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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 199 records · Page 11Linked to original sources
PubMed1991

A critical evaluation of AgNOR counting in benign naevi and malignant melanoma.

There is considerable variation in the quoted mean numbers of AgNORS per nucleus for benign melanonaevi and malignant melanomas. This is partly attributable to different approaches to AgNOR counting. This study summarizes our experience in devising an optimal technique for counting AgNORs. We show that it is essential to count intra-nucleolar AgNORs in addition to those lying outside the nucleolus to obtain clear separation of naevi from melanoma. Although this seems an onerous task, we further demonstrate that a maximum of only 30 nuclei need to be counted to obtain a mean AgNOR count per nucleus which is representative of the whole lesion. This compares with the arbitrary figure of 100 nuclei chosen by most workers. Only by optimizing and standardizing all aspects of the AgNOR technique including fixation, staining, and counting will mean AgNOR counts per nucleus become a useful quick, reproducible method which can be applied to lesions which pose diagnostic problems such as borderline melanocytic lesions.

Cell Nucleolus↗
PubMed1991

Measurement of the tissue distribution of immunoperoxidase staining with polyclonal anti-BCG serum in lung granulomata of mice infected with Mycobacterium tuberculosis.

Mice inoculated with Mycobacterium tuberculosis, strain H37Rv were used as a model of human tuberculosis. The microanatomical location of immunoperoxidase staining with a polyclonal anti-BCG serum was within macrophages and appeared granular rather than delineating whole bacilli. Immunoperoxidase staining appears to demonstrate degraded mycobacterial antigens from disrupted organisms and so reflects prior turnover of bacilli. On Ziehl-Neelsen staining, intact or almost intact bacilli are seen and so the extent of this form of staining reflects the current bacillary load. Both methods have limited sensitivity, but with larger mycobacterial loads the area of immunoperoxidase stain measured on a semi-automated image analyser correlated with the numbers of bacilli observed. The immunoperoxidase method will be useful in the evaluation of residual antigen in studying the pathogenesis of experimental murine tuberculosis. In human mycobacterial granulomata, this immunohistochemical technique should provide an alternative method of estimating the extent of bacillary load: this approach may also provide evidence of mycobacterial infection from residual antigen deposits in the tissue when whole bacilli have been successfully cleared.

Animals↗
PubMed1991

Re-evaluating silver-stained nucleolar organizer regions (AgNORs) in problematic cutaneous melanocytic lesions: a study with quantitation and pattern analysis.

Previous studies enumerating AgNORs in cutaneous melanocytic lesions have produced inconsistent results. It is probable that such inconsistencies arise from differences in fixation, staining technique, and counting strategies. Our group, having demonstrated an improved method of silver staining and having optimized counting, is now able to reconsider the role of AgNORs in evaluating borderline melanocytic lesions. Diagnostic problems similar to those encountered in routine practice have been examined. It is shown that only by counting intra- and extranucleolar AgNORs in combination with assessing the pattern of AgNOR dispersal is it possible to (1) discriminate dysplastic naevi from melanoma and (2) distinguish Spitz naevi and pigmented spindle cell naevi from melanoma. An analysis of AgNOR numbers alone results in considerable overlap between the groups studied. The value of assessing patterns of AgNOR dispersal within and outside clustered nucleolar structures is emphasized. Lesions labelled as minimal deviation melanoma (by experts in dermatopathology) were also investigated. The majority of these specimens form a distinct group lying apart from control naevi and melanomas. This finding, whilst of interest, is difficult to evaluate because of poorly defined diagnostic criteria.

Cytological Techniques↗
PubMed1990

Lymphokine receptor-directed therapy: a model of immune intervention.

We have proposed a multichain model for the high-affinity interleukin-2 (IL-2) receptor involving two IL-2-binding peptides, a 70/75 kilodalton (kD) and a 55 kD, reactive with the anti-Tac monoclonal antibody, which are associated in a receptor complex. With the use of coprecipitation analysis, radiolabeled interleukin-2 cross-linking procedures, and flow cytometric resonance energy transfer measurements, a series of additional peptides of molecular weight 22,000, 35,000, 40,000, 75,000 (non-IL-2 binding), 95,000-105,000, and 180,000 has been associated with the two interleukin-2-binding peptides. In contrast to resting T cells, the abnormal T cells of patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia, patients with select autoimmune disorders, and individuals rejecting allografts express the Tac peptide (p55) of the IL-2 receptor. To exploit this difference in Tac antigen expression, we have initiated therapeutic trials using unmodified anti-Tac, conjugates of anti-Tac with truncated Pseudomonas exotoxin PE-40, interleukin-2-truncated toxin fusion proteins, and alpha- and beta-emitting isotopic chelates of anti-Tac. Furthermore, by genetic engineering humanized hyperchimeric anti-Tac molecules have been prepared in which the molecule is entirely human IgG1, except for the small complementarity-determining regions that are retained from the mouse antibody. This "humanized" antibody manifested the ability to perform antibody-dependent cellular cytotoxicity absent in the original mouse monoclonal. The clinical application of anti-interleukin-2 receptor-directed therapy represents a new perspective for the treatment of certain neoplastic diseases and autoimmune disorders and for the prevention of allograft rejection.

Animals↗
PubMed1990

Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein. I. Relation between fibrin and immobilization of apo B-containing lipoprotein.

