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Biomedical subjects

J Gregory

Publications and source records attributed to J Gregory.

At least 55 records · Page 3Linked to original sources
PubMed1994

Immunohistochemical localization of parathyroid hormone-related protein (PTHrP) in human term placenta and membranes.

Parathyroid hormone-related protein (PTHrP), the major factor responsible for hypercalcaemia of malignancy, is widely expressed in normal adult and fetal tissues. In this study, the distribution of PTHrP was examined in human term placenta and membranes by immunohistochemistry using antisera to PTHrP 1-34 and 37-67. PTHrP was detected in cuboidal epithelial cells of amnion and in cytotrophoblastic cells of chorionic laeve and adherent maternal decidua. In placenta, PTHrP 1-34 was detected in the syncytiotrophoblast, while PTHrP 37-67 activity was mainly present in the brush border of the syncytiotrophoblast. This study also identified PTHrP 37-67 associated with fetal vessels of placental villi. These findings may reflect the cellular distribution of intact PTHrP or sub-fragments derived by post-translational processing. Postulated actions of PTHrP in the uteroplacental unit include transport of calcium across the placenta, stretch of membranes, inhibition of uterine contractility, growth and differentiation, and vasoregulation.

Amnion↗
PubMed1994

Total energy expenditure and energy intake in the pre-school child: a comparison.

In a cohort (n 81) of healthy children aged 1.5-4.5 years, measurements of energy intake and energy expenditure were compared. Energy intake was calculated following a 4 d weighed record completed by the mother or guardian of the child. Total energy expenditure was measured using the doubly-labelled water technique. Mean energy intake and expenditure in the cohort were 4773 kJ/d and 4928 kJ/d respectively. The mean relative bias between the techniques was 154 kJ/d. In the older children (3.5-4.5 years) the mean relative bias was only 37 kJ/d. At the population level the measurements of energy intake and energy expenditure were extremely close, and the study has provided sufficient confidence in weighed intake methodology for it to be used in a major nationwide study of dietary intake and nutritional status of children aged 1.5-4.5 years.

Age Factors↗
PubMed1994

Immunolocalisation of vascular endothelial growth factor in human endometrium.

Angiogenesis is an essential component of endometrial regeneration after menses in preparation for implantation. Vascular endothelial growth factor (VEGF) is a secreted angiogenic peptide with mitogenic activity specific for endothelial and trophoblast cells. VEGF-immunoreactivity was detected in glandular epithelium throughout the menstrual cycle by immunohistochemistry, but, showed cyclic variation in the stroma and the blood vessels. During the early proliferative phase, strong staining was seen in the glandular epithelial cells while staining in the stroma was confined to a subpopulation of stromal cells and endometrial blood vessels appeared negative. In contrast, very intense staining of the endometrial stromal cells was seen in the mid proliferative endometrium possibly due to increased synthesis of VEGF by oestrogen. In the late proliferative endometrium, staining was seen in the endothelial cells and the perivascular stromal cells around the endometrial blood vessels. The greatest degree of immunostaining of stromal cells was observed in the mid to late proliferative endometrium. Throughout the secretory phase no staining was seen around the endometrial blood vessels and staining of endometrial stromal cells was confined to early secretory endometrium. In the late secretory endometrium only the glands were positive to VEGF antibody. The observed increase in the immunostaining of stroma suggests increased production of VEGF from early to mid and late proliferative endometrium which parallels the increase in the oestradiol levels in the proliferative phase of the menstrual cycle. It is proposed that VEGF may serve as a paracrine mediator of the effects of ovarian steroids on endometrial vascular development.

Adult↗
PubMed1993

Occupation of low-affinity cholecystokinin (CCK) receptors by CCK activates signal transduction and stimulates amylase secretion in pancreatic acinar cells.

Based on the effects of monensin on binding of 125I-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of 125I-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors.

Amylases↗
PubMed1993

Ciliary ultrastructure in nasal brushings.

Normal ciliary ultrastructure is thought to be necessary for effective function. There has been little or no attempt to quantify ultrastructural abnormalities in nasal disease and assess their significance. In this study we measured nasal ciliary function and examined ciliary ultrastructure in nasal brushings from 35 patients with perennial nasal symptoms refractory to treatment. Ultrastructural defects included microtubular abnormalities, compound cilia and ciliary 'blebs'. The incidence of abnormal cilia was 16.7%, compared with 9% in controls, but there was only a poor correlation between ultrastructural defects and ciliary beat frequency. One patient had primary ciliary dyskinesia (PCD) with a typical clinical history and immotile cilia. However, only secondary ultrastructural abnormalities were seen. We have been unable to show that ciliary ultrastructural defects form the basis of impaired function. In patients with suspected PCD, nasal brushings should be taken for functional and ultrastructural studies; ideally, a further sample should be obtained for examination of possible primary ultrastructural abnormalities.

