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Biomedical subjects

D B Gould

Publications and source records attributed to D B Gould.

At least 19 recordsLinked to original sources
PubMed2005

Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly.

BACKGROUND: Porencephaly (cystic cavities of the brain) is caused by perinatal vascular accidents from various causes. Several familial cases have been described and autosomal dominant inheritance linked to chromosome 13q has been suggested. COL4A1 is an essential component in basal membrane stability. Mouse mutants bearing an in-frame deletion of exon 40 of Col4a1 either die from haemorrhage in the perinatal period or have porencephaly in survivors. A report of inherited mutations in COL4A1 in two families has shown that familial porencephaly may have the same cause in humans. OBJECTIVE: To describe three novel COL4A1 mutations. RESULTS: The three mutations occurred in three unrelated Dutch families. There were two missense mutations of glycine residues predicted to result in abnormal collagen IV assembly, and one mutation predicted to abolish the traditional COL4A1 start codon. The last mutation was also present in an asymptomatic obligate carrier with white matter abnormalities on brain magnetic resonance imaging. CONCLUSIONS: This observation confirms COL4A1 as a major locus for genetic predisposition to perinatal cerebral haemorrhage and porencephaly and suggests variable expression of COL4A1 mutations.

Adult↗
PubMed2001

The reform of health care funding.

It is argued that the history of health care in Hong Kong has been characterised by the lack of a coherent government policy concerning who should provide, use, and pay for services. This has led to the present fragmented funding and delivery system. Past reforms have been piecemeal and have failed to address fundamental issues. The Harvard Report offered a comprehensive solution, but its insurance-based approach to funding was politically unacceptable. Since funding determines patterns of service delivery, reform in that area is the necessary precondition for any substantive improvement in the quality and quantity of health care. Integrated funding mixes public and private money to overcome compartmentalisation between sectors. Without this, it is doubtful that a primary-led health care system could operate. Whether Government has the political will to implement its current proposals in the face of opposition, and whether these will provide a sufficient foundation for the development of primary-led health care, remains to be seen.

Health Care Reform↗
PubMed2000

Cloning, characterization, localization, and mutational screening of the human BARX1 gene.

The Bar subclass of homeodomain proteins was first identified for its role in Drosophila eye development. The Bar subclass homolog, Barx1, has since been cloned in mouse and in chick. The expression of Barx1 in developing teeth and craniofacial mesenchyme of neural crest origin makes it a strong candidate for the related human disorders of Axenfeld-Reiger syndrome (ARS) and iridogoniodysgenesis syndrome (IGDS). Here we report the cloning and characterization of a novel human Bar class gene, human BARX1. Screening of a human fetal craniofacial library resulted in the isolation of a 1.6-kb full-length transcript. Sequence analysis indicated that human BARX1, mouse Barx1, and chick Barx1 show 100% identity at the amino acid level within their homeodomains. Human BARX1 is expressed in a number of tissues including testis and heart by Northern analysis and in iris and craniofacial tissues by PCR of cDNA libraries. BARX1 chromosomal localization to 9q12 was determined by radiation hybrid mapping. Intron/exon boundaries were established, and primers were generated to PCR amplify all four exons. A mutation screen was conducted in 55 patients affected with ARS, IGDS, or related ocular malformations. While six sequence polymorphisms were detected, no disease-causing mutations of BARX1 were observed.

Amino Acid Sequence↗
PubMed2000

Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25.

Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.

Adolescent↗
PubMed1998

The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus.

Mf1 encodes a forkhead/winged helix transcription factor expressed in many embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme, meninges, endothelial cells, and kidney. Homozygous null Mf1lacZ mice die at birth with hydrocephalus, eye defects, and multiple skeletal abnormalities identical to those of the classical mutant, congenital hydrocephalus. We show that congenital hydrocephalus involves a point mutation in Mf1, generating a truncated protein lacking the DNA-binding domain. Mesenchyme cells from Mf1lacZ embryos differentiate poorly into cartilage in micromass culture and do not respond to added BMP2 and TGFbeta1. The differentiation of arachnoid cells in the mutant meninges is also abnormal. The human Mf1 homolog FREAC3 is a candidate gene for ocular dysgenesis and glaucoma mapping to chromosome 6p25-pter, and deletions of this region are associated with multiple developmental disorders, including hydrocephaly and eye defects.

