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S Hodgson

Publications and source records attributed to S Hodgson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Gene linkage and steady state RNAs suggest trans-splicing may be associated with a polycistronic transcript in Schistosoma mansoni.

Spliced leader (SL) trans-splicing generates the 5' end of mature mRNAs through the addition of a small exon to pre-mRNAs in some flagellates (kinetoplastida and euglenoids) and metazoans (nematodes and flatworms). Although SL addition in the kinetoplastida and a subset of nematode genes serves to resolve multicistronic mRNAs into monocistronic, capped mRNAs, information regarding the functional significance of trans-splicing in flatworms is limited. We describe here the identification and characterization of a closely linked gene upstream from the trans-spliced enolase gene in the flatworm Schistosoma mansoni. This gene produces a non-trans-spliced mRNA encoding a ubiquinol binding protein, UbCRBP, that is a component of the ubiquinol-cytochrome C reductase complex. The distance between the UbCRBP polyadenylation site and the enolase trans-splice acceptor site is exceptionally short, only 54 nucleotides. Primer extension (5' RACE), RT-PCR, and RNase mapping have identified steady state, cis-spliced RNAs which significantly overlap both the UbCRBP and enolase genes. These transcripts contain the 5' ends of mature UbCRBP mRNAs; extend through UbCRBP, across the intergenic region, and a significant distance 3' into the enolase gene. Interestingly, the close linkage between the UbCRBP and enolase genes is conserved in a second flatworm, Fasciola hepatica, which also trans-splices the downstream enolase gene. Taken together, the role of SL addition in resolving multicistronic transcripts in both C. elegans and the kinetoplastida, the conservation of UbCRBP/enolase gene linkage in two divergent trematodes, and the multicistronic organization of schistosome UbCRBP/enolase RNAs are consistent with the suggestion that these two genes are likely to be cotranscribed and that trans-splicing in flatworms may be associated with polycistronic transcripts.

Amino Acid Sequence↗
PubMed1997

Mutations and alternative splicing of the BRCA1 gene in UK breast/ovarian cancer families.

BRCA1 is a tumour suppressor gene located on chromosome band 17q21. It is estimated that mutations in the BRCA1 gene account for approximately 45% of the breast cancer families and almost all of the breast/ovarian cancer families. We have used single strand conformation polymorphism analysis, direct sequencing, allele specific oligonucleotide hybridisation, and reverse transcription polymerase chain reaction (RT-PCR) to look for mutations in the BRCA1 gene in 49 breast or breast/ovarian cancer families. Five distinct mutations, three novel and two previously observed, were detected in seven families. Each novel mutation was identified in one family: 3896delT in exon 11, a splicing mutation in the intron 9-exon 10 junction, and an inferred regulatory mutation. The 185delAG in exon 2 was found in three families sharing the same haplotype, but this haplotype is different from that shared by the Ashkenazi Jewish families, suggesting that the 185delAG in our families may have arisen independently. Another previously reported mutation, the 3875del4 in exon 11, was identified in one family. Of the 49 families examined, linkage analyses for both the BRCA1 and the BRCA2 regions were performed on 33 families, and mutations in the BRCA1 gene were identified in all but one family that have a lod score above 0.8 for BRCA1. All of the mutations cause either a truncated BRCA1, or loss of a BRCA1 transcript, thus are likely to be functionally disruptive. In addition, we found that alternative splicing is a common phenomenon in the processing of the BRCA1 gene. Seven variant BRCA1 transcripts were identified by RT-PCR; all but one maintained the BRCA1 open reading frame. We believe that alternative splicing may play a significant role in modulating the physiological function of BRCA1.

Alternative Splicing↗
PubMed1996

Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors.

Thirteen pairs of tumor and blood DNAs from breast cancer patients with estrogen receptor (ER) negative and progesterone receptor (PgR) positive tumors were screened for mutation analysis using SSCP method. Although neither germline nor somatic mutation of the ER gene in this series was detected, we found two types of sequence variants in exon 1 and exon 4, indicating two silent mutations in codon 10 (TCT to TCC) and codon 325 (CCC to CCG), respectively. These variants were recognized as polymorphic sites. Although the frequency of these polymorphic sites was not correlated with hormone receptor status, the variant in codon 325 tended to be seen more frequently in breast cancer patients than in non-cancer control cases (P = 0.057).

Base Sequence↗
PubMed1996

Body image distortion in anorexia and bulimia nervosa: the role of perceived and actual control.