Cilia↗
PubMed1993

11 beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon.

In the rat kidney 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) maintains normal in vivo specificity for mineralocorticoid receptor (MR) by converting the active steroid corticosterone to inactive 11-dehydrocorticosterone, leaving aldosterone to occupy the MR. Clinical observations support the hypothesis that 11 beta-HSD also protects the distal colonic MR from glucocorticoid excess. We have measured 11 beta-HSD mRNA and activity along the rat colon and have analyzed the distribution of 11 beta-HSD, MR, and glucocorticoid receptor (GR) mRNA within rat distal colon using in situ hybridization. Levels of 11 beta-HSD mRNA (1.7 and 3.4 kb) and activity were higher in distal vs. proximal colon, paralleling reported MR mRNA levels. Within the distal colon mucosa both 11 beta-HSD immunoreactivity and mRNA was observed in cells in the lamina propria but not in epithelial cells. MR mRNA was present in surface epithelial cells, but was also colocalized with the same 11 beta-HSD-expressing cells in the lamina propria. In contrast GR mRNA was more uniformly distributed. The localization of MR mRNA to nonepithelial cells in the lamina propria, possibly neuroendocrine cells, suggests that mineralocorticoid-regulated sodium transport across colonic epithelial cells may also involve a paracrine mechanism. As with the kidney, exposure of active mineralocorticoid to the MR in these cells in the lamina propria is dictated by 11 beta-HSD in an autocrine fashion.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

Toothbrushing and transient bacteremia in patients undergoing orthodontic treatment.

This study was made to determine whether and to what extent bacteremia occurred after toothbrushing in patients undergoing orthodontic treatment with fixed appliances. Twenty patients were selected, all with negative history of heart or hematologic disorders. These patients had not taken antibiotics or had a history of a cold in the previous 30 days. Blood samples of 20 ml were drawn before and 5 minutes after brushing. The immune status of the patients was tested by measurement of isohemagglutins and immunoglobulin levels. Blood samples were incubated in paired culture bottles containing trypticase soy broth (TSB) with an agar paddle and Columbia broth. All samples taken before brushing were negative for bacteria. Five of the 20 patients (25% of the sample) had positive blood tests after brushing. Both anaerobic and aerobic bacteria were identified from the blood samples. Those patients who were found to have a bacteremia did not display poor oral hygiene.

Bacteriological Techniques↗
PubMed1991

Localization of renal 11 beta-dehydrogenase by in situ hybridization: autocrine not paracrine protector of the mineralocorticoid receptor.

In the kidney, 11 beta-dehydrogenase (11 beta-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11 beta-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid. Observations from these clinical studies indicate that 11 beta-DH conveys specificity for the mineralocorticoid receptor in distal tubules and collecting ducts. However, while some studies do indicate 11 beta-DH activity in rat distal tubules and collecting ducts, immunohistochemical studies localize 11 beta-DH only to proximal tubules. to resolve this dilemma, we have performed in situ hybridization localization of 11 beta-DH mRNA in rat kidney tissue using 35S-labeled sense and antisense cRNA probes to rat 11 beta-DH. In contrast to our immunohistochemical studies in which 11 beta-DH protein was localized predominantly to proximal tubules in the inner cortex, 11 beta-DH mRNA was expressed in tubules in both the inner and outer cortex, most probably proximal and distal tubules, and in collecting ducts extending across the corticomedullary junction to the papillary tip. Weak hybridization was also seen in glomeruli, but no hybridization to the sense 11 beta-DH cRNA or to sections pretreated with RNase-A was observed. We conclude that renal 11 beta-DH is suitably located to prevent access of glucocorticoid to the MR in an autocrine and not a paracrine fashion. 11 beta-DH in proximal tubules may protect the glucocorticoid receptor.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

Tissue plasminogen activator: hospital experience.

Tissue plasminogen activator (t-PA) is administered safely and efficiently in the treatment of acute myocardial infarction (MI). A study of 74 patients administered t-PA for acute MI associated with a low complication rate showed an acceptable patency rate, and a good outcome.

Adult↗
PubMed1990

Predicting death from initial disease severity in very low birthweight infants: a method for comparing the performance of neonatal units.

