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Biomedical subjects

C Turner

Publications and source records attributed to C Turner.

At least 145 records · Page 8Linked to original sources

Actin-membrane interaction in focal adhesions.

Focal adhesions are regions of the plasma membrane where cells in tissue culture adhere strongly to the underlying extracellular matrix, and which at their cytoplasmic face serve to anchor bundles of actin microfilaments. They provide an experimental model for studying the links between the cytoskeleton and the extracellular matrix. Members of the integrin family of extracellular matrix receptors are prominent components, spanning the membrane in focal adhesions, but there is evidence that other membrane components are also needed for these structures to form. A number of proteins are concentrated at the cytoplasmic face of focal adhesions. Recent efforts have sought to determine the links between actin and the integrin cytoplasmic domains. Using in vitro binding assays, two potential bridges between actin and integrin have been identified. One involves talin, which has recently been shown to bind actin directly. The other involves the actin-binding protein, alpha-actinin, which has been found to interact with several integrins. The physiological significance of these two potential bridges between actin and integrin remains to be determined in vivo.

Actinin↗

Measurement of beta 2-microglobulin, retinol-binding protein, alpha 1-microglobulin and urine protein 1 in healthy children using enzyme-linked immunosorbent assay.

Enzyme-linked immunosorbent assays (ELISA) have been developed for the measurement of beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and urine protein 1 (UP1) in children. Results from random urine samples in 43 children (31 for B2M) are, when corrected for urine creatinine (geometric mean (range)): B2M 9.8 (6.0-40.7) micrograms/mmol, RBP 8.1 (less than 1-24.5) micrograms/mmol, A1M 0.4 (0.1-2.2) mg/mmol and UP1 17.8 (less than 2-309.4) micrograms/mmol. Fractional excretions (FE) in 23 children (14 for B2M) are (geometric mean (range)): FEB2M 0.04% (0.02-0.10%) and FEUP1 0.10% (0.01-1.21%). Results in overnight urine collections are also presented. Our results extend existing data for normal ranges in adults to include children and provide data on UP1 concentrations.

Adolescent↗

Dentists' voice control: effects on children's disruptive and affective behavior.

Voice control, a punishment technique based on loud commands, has been used widely in pediatric dentistry. This study examined whether (a) loudness is a necessary component of the technique, (b) voice control actually reduces children's disruptive behavior, and (c) after treatment, children's negative affect increases. Subjects were forty 3 1/2- to 7-year-olds who posed potential behavior problems and who were scheduled for cavity restoration. Children were assigned randomly to either loud- or normal-voice groups. Children who were assigned to either group but who were not disruptive formed a nonexperimental control group. Prior to and after treatment, children reported their feelings using the Self-Assessment Mannequin. Disruptive behavior was scored using the Behavior Profile Rating Scale. Results indicated that, following loud, but not normal voice commands, children reduced their disruptive behavior (p less than .004) and self-reported lower arousal (p less than .09) and greater pleasure (p less than .10). Theoretical and practical implications of these findings are discussed.

Arousal↗

Failure of benzene and phenol to serve as substrates for the peroxidatic action of catalase.

Evidence from several reports in the literature indicates a possible role for catalase in the metabolism of benzene. To investigate possible peroxidatic activity of catalase on benzene or its major metabolite, phenol, we employed an in vitro assay system that had been used previously to study the peroxidation of ethanol by catalase. Under conditions identical to those used to demonstrate catalase-mediated ethanol peroxidation we observed no peroxidase activity of catalase toward either benzene or phenol. We conclude that catalase is not involved in benzene metabolism and make the observation that, to date, no aromatic compounds have been demonstrated to be substrates for the peroxidatic mode of action of catalase.

Animals↗

Is alcohol a carcinogenic risk?

Consumption of alcoholic beverages has been implicated as a risk factor for the development of various cancers including oesophageal, oral, pharyngeal, laryngeal, liver and breast cancers. This article is a commentary on an earlier paper entitled 'Alcohol: a carcinogenic risk?' which challenges some of the evidence relating alcoholic beverage consumption to risk for these cancers. In the course of commenting on this paper, evidence is reviewed which shows a relationship between these cancers and consumption of alcoholic beverages, which is often found to be dose-related.

