the radiographic grading of the Japanese Orthopaedic Association. The average preoperative Merle d'Aubigné and Postel hip score was 13.8, and the average score at final followup was 16.6. Excellent or good results with a score greater than 14 were achieved in 96% of the hips at final followup. Radiographically, signs of progression of osteoarthrosis were not seen in 87% of the hips. Osteoarthrosis progressed during the postoperative course in 13% of the hips. Four patients (four hips) eventually had a total hip arthroplasty at 13.8 years (range, 12.5-15.3 years) after surgery. The survival rate of dome pelvic osteotomy, using clinical failure as an end point, was 82% at 15 years. Using radiologic failure as an end point, 61 hips in 54 patients (survival rate, 78%) survived at 15 years. Using hip replacement as an end point, 92 hips in 83 patients (survival rate, 82%) survived at 15 years. Dome pelvic osteotomy is an excellent and effective operation for pain relief and functional maintenance of the hip.

Adolescent↗
PubMed2002

[Effect of products of germ-line and somatic gene mutations on chromatin remodeling].

Chromatin remodeling is engaged in basic cell functions as DNA replication, recombination, DNA repair and transcription of genes. Chromatin is remodeled by ATP-dependent chromatin remodeling complexes and protein complexes covalently modifying histones. Germ-line mutations of the genes coding for proteins which participate in chromatin remodeling cause severe developmental diseases and they increase a risk of cancer development. Somatic mutations and translocations of such genes are associated with cancer development of certain tumors. Chromatin remodeling mechanisms can thus be targeted by special strategy of cancer therapy.

Chromatin↗