OBJECTIVES: To investigate (a) which clinical variables and physiological measures of disease severity best predict death in very low birthweight infants and (b) their use in comparing mortality between two neonatal units. DESIGN: Retrospective study of two cohorts of very low birthweight infants from overlapping time periods who received mechanical ventilation. SETTING: Two neonatal intensive care units (hospitals A and B). SUBJECTS: 262 Very low birthweight infants, 130 in hospital A, 132 in hospital B. MAIN OUTCOME MEASURE: Death in hospital. RESULTS: In hospital A the mean level of oxygenation in the first 12 hours of life, whether measured as inspired oxygen requirement (FIO2), arterial/alveolar oxygen (a/AO2) ratio, or alveolar-arterial oxygen difference (A-aDO2), was more closely associated with death than any of four "traditional" risk factors: low birth weight, short gestation, the diagnosis of respiratory distress syndrome, and male sex. Mean pH in the first 12 hours was as strongly associated with death as birth weight. Multiple logistic regression models were derived in infants from hospital A using the four traditional risk factors with measures of oxygenation and pH. The validity of each model was then tested in infants from hospital B. The model based on the four traditional risk factors alone predicted death in hospital B with only 31% sensitivity. Adding mean a/AO2 ratio and mean pH increased its sensitivity to 75%, and when mean a/AO2 ratio was replaced by mean FIO2 its sensitivity increased further to 81%. Based on crude mortality rates alone, the odds of death in hospital A versus hospital B were 0.67 (95% confidence interval 0.37 to 1.23). After correcting for traditional risk factors and mean FIO2 and mean pH, however, the odds of death in hospital A increased to 3.27 (1.35 to 7.92; p less than 0.01). This increased risk persisted after adjusting for the time difference between each cohort. CONCLUSIONS: Crude comparisons of hospital mortality can be highly misleading. Reliable assessment of neonatal outcome is impossible without correcting for major risk factors, particularly initial disease severity. International agreement on a minimum core dataset of clinical and physiological information could improve neonatal audit and help to identify effective treatments and policies.

Gestational Age↗
PubMed1990

Serum sialic acid and carcinoembryonic levels in the detection and monitoring of colorectal cancer.

Total sialic acid (TSA), total protein (TP), TSA normalized to total TP (TSA/TP), and carcinoembryonic antigen levels were determined in 146 consecutive colorectal patients. These results were compared with results from 73 people with nonmalignant gastrointestinal disease, and with results from 96 normal controls. All malignancies were staged according to the Astler-Coller modification of Dukes' classification for colorectal cancer. All blood samples were drawn before surgical therapy. The TSA/TP ratio for colorectal cancer was 13.4 (mg/gm) in contrast to 12.1 (mg/gm) for pathologic controls, and 9.7 (mg/gm) for normal controls. Student's t test showed a P value less than 0.001 for normal controls and a P value less than 0.001 for pathologic controls. The TSA/TP also showed statistical significance in Dukes A, B2, C, and D subgroups when compared with normal controls. There were only four patients with stage C1 carcinoma, thus statistical analysis would be questionable. In contrast, carcinoembryonic antigen levels showed no significant elevations until Dukes C2 tumors were encountered. These preliminary findings suggest that TSA/TP ratio may detect colorectal cancer patients with less tumor burden and be more beneficial as a tumor marker than CEA for monitoring patients with colorectal cancer.

Aged↗
PubMed1990

A further study of oxalate bioavailability in foods.

We extended the study of oxalate bioavailability by testing 7 additional food items: brewed tea, tea with milk, turnip greens, okra, peanuts and almonds. Nine normal subjects ingested a large serving of each of these items. The bioavailable oxalate was calculated from the increment in urinary oxalate during 8 hours after ingestion and bioavailability was determined as the percentage of total oxalate content in a given food item represented by bioavailable oxalate. Brewed tea and tea with milk, with a high oxalate content, had a low bioavailable oxalate level (1.17 and 0.44 mg. per load) because of the low oxalate availability (bioavailability of 0.08 and 0.03%). Turnip greens, with a satisfactory oxalate bioavailability (5.8%), had a negligible effect on urinary oxalate excretion, since oxalate content was relatively low (12 mg. per load). Okra, with a moderate oxalate content (264 mg. per load) had a negligible bioavailable oxalate (0.28 mg. per load). Only peanuts and almonds provided a moderate increase in oxalate excretion (3 to 5 mg. per load) due to the modest oxalate content (116 and 131 mg. per load) and oxalate bioavailability (3.8 and 2.8%). Thus, the ability of various oxalate-rich foods to augment urinary oxalate excretion depends not only on oxalate content but on the bioavailability.