The lipid that accumulates in some fibrous atherosclerotic lesions appears to be derived from plasma low density lipoprotein (LDL). An early stage in lipid accumulation may be immobilization of a fraction of the LDL, and this is released by incubation with proteolytic enzymes, of which the most effective is the fibrinolytic enzyme, plasmin. We have examined the relationship between release of fibrin degradation products (FDP) and LDL in controlled plasmin incubations of 42 samples of normal intima and atherosclerotic lesions from aortas of 10 patients. In three patients (group 1) no LDL was released from any of the 11 tissue samples although they comprised lesions as well as normal intima. In 2 more patients (group 2) LDL was consistently low. However, in 5 patients (group 3) substantial amounts of LDL were released from all 21 tissue samples, and there was a significant correlation between the amounts of FDP and LDL (P less than 0.001). In spite of this correlation there were marked differences in the ratio FDP/LDL, but analysis by SDS-polyacrylamide gel electrophoresis and immuno blotting of the FDP released showed no consistent pattern related to LDL binding. Although the ratio FDP/LDL showed a 4-fold range, in 6 lesions subjected to successive 2-h incubations with plasmin the ratio within each lesion remained constant, supporting the concept that fibrin and LDL are linked.

Aged↗
PubMed1990

Social support and pregnancy outcome.

A total of 509 women with a history of a low-birthweight (LBW, less than 2500 g) baby were recruited from the antenatal booking clinics of four hospitals and randomized to receive either a social support intervention in pregnancy in addition to standard antenatal care (the intervention group) or standard antenatal care only (the control group). At recruitment to the study, mean gestational age was 6 weeks, mean maternal age was 28.0 years, 86% of the women had one previous LBW baby, 11% had two and 2% had had three or more. The study population was socially disadvantaged: 77% of the women were working class, 18% had unemployed partners and 41% were smoking at booking. Social support was given by four research midwives in the form of 24-h contact telephone numbers and a programme of home visits, during which the midwives provided a listening service for the women to discuss any topic of concern to them, gave practical information and advice when asked, carried out referrals to other health professionals and welfare agencies as appropriate, and collected social and medical information. Pregnancy outcomes were assessed using obstetric case-note data (obtained for 507 women) and a postal questionnaire sent to all mothers 6 weeks after delivery (94% replied). Babies of intervention group mothers had a mean birthweight 38 g higher than that of control group babies; there were fewer very low-birthweight babies in the intervention group.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude to Health↗
PubMed1990

Improved silver staining of nucleolar organiser regions in paraffin wax sections using an inverted incubation technique.

A new simple modification to the silver staining of nucleolar organiser regions (AgNORs) was devised which, by performing the incubation with the slide inverted, results in minimal undesirable background staining, a persistent problem. Inverted incubation is facilitated by the use of a commercially available plastic coverplate. This technique has several additional advantages over other published staining protocols. In particular, the method is straightforward, fast, and maintains a high degree of contrast between the background and the AgNORs.

Humans↗
PubMed1989

Cerebral palsy among children born during the Dublin randomised trial of intrapartum monitoring.

In a randomised trial involving 13,079 liveborn children intrapartum care by electronic fetal heart rate monitoring, with scalp blood sampling when indicated, was associated with a 55% reduction in neonatal seizures. Reassessment, when aged 4, of the 9 children in the intensively monitored group and 21 in the control group who survived after neonatal seizures showed that 3 such children in each group had cerebral palsy. A fourth child in the intensively monitored group with cerebral palsy had had transient abnormal neurological signs during the neonatal period. 8 other children in the intensively monitored group and 7 in the control group who had not had abnormal neurological signs in the neonatal period also had cerebral palsy. 16 (78%) of the total of 22 cases of cerebral palsy had not shown clinical signs suggestive of intrapartum asphyxia. Thus, compared with intermittent intrapartum monitoring, intensive monitoring has little, if any, protective effect against cerebral palsy.

Asphyxia Neonatorum↗
PubMed1989

Routine formal fetal movement counting and risk of antepartum late death in normally formed singletons.

The routine recommendation to women to count fetal movements daily during late pregnancy for the prevention of antepartum late fetal death in normally formed singletons has been evaluated. 68,000 women were randomly allocated within thirty-three pairs of clusters either to a policy of routine counting or to standard care, which might involve selective use of formal counting or informal noting of movements. Antepartum death rates for normally formed singletons were similar in the two groups, regardless of cause of prior risk status. Despite the counting policy, most of these fetuses were dead by the time the mothers received medical attention. The study does not rule out a beneficial effect, but at best, the policy would have to be used by about 1250 women to prevent 1 unexplained antepartum late fetal death, and an adverse effect is just as likely. In addition, formal routine counting would use considerable extra resources.

Belgium↗
PubMed1989

The 'Know Your Midwife' scheme--a randomised trial of continuity of care by a team of midwives.

A team of four midwives provided the majority of care during pregnancy, labour and the puerperium to 503 women at low obstetric risk, over a 2-year period. Compared with standard hospital care randomly allocated to 498 women this 'Know Your Midwife' scheme was associated with greater continuity in all phases of maternity care. The scheme appeared very acceptable to women: they spent less time in the antenatal clinic, and overall, felt more satisfied, better prepared and better able to discuss problems. The scheme was characterised by less obstetric intervention particularly in respect of augmentation of labour and intrapartum analgesia; labours tended to be longer. Neonatal outcome was generally similar in the two groups but the size of the trial did not allow a precise assessment of differential effects in these terms. The 'Know Your Midwife' scheme is feasible. It should now be introduced more widely but in a way which allows continuing evaluation.

Continuity of Patient Care↗