PubMed Health⌕ Search

Biomedical subjects

G A Evans

Publications and source records attributed to G A Evans.

At least 19 recordsLinked to original sources
PubMed2006

Combined femoral and Chiari osteotomies for reconstruction of the painful subluxation or dislocation of the hip in cerebral palsy. A long-term outcome study.

In order to treat painful subluxation or dislocation secondary to cerebral palsy, 11 patients (12 hips) underwent combined femoral and Chiari pelvic osteotomies with additional soft-tissue releases at a mean age of 14.1 years (9.1 to 17.8). Relief of pain, improvement in movement of the hip, and in sitting posture, and ease of perineal care were recorded in all, and were maintained at a mean follow-up of 13.1 years (8 to 17.5). The improvement in general mobility was marginal, but those who were able to walk benefited the most. The radiological measurements made before operation were modified afterwards to use the lateral margin of the neoacetabulum produced by the pelvic osteotomy. The radiological migration index improved from a mean of 80.6% (61% to 100%) to 13.7% (0% to 33%) (p < 0.0001). The mean changes in centre edge angle and Sharp's angle were 72 degrees (56 degrees to 87 degrees; p < 0.0001) and 12.3 degrees (9 degrees to 15.6 degrees; p < 0.0001), respectively. Radiological evidence of progressive arthritic change was seen in one hip, in which only a partial reduction had been achieved, and there was early narrowing of the joint space in another. Painless heterotopic ossification was observed in one patient with athetoid quadriplegia. In seven hips the lateral Kawamura approach, elevating the greater trochanter, provided exposure for both osteotomies and allowed the construction of a dome-shaped iliac osteotomy, while protecting the sciatic nerve.

Adolescent↗
PubMed2003

Central core disease: clinical, pathological, and genetic features.

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.

Adolescent↗
PubMed2001

Fracture stiffness in callotasis determined by dual-energy X-ray absorptiometry scanning.

Assessing healing after distraction limb lengthening is essential to manage patients undergoing callotasis for leg lengthening or bone transport. Direct measurement of fracture stiffness can assess healing but the equipment may not be available. In addition, it requires removal of the fixator, which may be complicated for ring fixators. The present study investigates whether an equivalent measure of healing can be based on the mineral density pattern from dual-energy X-ray absorptiometry (DXA) scans. Nine consecutive patients undergoing callotasis were studied. Bending stiffness of the distraction segment was measured and DXA scans were performed regularly starting 6 weeks after completing distraction. In all, 23 simultaneous readings of bending stiffness and DXA scans were obtained. All density patterns showed a distinct minimum value of bone mineral density. We found a high and significant correlation between fracture bending stiffness and the square of the total mineral content at the location of minimum bone density (r2 = 0.77, P < 0.001). We conclude that DXA scans can be used reliably and effectively to determine fracture bending stiffness, valuable for determining both time of frame removal and delay in union.

Absorptiometry, Photon↗
PubMed2000

Identification of a 6-cM minimal deletion at 11q23.1-23.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer.

Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22-24 regions. Of these, the 11q22-24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11-p15.3 and p12-13), and one on 11q (q23.1-q23.2). The 11q23.1-q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1-23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.

Adenocarcinoma↗
PubMed2000

EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.

Hereditary multiple exostoses (HME) is a genetically heterogeneous disease characterized by the development of bony protuberances at the ends of all long bones. Genetic analyses have revealed HME to be a multigenic disorder linked to three loci on chromosomes 8q24 (EXT1), 11p11-13 (EXT2), and 19p (EXT3). The EXT1 and EXT2 genes have been cloned and defined as glycosyltransferases involved in the synthesis of heparan sulfate. EST database analysis has demonstrated additional gene family members, EXT-like genes (EXTL1, EXTL2, and EXTL3), not associated with a HME locus. The mouse homologs of EXT1 and EXT2 have also been cloned and shown to be 99% and 95% identical to their human counterparts, respectively. Here, we report the identification of the mouse EXTL1 gene and show it is 74% identical to the human EXTL1 gene. Expression studies of all three mouse EXT genes throughout various stages of embryonic development were carried out and whole-mount in situ hybridization in the developing limb buds showed high levels of expression of all three EXT genes. However, in situ hybridization of sectioned embryos revealed remarkable differences in expression profiles of EXT1, EXT2, and EXTL1. The identical expression patterns found for the EXT1 and EXT2 genes support the recent observation that both proteins form a glycosyltransferase complex. We suggest a model for exostoses formation based on the involvement of EXT1 and EXT2 in the Indian hedgehog/parathyroid hormone-related peptide (PTHrP) signaling pathway, an important regulator of the chondrocyte maturation process.

