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Biomedical subjects

S Farrington

Publications and source records attributed to S Farrington.

5 recordsLinked to original sources

Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-control study.

BACKGROUND: That sexual dysfunction occurs in schizophrenia is not in doubt. Previous studies have had weaknesses such as the use of selected populations or the absence of a control group. AIMS: To measure rates of sexual dysfunction in people with schizophrenia compared with the general population. METHOD: Sexual dysfunction was assessed by a self-completed gender-specific questionnaire. Ninety-eight (73%) of 135 persons with schizophrenia and 81 (71%) of 114 persons recruited as controls returned the questionnaire. RESULTS: At least one sexual dysfunction was reported by 82% of men and 96% of women with schizophrenia. Male patients reported less desire for sex, were less likely to achieve and maintain an erection, were more likely to ejaculate more quickly and were less satisfied with the intensity of their orgasms. Female patients reported less enjoyment than the control group. Sexual dysfunction in female patients was associated with negative schizophrenic symptoms and general psychopathology. There was no association between sexual dysfunction and type of antipsychotic medication. CONCLUSIONS: People with schizophrenia report much higher rates of sexual dysfunction than do the general population. Men and women with schizophrenia have a different pattern of sexual dysfunction.

Adult↗

WWOX: a candidate tumor suppressor gene involved in multiple tumor types.

We previously reported the construction of a P1-derived artificial chromosome (PAC) contig encompassing a set of homozygous deletions of chromosome 16q23-24.1 found in primary ovarian tumor material and several tumor cell lines. Using these PAC clones in a cDNA selection experiment, we have isolated a Sau3A fragment homologous to the WWOX transcript (GenBank accession no. ) from normal human ovarian surface epithelial (HOSE) cells. We demonstrate the homozygous deletion of WWOX exons from ovarian cancer cells and three different tumor cell lines. We also identify an internally deleted WWOX transcript from a further primary ovarian tumor. In three of these samples the deletions result in frameshifts, and in each case the resulting WWOX transcripts lack part, or all, of the short chain dehydrogenase domain and the putative mitochondrial localization signal. Sequencing revealed several missense polymorphisms in tumor cell lines and identified a high level of single nucleotide polymorphism (SNP) within the WWOX gene. This evidence strengthens the case for WWOX as a tumor suppressor gene in ovarian cancer and other tumor types.

Alternative Splicing↗

High mortality in a large-scale zebrafish colony (Brachydanio rerio Hamilton & Buchanan, 1822) associated with Lecythophora mutabilis (van Beyma) W. Gams & McGinnis.

Zebrafish (Brachydanio rerio) have become an important model system for studying vertebrate embryonic development and gene function through manipulation of genotype and characterization of resultant phenotypes. An established research zebrafish colony without substantial disease problems for more than 7 years of operation began experiencing appreciable mortalities in November of 1997. Young fish (fry), from five to 24 days after hatching, spontaneously developed elongate strands of organic material protruding from the mouth, operculum, and anal pore, leading workers in the laboratory to describe the infected fish as "bearded." Unlike typical freshwater fish fungal infections, the skin surface did not have evidence of fungal colonization. The disease was associated with progressive lethargy, reduced feeding, and subsequent mortality. From 10 to 100% of the fry in a given tank were affected. Initial examination indicated that the biofilm around the head of affected fry consisted of bundles of septate fungal hyphae, large numbers of mixed bacterial populations, and protozoans. Environmental samples of air and water in the laboratory were obtained to ascertain the source of the infective agent and to isolate and identify the fungus. A fungus identified as Lecythophora mutabilis was isolated repeatedly from infected fish and water samples from infected fish tanks, and from the main laboratory water supply tanks, but not from laboratory air. Some biofilm beards on fish were found to consist of relatively pure bacterial populations, and beards on occasional fish examined in the later part of the study consisted of hyphae and spores of the oomycete genus Aphanomyces. Lecythophora mutabilis did not invade tissues; however, elimination of the epizootic correlated with reduction in the number of L. mutabilis conidia in the water following modification of the laboratory water system by use of new filtration and sterilization systems. We conclude that the dense hyphal strands of L. mutabilis composing the predominant biofilm type, along with mixed bacteria and protozoa, contributed to the die-off in young fry by occluding the oral cavity and/or gills, leading to starvation and/or asphyxiation.

Air Microbiology↗

A large-scale insertional mutagenesis screen in zebrafish.

It is estimated that approximately 2500 genes are essential for the normal development of a zebrafish embryo. A mutation in any one of these genes can result in a visible developmental defect, usually followed by the death of the embryo or larva by days 5-7 of age. We are performing a large-scale insertional mutagenesis screen in the zebrafish with the goal of isolating approximately 1000 embryonic mutations. We plan to clone a significant fraction of the mutated genes, as these are the genes important for normal embryogenesis of a vertebrate. To achieve this goal, we prepared approximately 36, 000 founder fish by injecting blastula-stage embryos with one of two pseudotyped retroviruses. We estimate that together these fish harbor between 500,000-1,000,000 proviral insertions in their germ lines. The protocol we have devised and the size of our facility allow us to breed approximately 80,000-150,000 of these insertions to homozygosity within 2 years. Because a pilot screen conducted earlier in our laboratory revealed that the frequency of mutations obtained with this type of insertional mutagen is 1 embryonic lethal mutation per 70-100 proviral insertions, screening 100,000 insertions should yield at least 1000 mutants. Here we describe the protocol for the screen and initial results with the first of the two retroviral vectors used, a virus designated F(5). We screened an estimated 760 insertions among F(3) progeny from 92 F(2) families and obtained 9 recessive embryonic lethal mutations. Thus, the efficiency of mutagenesis with this viral vector is approximately one-ninth that observed with the chemical mutagen ENU in zebrafish. We have also obtained two dominant mutations, one of which is described here. As expected, mutated genes can be readily identified. So far, genes mutated in four of the nine recessive mutants and one of the two dominant mutants have been cloned. Further improvements to this technology could make large-scale insertional mutagenesis screening and rapid gene cloning accessible to relatively small zebrafish laboratories.

Alleles↗