Linkage analysis in manic-depressive illness.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A F Wright
Publications and source records attributed to A F Wright.
Specific polyclonal and monoclonal antibody prevents paraquat accumulation into rat lung slices.
Sheep polyclonal and mouse monoclonal antibodies have been produced that bind to the bipyridyl herbicide, paraquat. The binding capacities and affinities of the various antibody solutions (serum, ascites, purified tissue culture supernatant) to paraquat were determined using a radioimmunoassay. All antibody solutions bound paraquat with high affinity (Ka = 10(9)-10(10) l/mol). The sheep polyclonal antisera, the mouse ascites fluid, and the purified culture supernatant had mean binding capacities of 8, 1 and 22 micrograms paraquat/ml respectively. All the antibody preparations were able to prevent the in vitro accumulation of paraquat into rat lung tissue. The amount of antibody to achieve this was dependent upon the binding capacity of the antibody solution, i.e. when the binding capacity of the antibody was equal to the amount of paraquat present in the incubation medium a total blockade of uptake was achieved. When antibody was added to lung tissue that had been accumulating paraquat for 1 hr, the inhibition of uptake was immediate and was complete for at least 2 hr. Both the radioimmunoassay and lung slice experiments indicate that an equivalent of 1 mg of IgG is required to bind 2.5 micrograms of paraquat ion. Preincubation of lung tissue with antibody did not affect the subsequent accumulation of paraquat, nor did it result in a detectable degree of intracellular neutralisation of paraquat as measured by paraquat's ability to stimulate the pentose phosphate pathway. The rate of efflux of paraquat from lung slices prepared from rats dosed intravenously with paraquat was not increased by the presence of antibody in the incubation medium. In conclusion, neutralising antibodies to paraquat have been produced. They bind to paraquat in solution with high affinity and render the paraquat unavailable for its in vitro accumulation into lung cells.
Animals↗
A study of genetic linkage heterogeneity in adult polycystic kidney disease.
The mutation for adult polycystic kidney disease (APKD) has previously been localised to chromosome 16 by the demonstration of genetic linkage with the loci for the alpha-chain of haemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on only nine families so that the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purposes of detection of the disease, and complicate the characterisation of APKD at the molecular level. Therefore further families were studied to address this question. A total of 28 northern European pedigrees were analysed, all apparently unrelated, and with origins in England, Scotland, Holland and eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the APKD locus in this population.
Adult↗
Studies of genetic linkage between adult polycystic kidney disease and three markers on chromosome 16.
Adult polycystic kidney disease (APKD) is a common genetic disorder that is inherited as an autosomal dominant trait. Recent reports show that, in some families, the APKD gene shows close genetic linkage to two chromosome 16 specific genetic markers. We have been conducting a genetic linkage study using 29 polymorphic isoenzyme and antigenic markers in 184 members of 12 APKD families. We present here the results of linkage analysis using three of these markers which have also been reported to be located on chromosome 16: phosphoglycolate phosphatase (PGP), glutamate pyruvate transaminase (GPT), and haptoglobin (HP). The results show that APKD is closely linked to the PGP locus on the short arm of chromosome 16 (16p13----p12), which is consistent with the previously reported linkage both to PGP and to the alpha globin locus. The genetic distance between PGP and APKD shows a maximum likelihood value of the recombination fraction at zero with a lod score of 5 X 5. There is no evidence of linkage between APKD and either GPT or HP. The PGP polymorphism potentially provides a useful predictive test to complement the use of alpha globin probes in genetic counselling. These tests should provide an efficient means of primary screening of family members at risk, as well as introducing the possibility of prenatal diagnosis.
Alanine Transaminase↗
Manic depressive psychosis with mental retardation and flexion deformities: a clinical and cytogenetic study.
Five mentally handicapped patients are described in whom a bipolar manic depressive psychosis was associated with flexion deformities, involving principally the fingers. The effect of increasing degrees of retardation on the clinical presentation of the affective psychosis is discussed. Surgical treatment of the flexion deformity brought about considerable improvement in one patient. These five patients were further investigated cytogenetically using high resolution banding techniques. The results obtained were interesting but inconclusive. There would seem to be a definite place for further cytogenetic investigations of some of the more distinctive psychotic disorders using this technique.
Bipolar Disorder↗
Linkage relationships between X-linked retinitis pigmentosa and nine short-arm markers: exclusion of the disease locus from Xp21 and localization to between DXS7 and DXS14.