Amino Acid Sequence↗
PubMed1999

Molecular cytogenetics localizes two new breakpoints on 11q23.3 and 21q11.2 in myelodysplastic syndrome with t(11;21) translocation.

Translocation t(11;21)(q24;q11.2) is a rare but recurrent chromosomal abnormality associated with myelodysplastic syndrome (MDS) that until now has not been characterized at the molecular level. We report here results of a molecular cytogenetic analysis of this translocation in a patient with refractory anemia. Using FISH with a panel of 11q and 21q cosmid/YAC probes, we localized the chromosome 11 breakpoint at q23.3 in a region flanked by CP-921G9 and CP-939H3 YACs, distal to the HRX/MLL locus frequently involved in acute leukemias. The chromosome 21 breakpoint was mapped in a 800-kb fragment inserted into the CP-145E3 YAC at 21q11.2, proximal to the AML1 gene. It is noteworthy that in all four cases with a t(11;21) reported until now, a second der(11)t(11;21) and loss of normal chromosome 11 could be observed either at diagnosis or during the course of the disease. Since in our case heteromorphism was detected by FISH on the centromeric region of the two der(11), the second der(11) chromosome could be the result of a mitotic recombination that had occurred on the long arm of chromosome 11, rather than of duplication of the original der(11). Constancy of secondary karyotypic changes resulting in an extra copy of the putative chimeric gene at der(11), loss of 11 qter sequences, and partial trisomy 21 suggest that neoplastic progression of MDS cases with a t(11;21) may be driven by the same mechanism(s).

Chromosome Banding↗
PubMed1999

Refined mapping of two regions of loss of heterozygosity on chromosome band 11q23 in lung cancer.

11q23-24 chromosome is a region containing frequent allelic loss (loss of heterozygosity; LOH) in human cancers. To examine cancer-related allelic loss in the region between D11S940 and APOC3, we used 17 polymorphic markers and allotyped 28 lung cancer-derived cell lines and their corresponding matched lymphoblastoid cell lines. LOH was found in 71.4% (20/28) of the lung cancer cell lines and was localized to two distinct minimal regions of loss. One region is bracketed by markers D11S1647 and NCAM2 and contains the gene encoding the beta isoform of the A subunit of the human protein phosphatase 2A (PPP2R1B). Recently, mutations in this gene were described in lung and colon cancers, suggesting that PPP2R1B functions as a tumor-suppressor gene. A second minimal region of loss was defined between markers D11S1792 and D11S1885, a region estimated to be less than I Mb. Thus, chromosome 11 likely harbors two sites of suppressor oncogene activity in lung cancer, one defined by the PPP2R1B gene and the second located telomeric to PPP2R1B. This study facilitates the identification and cloning of a second critical tumor-suppressor gene involved in lung cancer, and possibly a variety of other cancers, on human chromosome band 11q23.

Carcinoma, Small Cell↗
PubMed1998

Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family.

Here we report the expression of a fork head domain protein in human T helper cells. We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR. The cDNA contains a 546-nucleotide (nt) open reading frame (ORF) that codes for the carboxyl-terminal 180 amino acids (aa) of the recently identified fkhrl1 gene. This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family. In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa. We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein. This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product. The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes. Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth.

Amino Acid Sequence↗
PubMed1998

Alterations of the PPP2R1B gene in human lung and colon cancer.

The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene. Sequencing of the PPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of 13) of primary colon tumors. One deletion mutation generated a truncated PP2A-Abeta protein that was unable to bind to the catalytic subunit of the PP2A holoenzyme. The PP2R1B gene product may suppress tumor development through its role in cell cycle regulation and cellular growth control.

Amino Acid Sequence↗
PubMed1998

Organization and evolution of olfactory receptor genes on human chromosome 11.

Olfactory receptors (OR) are encoded by a large multigene family including hundreds of members dispersed throughout the human genome. Cloning and mapping studies have determined that a large proportion of the olfactory receptor genes are located on human chromosomes 6, 11, and 17, as well as distributed on other chromosomes. In this paper, we describe and characterize the organization of olfactory receptor genes on human chromosome 11 by using degenerate PCR-based probes to screen chromosome 11-specific and whole genome clone libraries for members of the OR gene family. OR genes were identified by DNA sequencing and then localized to regions of chromosome 11. Physical maps of several gene clusters were constructed to determine the chromosomal relationships between various members of the family. This work identified 25 new OR genes located on chromosome 11 in at least seven distinct regions. Three of these regions contain gene clusters that include additional members of this gene family not yet identified by sequencing. Phylogenetic analysis of the newly described OR genes suggests a mechanism for the generation of genetic diversity.

