Search PubMed⌕ Search

Biomedical subjects

K W Brown

Publications and source records attributed to K W Brown.

At least 55 records · Page 3Linked to original sources
PubMed1994

Loss of heterozygosity on chromosome 18q is associated with muscle-invasive transitional cell carcinoma of the bladder.

Somatic allelic loss is regarded as a hallmark of tumour-suppressor gene (TSG) inactivation. Thirty-one human bladder transitional cell carcinomas (TCCs) were examined for allelic loss at five chromosome 18q loci, including the DCC gene (deleted in colorectal carcinoma) and at chromosome 11p15 in a restriction fragment length polymorphism analysis. Allelic loss was observed at one or more 18q loci in 9/26 (35%) samples, associated with muscle-invasive disease (P < 0.02). Allelic loss was observed at DCC in 8/24 (33%) samples, associated with muscle-invasive disease (P = 0.05). Three out of the five evaluable recurrent TCCs exhibited allelic loss at DCC, two of which were superficial. No allelic losses were detected at other 18q loci in tumours which retained both DCC alleles. Allelic loss was observed at 11p15 in 5/20 (25%) tumours. These data suggest the presence of a late-acting TSG located on 18q in TCC bladder cancer. DCC is a candidate gene since it lies within the region of most common deletion (18q21.3-qter).

Alleles↗
PubMed1994

Allelic methylation of H19 and IGF2 in the Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with associated embryonal tumours. Most BWS cases are sporadic but familial cases occur in 15% of patients and in these there is linkage to chromosome 11p15. In addition, a small number of patients have cytogenetic abnormalities involving chromosome 11p15. Approximately 20% of sporadic BWS patients have uniparental paternal disomy (UPD) of chromosome 11p15. This finding together with the observation that penetrance in familial cases depends on parental transmission, suggests that the gene(s) for BWS are imprinted. The recent demonstration of biallelic expression of the otherwise maternally imprinted IGF2 gene in some BWS patients implicates excess IGF2 expression in the disease. Here we have analysed the allele-specific methylation patterns in the IGF2 gene and in the neighbouring and reciprocally imprinted H19 gene in a group of 42 BWS patients, 10 of which were mosaic UPD cases. We found that allelic methylation of both genes was normal in all non-UPD cases, with the paternal allele being methylated, and was increased in UPD cases in proportion with the disomic lineage. These findings suggest that sporadic BWS is not associated with a general alteration of methylation imprinting of the IGF2 and H19 genes. The methylation assay used in this study thus also offers a simple and reliable diagnostic test of UPD for 11p15.5. An unexpected finding was a distortion of the frequency of AvaII alleles at the IGF2 locus exclusively in UPD BWS cases (P < 0.001). This further implicates the IGF2 gene in aspects of the BWS phenotype.

Alleles↗
PubMed1994

Rapid and specific diagnosis of t(11;22) translocation in paediatric Ewing's sarcoma and primitive neuroectodermal tumours using RNA-PCR.

One case of paediatric Ewing's sarcoma and two peripheral primitive neuroectodermal tumours/extra-osseous Ewing's sarcoma were studied for the characteristic t(11;22) translocation, using a recently described RNA-polymerase chain reaction method (RNA-PCR). PCR products of the expected sizes were obtained from RNA derived from the Ewing's sarcoma and the peripheral primitive neuroectodermal tumours, but not from other paediatric malignancies. Direct sequencing of the RNA-PCR products confirmed the presence of the EWS-FLI-1 fusion transcript. In one case the presence of the translocation was confirmed by cytogenetic analysis. These results highlight the potential use of PCR for the rapid demonstration of diagnostically important tumour specific chromosome rearrangements.

Adolescent↗
PubMed1993

Low frequency of mutations in the WT1 coding region in Wilms' tumor.

A series of twenty unselected Wilms' tumors were analysed for alterations in the WT1 tumor suppressor gene. The entire coding region of WT1 was amplified by RNA-PCR, and then screened for mutations by single-strand conformational polymorphism analysis (SSCP). This method was shown to be capable of detecting point mutations in the WT1 gene, by using an experimentally produced mutation. A single mutation, a 226 bp intragenic deletion, was detected in a tumor from a patient with the WAGR syndrome. These results suggest that alterations in the WT1 gene may be involved in only a subset of Wilms' tumors, and that other loci need to be investigated as potential suppressor genes in sporadic Wilms' tumors.

Genes, Wilms Tumor↗
PubMed1992

Paternal origin of 11p15 duplications in the Beckwith-Wiedemann syndrome. A new case and review of the literature.

A boy suffering from the Beckwith-Wiedemann syndrome (BWS) was found to have partial trisomy of the short arm of chromosome 11 [46,XY,der(5)t(5;11)(p15.2;p14)]. Both his parents were phenotypically normal, but his father carried a balanced translocation between chromosomes 5 and 11 [46,XY,t(5;11)(p15.2;p14)]. DNA analysis of polymorphic markers on 11p15 confirmed the paternal origin of the duplicated material in the child. This case is the sixth report of paternal duplication of 11p15 in BWS. These results are discussed in relation to the possible role of genomic imprinting in BWS and in Wilms' tumor.

Beckwith-Wiedemann Syndrome↗
PubMed1992

A twin study of odor identification and olfactory sensitivity.