Linkage data between X-linked retinitis pigmentosa (XLRP) and nine X-chromosomal markers are reported. To test the assignment of XLRP to the Xp21 region (as considered at Human Gene Mapping 8), an analysis of XLRP and six markers flanking this region was undertaken. The XLRP locus was found to be excluded from the chromosome distal to ornithine transcarbamylase (OTC) (P = 6.5 X 10(-5]. Further data were accumulated with three more probes proximal to DXS7 (L1.28), the closest linked probe. Multipoint analysis of these data suggests a posterior probability of .94 that XLRP is proximal to DXS7 (L1.28), which has been mapped to the region Xp11.3.
Chromosome Mapping↗
The development of mouse monoclonal antibodies that bind and neutralize paraquat.
Mouse hybridomas have been produced that produce antibody that can bind to the bipyridyl herbicide paraquat with high affinity (Ka = 1.2 X 10(10) litres/mole). In addition, one cell line, 321, secretes antibody in the concentration range 60-100 micrograms/ml of culture, and 5 mg/ml in ascites fluid. Such high concentrations make it feasible to produce gram quantities of antibody with relative ease and low cost. The antibody is of class and sub-class IgG1 and can be readily purified by protein A and paraquat specific affinity chromatography. Radioimmunoassays and in vitro neutralization studies have demonstrated that 1 mg of antibody is required to bind 2.5 micrograms of paraquat. When antibody binds to paraquat in vitro it renders the paraquat unavailable for accumulation into rat lung tissue.
Animals↗
Hidden psychiatric illness: use of the general health questionnaire in general practice.
A 10% random sample comprising 234 adults attending a general practitioner was studied to obtain an estimate of conspicuous and hidden psychiatric morbidity and to determine the value of the general health questionnaire in improving case recognition in general practice. Patients completed the 28-item general health questionnaire before seeing the general practitioner, who completed a rating sheet without seeing the general health questionnaire score. The doctor identified a psychiatric component in 38% of men and 53% of women and diagnosed psychiatric disorder in 22% of men and 31% of women. Using a cut off point of nine or above, high general health questionnaire scores were found in 25% of men and 29% of women. Agreement between the general health questionnaire and the doctor's assessment was better for males (misclassification rate 16%) than for females (20%). A subsample of patients scoring over the recommended threshold (five or above) on the general health questionnaire were interviewed by the psychiatrist to compare the case detection of the general practitioner, an independent psychiatric assessment and the 28-item general health questionnaire at two different cut-off scores. The general health questionnaire may be a useful tool for improving recognition of psychiatric morbidity in general practice if the cut-off point is raised above that recommended for epidemiological research.
Family Practice↗
Use of the general health questionnaire in clinical work.
Explore the source record for details and available documents.
Adolescent↗
Genetic linkage between X-linked retinitis pigmentosa and DNA probe DXS7 (L1.28): further linkage data, heterogeneity testing, and risk estimation.
Further linkage data relating X-linked retinitis pigmentosa and DNA probe DXS7 (L1.28) is presented in this paper. The current mean estimate of the recombination fraction (theta) including this and all published data, is 0.09, with confidence limits 0.04 to 0.17 (maximum Lod score of 14.01 at a theta of 0.08). There is no evidence for heterogeneity of recombination fraction between the 13 families for which data are available. However, it is argued that heterogeneity should be assumed to exist for the purposes of risk estimation. Mean estimates and variances of risk are calculated for hypothetical families each with different linkage data. In families in which no recombination has been observed, the mean and variance of risk are sufficiently small for the clinical use of this probe to be acceptable to many.
DNA↗
DNA analysis in human disease.
The analysis of human DNA using recombinant DNA technology is fast becoming an integral part of the diagnosis, assessment, and prevention of inherited and somatic genetic disease. The rationale underlying these methods of analysis is discussed, and the nature and extent of mutational change in heritable disorders and neoplastic development is outlined.
DNA↗
A genetic linkage study of choroideremia.
One hundred and twenty-two members of 15 choroideremia families have been used in a genetic linkage study of choroideremia (TCD) using four DNA probes situated on the X chromosome. Linkage was analysed using DNA probes DXS14 (p58-1), DXYS1 (pDP 34), DXS178 (p212) and DXS177 (lambda 2.7). Statistically significant linkage was demonstrated with DXYS1 (theta = 0.00, lod 4.95), in agreement with the findings of Nussbaum et al. (1985). Evidence consistent with loose linkage to TCD was also found with DXS14 (theta = 0.31, lod 0.23), DXS178 (theta = 0.18, lod 1.41) and DXS177 (theta = 0.27, lod 0.20). The results suggest that TCD is located in the region Xq13-q21. Probe DXYS1 is likely to prove useful in the prenatal diagnosis of this condition.