Amino Acid Sequence↗
PubMed1998

Sequence survey of the Giardia lamblia genome.

The parasitic protozoan Giardia lamblia represents one of the earliest diverging lineages in the evolutionary history of eukaryotic organisms as well as an important human pathogen. A representative sampling of gene sequences from this early diverging protozoan could provide insights into genotypic and phenotypic innovations associated with the origin of eukaryotes. Currently, known giardial gene sequences are heavily biased toward a few gene families, including variant surface proteins (VSPs), structural proteins, and ribosomal RNA genes. One-pass sequences of Giardia genomic DNA were obtained using vector flanking priming sequences on the ends of cosmids in two independent libraries. Comparisons of 2304 of these sequences against the GenBank database identified 205 potential giardial genes with BLAST scores P(n) < 10(9). These coding regions encompass a wide range of metabolic, repair, and signaling enzymes, and include some genes not predicted by our current understanding of Giardia biochemistry. The efficiency of identification of putative genes is consistent with earlier findings that coding regions in the Giardia genome are densely packed and do not appear to contain introns. Our current results suggest that direct genome sequencing is an efficient method for identifying giardial genes for evolutionary and biochemical studies.

Animals↗
PubMed1998

Loss of heterozygosity in squamous cell carcinomas of the head and neck defines a tumor suppressor gene region on 11q13.

Tumor suppressor genes APC, RB1, and DCC, as well as genes localized to 3p and 11q, have been implicated in the development of a number of human tumors. To determine whether allelic deletions occur at these loci in squamous cell carcinomas (SSCs) of the head and neck, 25 primary, 1 metastatic, and 3 recurrent tumors, along with the corresponding constitutional tissues, were analyzed by using a battery of polymorphic DNA markers. For two primary tumors, we also analyzed subsequent metastatic tumors of the lung. Polymerase chain reaction-based restriction fragment length polymorphism studies demonstrated loss of heterozygosity for the APC gene in 2 of 12 (17%), the RB1 gene in 5 of 22 (23%), and the DCC gene in 5 of 13 (38%) informative cases. Alleles on chromosomes 3p, 11q13, and 18q21.1 were lost in 7 of 20 (35%), 9 of 23 (39%), and 4 of 17 (24%) informative cases, respectively. A breakpoint was identified within the chromosomal region 3p13-21.2 in a SCC of the tongue. Breakpoints within 11q13 were identified in 2 additional tumors. Thus, allelic deletions of DCC, 3p, and 11q13 appear to be common in head and neck cancers, suggesting that these genes play a critical and complex role in the development of these tumors. Furthermore, the present study provides definitive evidence for a tumor suppressor gene at chromosome band 11q13 and localizes this gene to the INT2-D11S533 interval for future cloning and sequencing.

Carcinoma, Squamous Cell↗
PubMed1998

Mechanisms of cytokine signal transduction: IL-2, IL-4 and prolactin as hematopoietin receptor models.

Cytokines, hormones and hematopoietic growth factors transduce biological signals across the cell membrane via a highly conserved family of single membrane-spanning receptors. The intracellular signal transducing machinery responsible for mediating these responses has remained largely unknown. However, recent identification of a homologous class of tyrosine kinases, Janus Kinases (JAKs), and a related family of transcription factors, signal transducers and activators of transcription (STATs), has shed new light on the molecular mechanisms responsible for mediating hematopoietin signaling and immune response. Current research efforts within the field of cytokine signaling have now shifted to understanding how these molecules are activated by hematopoietic receptors, positively and negatively regulated by kinases and phosphatases, and how they impact on gene transcription to ultimately coordinate cell homeostasis, proliferation and differentiation. This article will review some of our results identifying the involvement of JAKs, STATs, and secondary effector molecules activated following engagement of hematopoietic receptors for IL-2, IL-4, and prolactin. Here, we provide evidence for the ingenious ability of cytokine receptors to selectively recruit and activate these proteins among a repertoire of possible alternative biochemical messengers as a means to affect unique and general cell responses.

Animals↗