Alcoholic Beverages↗

How much alcohol is in a 'standard drink'? An analysis of 125 studies.

A group of researchers have undertaken a review of 125 international, published, epidemiological studies that relate various physical harms to different levels of alcohol consumption. For this review it was necessary to be able to compare the data from the different studies directly. The different measures of alcohol quoted in the studies were converted to the standard measure of grammes of alcohol. The present paper discusses the problems involved in doing this, and gives details of the conversion methods used.

Alcoholic Beverages↗

Prediction of acute renal failure after birth asphyxia.

Twenty-one babies of 34-41 weeks' gestational age with birth asphyxia (5 minute Apgar score less than or equal to 5 or umbilical artery pH less than or equal to 7.2) were studied during the first two days of life to find out whether the urinary excretion of tubular markers of renal function is of value in the early diagnosis of acute renal failure. Urinary retinol binding protein, myoglobin, and N-acetyl-beta-D-glucosaminidase (NAG), expressed as a ratio with urinary creatinine, were measured and excretion profiles repeated at 3-6 days in 15 infants and at 7-14 days in 11 infants. Plasma creatinine concentration, creatinine clearance, plasma myoglobin concentration, and fractional sodium excretion were measured where possible in asphyxiated infants. Control data were obtained from 50 healthy infants: 28 gave urine samples alone, 17 urine and blood, and five blood alone. Normal urinary values were derived from 17, 25, and three infants, respectively, for the three time periods. The number of control samples was limited for ethical reasons. Four asphyxiated infants had acute renal failure (group 1), four had tubular dysfunction without glomerular disturbance (group 2) and 13 had normal renal function (group 3). Group 1 were clearly identified by greatly increased urinary retinol binding protein (greater than 27,000 micrograms/mmol creatinine) and myoglobin (greater than 1500 micrograms/mmol creatinine) excretion measured in the first two days of life. In control infants the range of excretion of retinol binding protein within the same time period was 3 to 967 micrograms/mmol creatinine and urinary myoglobin was undetectable. Excretion of NAG failed to discriminate between groups 1 and 2. Acute renal failure occurred only in infants who had heavy myoglobinaemia. Tubular dysfunction in group 2 was transient and not accompanied by plasma electrolyte disturbances. We conclude that measurement of urinary excretion of retinol binding protein or myoglobin after birth is helpful in the early diagnosis of acute renal failure.

Acetylglucosaminidase↗

Quantitative microfocal radiography of children with renal osteodystrophy; comparison with laboratory and histological findings.

High definition microfocal radiography permitted the quantitative assessment of the radiographic features of renal osteodystrophy in the phalanges of 11 children in stable chronic renal failure, treated with phosphate binders for 1 year. The most consistent feature was subperiosteal cortical resorption, expressed as a ratio total length of resorbed subperiosteal bone/total length subperiosteal bone x 100. It was found that the extent of resorbed bone was significantly greater in the middle phalanx and on the ulnar surface of the phalanges. The radiological findings over the duration of the disease were compared with laboratory assessments and bone histomorphometry. The extent of the percentage of subperiosteal resorption at base line and its change during the study period correlated significantly with the level of serum parathyroid hormone levels and its change over the same period. No other significant correlations were found between radiographic features and laboratory assessments or with bone histomorphometry.

Adolescent↗

Modulation of sleep by trimipramine in man.

We have studied the acute effect of trimipramine (25, 50 and 75 mg) on nocturnal sleep in 6 young men. Fluoxetine (60 mg) and diazepam (10 mg) were included as controls for the potential changes in sleep measures. Trimipramine reduced awake activity, Stage 1 (drowsy) sleep, and the duration of rapid eye movement (REM) sleep. Non-REM (Stage 2) sleep was increased. Residual effects of trimipramine were present the next morning (9 h after ingestion) with impaired coding ability. The effects of trimipramine on sleep and daytime alertness are consistent with its complex pharmacological profile. Reduced wakefulness and sedation are most likely due to synergism between histamine H1, alpha 1-adrenoceptor, and dopamine receptor antagonism. Anticholinergic activity and possibly blockade of alpha 1-adrenoceptors would disturb the balance of transmitter activities which facilitates the optimal appearance of REM sleep. In this way the effects of trimipramine on nocturnal wakefulness and REM sleep are similar to drugs which inhibit the uptake of noradrenaline.

