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David Ng

Publications and source records attributed to David Ng.

16 recordsLinked to original sources
PubMed2006

Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in adults in western countries. A genome scan of CLL-prone families revealed a lod score of one in band 13q22.1. To investigate this finding, we selected 6 CLL families consisting of 63 individuals (CLL affected, n=19; unaffected, n=44) for fine mapping of a 23-megabase region in 13q14.2-q22.2. Interphase fluorescence in situ hybridization (FISH) revealed 13q14 deletion in 85% (11/13) of CLL patients. Four CLL families shared a 3.68-Mb minimal region in 13q21.33-q22.2. Two asymptomatic siblings who shared the 13q21.33-q22.2 at-risk haplotype exhibited CD5+ monoclonal B-cell lymphocytosis (MBL) on flow cytometry. One of these individuals also had a 13q14 deletion by FISH. These 2 individuals with MBL shared the at-risk haplotype with their CLL-affected relatives, providing further evidence of the relationship between CLL and MBL, as well as of the biologic significance of this novel region. Using direct DNA sequencing analysis, we screened 13 genes for mutations, but no frameshift or nonsense mutations were detected. Our studies revealed that 11 of the 13 genes in the candidate region were expressed in immune tissues, supporting their functional relevance in investigations of familial CLL. In conclusion, we identified a novel candidate region that may predispose to familial CLL.

Adult↗
PubMed2006

Maggot debridement therapy for serious horse wounds - a survey of practitioners.

Hoof disease and injuries are common and serious problems for equines. Maggot debridement therapy (MDT) has been used to treat problematic wounds in humans, but has been used only rarely in other animals. US veterinarians who had employed MDT were surveyed to investigate their reasons for the choice of this treatment and their clinical experiences with it. Between 1997 and 2003, 13 horses were treated by eight veterinarians who used MDT to control infection or debride wounds, which could not easily be reached surgically or were not responding to conventional therapy. Seven animals were lame, and six were expected to require euthanasia. Following maggot therapy, all infections were eradicated or controlled, and only one horse had to be euthanased. No adverse events were attributed to maggot therapy for any of these cases, other than presumed discomfort during therapy. The data collected suggest that maggot therapy could be useful for treating some serious equine hoof and leg wounds.

Animals↗
PubMed2006

Combined C-11 methionine and F-18 FDG PET imaging in a case of neurosarcoidosis.

PURPOSE: PET scanning of the brain with F-18 FDG and C-11 methionine (MET) is useful for characterizing brain lesions discovered at MRI or CT. Most positive PET scans indicate malignancy. However, this case report demonstrates positive F-18 FDG and C-11 MET PET scans in a patient with a nonmalignant condition, neurosarcoidosis. MATERIALS AND METHODS: We detail the history and evaluation of a 59-year-old woman who presented with ataxia. The patient's evaluation included a contrast-enhanced MRI followed by PET scanning of the brain with C-11 MET and of the brain and trunk with F-18 FDG. The patient subsequently underwent biopsy of a lesion as directed by MRI and PET. RESULTS: The MRI demonstrated multiple enhancing leptomeningeal lesions consistent with metastatic disease. PET with F-18 FDG and C-11 MET demonstrated lesions in both cerebellar hemispheres with F-18 FDG accumulation in the mediastinum and left hilum. Biopsy of a brain lesion directed by MRI and PET revealed sarcoidosis. CONCLUSIONS: In evaluating brain lesions, PET with F-18 FDG and C-11 MET can help localize the lesion best suited for biopsy. However, not all lesions that have increased uptake on C-11 MET or F-18 FDG PET are malignant. Granulomatous inflammatory diseases such as neurosarcoidosis should also be considered in the differential diagnosis.

Biopsy↗
PubMed2006

High-density mapping and follow-up studies on chromosomal regions 1, 3, 6, 12, 13 and 17 in 28 families with chronic lymphocytic leukaemia.

A subset of chronic lymphocytic leukaemia (CLL) shows familial aggregation. Studies show an increased risk for CLL and other lymphoproliferative disease among first-degree relatives of affected individuals. A genome-wide scan of 18 CLL families in 2003 detected LOD or non-parametric linkage scores > or = 1.0 on chromosomes 1, 3, 6, 12, 13 and 17. Follow-up study with 28 families showed no evidence of linkage at 1p22.1-p21.2, 3q22.1, 3q26.2, 6q22.31-q23.2, 12q24.23, 14q32.13, 17p13.3. Chromosome 13q21.33 remains a region of interest with a P-value of 0.013 (marker D13S1291) and warrants additional molecular investigation as a susceptibility region for CLL.

Chromosome Mapping↗
PubMed2005

Treating wounds in small animals with maggot debridement therapy: a survey of practitioners.

