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D Collier

Publications and source records attributed to D Collier.

At least 73 records · Page 4Linked to original sources

Failure to find linkage between schizophrenia and genetic markers on chromosome 21.

We sought evidence for the involvement of mutations in the amyloid precursor protein gene (APP) in the pathogenesis of schizophrenia in two ways. First, linkage analysis was performed in a sample of 24 families multiply affected with schizophrenia. The genotypes were studied for GT12 (D21S210), a highly polymorphic microsatellite marker at the APP locus. Second, we used single strand conformation analysis (SSCA) to screen for mutations in exon 17 of APP in one affected member from each family and in a sample of 44 unrelated patients. In addition, we looked for linkage between schizophrenia and a series of highly polymorphic markers situated at approximately 20cM intervals along the long arm of chromosome 21. We were unable to find evidence for linkage to GT12 or the other markers studied. SSCA did not reveal any mutations in exon 17 of AP. We conclude that mutations within APP are an unlikely cause of schizophrenia. Moreover, this study provides no evidence for a major gene for schizophrenia on chromosome 21, and linkage can be excluded from much of this region under some genetic models.

Adult↗

A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11.

We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis-specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease.

Alleles↗

The dopamine D3 receptor gene: no association with bipolar affective disorder.

Bipolar affective disorder and schizophrenia share many clinical and genetic characteristics, and are thought by some to be different expressions of the same underlying disorder. A recent study showed an excess of homozygosity at a BalI polymorphism in the dopamine D3 receptor gene in schizophrenic patients compared with controls, from two independent centres. We have found no evidence of such an excess in a comparable sample of patients with bipolar affective disorder compared with matched controls. If these findings are confirmed then at least one genetic distinction between these two disorders will have been ascertained and doubt cast upon theories of a common genetic aetiology.

Alleles↗

Association between schizophrenia and homozygosity at the dopamine D3 receptor gene.

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a BalI polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p = 0.005, p = 0.008). When pooled data were analysed, this difference was highly significant (p = 0.0001) with a relative risk of schizophrenia in homozygotes of 2.61 (95% confidence intervals 1.60-4.26).

Adult↗

Intercalation of ethidium bromide into a triple-stranded oligonucleotide.

We have examined the ability of a cationic planar chromophore, ethidium bromide, to intercalate into a short, defined triple helix. Using UV absorption, fluorescence spectroscopy and a gel retardation assay we demonstrate that ethidium bromide is able to bind to a triple helix with a lower affinity than to the corresponding duplex. Energy transfer from base triplets to ethidium shows that ethidium is intercalated into the triple helix. The spectroscopic characteristics of ethidium intercalated into a triplex are similar to those observed for intercalation into duplex DNA.

Base Sequence↗

Primary mitochondrial activity of gossypol in yeast and mammalian cells.

Gossypol showed primary antimitochondrial activity in yeast cells in that the drug (1) inhibited growth of cells utilizing mitochondrial substrates as carbon and energy sources, and (2) selectively inhibited mitochondrial protein synthesis. Primary antimitochondrial activity was demonstrated in guinea-pig keratinocytes (GPK) by early arrest of growth and loss of viability in medium with glutamine (a mitochondrial substrate) as carbon and energy source compared with cells utilizing glucose. Gossypol depressed oxygen uptake directly in respiring cells. Gossypol interacted with the known antimitochondrial agents ethidium bromide and 5-fluorouracil (FU), potentiating the activity of FU but reversing that of ethidium bromide in yeast and GPK. Also, the activity of the mitochondrial inhibitor oligomycin was reversed by the presence of gossypol in yeast cells but not tested in GPK. The uptake and retention of the mitochondria-specific dye rhodamine 123 were much depressed by gossypol in GPK. Gossypol showed little or no inhibitory effects in yeast or GPK in the presence of ethanol (0.2-0.5%). The drug was not mutagenic with respect to the yeast mitochondrial system. It was tentatively suggested that mitochondrial perturbation could explain the antifertility effect of gossypol if it is assumed that mitochondria have a special role to play in spermatogenesis and sperm motility, making these tissues more sensitive to mitochondrial inhibitors than somatic cells.

Animals↗

Effect of lumbar puncture on flow of cerebrospinal fluid.

The rate at which isotopes descend from the cisterna magna to the lumbar subarachnoid space is highly variable. In monkeys, with and without previous lumbar puncture, transit time was measured. In animals with a previous lumbar puncture, transit times were 10 to 120 minutes; in monkeys without a previous lumbar puncture, transit times were 120 to 180 minutes. In experimental studies of cerebrospinal fluid circulation, the effect of lumbar puncture must be controlled.

Animals↗

Identification of an anteriorly displaced meniscus in vitro by means of three-dimensional image reconstructions.

Computerized tomography has some limitations for diagnosis of internal derangements of the TMJ. The use of three-dimensional image reconstructions of CT data may enhance the diagnostic utility of CT. In a cadaver simulation, three-dimensional imaging was able to demonstrate the location of a displaced meniscus which was not obvious in two-dimensional sections. Location of the meniscus was aided by the use of a "transparency mode" in displaying the data.

Cartilage, Articular↗

Doxorubicin hydrochloride, cyclophosphamide, and 5-fluorouracil combination in advanced prostate and transitional cell carcinoma.

The suggested activity of doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and 5-fluorouracil as single agents in the treatment of advanced prostate and/or transitional cell carcinoma led us to examine the response to these drugs used in combination. Combination chemotherapy has the theoretical advantages of additive antitumor effect without additive toxicity to the host. One of 8 patients with Stage D, endocrine unresponsive prostatic adenocarcinoma achieved an objective response. There were five stable and one subjective responses. Only 1 patient showed progression during the initial six-week trial. Two of 3 patients with transitional cell carcinoma had an objective response. This three-drug combination was well tolerated by elderly patients and on the basis of this small series further trials are warranted.

Acid Phosphatase↗

The drinking habits of residents of a rehabilitation program with a controlled drinking option: a preliminary report.

Residents of an alcoholism rehabilitation program with a controlled drinking option were asked to give daily reports on their drinking. Program staff were also asked to report evide-ce of resident drinking. A comparison of information from these two sources showed, among other things, that residents were generally reluctant to report drinking which was proscribed the the program. Such drinking as was reported varied from isolated, non-problematic, small quantity drinking, to heavy, regular and problem-producing drinking. In general, residents' drinking did not prevent them from work while in residence. The men's reluctance to report proscribed drinking is seen as largely accounted for by the system of fines for intoxication and drinking without rights. It is concluded that it would be premature to recommend the program's drinking policies to other residential programs, but future experimentation is indicated.t is concluded that it would be premature to recommend the program's drinking policies to other residential programs, but future experimentation is indicated.

Alcohol Drinking↗

No association between RFLPs at the porphobilinogen deaminase gene and schizophrenia.

An association study of restriction fragment length polymorphisms (RFLPs) in the porphobilinogen deaminase (PBGD) gene and schizophrenia was conducted. RFLPs detected by MspI, PstI, ApaLI and BstNI in intron 1 of the gene were studied in 49 patients and 79 controls. There were no significant differences between the groups in allele frequencies, genotype counts or haplotype distribution.

Adult↗