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S Richards

Publications and source records attributed to S Richards.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1989

Analysis of a new class I gene mapping to the Hmt region of the mouse.

The major histocompatibility complex (MHC) of the BALB/c mouse contains three genes encoding classical class I molecules, as well as at least 32 nonclassical class I genes. Although much is known about the genes encoding the classical class I molecules, the majority of the nonclassical genes have not been characterized. This report describes a newly identified nonclassical class I gene, Thy19.4, which contains an open reading frame and resembles in several regards the genes encoding classical class I molecules. The similarities include shared amino acid sequence motifs which suggest that the putative Thy19.4 molecule may assume a tertiary structure similar to that of the classical class I molecules, as well as widespread transcription in a variety of tissues. However, unlike the classical class I genes, the Thy19.4 gene maps approximately 1 cm distal to the Tla region of the MHC, in the same region as the gene encoding the Hmt element of the maternally transmitted antigen.

Amino Acid Sequence↗
PubMed1989

Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults.

We report the analysis of prognostic factors in a cohort of 660 patients entered in the first Medical Research Council trial in chronic lymphocytic leukaemia (CLL) between 1978 and 1984. The majority (94%) of patients were aged 50 or over and the number of men (M) was almost twice that of women (F) with an M:F ratio of 1.8:1. The M:F ratio was lower, 1.5:1, in patients aged 70 or over. Stage A CLL was the most common, and stage C the least common, among women of all ages, in contrast to men for whom stage A only predominated in the older age group. As the majority of CLL patients are elderly we have examined the causes of death in great detail. 29% of deaths were unrelated to CLL, mainly other cancers (12%) and cardiovascular complications (16%). The majority of deaths in patients presenting with stages B and C were from CLL-related causes, whilst almost half of the deaths in patients presenting with stage A were not obviously related to CLL. Univariate analysis disclosed that the A, B, C staging system was the most important factor considered; stratified and multivariate analysis showed that age and response to treatment were the main prognostic factors after stage. Women always fared better than men and this was independent of stage and age. This and other features documented in the trial suggest a major biological difference between the sexes which has not been widely recognized. The significant influence of treatment response on patients' survival suggests that the search for better treatments in CLL may be rewarding. The improved median survival of stage C patients recorded in this trial, 41 months, compares favourably with previous reports and may have resulted from better treatment.

Age Factors↗
PubMed1989

Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up.

Cytogenetic, clinical and laboratory features at diagnosis were examined in a group of 80 children with acute lymphoblastic leukaemia (ALL) who had been followed up for a minimum of 5 1/2 years. The 17 (21%) with high hyperdiploidy tended to have low leucocyte counts and common ALL, but their favourable outcome (75% event-free survival) was independent of these factors. No patient with hypodiploidy survives while the pseudodiploid and normal groups have an intermediate prognosis. Cytogenetic analysis showed examples of patients with the well-recognized translocations and a number with apparently unique ones. Among the latter were some long-term survivors. We conclude that cytogenetic analysis identifies a good risk group of patients who remain well on long-term follow-up, but that the presence of a translocation does not necessarily imply a poor outcome.

Child↗
PubMed1989

Electrophysiologic study of rabbit proximal tubular cell monolayers in primary culture.

Primary cultures of renal cortical cells prepared by selective sieves have been found to display some characteristics of renal proximal tubular epithelium but their site of origin has not been confirmed by electrophysiologic studies. Cells were cultured in a defined medium on collagen gels. Confluency was approached after 7-10 days but gels were found to have zero transepithelial resistance unless they were allowed to contract spontaneously. With the appearance of a nonzero resistance, there was a change in morphology to a more columnar cell with better developed microvilli. These structural features were particularly prominent in clusters of proliferating cells observed on and around remnants of original tubules embedded in the gel. In noncontracted cultures there was no focal cell clustering and cells were squamous-like with rudimentary microvilli, similar in appearance to cells grown on plastic culture dishes. Measurements made in contracted monolayers yielded an average transepithelial resistance of 6.5 omega cm2, a spontaneous transepithelial potential difference of +0.9 mV, measured with respect to the serosa, and an apical membrane potential of -75 mV when cells were bathed in 0.4 mM K and -49 mV when cells were bathed in 4 mM K media. Mucosal protamine (50 micrograms/ml) increased transepithelial resistance by 22%, suggesting that the epithelial cell tight junctions were responsive to external stimuli. Monolayers were anion selective, giving a dilution potential (lumen-directed NaCl gradient) of -2.6 mV with respect to the serosa. These experiments show that primary culture of rabbit renal cortical cells separated by differential sieves displays electrophysiologic and morphologic characteristics of a proximal renal tubular epithelium. Confluency and attainment of differentiated morphology and function are promoted when monolayer cells are not bound to an unyielding substrate.