Choroid↗
A study of genetic linkage heterogeneity in adult polycystic kidney disease.
The mutation for APKD has previously been localized to chromosome 16 by the demonstration of genetic linkage with both the alpha-chain of hemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on a limited number of families, and the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purpose of detection of the disease and complicate the characterization of the APKD mutation at the molecular level. Therefore, further families were studied to resolve this issue. A total of 27 Northern European pedigrees were analyzed, all apparently unrelated and with origins in England, Scotland, Holland, and Eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the disease locus in this population.
Adult↗
A genetic linkage study of a kindred with X-linked retinitis pigmentosa.
A large kindred with X-linked retinitis pigmentosa (XLRP) was investigated clinically and by means of genetic linkage with a view to developing methods of carrier detection and early diagnosis. A restriction fragment length polymorphism, identified by recombinant DNA probe L1.28, showed close genetic linkage to XLRP in this kindred and is a potentially useful marker for the purposes of genetic counselling.
Adolescent↗
Quantitation of specific myeloid cells in rat bone marrow measured by in vitro 35S-sulphate incorporation.
A biochemical measurement which can be used for quantitation of specific early myeloid cells in rat bone marrow has been developed. This measurement consists of a rapid, simple assay for the in vitro quantitation of 35S-sulphate incorporation into rat bone marrow cells. Incubation of bone marrow cells with 35S-sulphate led to a time-dependent increase in radioactivity obtained in perchloric acid insoluble fractions of bone marrow cell suspensions. This incorporation was inhibited by cyanide and puromycin. Autoradiography has demonstrated the radiolabel to be specifically associated with immature cells of the myeloid series. The cells most active in this respect were eosinophils. When rats were treated with endotoxin, the rate of 35S-sulphate incorporation was increased. Cell number measurements, using conventional histopathology and a Coulter Counter, demonstrated that endotoxin caused an initial release of mature granulocytes from the bone marrow. The regeneration of this mature population in the marrow was rapid, and was characterized by an increase in the number of immature cells and a concomitant increase in the rate of 35S-sulphate incorporation measured in preparations of bone marrow cells in vitro. Furthermore, this response to endotoxin has demonstrated that Coulter Counting techniques can be used to distinguish specific populations of cells (e.g. mature granulocytes) within the bone marrow.
Animals↗
Beta-adrenoceptor binding defects in cell lines from families with manic-depressive disorder.
Binding of 125I-iodohydroxybenzylpindolol to beta-adrenoceptors has been examined in lymphoblastoid cell lines from members of 5 families affected by manic-depressive disorder. Cell lines from 6 manic-depressives, 7 unaffected relatives and 11 non-psychiatric controls were examined. Binding was reduced to less than half of control values in cell lines from 4 out of 6 manic-depressives and only 1 out of 18 unaffected relatives or controls. All the cell lines with reduced beta-adrenoceptor binding came from 3 families; members of the remaining 2 families showed normal binding. These findings suggest that genetic heterogeneity is present in manic-depressive disorder and that a beta-adrenoceptor defect may influence genetic susceptibility to the disorder.
5'-Nucleotidase↗
Genetics, ageing and dementia.
The contribution of genetic differences to variation in ageing and the relationship of ageing to certain types of dementia are discussed. Neuropathological changes commonly found in the ageing brain are present in more severe form in Alzheimer-type dementia, Down's syndrome, multi-infarct dementia, and a substantial number of patients with Parkinson's disease. An increased frequency of ageing-associated changes outside the brain have been reported in Alzheimer-type dementia, Down's syndrome, and multi-infarct dementia, although the evidence is generally meagre and in many cases requires further corroboration. Genetic studies of Alzheimer-type dementia support the existence of heterogeneity on the basis of family history and age of onset; early onset is associated with greater genetic risk and severity of abnormality. The increasing evidence of an association between DNA damage, premature ageing, and neuronal cell loss may provide insights into the aetiology of these and other forms of dementia.
Aged↗
A difficult case. Does it help to know your patient?
Explore the source record for details and available documents.
Adrenal Gland Neoplasms↗