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Biomedical subjects

S Richards

Publications and source records attributed to S Richards.

At least 19 recordsLinked to original sources
PubMed1992

Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen.

The APO-1 antigen as defined by the mouse monoclonal antibody anti-APO-1 was previously found to be expressed on the cell surface of activated human T and B lymphocytes and a variety of malignant human lymphoid cell lines. Cross-linking of the APO-1 antigen by anti-APO-1 induced programmed cell death, apoptosis, of APO-1 positive cells. To characterize the APO-1 cell surface molecule and to better understand its role in induction of apoptosis, the APO-1 protein was purified to homogeneity from membranes of SKW6.4 B lymphoblastoid cells by solubilization with sodium deoxycholate, affinity chromatography with anti-APO-1 antibody, and reversed phase high performance liquid chromatography. Each purification step was followed by an APO-1-specific solid phase enzyme-linked immunosorbent assay using the monoclonal antibody anti-APO-1. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the APO-1 antigen was found to be a membrane glycoprotein of 48-kDa. Endoproteinase-cleaved peptides of the APO-1 protein were subjected to amino acid sequencing, and corresponding oligonucleotides were used to identify a full-length APO-1 cDNA clone from an SKW6.4 cDNA library. The deduced amino acid sequence of APO-1 showed sequence identity with the Fas antigen, a cysteine-rich transmembrane protein of 335 amino acids with significant similarity to the members of the tumor necrosis factor/nerve growth factor receptor superfamily. The APO-1 antigen was expressed upon transfection of APO-1 cDNA into BL60-P7 Burkitt's lymphoma cells and conferred sensitivity towards anti-APO-1-induced apoptosis to the transfectants.

Amino Acid Sequence↗
PubMed1992

Diagnosis of Duchenne and Becker muscular dystrophies by polymerase chain reaction. A multicenter study.

OBJECTIVE--To assess the efficiency, reliability, and ease of use of DNA diagnosis for Duchenne and Becker muscular dystrophies (DMD/BMD) using the polymerase chain reaction (PCR). DESIGN--DNA from the patients was screened for deletion mutations using multiplex PCR, and the results were compared with those obtained by Southern blot analysis. The PCR multiplex reaction detects nine specific "hot-spot" exons in the dystrophin gene while the Southern analysis detects 66 specific dystrophin gene restriction fragments. The multiplex reaction requires 50-fold less DNA than Southern analysis and thus is considerably more sensitive. SETTING--Fourteen university-affiliated and private genetic disease diagnostic laboratories. PATIENTS--Male patients with clinical signs of DMD/BMD. Cases were selected for analysis randomly, without knowledge of whether a deletion was present within the dystrophin gene. MAIN OUTCOME MEASURES--The percentage of cases that were detectable by multiplex PCR in comparison with Southern analysis, the frequency, extent, and location of the detected deletion mutations. In some cases, duplication mutations were monitored. RESULTS--The accuracy of a single PCR multiplex amplification (nine exons) was compared with Southern analysis with 10 cDNA probes that cover the full length of the gene. The multiplex PCR analytic method detected 82% of those deletions detected by Southern analysis methods. In one of 745 analyses, the multiplex method suggested a single exon deletion, which was not confirmed by Southern analysis, representing a false-positive rate of 0.013%. CONCLUSIONS--Multiplex PCR represents a sensitive and accurate method for deletion detection of 46% of all cases of DMD/BMD. The method requires 1 day for analysis, is easy to perform, and does not use radioactive tracers. As such, multiplex PCR represents an efficient and rapid method for prenatal or postnatal diagnosis of DMD/BMD.

Blotting, Southern↗
PubMed1992

Psychological aspects of donor insemination: evaluation and follow-up of recipient couples.

OBJECTIVE: To evaluate the utility of psychological screening for couples entering a donor insemination program. DESIGN: Each spouse completed questionnaires. A psychologist reviewed them and rated the psychological fitness of the couple for participation in the program. Follow-up questionnaires were sent to each couple at a mean of 11 months after entry into the program. SETTING: Applicants for donor insemination were studied in an infertility program in a large, tertiary referral center. PATIENTS, PARTICIPANTS: Consecutive applicants to enter the donor insemination program were required to participate in the initial evaluation. INTERVENTIONS: Couples judged by the psychologist to be at risk for a poor psychological outcome had an assessment and counseling interview with the psychologist before proceeding with insemination. MAIN OUTCOME MEASURES: Initially, the Stress and Infertility Questionnaire measured specific anxieties related to donor insemination, marital and sexual impact, and attitudes about confidentiality; the Brief Symptom Inventory measured psychological distress; and the Dyadic Adjustment Inventory assessed marital satisfaction. At follow-up, 48% of couples returned a modified version of the Stress and Infertility Questionnaire and the other two questionnaires. RESULTS: The psychologist's rating was predictive of pregnancy rates (59% for excellent candidates, 41% for acceptable couples, and 14% for couples psychologically at risk). At-risk couples were more likely to drop out of the program (50% versus only 20% of other couples). Sexual problems were reported by 59% of women and 53% of men. Couples believed that a child should not be told of the donor insemination (74% of wives and 80% of husbands). Initially, 64% of wives and 70% of husbands chose total secrecy with families or friends, and these attitudes shifted little over time. CONCLUSION: This screening procedure is cost-effective and suggests that psychological intervention should be attempted with at-risk couples.

