Search PubMedSearch

Biomedical subjects

D Forrest

Publications and source records attributed to D Forrest.

34 records · Page 2Linked to original sources

Altered structure and expression of c-myc in feline T-cell tumours.

The c-myc gene is rearranged in a subset of feline T-cell lymphosarcomas. Detailed mapping of c-myc rearrangements showed that some result from feline leukaemia virus (FeLV) proviral integration within or upstream of c-myc, but one case involves a complex 3' alteration and amplification which is apparently not directly virus-induced. S1 nuclease mapping of RNA from normal cells using c-myc probes revealed two presumptive 5' ends, each corresponding to a promoter-like sequence (P1 and P2), and a major 3' discontinuity which mapped to the 3'-most of two possible polyadenylation signals. Analysis of RNA from a series of tumours revealed different modes of c-myc expression. All tumours produced P1 and P2 transcripts with apparently normal structure except for one case where an insertion in intron 1 displaced exon 1 sequences. The abundance ratio of P1/P2 transcripts varied considerably and was high in tumours which carry a rearrangement adjacent to c-myc, but some other T-cell tumours with no apparent myc alteration displayed an equally high ratio. However, a consistent feature was the lack of detectable RNA from normal c-myc alleles in tumours which express a rearranged c-myc allele or a transduced FeLV v-myc gene. We suggest that this may prove to be a useful indicator of the presence of an oncogenically active myc gene, whether this is a rearranged c-myc or transduced v-myc sequence.

Alleles

Conservation of the c-myc coding sequence in transduced feline v-myc genes.

We have cloned the normal feline c-myc locus and determined the nucleotide sequence of all three exons. The feline c-myc gene shows close homology to other mammalian c-myc genes, particularly human c-myc. The feline and human sequences are colinear within the open reading frame for the putative c-myc product but show insertions and deletions relative to each other outside this domain. We have also analyzed a cloned FeLV provirus, CT4, which contains the host-derived myc gene. In this provirus the v-myc sequences are located at the 3' end of the pol gene, replacing pol and env sequences. Nucleotide sequence analysis of CT4 shows an open reading frame for a v-myc gene product which may be expressed without fusion to any viral protein sequences. This contrasts with another FeLV v-myc (LC), in which myc and gag sequences were found to be fused. Unlike previously identified avian v-myc genes, the feline v-myc genes contain exon 1-derived sequences, but these have been truncated or internally deleted. The FeLV CT4 v-myc sequence shows very few coding changes relative to c-myc and the FeLV LC v-myc coding sequence is unchanged relative to c-myc apart from fusion to gag. These results are discussed in relation to the mechanism of transduction and activation of myc by FeLV.

Amino Acid Sequence

Self-esteem of abused children.

Thirty-seven children admitted to hospital with a diagnosis of abuse at an average of 5.5 years previously were compared with 37 non-abused children matched for age, sex, ethnic group, school and social class. The mean age of the children with 8.9 years (range 4.6-14.0 years). Self-esteem in the children was assessed by means of a structured interview with the child and the Piers-Harris Self-Concept Scale. The abused children saw themselves as having significantly fewer friends than the comparison children and they played with friends less often. They were less ambitious than the non-abused children with regard to the sort of occupation they would like as adults and were significantly lower in self-concept on the Piers-Harris Self-Concept Scale. These results show that, as well as providing treatment for abusive parents, a long-term program which aims at improving interpersonal relationship skills and self-esteem is required for abused children.

Adolescent

Self-esteem and early background of abusive mothers.

Thirty-six mothers whose children had been abused were interviewed and compared with 36 mothers matched for social class and ethnic background. The abuse group mothers had lower self-esteem than the comparison mothers as judged by their desire that their children should not grow up to be like themselves or their partners. They were also less likely to discuss their problems with other people. They were less likely than the comparison mothers to have been brought up by their own parents. They had significantly more negative feelings than the comparison mothers towards their fathers when they were children and these negative feelings persisted into adult life. It is important that emphasis on treatment programs for these mothers should be placed on building up self-esteem and skills in interpersonal relationships.

Child

Mothers of abused children. A comparison study.

A group of 36 mothers whose children had suffered from child abuse at an average of 5 1/2 years previously was compared with a group of mothers of similar social class where there had been no reported instances of abuse of their children. There was no significant difference between the two groups with regard to marital, housing, or financial problems or in physical health. Statistically significant differences were found between the abuse and comparison group mothers in the following areas: the abuse group mothers (1) were less likely to have been brought up by their own parents; (2) had more negative feelings towards their fathers; (3) were more likely to have received help for an emotional disorder; (4) had higher expectations for their children; (5) perceived a greater number of personality problems in their children; and (6) were more likely to have assertive, demanding, and suspicious personality traits. It is possible that these maternal factors will influence the emotional development of their children.

Child

Long-term effects of nonorganic failure to thrive.