Amino Acid Sequence↗
PubMed1998

Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.

Genetic linkage, genome mismatch scanning, and analysis of patients with alterations of chromosome 6 have indicated that a major locus for development of the anterior segment of the eye, IRID1, is located at 6p25. Abnormalities of this locus lead to glaucoma. FKHL7 (also called "FREAC3"), a member of the forkhead/winged-helix transcription-factor family, has also been mapped to 6p25. DNA sequencing of FKHL7 in five IRID1 families and 16 sporadic patients with anterior-segment defects revealed three mutations: a 10-bp deletion predicted to cause a frameshift and premature protein truncation prior to the FKHL7 forkhead DNA-binding domain, as well as two missense mutations of conserved amino acids within the FKHL7 forkhead domain. Mf1, the murine homologue of FKHL7, is expressed in the developing brain, skeletal system, and eye, consistent with FKHL7 having a role in ocular development. However, mutational screening and genetic-linkage analyses excluded FKHL7 from underlying the anterior-segment disorders in two IRID1 families with linkage to 6p25. Our findings demonstrate that, although mutations of FKHL7 result in anterior-segment defects and glaucoma in some patients, it is probable that at least one more locus involved in the regulation of eye development is also located at 6p25.

Amino Acid Sequence↗
PubMed1996

Venous air embolism retrieval catheters cannot capture bubbles; an air lock is required.

Differently designed right atrial venous air embolism retrieval catheters were tested in vitro in clinical simulations to determine if increasing numbers of aspirating orifices enhance the recovery of air bubbles by aspirating through these catheters. Air bubbles of 1.5 to 2.0 mm diameter were directly observed to pass against the aspirating orifices while catheters were vertically suspended in a 3.7 cm diameter glass cylinder filled with hetastarch. Essentially, no air, only fluid, was recovered by any of these submerged catheters upon aspiration. Only when an orifice was positioned above a fluid level could air be retrieved.

Cardiac Catheterization↗
PubMed1996

Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25.

Autosomal dominant iridogoniodysgenesis anomaly (IGDA) is characterized by iris hypoplasia and goniodysgenesis with frequent juvenile glaucoma. IGDA is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior chamber of the eye. After eliminating candidate regions for other ocular disorders, a genome-wide scan for IGDA was performed using linkage analysis. Approximately 95% of the genome was excluded with >300 microsatellite markers before significant linkage was demonstrated between IGDA and chromosome 6 markers in two families. From haplotype analysis and identification of recombinants, the IGDA locus is mapped to an 8.3-cM interval distal to D6S477, at 6p25. Our linkage results are consistent with the ocular findings in rare cases of individuals with chromosomal anomalies involving deletions of 6p. This suggests that there is a major gene involved in eye anterior segment development at 6p25.

Chromosome Mapping↗
PubMed1994

Internal carotid artery dissection after remote surgery. Iatrogenic complications of anesthesia.

BACKGROUND: Subintimal dissection with acute occlusion of the internal carotid artery resulting in acute cerebral infarction has not been reported as an iatrogenic complication of general anesthesia. CASE DESCRIPTIONS: An anesthetist stretched the neck of a 44-year-old man by anchoring an anesthesia mask posterior to the angle of the jaw with overlying fingers as the patient struggled during an insufficient inhalational mask anesthetic. A 33-year-old man received an endotracheal anesthetic without struggle, but as he was turned from a supine to a prone position, his head and neck were not immobilized to rotate with his torso during the move. The next day both patients suffered acute cerebral infarctions secondary to ICA dissections and occlusions (angiographically demonstrated). CONCLUSIONS: Stretching the soft neck tissues of anesthetized patients can cause internal carotid artery dissection and acute cerebral infarction.

Adult↗