Adult↗
PubMed1992

A simple protocol for the automation of DNA cycle sequencing reactions and polymerase chain reactions.

Automated DNA sequencing methods using robotic workstations have been previously reported, however it is often an arduous task to import these technologies into a laboratory. We describe protocols making use of a Beckman Biomek 1000 robotic workstation to prepare polymerase chain reactions (PCRs) and "cycle sequencing" reactions to be performed in a Perkin Elmer Cetus System 9600 thermocycler. The combination of these two instruments allows a high throughput of PCR and DNA sequencing reactions. The programs described are freely available via anonymous file transfer protocol (FTP).

Bacteriophage M13↗
PubMed1992

How many people think they have hay fever, and what they do about it.

Little is known about the number of people who perceive themselves to be sufferers of hay fever. This study investigated how many people between the ages of 15 and 59 years perceived themselves to be hay fever sufferers and how they treated themselves. The study was carried out in a general practice in Arnold, Nottingham, using a postal questionnaire, to which the response rate was 77% from a sample size of 1062. Of the 813 respondents, 232 (29%) claimed to have had hay fever within the last two years. The prevalence of hay fever decreased significantly with age, and was associated with a history of asthma. One hundred and twenty five sufferers (54%) used over the counter treatments for their hay fever, and one third of these said that they felt drowsy after using them. These findings point to the need for general practitioners to be aware that a number of people, more than has been indicated by previous surveys, perceive themselves to be hay fever sufferers and are prepared to treat themselves using over the counter preparations.

Adolescent↗
PubMed1992

Children under two years treated according to the Medical Research Council UKALL VIII study and trial 1980-1984 (on behalf of the Medical Research Council Working Party on Leukaemia in Childhood).

Ten per cent of children entered into the national leukaemia study UKALL VIII were under 2 years at diagnosis. The 6 year event-free survival of this cohort was 39%. Specific adverse features were age under 1 year, high initial white cell count and null cell ALL. Those with common ALL, WBC 10-50 x 10(9) 1-1 and especially those aged 18 months or older did not have an adverse prognosis compared with the whole trial entrants. Overall, however there was a doubling of CNS relapse rate and of both induction and remission deaths. Those with a WBC under 10 x 10(9) 1-1 had a high haematological relapse rate. The type of leukaemia and method of management rather than specifically the age appeared to be the predictor for poor outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

MRC UKALL X. The UK protocol for childhood ALL: 1985-1990. The Medical Research Council Working Party on Childhood Leukaemia.

MRC UKALL X, the successor of UKALL VIII ran from 1985 to 1990 and accrued 1614 patients aged 0-15 years. After standard induction all children except those with initial white cell count greater than 100 x 10(9)/1 were randomised to one of four regimens; +/- early intensification +/- late intensification. CNS protection for all comprised cranial irradiation and intrathecal methotrexate with continuing treatment for two years. At a median follow up of four years the overall event free survival for all children is 66% (SE 1.5). This is a significant improvement over the previous MRC UKALL VIII trial. Age, sex and leucocyte count were highly significant prognostic factors. Analysis of the results indicates that the regimen containing both intensifications is superior. The strategy of early and late intensification has been adopted in the successor protocol MRC UKALL XI in which patients are additionally randomised to receive high dose methotrexate.

Adolescent↗
PubMed1991

Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.

Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.

Alleles↗
PubMed1991

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.

Fragile X syndrome is the most frequent form of inherited mental retardation and is associated with a fragile site at Xq27.3. We identified human YAC clones that span fragile X site-induced translocation breakpoints coincident with the fragile X site. A gene (FMR-1) was identified within a four cosmid contig of YAC DNA that expresses a 4.8 kb message in human brain. Within a 7.4 kb EcoRI genomic fragment, containing FMR-1 exonic sequences distal to a CpG island previously shown to be hypermethylated in fragile X patients, is a fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes. This fragment contains a lengthy CGG repeat that is 250 bp distal of the CpG island and maps within a FMR-1 exon. Localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.

Alleles↗
PubMed1991

Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood).

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Acute myeloid leukaemia in childhood: the costs and benefits of intensive treatment.