Fourteen children admitted to the hospital at an average age of 12.5 years previously were reviewed in comparison with a group of children matched for age, sex, social class, and ethnic group. The children in the study group were smaller in height and weight, than children in the comparison group. They had lower scores on the verbal intelligence scale of the Wechsler Intelligence Scale for Children--Revised, poorer language development, and less well-developed reading skills. They had lower social maturity and a higher incidence of behavioral disturbances. There were no differences between the study and comparison groups in family size, maternal age, family health, social isolation, and mothers' childhood experiences. The study group mothers had less knowledge about their children's education, were more anxious, and had a tendency toward concrete thinking. To prevent the long-term adverse effects of nonorganic failure to thrive, a more active, practical, and long-term program, begun at the time of presentation, is recommended.

Adolescent

Persisting characteristics of parents of battered children.

To study the personality of mothers whose children had suffered from child abuse in the past, a group of 36 such mothers was compared with a control group of mothers matched for social class. There was no difference between the two groups in pregnancy experience, in general health or in the number of family problems they had. The mothers from the study group had higher expectations for their children and perceived their children as having more personality problems than did the control mothers. The study-group mothers were less likely to have been brought up by their own parents, had more negative feelings towards their fathers, and were more likely to have received help for an emotional disorder than the control mothers. On formal testing, they were more likely to have suspicious, assertive, and demanding personality characteristics. As the majority of abused children remain in their natural families, these maternal factors are likely to influence the emotional development of their children. The children, as well as the parents, from families where child abuse has occurred should receive long-term supportive treatment to try to ameliorate some of the effects of these parental characteristics.

Adult

Development in children following abuse and nonorganic failure to thrive.

Thirty-nine children who had been abused an average of 5 1/2 years earlier and 14 children who had been admitted to the hospital with nonorganic failure to thrive (NOFTT) 13 years earlier were studied to look at similarities and differences in their development. Each group was studied in relation to a comparison group matched for age, sex, social class, and ethnic background. The abused children and those with NOFTT were similar in their language ability, and were significantly behind their comparison groups in language development, reading age, and verbal intelligence. The abused children, but not the group who had NOFTT, were significantly behind their comparison group in general intelligence, interpersonal relations, and self-concept, but in contrast to the children with NOFTT they were not delayed in social maturity. The long-term adverse sequelae of these two conditions emphasize the need for a long-term, child-centered approach.

Adolescent

Reliability of mothers' reports of birth data.

To determine the reliability of recall of birth and early childhood events, a group of 47 mothers was asked details of their child's birth and about any child-rearing problems at an average of 5-6 years after the birth. Thirty-four of these mothers were asked similar questions 3 years later. The information given by the mothers was compared with the information documented in the hospital records when the children were born. The mothers overestimated the length of pregnancy and overestimated the number of neonatal problems. Only half could recall the birth weight accurately. When asked the same questions 3 years later there was a tendency for memory to have mellowed with fewer pregnancy complications and child-rearing difficulties being recalled than on the previous interview. Information given by mothers about such objective data as length of gestation, birth weight and obstetric complications is not necessarily accurate. Less objective data may be recalled even less accurately.

Attitude

The development of abused children.

Thirty-nine children were reviewed who had suffered child abuse at an average of 5 1/2 years earlier. In comparison with a group matched for socio-economic status, the abused children performed significantly lower on the Wechsler Intelligence Scale, and were more delayed in language development and reading ability. Their teachers' assessments of behaviour showed significantly more abnormal profiles than in the comparison group. These differences could not be accounted for by the small proportion of known head-injuries in the abused group. Child abuse has long-term effects, so it is necessary that these children are thoroughly assessed at first presentation, and that they are followed with a specific programme aimed at preventing these sequelae.

Adolescent

Retroviral transduction of T-cell antigen receptor beta-chain and myc genes.

Support for multistage models of oncogenesis has been provided by several highly leukaemogenic retrovirus isolates that have transduced more than one host cell gene. Where functional studies have been performed, these retroviral oncogenes show synergy for in vitro transformation and leukaemogenesis. In naturally occurring feline leukaemias associated with feline leukaemia virus (FeLV), retroviral transduction of myc is a frequent oncogenic mechanism. But evidence suggesting that the FeLV v-myc genes might be insufficient for leukaemogenesis was provided by the latency (12 weeks) and clonality of FeLV/v-myc-induced tumours and the absence of demonstrable in vitro transformation by these viruses. In the search for secondary leukaemogenic events in FeLV/v-myc tumours, we have identified a case of FeLV transduction of a T-cell antigen receptor beta-chain gene. The proviruses carrying this gene (which we have named v-tcr) were a separate population from those carrying v-myc. In its normal role, the T-cell receptor beta-chain forms part of a multimeric complex involved in antigen recognition and T-cell activation. We suggest that v-tcr is a novel viral oncogene which assisted v-myc in the genesis of a naturally occurring case of thymic lymphosarcoma.

Animals