Adult↗

Exposure to 1 ppm ozone attenuates the immediate antigenic response of canine peripheral airways.

The effect of oxidant exposure on the immediate airway response to immunologic challenge is controversial. We investigated the response of canine peripheral airways to antigen aerosol, 1-3 h and 24 h after a 5-min exposure to 1 ppm ozone. In dogs that were natively sensitive to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using the wedged bronchoscope technique. In eight dogs, four sublobar segments of each lung were wedged: two were exposed to ozone for 5 min and two (control) received air with 5% CO2. Ozone caused a mean ( +/- SE) increase in Rcs of 75 +/- 15%, which returned to baseline after 1-3 h. The increase in Rcs elicited by subsequent administration of antigen aerosol (25 microliters, 0.27 mg protein/ml) to the ozone-exposed segments (312.0 +/- 70.6%) was attenuated by 22% compared to controls (398.9 +/- 83.0%; p less than .05). In another series of experiments (n = 5), segments were exposed to ozone or air and challenged with antigen 24 h later and a significant attenuation (38%) of the antigen-induced increase in Rcs was detected compared to controls (178.5 +/- 57.9 vs 289.0 +/- 62.2; p less than .05). Cellular influx of polymorphonuclear leukocytes (PMNs) was not detected by bronchoalveolar lavage (BAL) 1-3 h after ozone, but was found after 24 h (19.8 vs. 4.7%; p less than .01). A significant increase in PMNs was detected in exposed subepithelial tissues 1-3 h after ozone compared to unexposed tissues. Tissue PMNs were not significantly different from unexposed tissues after 24 h, but a shift toward degranulation of mast cells was detected in ozone-exposed tissues at this time. These data suggest that the Rcs response to antigen is attenuated 1-3 h and 24 h after acute (5 min) exposure to 1 ppm ozone, and this effect occurs independently of PMNs in the airways.

Administration, Inhalation↗

Renal tubular proteinuria and microalbuminuria in diabetic patients.

The urinary extraction of albumin, retinol binding protein, and N-acetyl-beta-D-glucosaminidase were studied in 60 children with insulin dependent diabetes mellitus and in 45 normal children to find out whether the renal tubules played a part in causing the early increase in urinary excretion of albumin that occurs in diabetes mellitus. Two overnight urine samples were collected and the protein excretion measured and expressed as the geometric mean of the protein to creatinine ratio (urinary albumin:creatinine ratio, urinary retinol binding protein:creatinine ratio, and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, respectively). The excretion of all three proteins was significantly higher in the diabetic children with 15 (25%) of urinary albumin:creatinine ratio, 16 (27%) of urinary retinol binding protein:creatinine ratio, and 43 (72%) of urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio values being above the normal range. Significant correlations were observed between urinary albumin:creatinine ratio and urinary retinol binding protein:creatinine ratio, urinary albumin:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, and urinary retinol binding protein:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio. There were also significant correlations between glycated haemoglobin 1c (HbA1c) and these proteins, especially N-acetyl-beta-D-glucosaminidase. No correlations were observed with the fractional excretion of sodium, flow rate of urine, glomerular filtration rate, or blood pressure. These data show that tubular abnormalities are present early in the course of insulin dependent diabetes mellitus and suggest that the early increase in urinary excretion of albumin may be at least partly tubular in origin, and that glycaemic control may influence this aspect of proximal tubular function.

Acetylglucosaminidase↗

Safety and efficacy of calcium carbonate in children with chronic renal failure.