Animals↗
PubMed1988

Evidence for filaggrin as a component of the cell envelope of the newborn rat.

A substrate of transglutaminase, specific to the epidermis, was identified, by fluorescent and radioactive labelling with the lysine analogues dansylcadaverine and [14C]putrescine respectively, in newborn-rat epidermal homogenates and whole-skin organ cultures. The labelled analogues were preferentially incorporated into the stratum-corneum protein filaggrin in a Ca2+-dependent manner in both 'in vitro' systems. When filaggrin was labelled in vivo with [3H]histidine and then incubated with rat epidermal preparations, the label was rendered SDS/thiol-insoluble. Incorporation of [3H]filaggrin into the insoluble envelope fraction was Ca2+-dependent and inhibited by EDTA and exogenous amines. Antisera to newborn-rat filaggrin cross-reacted with purified newborn-rat cell envelopes, and this reaction was blocked by adsorbing the antiserum with purified filaggrin. Quantification of the 'envelope-bound' filaggrin showed it to be a significant component, accounting for approx. 10% of the cell-envelope protein.

Animals↗
PubMed1988

The UK Medical Research Council CLL trials 1 and 2.

The Medical Research Council (MRC) Working Party on Leukaemia in Adults has conducted two randomised trials in CLL since 1978. CLL 1 ran from 1978 to 1984 and recruited 660 eligible patients. The number of males was twice the number of females and the distribution of cases by stage was different in the sexes: 58% of females were stage A, 25% stage B and 17% stage C; in males the proportions for stages A, B and C were 40%, 30% and 30% respectively. The most important prognostic factor was stage (A, B, C), followed by age, sex and response to treatment, which were confirmed as independent variables by stratified log-rank and Cox multivariate analyses. Causes unrelated to CLL accounted for 28% of all deaths and were more common in older patients and in stage A disease. No significant difference was observed between the CLL 1 treatment schedules: chlorambucil, penta Cop and splenic irradiation (SI), although a somewhat better survival was seen for patients treated by SI. (When CLL deaths only were considered SI appeared superior to chlorambucil (p less than 0.05]. CLL 2 started in 1984 and is still accruing patients; 556 had been entered by July 1988. This trial compares early versus delayed therapy for stage A, chlorambucil with and without prednisolone for stages B and C in patients with a small or nonpalpable spleen, and SI vs chlorambucil with or without prednisolone for stages B and C in patients with a larger spleen (greater than or equal to 5 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

Medical Research Council Childhood Leukaemia Trial VIII compared with trials II-VII: lessons for future management.

This improvement in medium disease-free survival is probably a result of sustained early cell kill, and UKALL VIII has enabled us to define risk categories requiring even further continuous intensification, as now introduced in MRC UKALL X. Thanks to the greater availability of blood products, for example, the rational use of antibiotics and the development of expertise amongst nurses and doctors, such sustained therapy can now be delivered on a multi-centre basis, but only in experienced centres. The monitoring and removal of morbidity are essential if the advantages of this more sustained chemotherapy are to be realised. All elements of therapy require controlling and patients, parents and, above all, doctors must comply with protocol requirements in order to build further upon these initial promising results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Long survival in childhood lymphoblastic leukaemia.