Many small animals succumb to complications of serious wounds. Sometimes infection and sepsis overwhelm the animal; sometimes the costs of intensive care overwhelm the owner. Maggot therapy, a method of wound debridement using live fly larvae, could provide effective, simple, low cost wound care. All eight US veterinarians who had been provided with medicinal maggots were surveyed to determine if this treatment was being used for small animals, and for what indications. At least two dogs, four cats and one rabbit were treated with maggot therapy between 1997 and 2003. The most common indications for using maggot therapy were to effect debridement and control infection, especially if the wound failed to respond to conventional medical and/or surgical therapy. Practitioners reported the treatments as safe and often beneficial. Amputation and euthanasia may have been avoided. It is concluded that maggot therapy may have utility for small animals, and should be evaluated further.

Animals↗
PubMed2005

ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins.

The archaeal ATPase complex PAN, the homolog of the eukaryotic 26S proteasome-regulatory ATPases, was shown to associate transiently with the 20S proteasome upon binding of ATP or ATPgammaS, but not ADP. By electron microscopy (EM), PAN appears as a two-ring structure, capping the 20S, and resembles two densities in the 19S complex. The N termini of the archaeal 20S alpha subunits were found to function as a gate that prevents entry of seven-residue peptides but allows entry of tetrapeptides. Upon association with the 20S particle, PAN stimulates gate opening. Although degradation of globular proteins requires ATP hydrolysis, the PAN-20S complex with ATPgammaS translocates and degrades unfolded and denatured proteins. Rabbit 26S proteasomes also degrade these unfolded proteins upon ATP binding, without hydrolysis. Thus, although unfolding requires energy from ATP hydrolysis, ATP binding alone supports ATPase-20S association, gate opening, and translocation of unfolded substrates into the proteasome, which can occur by facilitated diffusion through the ATPase.

Adenosine Triphosphatases↗
PubMed2005

Retrospective family study of childhood medulloblastoma.

Medulloblastoma is the most common malignant central nervous system tumor of childhood and can occur sporadically or in association with inherited cancer susceptibility syndromes such as the nevoid basal cell carcinoma syndrome (NBCCS). To determine whether an association existed between the risk of developing medulloblastoma and undiagnosed syndromes, we retrospectively reviewed clinical data on 33 patients with medulloblastoma from a single institution and compared them with their unaffected relatives (n = 46). Six patients had tumors showing desmoplastic histology. Two of the six met diagnostic criteria for NBCCS. One NBCCS patient had a missense mutation of patched-1 (PTCH1); the other had no identifiable PTCH1 mutation. Two patients with isolated desmoplastic medulloblastoma had an insertion and splice site mutation, respectively, in suppressor of fused (SUFU). All patients with nondesmoplastic medulloblastoma histology received molecular testing for SUFU. None of these patients had an identifiable mutation in PTCH1 or SUFU. We performed a clinical evaluation for Greig cephalopolysyndactyly syndrome (GCPS) in four medulloblastoma families, who exhibited macrocephaly as the only finding consistent with the diagnosis of GCPS. Molecular analysis of GLI3 in these four families was negative. There was a paucity of clinical findings among the majority of medulloblastoma patients in this study group to suggest a definable cancer genetic syndrome. We conclude that clinically recognizable syndromes are uncommon among patients with medulloblastoma, however, PTCH1 and SUFU mutations are present at a low but significant frequency.

Adolescent↗
PubMed2004

Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.

Lenz microphthalmia is inherited in an X-linked recessive pattern and comprises microphthalmia, mental retardation, and skeletal and other anomalies. Two loci associated with this syndrome, MAA (microphthalmia with associated anomalies) and MAA2, are situated respectively at Xq27-q28 (refs. 1,2) and Xp11.4-p21.2 (ref. 3). We identified a substitution, nt 254C-->T; P85L, in BCOR (encoding BCL-6-interacting corepressor, BCOR) in affected males from the family with Lenz syndrome previously used to identify the MAA2 locus. Oculofaciocardiodental syndrome (OFCD; OMIM 300166) is inherited in an X-linked dominant pattern with presumed male lethality and comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. Given their phenotypic overlap, we proposed that OFCD and MAA2-associated Lenz microphthalmia were allelic, and we found different frameshift, deletion and nonsense mutations in BCOR in seven families affected with OFCD. Like wild-type BCOR, BCOR P85L and an OFCD-mutant form of BCOR can interact with BCL-6 and efficiently repress transcription. This indicates that these syndromes are likely to result from defects in alternative functions of BCOR, such as interactions with transcriptional partners other than BCL-6. We cloned the zebrafish (Danio rerio) ortholog of BCOR and found that knock-down of this ortholog caused developmental perturbations of the eye, skeleton and central nervous system consistent with the human syndromes, confirming that BCOR is a key transcriptional regulator during early embryogenesis.

