PubMed Health⌕ Search

Biomedical subjects

D Knowles

Publications and source records attributed to D Knowles.

32 records · Page 2Linked to original sources
PubMed1988

Detection of Anaplasma-marginale-infected tick vectors by using a cloned DNA probe.

Anaplasmosis is the most widely distributed of several important tick-borne diseases that constrain cattle production throughout much of the world. Evaluation of the effectiveness of disease control strategies that integrate vaccination with tick control requires the ability to monitor tick and cattle infection rates. To detect Anaplasma marginale in ticks and bovine erythrocytes, a 2-kilobase DNA fragment from a cloned A. marginale gene coding for a surface protein having a Mr of 105,000 was prepared and evaluated as a probe. The probe was species specific and detected A. marginale DNA derived from infected bovine erythrocytes and adult Dermacentor ticks infected either as nymphs or adults. Tick infection was confirmed by microscopy and test feeding on a susceptible calf. The sensitivity of the probe is suitable for detecting infected ticks in experimental and field epizootiology studies.

Anaplasma↗
PubMed1985

In vivo responses to Mycobacterium leprae: antigen presentation, interleukin-2 production, and immune cell phenotypes in naturally occurring leprosy lesions.

To investigate the immune defect in lepromatous leprosy we studied immune cell phenotypes, lymphocyte activation states, and interleukin-2 (IL-2) production in naturally occurring leprosy skin lesions. Mouse hybridoma monoclonal antibodies reacting with the IL-2 receptor (anti-Tac), unbound IL-2 (DMS-1), antigen-presenting Langerhans' cells (OKT6) and the OKT4-Leu3 and OKT8 T-lymphocyte subpopulations were used with indirect horseradish peroxidase and alkaline phosphatase techniques on frozen biopsy sections. The percentage of Tac+ lymphocytes and the number of OKT6+ cells in the epidermis and dermal granuloma were significantly correlated in naturally occurring lesions (correlation coefficient 0.79) and were higher in tuberculoid than in lepromatous lesions. Leu3 antigen was expressed by 70-90% of Tac+ cells in tuberculoid lesions. Although the percentage of cells producing IL-2 was low in lesions of both lepromatous and tuberculoid patients, it was about 15 times greater in tuberculoid than in lepromatous lesions (0.032 +/- 0.037 tuberculoid vs 0.0019 +/- 0.023 lepromatous). There was an association between the number of OKT6+ cells and the percentage of IL-2-producing cells, but the association was weaker than that of OKT6+ cells and the percentage of IL-2 receptor-bearing cells (r = 0.2), implying that IL-2 production is not an intervening variable in the latter association. The absolute number of OKT4-Leu3+ lymphocytes was significantly different in different clinical leprosy groups and was positively correlated with host resistance (mean OKT4-Leu3+ cells/mm2 in 6 micron sections; 1412 +/- 288 tuberculoid, 400 +/- 93 borderline lepromatous, 200 +/- 100 polar lepromatous; r = 0.95). Absolute numbers of OKT8+ cells/mm2 in lesions were not significantly different. We conclude that there is a relative paucity of OKT4-Leu3+ cells as well as IL-2-producing cells at the local level in lepromatous leprosy lesions. Possible functional relationships between these findings and the failure of macrophage activation and destruction of Mycobacterium leprae in lepromatous leprosy are discussed.

Adolescent↗
PubMedDate not supplied

Using DRGs in developing referral policies for coronary care within a local health district.

This paper presents the results of a study into some specific aspects of the management of coronary heart disease within one district health authority. In particular, it is concerned with the appropriate balance of inpatient coronary care between the district general hospital and community hospitals in the light of current and potential changes in the clinical management of coronary cases. The study is an example of a multidisciplinary approach to local health planning which is beginning to emerge within the Exeter Health District, the methodology of which may be applicable to client groups within the medical specialties other than coronary cases, such as strokes or respiratory disorders. It also illustrates the use of spatial analysis and diagnosis-related groups in local planning.

Coronary Care Units↗
PubMedDate not supplied

Fragmentation of the ribosome to investigate RNA-ligand interactions.

RNA molecules perform a variety of important and diverse functions and, therefore, an understanding of their structure and interaction with proteins and ligands is essential. Large RNA molecules (for example, the ribosomal RNAs) are complex and hence reports describing their fragmentation into functional subdomains has provided a means for their detailed analysis. We present here an in vivo approach to study RNA-ligand interactions. This is based on the concept that an RNA fragment could mimic a drug-binding site present on the intact molecule. Overexpression of the fragment would sequester the drug thereby permitting the continued functioning of the ribosome and, thus, ensuring cell viability. Accordingly, a fragment of 16S rRNA encompassing the spectinomycin-binding domain in helix 34 (nucleotides 1046-1065 and 1191-1211) was cloned and in vivo expression resulted in drug resistance. Furthermore, an RNA fragment lacking flanking sequences to helix 34 was also selected from among a pool of random rRNA fragments and shown to confer spectinomycin resistance. A similar in vitro approach is also described for the analysis of rRNA molecules that interact with the yeast elongation factor 3 (EF-3).

Anti-Bacterial Agents↗
PubMedDate not supplied

Monoclonal antibodies to E92, an endothelial cell surface antigen.

Two hybridoma-derived monoclonal antibodies have been developed that react with an antigen of molecular weight 92,000 daltons on the surface of human endothelial cells. Cultured human umbilical vein endothelial cells were used for immunization, but the antigen is present on arterial, venous and capillary endothelium, as determined by biotin-avidin immunoperoxidase staining of tissue sections. With this technique, other cell types in the tissues which were examined were not reactive, except for scattered fibroblasts and histiomonocytic cells, trophoblastic cells of the placenta, and benign immature mesenchymal cells in a renal cystadenocarcinoma. By cytofluorography, the antibodies were found to be unreactive with granulocytes, T lymphocytes, B lymphocytes, and the majority of monocytes. Fibroblasts were reactive with the antibodies, but the fluorescence tracings indicated a lower density of antigen on these cells than on endothelial cells. Immunoreactivity of fibroblasts could be decreased by treatment of the cells with thrombin, trypsin, or neuraminidase, whereas these enzymes did not affect the immunoreactivity of endothelial cells. The reactive antigen (E92) does not appear to be any of several previously described endothelial cell proteins, because of its molecular weight and its absence on other cell types. The presence of E92 on trophoblastic cells of the placenta and immature mesenchymal cells, as well as fibroblasts and endothelial cells, may indicate that it is a primitive antigen of mesodermal tissue that is lost by most cell types during differentiation.

Adenocarcinoma↗
PubMedDate not supplied

Clinical risk management.

Managing clinical risk involves all staff with clinical and managerial responsibilities. This article draws attention to some key steps in risk management and ways to deal with the problems when things do go wrong.

Clinical Competence↗