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Biomedical subjects

D Sykes

Publications and source records attributed to D Sykes.

18 recordsLinked to original sources

Changes in transcripts of basement components during rat liver development: increase in laminin messenger RNAs in the neonatal period.

The expression of laminin and type IV collagen messenger RNA in rat liver was investigated in relation to liver development. Levels of messenger RNA for laminin chains A, B1 and B2, and alpha 1 and alpha 2 chains of type IV collagen were studied by Northern-blot and dot-blot analysis. Although the expression of messenger RNAs for laminin B1 and B2 chains was higher in 19-day gestational fetal liver when compared with the adult, the highest level was detected in 15-day newborns. This finding coincides with the final establishment of the mature liver. Laminin A messenger RNA was not detected in the 19-day gestational fetus or in the neonatal period. In contrast, alpha 1-(IV) and alpha 2-(IV) collagen messenger RNAs maintained high levels in the early neonate and then decreased gradually after 15 days. Our findings suggest that during late stages of liver ontogeny the main components of liver basement membrane proteins undergo a significant alteration in their synthesis. The data further suggest that laminin may play a role in the final stages of hepatic differentiation.

Animals

Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people.

An oral glucose tolerance test (OGTT, 75 g WHO criteria) was applied to healthy elderly subjects (mean age 76 years) within a week of measurement of random blood glucose and glycosylated haemoglobin (HbA1). The 'Corning' method was used to assay HbA1 (established normal range for our laboratory 5-8%). Sixty-five subjects (38 women) of whom 54 were not diabetic on WHO criteria for OGTT participated in the study. Five of the 54 patients with non-diabetic OGTT results had abnormal HbA1 (greater than 8%). These five subjects had no evidence of impaired glucose tolerance. Eleven subjects had diabetic OGTT results of whom only four had raised HbA1 assay results. Seven subjects had normal HbA1 in spite of diabetic OGTT. The mean HbA1 in the group of subjects with normal OGTT (n = 52) was 6.7% (SD 1.05, range 4.6-8.7%). It appears from our study that the normal range of HbA1 in elderly subjects is not markedly different from established normal values. The poor sensitivity (36%) and predictive value (44%) of abnormal HbA1 in detecting diabetes, as shown in our study, would not permit its use for screening purposes nor as a confirmatory test for diabetes in elderly subjects.

Aged

The effect of hemiplegia on blood pressure measurement in the elderly.

The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable.

Aged

The truncated glucocorticoid receptor in the P1798 mouse lymphosarcoma is associated with resistance to glucocorticoid lysis but not to other glucocorticoid-induced functions.

Glucocorticoid receptors in lines of the P1798 mouse lymphosarcoma either sensitive or resistant to glucocorticoid-induced lysis have been characterized and their functional significance determined. The glucocorticoid receptor from the cortisol-sensitive tumor is an Mr approximately 98,000 protein with a Stokes radius of 7.4 nm in the oligomeric, non-DNA-binding state and 5.6 nm in the transformed, DNA-binding state. This receptor binds glucocorticoid and reacts with the BUGR-2 monoclonal antibody. In contrast, two abnormal receptor species were identified in the cortisol-resistant tumor. One is an Mr approximately 98,000 non-steroid-binding but immunologically reactive protein. The other is an Mr approximately 45,000 species which contains both steroid- and DNA-binding sites but exhibits little or no reactivity with BUGR-2, suggesting that its NH2 terminus is truncated in a region within or adjacent to the BUGR epitope. This species had Stokes radii of 5.8 and 3.5 nm in nontransformed and transformed states, respectively. In both tumor lines, glucocorticoids stimulated the activities of glutamine synthetase and 5'-nucleotidase and the synthesis of glucocortin. However, glucocorticoid-induced tumor regression occurred only in the cortisol-sensitive tumor. Additionally, the glucocorticoid inducibility of a specific protein in the sensitive, but not in the resistant, tumor was demonstrated, as well as the presence of a protein specific to the resistant line. Taken together, these results suggest that the truncated glucocorticoid receptor in the P1798 lymphosarcoma is functional, although possibly in a more restricted gene-specific manner, and that the lysis defect, while possibly resulting from a truncated receptor, may also result from the inability of glucocorticoids to induce a critical protein in the pathway of programmed cell death and/or from the presence of a protein which inhibits the lytic response.

5'-Nucleotidase

Opportunistic screening of visual acuity of elderly patients attending outpatient clinics.