Abnormalities, Multiple↗
PubMed2004

Gonadal mosaicism in severe Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS, MIM #146510) is characterized by central and postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited in an autosomal dominant pattern. Here, we describe a family with two affected children manifesting severe PHS with mental retardation, behavioral problems, and intractable seizures. Both parents are healthy, with normal intelligence, and have no malformations on physical, laryngoscopic, and cranial MRI exam. The atypical presentation of these children and the absence of parental manifestations suggested an autosomal recessive mode of inheritance or gonadal mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15 (c.3385_3386delTT) predicting a frameshift and premature stop at codon 1129 (p.F1129X) in the children while both parents have wild type alleles. Genotyping with GLI3 intragenic markers revealed that both children inherited the abnormal allele from their mother thus supporting gonadal mosaicism as the underlying mechanism of inheritance (paternity was confirmed). This is the first reported case of gonadal mosaicism in PHS. The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. We conclude that the phenotypic spectrum of PHS can include severe CNS manifestations and that recurrence risks for PHS should include a proviso for gonadal mosaicism, though the frequency cannot be calculated from a single case report. Published 2003 Wiley-Liss, Inc.

Abnormalities, Multiple↗
PubMed2004

Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1.

Retinal bipolar cells are interneurons that transmit visual signals from photoreceptors to ganglion cells. Although the visual pathways mediated by bipolar cells have been well characterized, the genes that regulate their development and function are largely unknown. To determine the role in bipolar cell development of the homeobox gene Vsx1, whose retinal expression is restricted to a major subset of differentiating and mature cone bipolar (CB) cells, we targeted the gene in mice. Bipolar cell fate was not altered in the absence of Vsx1 function, because the pan-bipolar markers Chx10 and Ret-B1 continued to be expressed in inner nuclear layer neurons labeled by the Vsx1-targeting reporter gene, tauLacZ. The specification, number, and gross morphology of the subset of on-center and off-center (OFF)-CB cells defined by tauLacZ expression from the Vsx1 locus were also normal in Vsx1(tauLacZ)/Vsx1(tauLacZ) mice. However, the terminal differentiation of OFF-CB cells in the retina of Vsx1(tauLacZ)/Vsx1(tauLacZ) mice was incomplete, as demonstrated by a substantial reduction in the expression of at least four markers (recoverin, NK3R, Neto1, and CaB5) for these interneurons. These molecular abnormalities were associated with defects in retinal function and documented by electroretinography and in vitro ganglion cell recordings specific to cone visual signaling. In particular, there was a general reduction in the light-mediated activity of OFF, but not on-center, ganglion cells. Thus, Vsx1 is required for the late differentiation and function of OFF-CB cells and is associated with a heritable OFF visual pathway-specific retinal defect.

Animals↗
PubMed2003

Designation of the TARP syndrome and linkage to Xp11.23-q13.3 without samples from affected patients.

The Robin sequence is a well-known cause of cleft palate and can be sporadic or familial, isolated or syndromic. We present a four-generation family with a lethal disorder inherited in an X-linked recessive pattern that includes Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava. We have designated this disorder "TARP" syndrome. All affected males die in infancy of unknown causes. An X-chromosome linkage scan was performed using 14 unaffected members of a single large family and 40 STRP markers. The gene was mapped to an 11-cM region in Xp11.23-q13.3. Markers DXS1003 and DXS8092 flank the region and three-point linkage analyses revealed a maximum LOD score of 2.75 at marker DXS1039. We have designated this locus as TARP. This locus was mapped without genotyping any affecteds and demonstrates that rare, lethal disorders can be evaluated by genetic linkage, even when no affected probands are available for study.

Chromosome Mapping↗
PubMed2002

Genetic heterogeneity of syndromic X-linked recessive microphthalmia-anophthalmia: is Lenz microphthalmia a single disorder?

Nonsyndromic congenital microphthalmia or anophthalmia is a heterogeneous malformation with autosomal dominant, autosomal recessive, and X-linked modes of inheritance. Lenz microphthalmia syndrome comprises microphthalmia with mental retardation, malformed ears, skeletal anomalies, and is inherited in an X-linked recessive pattern. Prior studies have shown linkage of both isolated (or nonsyndromic) anophthalmos (ANOP1, [MIM 301590]) and Lenz syndrome [MIM 309800] to Xq27-q28. Nonsyndromic colobomatous microphthalmia [MIM 300345] has been linked to Xp11.4-Xq11.1. We describe a five-generation African-American family with microphthalmia or anophthalmia, mental retardation, and urogenital anomalies, in an X-linked recessive inheritance pattern, consistent with Lenz syndrome. Initial linkage analysis with microsatellite markers excluded the region in Xq27-q28 previously reported as a candidate region for ANOP1 [MIM 301590]. An X-chromosome scan revealed linkage to a 10-cM region between markers DXS228 and DXS992 in Xp11.4-p21.2. Multipoint analysis gave a maximum LOD score of 2.46 at marker DXS993. These data show that X-linked recessive syndromic microphthalmia exhibits genetic heterogeneity. In addition, it suggests that Lenz microphthalmia syndrome, previously thought to be a single disorder, may represent an amalgam of two distinct disorders.

Abnormalities, Multiple↗