The safety and clinical efficacy of calcium carbonate therapy in children with chronic renal failure were assessed in 68 patients (average age 8.38 years) during a mean follow-up period of 19.9 months (range 1.2-49.4). Forty-seven episodes of hypercalcaemia occurred in 29 children (3.5 episodes per 100 patient-months). There were no significant differences in mean GFR or biochemical parameters between these patients at the start of calcium carbonate therapy and the group of children who never experienced hypercalcaemia. Good control of secondary hyperparathyroidism and a significant reduction in serum aluminum were achieved. Two of 23 hypercalcaemic patients showed nephrocalcinosis on ultrasonography. 99Tc pyrophosphate scanning failed to detect any other ectopic calcification. The incidence of hypercalcaemia increased significantly when the GFR was less than 15 ml/min per 1.73 m2 and was most frequent in children receiving dialysis (48 episodes per 100 patient-months). The decrease in GFR during therapy was significantly more in the hypercalcaemic group compared to the normocalcaemic group (P less than 0.01), despite no irreversible acute effects of hypercalcaemia being observed on the rate of decline of GFR. We believe that the reduced renal homeostatic reserve is a major factor predisposing to hypercalcaemia. Consequently calcium carbonate is safe to use in children with severe chronic renal failure with close biochemical monitoring; the benefits over aluminium phosphate binders far outweigh the risks of hypercalcaemia and ectopic calcification.

Adolescent↗

Immunohistochemical staining and radionuclide imaging of canine tumors, using a monoclonal antibody recognizing a synthetic carbohydrate antigen.

The in vitro and in vivo binding of a monoclonal antibody (MAB) that recognizes a tumor-associated carbohydrate antigen was studied in dogs. Monoclonal antibody 155H.7 was raised in response to innoculation of mice with beta-galactose(1-3)beta N-acetylgalactosamine conjugated to human serum albumin. Avidin-biotin-complex immunohistochemical staining of cryostat sections of normal and neoplastic canine tissue specimens revealed heterogenous binding of MAB 155H.7 to the cells of many canine mammary and lung carcinomas and homogenous staining of many sarcomas, including osteogenic sarcoma. In addition, there was variable staining of a variety of normal tissues including some ductual epithelium, peripheral nerve fibers, and some endothelial cells and fibroblasts. Immunoscintigraphy with 131I-labeled MAB 155H.7 was used to study the in vivo distribution of the antibody. The 131I-labeled MAB 155H.7 was administered to 1 clinically normal dog, 7 dogs with osteogenic sarcoma, 1 dog with undifferentiated sarcoma, and 2 dogs with mammary tumor. Scintigraphy revealed concentration of radioactivity in 8 of 10 tumor sites within 24 hours after MAB administration. The ratio of 131I in tumor sites to 131I in the surrounding normal tissues, compared with the similar ratio of 99mTc-labeled erythrocytes ranged from 1.1 to 4.3, in tumor vs normal tissue with a mean value of 2, confirming tumor localization of the radiolabeled MAB in excess of that associated with enhanced tumor vascularization.

Animals↗

Efficacy of brachytherapy with californium-252 neutrons versus cesium-137 photons for eradication of bulky localized cervical cancer: single-institution study.

A fast-neutron-emitting radioisotope, 252Cf, is being tested in clinical trials of neutron brachytherapy for cervical cancer. The efficacy for histological eradication of bulky stage IB cervical tumors (mean diameter, approximately 6 cm) using combined radiation and surgery was studied in 65 patients treated with 137Cs or 252Cf before surgery during 1983-1986. Forty-four patients were treated with 137Cs and 21 were treated with 252Cf at equivalent doses of radiation. Fifteen of the 44 specimens (34%) were positive after 137Cs therapy. Only one of the 21 specimens was positive after 252Cf therapy (P = .025), and that patient was treated in a delayed schedule 21 days after the start of external-beam irradiation rather than early in the course. 252Cf therapy required a much lower radiation dose and shorter treatment time. The study compared tumor destruction of an identically staged human cervical tumor in situ by direct histological means, using 252Cf neutron therapy or conventional photon therapy at an identical and equivalent dose adjusted by a relative biological effectiveness of 6.0 for 252Cf.

Adult↗