A standard Snellen letter chart was used to screen the visual acuities of 202 elderly patients while they attended outpatients clinics. Patients overestimated the adequacy of their vision: only 34 patients reported inadequate vision while 72 had significant measured visual impairment. Of these, 30 patients had refractive errors and 42 primarily non-refractive problems. Thirty patients were examined by an ophthalmologist, of whom 24 had previously undiagnosed conditions. Eighteen patients had treatable conditions, predominantly cataracts and glaucoma. Ten patients with untreatable conditions had the benefit of a definitive diagnosis, most commonly of age-related macular degeneration, and an assessment of eligibility for registration of blindness. The routine assessment of elderly patients should include objective screening of their visual acuity.

Aged

Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?

OBJECTIVE: To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN: Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING: Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS: 50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES: Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS: Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS: The findings suggest that in the presence of atrial fibrillation physicians' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.

Aged

Patient-controlled analgesia in postoperative pain: the relation of psychological factors to pain and analgesic use.

The surgical experience is often characterized by fear, stress, and pain. Whenever an individual has to confront a painful or stressful event such as surgery, the individual's opportunity to control some aspect of the situation may actually influence the degree of pain experienced. Patient-controlled analgesia (PCA) is a relatively new method of analgesic administration that allows the postoperative patient to self-administer analgesic drug. The present study examined the relationship of psychological variables, including anxiety, depression, coping strategies, and social support, to pain and PCA use in a sample of 80 adults who underwent orthopaedic surgeries. Regression analyses controlling for age and type of opioid revealed that the psychological measures were important predictors of pain and PCA use. Patients with higher anxiety levels and less social support had higher postoperative pain and made more frequent PCA demands.

Age Factors

Isolation and characterization of cortisol-sensitive and -resistant P1798 mouse lymphosarcoma cell lines.

Three cell lines have been isolated and characterized from the P1798 mouse lymphosarcoma. One line, derived from a glucocorticoid-resistant tumor, was glucocorticoid-resistant in vitro. The other two cell lines, derived from glucocorticoid-sensitive and -resistant parental tumors, respectively, were shown to be glucocorticoid-sensitive in vitro. The glucocorticoid receptor from all three cell lines bound glucocorticoid with similar affinity and capacity. However, based on Sephacryl S-300 gel filtration, the glucocorticoid receptor from the resistant cell line was smaller than that of the two sensitive cell lines. Moreover, the glucocorticoid receptor from the resistant cell line accumulated to a greater extent in the nucleus. This resistant cell line thus resembles the nti variant of the S49 lymphoma cell line. All three cell lines were tumorigenic and metastatic when reimplanted into mice, contained the normal mouse diploid complement of 40 chromosomes and exhibited the same responsiveness to cortisol in vivo as they did in vitro. It is concluded that the ready passage of these cell lines in vitro or in vivo and the presence of the small receptor in the resistant line should make them excellent model systems for the study of glucocorticoid resistance.

Animals

Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro.

A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.

Autolysis

Factors influencing total cholesterol and high-density lipoprotein cholesterol concentrations in a population at high coronary risk.

Serum total cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 1122 men and 1147 women aged between 25 and 64 years during the first Belfast MONICA survey, and the results subjected to multiple regression analysis. In both men and women, total cholesterol increased with age. Although HDL-cholesterol showed little variation with age, the values were considerably higher in women than men. Total cholesterol increased with body mass index while HDL-cholesterol decreased, and these findings persisted after adjustment for age. Regular exercise was associated with higher HDL-cholesterol values, even after adjustment for age and body mass index. Among men and women who abstained from alcohol, lower values of HDL-cholesterol were observed. In both sexes, cigarette smoking was associated with significant increases in total cholesterol values and decreases in HDL-cholesterol values, though some of these findings became apparent only after adjustment for other relevant factors. Perhaps surprisingly, a measure of health knowledge showed no association with blood lipid concentrations.

Adult

Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro.

Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.

Alginates

Immunoglobulin E-dependent stimulation of human alveolar macrophages: significance in type 1 hypersensitivity.

Human alveolar macrophages were obtained during diagnostic bronchoalveolar lavage. Cells were cultured, and morphological examination (including electron microscopy) revealed that not more than 5% of the cultured cells were identifiable as cells other than alveolar macrophages. The cells were sensitized with human myeloma immunoglobulin E. and then challenged with anti-immunoglobulin E anti-sera. The experiments employed a highly specific monoclonal antibody and three affinity purified reagents. The formation of immunoglobulin E/anti-immunoglobulin E complexes facilitated release from alveolar macrophages of leukotriene B4, prostaglandin F2 alpha, thromboxane B2 and the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase. There was no release of active oxygen species, with this stimulus, as measured by lucigenin chemiluminescence. Immunoglobulin E receptors were identified histochemically on the surface of human alveolar macrophages, and were visualized as conjugates with colloidal gold by electron microscopy. These results support the view that human alveolar macrophages may contribute to type 1 hypersensitivity reactions in the lung.

Asthma