Long term follow-up of 378 children with acute lymphoblastic leukaemia (ALL) treated at a single centre showed that at six years from diagnosis 202 (53%) were alive, of whom 140 (37%) remained in first remission. Only three children had a first relapse after six years. Children who survived six years despite a single extramedullary relapse in the testis or CNS were likely to remain in second remission but patients with previous marrow or with multiple relapses continued at risk for up to ten years from diagnosis. Presenting factors influencing event-free survival were: leucocyte count, age and sex. After allowing for these factors morphological (FAB) subtype and liver enlargement retained their prognostic significance. Immunological type of ALL was not of independent prognostic significance, except for the small number of patients with B-ALL. Most factors lost their significance after 2-4 years. It is concluded that patients alive 6 years from diagnosis without relapse or even with a single extramedullary relapse of ALL, have a high chance of prolonged survival and cure.

Child↗
PubMed1987

The effect of sucrose on the colonization of acrylic by Candida albicans in pure and mixed culture in an artificial mouth.

The roles of sucrose and microbial interactions in the colonization of acrylic by Candida albicans in an artificial mouth were investigated. The acrylic was colonized by pure cultures of the organism but a visible plaque was not produced whether or not sucrose was present. Salivary bacteria had no effect in the absence of sucrose but when sucrose was present the numbers of C. albicans were significantly increased. It is suggested that this phenomenon is related to the production of extracellular polysaccharides by salivary streptococci in the presence of sucrose. In mixed culture of C. albicans and Streptococcus salivarius CJ2, growth of the latter was inhibited in the presence of sucrose. This inhibition was due to factors other than pH, although no such antagonism could be demonstrated on solid media.

Candida albicans↗
PubMed1987

Oral methotrexate is as effective as intramuscular in maintenance therapy of acute lymphoblastic leukaemia.

It has been postulated that variations in methotrexate absorption may influence the outcome of treatment in lymphoblastic leukaemia. One hundred and forty four children with acute lymphoblastic leukaemia not of the T cell type were randomised to receive continuing treatment with daily 6-mercaptopurine, vincristine, and prednisolone six weekly and methotrexate once weekly, either as a single oral dose or an intramuscular injection. Analysis of results with a minimum follow up of three and a half years has shown that the route of administration of methotrexate has had no influence on relapse at any site, but more children receiving intramuscular methotrexate died in remission. These results indicate that oral methotrexate is as effective as intramuscular methotrexate in continuing treatment of lymphoblastic leukaemia.

Administration, Oral↗
PubMed1987

Familial acanthosis nigricans. A longitudinal study.

The triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN) is known to have a familial tendency. In order to better understand the natural history and possible treatment of this disorder, we studied the clinical course of two families in which all female progeny were affected. A rapid progression of the HAIR-AN syndrome was apparent during the peripubertal period and early reproductive years. Beyond this period, the progression of HAIR-AN appeared quite variable. Rapid weight gain was a major stimulant for increasing insulin resistance and hyperandrogenemia. In the one subject with a postmenarcheal onset of the syndrome, prolonged weight reduction was associated with an improvement in the dermatologic manifestation as well as in the hyperandrogenism and insulin resistance. Oral contraceptives appear to improve the dermatologic symptoms of the HAIR-AN syndrome.

Acanthosis Nigricans↗
PubMed1987

The significance of random breath alcohol sampling in the accident and emergency department.

Using a detailed questionnaire, 126 patients attending an accident and emergency department were screened for drinking problems. Eleven per cent (14) were identified as having established drinking problems, but only two of these had received help from professional agencies. In all, 39% (50) were identified as being adversely affected by their drinking habits. A breath alcohol test (BT) alone, on the same patients failed as a screening device for hidden drinking problems in these circumstances, and we do not recommend its use. The simple 'CAGE' questionnaire was a little more sensitive, but asking more questions identified more problems. A positive BT in the presence of a positive CAGE occurred in three patients and although insensitive it was absolutely specific for a serious drinking problem. A significant number of patients who attend an accident and emergency department have a drinking problem. The most effective method of detecting this is to ask patients about their drinking habits.

Adolescent↗