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Biomedical subjects

K A Ward

Publications and source records attributed to K A Ward.

85 records · Page 5Linked to original sources

Inhibition of wool follicle DNA synthesis by mimosine and related 4(1H)-pyridones.

The in vitro incorporation of [3H]thymidine has been examined in thin slices of sheep skin. Most of the radioactivity (88%) was incorporated into the bulb cells of the wool follicles, and the technique is therefore suitable for the study of some aspects of wool follicle DNA synthesis. The effect of mimosine and a number of related 4(1H)-pyridones on [3H]thymidine incorporation into sheep skin slices was examined. Mimosine was shown to inhibit the incorporation at a concentration of 0-2 mM. At this concentration, the incorporation of [3H]uridine or [14C]leucine was not affected. The inhibition of [3H]thymidine incorporation was time dependent, 2 h of incubation being required for maximal inhibition of DNA synthesis, and was readily reversible by removal of mimosine from the incubation medium. The 3-hydroxyl-4-oxo function of the pyridone ring appears to be directly involved in DNA synthesis inhibition. The amino acid side chain is not a toxophoric centre, but changes in its polarity have been shown to affect the inhibitory activity. The results suggest that the primary action of mimosine on the inhibition of wool biosynthesis in vivo is the inhibition of follicle bulb cell DNA synthesis and consequently of cell division.

Animals↗

Preparation of metabolically active cell suspensions from wool roots.

A method is described for the preparation of metabolically active cell suspensions from plucked wool roots using the proteolytic enzyme trypsin. The suspensions consist of a heterogeneous population of cells which appear similar in morphology to follicle bulb cells, differentiating keratinocytes and possibly cells of the inner root sheath. The concentrations of trypsin and of inorganic ions for optimum activity of the suspensions have been determined, and the inclusion of EGTA was found to increase the yield of cells. The cell suspensions incorporate [14C]leucine, [3H]uridine and [3H]thymidine into acid-insoluble products, and are sensitive to the action of cycloheximide and emetine, but not to chloramphenicol or rifampin. Autoradiography has shown that the cells believed to be derived from the follicle bulbs show the greatest activity.

Animals↗

The composition of rat liver microsomes. The structural proteins of rat liver microsomes.

1. The structural-protein component of microsomal membranes was isolated by three separate methods. Analysis by polyacrylamide-gel electrophoresis indicated that the microsomal structural component is made up of a heterogeneous group of proteins. These proteins were further characterized by their phospholipid-binding capacity. The electrophoretic patterns of microsomal structural proteins were found to differ significantly from those of mitochondrial structural proteins. 2. The reticulosomal fraction was also characterized by electrophoresis with reference to total microsomal proteins, microsomal structural proteins and ribosomal proteins. The reticulosomes gave an electrophoretic pattern significantly different from those of the other three preparations examined. It is suggested that reticulosomes consist largely of enzymic proteins of the endoplasmic reticulum.

Animals↗

Detection of human papillomavirus by the polymerase chain reaction in histologically normal penile skin adjacent to penile warts.

BACKGROUND AND OBJECTIVES: Anogenital warts frequently recur following ablative treatment, and in the female, has been attributed to the presence of latent HPV infection outside the treatment margins. GOAL OF THIS STUDY: To determine whether HPV DNA sequences were detected by PCR in histologically normal penile skin adjacent to penile warts and to correlate recurrence of warts following surgical ablation to the presence of HPV DNA in histologically normal penile skin. STUDY DESIGN: Prospective cohort study of 25 heterosexual men with penile warts. Biopsies of clinically healthy penile skin 1 cm from the nearest penile lesion (wart with/without surrounding acetowhite changes) were processed for histology and HPV DNA analysis. The penile wart was processed for HPV DNA analysis only. Recurrence of penile warts was correlated to HPV status of adjacent histologically normal penile skin using Fisher's exact test (FET). RESULTS: Sequences homologous to HPV DNA were detected in 77% of biopsies of histologically normal penile skin. Agreement in HPV DNA type between penile wart and the adjacent histologically normal penile skin was only 30%. Recurrence of warts was noted in 46% of men by 16 weeks, and was not predicted by the detection of HPV DNA in the adjacent histologically normal penile skin (P = 0.16, FET). CONCLUSIONS: These findings suggest that extending the treatment margins 1 cm beyond the visible lesion is ineffective in eradicating the virus and preventing recurrence of warts.