Adult↗
PubMed1990

Caffeine ingestion prior to incremental cycling to exhaustion in recreational cyclists.

Nine male recreational cyclist served as subjects in this experiment which included a control, placebo and caffeine trial. The aim of the experiment was to determine whether a 10 mg.kg-1 dose of caffeine given three hours prior to an incremental cycle ergometer exercise test, for caffeine naive subjects, would increase the time to exhaustion and therefore increase the amount of work undertaken by the cyclists. The cyclists initially worked at 100 watts for three minutes and then increased the workload by 50 watts every three minutes until exhaustion. Blood was drawn at the beginning of the test and every three minutes from an ante-cubital vein and was analysed for blood lactate, glucose and free fatty acids (FFA). Respiratory analysis was also undertaken and heart rate was monitored throughout the test. Subjects in the caffeine trial worked significantly longer and performed more work (p less than 0.05) than they did in either the control or placebo trials. FFA's were also significantly higher in this trial (p less than 0.05) and the lactate threshold was moved to the right as a percentage of the VO2max, which suggests less acidity and a decreased bicarbonate flushing. The respiratory exchange ratio data was significantly lowered (p less than 0.05) during workloads between 250 and 450 watts. No changes were seen in blood glucose or heart rates during the experiment. In conclusion, we feel that a 10 mg.kg-1 dose of caffeine is an ergogenic aid during incremental exercise when it is taken 3-4 hours prior to the exercise in fasting subjects who have diets low in caffeine.

Adult↗
PubMed1990

Technical improvements in the immunoperoxidase study of renal biopsy specimens.

Sixty five renal biopsy specimens were used to compare a direct immunofluorescence technique on frozen sections with immunoperoxidase techniques on paraffin wax sections. For the immunoperoxidase techniques, dewaxed sections were treated with protease at 37 degrees C. Sections were examined at intervals on a microscope and digestion was stopped when plasma was removed from glomerular capillary loops. This permitted intense staining of immunoproteins on immunoperoxidase. There was agreement between immunoperoxidase and immunofluorescence in the staining for IgG, IgA, and IgM in 50 biopsy specimens and discordant findings did not affect the diagnosis. Immunoperoxidase did not detect C3 in 16 biopsy specimens. Findings with antiserum to another complement component, C9, detected by immunoperoxidase correlated with C3 findings detected by immunofluorescence in 17 biopsy specimens. It is concluded that microscopical observation of the progress of digestion permits optimal staining by immunoperoxidase methods, thus overcoming the problem of variability in proteolytic digestion of sections. Inconsistency in the demonstration of complement deposition can be avoided by staining for C9 rather than C3.

Complement C3↗
PubMed1990

Pharmacokinetic study of controlled-release choline theophyllinate in elderly patients.

Controlled-released choline theophyllinate tablets (Sabidal SR 270, Zyma) were administered to 17 elderly patients aged between 68 and 86 years (mean 76 +/- 7 years) until steady state was obtained. The dosage form was one tablet every 12 hours for four days. Plasma theophylline concentrations were measured by high-performance liquid chromatography after the first dose and during the fourth day for a 12-hour period. The tablets showed evidence of controlled-release properties: the maximum plasma concentration (10.8 +/- 2.5 mg/l) was obtained after 3.4 +/- 1.6 hours. The mean trough level was 6.6 +/- 1.5 mg/l and the difference between the peak and trough levels was 4.1 +/- 1.2 mg/l. The mean steady-state plasma theophylline concentration was 8.5 +/- 2.2 mg/l. The mean elimination half-life was 14 +/- 7 hours. The mean volume of distribution was 0.8 +/- 0.4 l/kg. The mean total body clearance was 0.05 +/- 1/h/kg. All values, the half-life excepted, were found to be within the ranges for the patients reported in the literature. The values show the usual interindividual variation.

Aged↗
PubMed1989

Effect of an inhaled mast cell stabiliser, N-acetyl-aspartyl-glutamate (Zy15109) on allergen-induced immediate bronchoconstriction.

We have studied the effect of a mast cell stabiliser, the magnesium salt of N-acetyl aspartyl glutamic acid (NAAGA) on allergen-induced immediate bronchoconstriction in 12 atopic subjects. Inhaled NAAGA, at a dose of 60 mg thrice daily for 1 week, offered no protective effect on the airways against allergen challenge when compared with a matched placebo. The drug was well tolerated with no adverse effects observed.

Adult↗