Response to treatment and resource implications were compared in two groups of children with acute myeloid leukaemia (AML) treated during consecutive periods. Event-free survival at 5 years improved from 12% (SE 3.4) during 1972-82 (group A) to 45% (SE 6.9) during 1983-87 (group B). The median time spent in hospital increased from 35 to 170 d. Allogeneic marrow transplantation was offered to all eligible children in group B. Eleven of the 53 children had a suitable donor and 10 proceeded to bone marrow transplantation (BMT). The relapse rate was lower after BMT than after chemotherapy, although not significantly so. We conclude that there has been a real improvement in prognosis for children with AML; that modern treatment requires intensive hospital resources and that these results should encourage further efforts to improve outlook and to explore treatments not involving radiation.

Acute Disease↗
PubMed1991

The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.

From 1979-85, 2435 patients with a transient ischaemic attack or minor ischaemic stroke were randomly allocated to receive long term "blind" treatment with aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (n = 806) or placebo (n = 814). No patient was lost to follow up. The "intention to treat" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986. There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin, but the lower dose was undoubtedly less gastrotoxic. Also, there was no definite difference in the response of males and females to aspirin. The odds of suffering a major stroke, myocardial infarction or vascular death were 15% less in the combined aspirin groups compared with the placebo group (95% confidence interval 29% reduction to 3% increase in odds) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25%. There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring.

Aged↗
PubMed1991

A fast expanding role: Developments in practice nursing.

Practice nursing is an exciting and expanding specialty. With the growth of nurse-run clinics, the development of the practice nurse's role seems assured. Nevertheless, the scope and potential of the role is determined by individual nurses' needs and requirements.

Health Facilities, Proprietary↗
PubMed1990

Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia.

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Testicular irradiation in childhood lymphoblastic leukaemia. Medical Research Council Working Party on Leukemia in Childhoods.

The effect of randomly allocated testicular irradiation on the subsequent incidence of testicular infiltration and disease-free survival was assessed in two Medical Research Council Childhood Leukemia Trials. UKALL VI and UKALL VII. None of the 83 boys who actually received testicular radiotherapy subsequently developed gonadal disease. whereas 18 of the 163 who were not irradiated did. Despite this there is no apparent difference in disease-free survival for those randomized to receive testicular irradiation compared to those who were not, after a minimum of 8 years follow up. Although prophylactic testicular irradiation appears to prevent subsequent gonadal relapse there is no evidence that it improves overall prognosis when adequate systemic chemotherapy is used. As it has considerable long-term side effects it cannot be recommended as routine therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Neurotoxicity in lymphoblastic leukaemia: comparison of oral and intramuscular methotrexate and two doses of radiation.

Serial cranial computed tomograms were carried out in 136 children with acute lymphoblastic leukaemia who were receiving 24 Gy or 18 Gy of cranial irradiation and continuing treatment with doses of methotrexate given weekly orally or intramuscularly. The findings were correlated with treatment variables, the development of fits, and the intelligence quotient (IQ). Reversible brain shrinkage, attributed to treatment with steroids, was found on 87 of 114 initial scans (76%); 14 showed changes in white matter during treatment (10%), and calcification was found in 13 either during or after treatment (10%). Eight children (6%) had fits, and in six of the eight there were changes in white matter or calcification on the scans. Comparison of the two radiotherapy dosages showed no difference in the incidence of abnormalities seen on computed tomography, fits, or serial IQ measurements, but children receiving intramuscular methotrexate had a higher incidence of calcification and a lower mean IQ at one year than those who received the drug orally, although this difference was not apparent later. Younger children were more likely to develop changes on computed tomograms and fits, and to have low IQs on completion of treatment, with changes most apparent in those less than 2 years of age. There were highly significant correlations between abnormalities on computed tomography, fits, and IQ. These findings confirm the neurological vulnerability of younger children with acute lymphoblastic leukaemia, show an association between abnormalities on computed tomography and intellectual deficit, and suggest that methotrexate is more toxic when given intramuscularly than orally. They provide no evidence that 18 Gy of cranial irradiation is less toxic than 24 Gy, and indicate the need for alternative treatment regimens.

Administration, Oral↗
PubMed1989

Genetic and molecular mapping of the Hmt region of mouse.

We have mapped a new region of the mouse major histocompatibility complex (MHC) that contains the nuclear gene, Hmt, for the maternally transmitted antigen, Mta. The Hmt region of chromosome 17 lies between a recombinational breakpoint distal to Tla and another proximal to Tpx-1, thus including Pgk-2. A novel MHC class I gene fragment, R4B2, was cloned and mapped to this region as was another new class I gene, Thy19.4. Both lie proximal to Pgk-2, within the distal inversion in t-haplotypes. The presence of several other MHC class I genes in the Hmt region is predicted from analysis of the recombinants that define the region.

Amino Acid Sequence↗