Adolescent↗

Effect of enteral diets on whole body and gut growth in unstressed rats.

The composition of enteral feeding formulas may have different effects on total body and gut growth. We studied the growth effects in rats of a complex solid fiber-based diet (Prolab Rodent Diet) with that of three isocaloric and isonitrogenous commercially available liquid feeding formulas which differ in their type of protein (Osmolite HN, an intact protein formula; Reabilan HN, a peptide formula; and Vivonex-TEN, an amino acid formula). Total body weight gain was greatest with the rodent diet (93 +/- 2 g/10 days), followed by the peptide diet (72 +/- 5 g/10 days) and intact protein diet (58 +/- 8 g/10 days). Weight gain was significantly lower on the amino acid diet (43 +/- 7 g/10 days). Proximal and mid gut mass was comparable with all four diets, but distal gut mass was significantly lower with the amino acid diet. Somatomedin C levels on the rodent diet (13.3 +/- 1.8 nM), and the peptide diet (14.0 +/- 3.3 nM) were significantly higher than somatomedin C levels on the amino acid diet (8.0 +/- 1.0 nM). Somatomedin C levels on the intact protein diet (9.6 +/- 1.4 nM) were intermediate between the rodent diet and amino acid diet. We conclude that growth effects vary with different enteral diets (unrelated to total calories and protein) and may result from differences in the generation of tissue growth factors.

Amino Acids↗

The role of early colposcopy in the management of females with first episode anogenital warts.

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically-confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear (P < 0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

Adolescent↗

Response of tumours to hyperglycaemia: characterization, significance and role in hyperthermia.

The response of both neoplastic and surrounding normal tissue to hyperthermia is influenced by a number of physical, physiological, biological and immunological factors. Two physiological factors that play an important role are blood flow and pH. Temperature distributions within neoplastic and surrounding normal tissue during hyperthermia are influenced by convective heat transfer between the blood and tissue bed. A number of in vitro studies have illustrated that lowering media pH sensitizes cells to hyperthermia. It has been suggested that pharmacological agents could be used in conjunction with hyperthermia treatment to improve cancer treatment if these agents decrease tumour blood flow and/or decrease tumour pH. One agent that has been studied extensively for this purpose is glucose. The objective of this paper is to review the results on the effect of hyperglycaemia on normal and tumour tissue blood flow and pH and its role in hyperthermia. After a brief discussion of the role of tumour pH and blood flow in hyperthermia treatment, data available in the literature on the effect of hyperglycaemia on normal and tumour tissue blood flow and pH are reviewed. Finally, the role of hyperglycaemia in hyperthermia treatment is discussed, and various studies involving the combined treatment are summarized. Key unanswered questions and directions for future research are pointed out.

Animals↗

Perspective: cerebral palsy as a model of bone development in the absence of postnatal mechanical factors.

To ensure optimal skeletal development, mechanical loading is imperative. The consequences of the removal of, or complete absence of, mechanical loading are illustrated by the clinical condition of cerebral palsy (CP). Clinical and radiological evaluation of children with CP provides an insight into how the growing skeleton develops when mechanical loading is reduced due to non-physiological muscle function. The poor bone status or "physiologic osteopenia" that these children suffer is multifactorial compromised of both mechanical and non-mechanical effects; primarily it is the lack of normal loading from the musculature which causes the development of a bone incapable of withstanding daily activities. Fractures occur during daily activities such as dressing and handling. Increased bone resorption during periods of immobilisation after fracture or surgery, also increases bone fragility. Trials of physical, nutritional and pharmacological treatments in CP children result in increased bone mineral density. Trials that include fracture prevention as the primary end point are required in this vulnerable group of children.

Bone Development↗