Interindividual variation in odor identification and olfactory sensitivity has been explained primarily with reference to age, sex and/or experiential factors. A twin study of olfaction can, therefore, substantially contribute to current research in this area. Thirty-nine monozygotic and twenty dizygotic twin pairs have completed the University of Pennsylvania Smell Identification Test (UPSIT), an olfactory preference questionnaire, and two odor detection threshold tests (phenyl ethyl alcohol and butanol). A genetic influence on odor identification, as assessed by the UPSIT, has been demonstrated. Future plans and directions for this research program are discussed.

Adult↗
PubMed1992

Sub-syndromes of tardive dyskinesia and some clinical correlates.

Syndromes of dyskinetic movements in subjects (N = 70) with chronic schizophrenia were investigated, using principal components analysis of AIMS ratings. Consonant with previous research, three discrete groupings were found, namely dyskinetic movements of lips-jaw-tongue, limb-truncal and facial movements. These were then related to demographic, psychological and movement disorder variables. The limb-truncal, but neither the lips-jaw-tongue nor facial movements components, were associated with negative symptoms and cognitive impairment.

Aged↗
PubMed1992

The influence of topography on the cognitive and psychopathological effects of tardive dyskinesia.

OBJECTIVE: The purpose of the study was to investigate the influence of the topography of dyskinetic movements on their effect on cognitive impairment and negative symptoms. METHOD: Eighty-four inpatients who satisfied DSM-III-R criteria for schizophrenia were rated for tardive dyskinesia, akathisia, and drug-induced parkinsonism, as well as negative symptoms, with the Scale for the Assessment of Negative Symptoms and for cognitive state with the Mini-Mental State examination. The subjects were then divided into those without tardive dyskinesia (N = 45), those with orofacial dyskinesia (N = 19), and those with limb-truncal dyskinesia (N = 20). Differences among the groups were assessed with multiple analysis of covariance (MANCOVA), with age, akathisia, and drug-induced parkinsonism ratings as the covariates. Post hoc Spjotvoll and Stoline tests were then undertaken. RESULTS: MANCOVA revealed a significant difference among the groups. Post hoc tests showed that the group with limb-truncal dyskinesia had significantly lower scores on the Mini-Mental State Examination and higher scores on the Scale for the Assessment of Negative Symptoms. The group with orofacial dyskinesia was significantly different from the nondyskinetic group only on the total score for the Scale for the Assessment of Negative Symptoms and the attention subscale. There were no significant differences between the dyskinetic groups. CONCLUSIONS: After correction for the important confounding variables of age, akathisia, and drug-induced parkinsonism scores, those with limb-truncal and, to a lesser degree, orofacial dyskinesia differed significantly from nondyskinetic comparison subjects in ratings of cognitive impairment and negative symptoms.

Akathisia, Drug-Induced↗
PubMed1992

Syndromes of chronic schizophrenia and some clinical correlates.

Subtypes of the features of chronic schizophrenia were investigated. As in previous research, three discrete syndromes were found. These were then related to demographic, psychological, and movement-disorder variables. Possible pathophysiological mechanisms are discussed in terms of known neostriatal functions.

Akathisia, Drug-Induced↗
PubMed1992

Inactivation of the remaining allele of the WT1 gene in a Wilms' tumour from a WAGR patient.

A candidate gene (WT1) has recently been described for the 11p13 tumour-suppressor gene involved in the development of Wilms' tumour. This gene encodes a zinc finger protein which can bind to a specific DNA sequence. We have found a 226 base deletion in the mRNA from a unilateral Wilms' tumour, which would cause a frameshift that completely deletes the zinc finger domain. The tumour developed in a patient suffering from the WAGR syndrome, who had a constitutional 11p13 deletion, and so the 226 base deletion represents the inactivation of the remaining WT1 allele in the tumour. This provides further direct evidence that loss of function of WT1 is an essential step in the development of Wilms' tumour.

Abnormalities, Multiple↗
PubMed1992

Social skills and their correlates: preschoolers with developmental delays.

Fifteen preschool-age children with mild mental retardation (developmental delays) from mainstreamed schools were observed during two structured play sessions with matched peers without mental retardation. Children with developmental delays spent more time alone and when they played, showed less social play. The two groups did not differ on communication behaviors that maintained play or in negative affect; however, the children with developmental delays evidenced more disruptive entry, more regressive behaviors, and less positive affect. Families were interviewed concerning their attitudes about, and teaching of, social skills. For the children without mental retardation, level of social play was positively related to the family's teaching and the child's communication abilities. For the children with delays, social play related to developmental age and communication ability but not to family teaching.

Child, Preschool↗
PubMed1991

The association among negative symptoms, movement disorders, and frontal lobe psychological deficits in schizophrenic patients.

Neuropsychological tests of frontal lobe function were undertaken in 46 chronic schizophrenic patients who were also rated for movement disorders and negative symptoms. "High" and "low" SANS groups were formed by segregating around the median value. The "high" SANS group was found to differ significantly in terms of the severity of tardive dyskinesia (TD) and drug-induced parkinsonism, and frontal psychological tests. A possible mechanism is discussed within the context of known neostriatal psychological function.

Antipsychotic Agents↗
PubMed1991

Tardive dyskinesia and positive symptoms of schizophrenia.

Positive symptoms and movement disorders were rated in 44 schizophrenic inpatients. A significant negative correlation was demonstrated between tardive dyskinesia and positive symptoms. Possible explanatory mechanisms are discussed.

Akathisia, Drug-Induced↗