It has been suggested that a desire for control is a central factor in eating disorders. There is, however, little evidence to support this clinical hypothesis. This experimental study examines the effects of actual and perceived control on a symptom of anorexia and bulimia nervosa-body image distortion. Using a learned helplessness paradigm, it was shown that eating-disordered and comparison women respond differently to manipulations of control. Anorexic and bulimic women appear to have a cognitive style of "mistaken pessimism," overestimating body size more when an easy task is perceived as difficult. In contrast, the comparison women are "mistaken optimists" overestimating less when they see a difficult task as being easy. The clinical implications are discussed and further research is proposed to extend these preliminary findings.

Adult↗
PubMed1996

Familial psychiatric presentation of Huntington's disease.

Symptoms of schizophrenia may be encountered in Huntington's disease (HD) but usually when the full clinical syndrome is apparent; prechoreic psychosis is relatively uncommon. We describe a family where all four members affected with HD presented first with a severe psychiatric syndrome, which in three cases was schizophreniform in nature. Two other living members with no current signs of motor disorder have received psychiatric treatment, one for schizophrenia. Concurrence of psychosis and Huntington's disease in this family is unlikely to have occurred by chance, suggesting that there is some feature in this family which gives rise to the psychotic presentation. Families such as this may contribute to the investigation of genetic factors associated with psychiatric illnesses.

Adult↗
PubMed1995

RNA trans-splicing in flatworms. Analysis of trans-spliced mRNAs and genes in the human parasite, Schistosoma mansoni.

Characteristics of trans-splicing in Schistosoma mansoni were examined to explore the significance and determinants of spliced leader (SL) addition in flatworms. Only a small subset of mRNAs acquire the SL. Analysis of 30 trans-spliced mRNAs and four genes revealed no discernable patterns or common characteristics in the genes, mRNAs, or their encoded proteins that might explain the functional significance of SL addition. While the mRNA encoding the glycolytic enzyme enolase is trans-spliced, mRNAs encoding four other glycolytic enzymes are not, indicating trans-splicing is not prevalent throughout this metabolic pathway. Although the 3' end of flatworm SLs contribute an AUG to mRNAs, the SL AUG does not typically serve to provide a methionine for translation initiation of reading frames in recipient mRNAs. SL RNA expression exhibits no apparent sex, tissue, or cell specificity. Trans-spliced genes undergo both cis- and trans-splicing, and the sequence contexts for these respective acceptor sites are very similar. These results suggest trans-splicing in flatworms is most likely associated either with some property conferred on recipient mRNAs by SL addition or related to some characteristic of the primary transcripts or transcription of trans-spliced genes.

Animals↗
PubMed1995

Loss of heterozygosity of the oestrogen receptor gene in breast cancer.

DNA from 67 primary breast carcinoma biopsies has been examined for loss of heterozygosity (LOH) using the microsatellite (TA)n repeat marker positioned 1 kb upstream of the oestrogen receptor (ER) gene. Forty-seven (70.1%) of the cases were informative; nine of these (19.1%) were positive for LOH. In three of the nine cases, there was total loss, and in the other six cases there was a marked reduction in the intensity of signal from one allele. LOH correlated weakly with histological grade and age, but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues.

Base Sequence↗
PubMed1995

Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis.

DESIGN: A case of Nance-Horan syndrome in a male is presented, with some features of the condition in his carrier mother and her mother. It is proposed that Nance-Horan syndrome might be a contiguous gene syndrome mapping to chromosome Xp21.2-p22.3. SETTING: The proband had congenital cataract microphthalmia and dental abnormalities including screwdriver shaped incisors and evidence of enamel pitting hypoplasia. The region Xp21.2-p22.3 also contains the tooth enamel protein gene, amelogenin (AMGX). RESULTS: Using molecular genetic techniques, we have shown that there is no evidence that the AMGX gene is deleted in this case of the Nance-Horan syndrome.

Abnormalities, Multiple↗
PubMed1994

Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T.

Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK. PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district. It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life. By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%). Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%). Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months). PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule. Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose. These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.

Child, Preschool↗
PubMed1994

APC mutation associated with late onset of familial adenomatous polyposis.

Familial adenomatous polyposis is an autosomal dominantly inherited disorder. Mutation studies in the corresponding gene (APC) may provide information for predictive tests for persons at risk in affected families. We report here a new mutation in exon 6 (codon 233) of the APC gene and clinical data in a large family with late onset of the disease in most affected persons.

Adenomatous Polyposis Coli↗
PubMed1993

The relationship between information-seeking and information-avoiding coping styles and the reporting of psychological and physical symptoms.

The present paper describes a prospective study of the relationship between information-seeking and information-avoiding coping styles ('monitoring' and 'blunting') and the reporting of both psychological and physical symptoms. The results suggested that blunting was directly associated with the reporting of both psychological symptoms and symptoms associated with opportunistic infections (such as colds, 'flu etc.). Furthermore, this association between blunting and symptom report was independent of initial symptom levels and of some other factors which have been shown to influence health status (i.e. the frequency of negative life experiences, the frequency of daily hassles and levels of trait anxiety). No significant relationships were found between monitoring and symptom report. It is argued that the most likely explanation of these results is that high blunters report more illness symptoms as a result of failing to respond to initial illness cues or seeking remedial treatment only at a later stage in the development of a disorder.

Adaptation, Psychological↗
PubMed1993

PAX6 mutations in aniridia.

Aniridia is a congenital malformation of the eye, chiefly characterised by iris hypoplasia, which can cause blindness. The PAX6 gene was isolated as a candidate aniridia gene by positional cloning from the smallest region of overlap of aniridia-associated deletions. Subsequently PAX6 intragenic mutations were demonstrated in Smalleye, a mouse mutant which is an animal model for aniridia, and six human aniridia patients. In this paper we describe four additional PAX6 point mutations in aniridia patients, both sporadic and familial. These mutations highlight regions of the gene which are essential for normal PAX6 function. In addition, the frequency at which we have found PAX6 mutations suggests that lesions in PAX6 will account for most cases of aniridia.

Amino Acid Sequence↗
PubMed1992

Abnormal expression of wild type p53 protein in normal cells of a cancer family patient.

Mutations in the p53 gene are the commonest specific genetic change in human cancer. In normal tissues, p53 protein is present in such low quantities that it is not readily detectable by immunochemical techniques. However, in many tumour cells large amounts of p53 protein accumulate and can be seen by simple immunohistochemical staining; this is generally attributed to the accumulation of stabilised, mutant protein. We have found a mother and daughter, who both have a history of breast cancer, who show strong immunohistochemical staining of p53 in most of their normal epithelial and mesenchymal cells. Their family has a history of multiple cancers developing at an early age. Detailed protein analysis and gene sequencing of material obtained from cultured cells, grown from a skin biopsy taken from the daughter, suggest that her cells contained large quantities of normal (unmutated) p53. We suggest that this phenotype defines a new inherited cancer susceptibility syndrome that is distinct from the germ-line mutations in p53 found in some Li-Fraumeni families. This new syndrome affects p53 tumour suppressor function through an indirect mechanism that stabilises normal p53. It remains to be established whether this mechanism also contributes to the accumulation of p53 in sporadic cancers.

Adult↗
PubMed1992

The human PAX6 gene is mutated in two patients with aniridia.

Aniridia is an inherited ocular disorder of variable expressivity characterized by iris hypoplasia. A candidate aniridia gene, AN, which is the human homologue of the mouse Pax-6 gene, has recently been isolated by positional cloning from the WAGR region of 11p13. Here we describe mutations in this gene in two cases of sporadic aniridia, one detected at the DNA level and one at the RNA level, both of which are predicted to affect protein function. Mutations in Pax-6 have been described previously in Small eye, the proposed mouse model for aniridia. We present new phenotypic evidence for the validity of this mouse model.

Animals↗
PubMed1992

Primary prevention of haemophilus influenzae type b.

Routine immunisation of infants against Haemophilus influenzae type b (Hib) has the potential to prevent up to 1200 cases of serious infection and 60 deaths every year in the United Kingdom. Sara Hodgson reports the findings of a study in the Oxford region to determine the safety and immunogenicity of the Hib conjugate vaccine PRP-T when given to British infants in concurrence with primary immunisations, according to the accelerated schedule of two, three and four months of age.

Bacterial Vaccines↗
PubMed1991

A quality assurance audit of Illawarra PADP Scheme home glucose meters and evaluation of their use by patients.

A total of 187 home glucose meters have been issued to Illawarra residents by the Program of Aids for Disabled Patients (PADP) Scheme operating out of Port Kembla District Hospital in a 5-year period ending 31 December 1989. These meters, representing a valuable health resource, have been loaned to patients without audit or follow up. Sixteen per cent of meters were unable to be located and 33.2% could not be located using existing PADP records. Of those meters which could be tested, 16.4% were inaccurate; the recipient's technique was inadequate for accurate results in 36.1% of instances. This survey has revealed a significant loss of health resources in addition to inadequate clinical assessment and supervision.

Adolescent↗