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Biomedical subjects

L Gray

Publications and source records attributed to L Gray.

At least 127 records · Page 7Linked to original sources
PubMed1991

Adenylate cyclase toxin from Bordetella pertussis. Conformational change associated with toxin activity.

Adenylate cyclase (AC) toxin from Bordetella pertussis interacts with and enters eukaryotic cells to catalyze the production of supraphysiologic levels of cyclic AMP. Although the calmodulin-activated enzymatic activity (ability to convert ATP to cyclic AMP in a cell-free assay) of this molecule is calcium independent, its toxin activity (ability to increase cyclic AMP levels in intact target cells) requires extracellular calcium. Toxin activity as a function of calcium concentration is biphasic, with no intoxication occurring in the absence of calcium, low level intoxication (200-300 pmol of cyclic AMP/mg of Jurkat cell protein) occurring with free calcium concentrations between 100 nM and 100 microM and a 10-fold increase in AC toxin activity at free calcium concentrations above 300 microM. The molecule exhibits a conformational change when free calcium concentrations exceed 100 microM as demonstrated by shift in intrinsic tryptophan fluorescence, an alteration in binding of one anti-AC monoclonal antibody, protection of a fragment from trypsin-mediated proteolysis, and a structural modification as illustrated by electron microscopy. Thus, it appears that an increase in the ambient calcium concentration to a critical point and the ensuing interaction of the toxin with calcium induces a conformational change which is necessary for its insertion into the target cell and for delivery of its catalytic domain to the cell interior.

Adenylate Cyclase Toxin↗
PubMed1991

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation.

Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Rapid development of a sensory attribute in young chickens.

Development of a consistent pattern in responses to frequency changes is revealed with individual differences scaling. Newborn chicks respond to changes in a background tone to which they have become habituated with momentary delays in their otherwise regular peeping. Durations of these delays are used as measures of perceived difference between all possible pairs of five frequencies between 500 and 608 Hz. Coordinates of five points are calculated to create a map of these frequencies such that distances between points are maximally correlated with delays. A steeply sloped s-shaped curve describes the rapid emergence, from the beginning to the middle of the first postnatal day, of maps that explain significantly more of the input data than expected by chance. This implies that over a few hours birds come to reliably rank different frequencies along a consistent scale. Controlled rearing conditions of decreased external stimulation or early exposure to frequency changes have no effect on this development. In conclusion, scaling is a replicable way to evaluate the development of consistent responses to frequency changes. Similar processes are likely important in other aspects of perceptual development, learning, and memory.

Acoustic Stimulation↗
PubMed1991

Development of a frequency dimension in chickens (Gallus gallus).

Multidimensional scaling is used to examine the consistency of neonates' responses to frequency changes. Chickens at 0 and 4 days of age were presented with all possible transitions between pairs of five pure tones at 500, 525, 551, 578, and 608 Hz. Subjects were habituated to one stimulus, and the duration of an unconditioned delay in their otherwise ongoing peeps was measured after the frequency of the stimulus was changed. Durations of these delays can be used as measures of how different animals perceive two frequencies to be. Scaling solutions show that a nonrandom, adult-like ordering of frequencies emerges between 0 and 4 days of age.

Age Factors↗
PubMed1991

The role of torsion in cervical spine trauma.

A dynamic servocontrolled torsion machine has been used to characterize cervical injury due to pure rotation of the head. Resultant force moment, torque, and applied rotation have been measured. Torque applied to the base of the skull resulted in injury to the atlantoaxial joint. No evidence of lower cervical injury was observed by computed tomography, magnetic resonance imaging, in situ fluoroscopy, or visual inspection. Torque applied directly to the lower cervical spine induced ligamentous injury and unilateral facet dislocation; however, the torque to injure the lower cervical spine was significantly greater than the torque to injure the atlantoaxial joint. It was concluded that pure rotation of the head does not mediate lower cervical ligamentous injury because of the comparative weakness of the atlantoaxial joint.

Aged↗
PubMed1991

Reduced osmotic thirst in healthy elderly men.

In response to water deprivation or heat stress, healthy elderly men experience reduced thirst compared with a young control group. Because water deprivation and heat stress produce hypertonicity as well as reduced extracellular fluid volume, the aim of this study was to determine whether the elderly also experience reduced thirst in response to hypertonicity without extracellular fluid volume depletion. To achieve this, after an overnight fast, healthy community-dwelling nonsmoking old (65-78 yr, n = 7) and young (20-32 yr, n = 7) men received 120-min hypertonic (0.855 M) and isotonic (0.154 M) saline infusions (0.06 ml.min-1.kg-1) in double-blind randomized order at least 2 wk apart. Both groups had increased thirst (P less than 0.001) and water intake (P less than 0.05) after the hypertonic saline infusion compared with the isotonic saline infusion. However, despite similar plasma sodium increases and less plasma volume expansion during the hypertonic saline infusion compared with the young group, the old group was less thirsty (P less than 0.01) and drank less room-temperature tap water (young 11.1 +/- 1.2 ml/kg, old 3.9 +/- 0.6 ml/kg, P less than 0.001). This reduced thirst in the old group seemed to be mainly due to a lower thirst sensitivity (P less than 0.05) to hypertonicity, although there was also a tendency toward an increased thirst threshold. Plasma arginine vasopressin increases were similar for the old and young groups with hypertonic saline, without significant changes during the isotonic saline infusion in either group.

Adult↗
PubMed1991

Synthesis and secretion of high- and low-molecular-weight forms of the enzyme-releasing peptide (ERP) from the macrophage-like cell line THP-1.

Neutrophil enzymes have been implicated as a source of lung injury in patients with the adult respiratory distress syndrome (ARDS) and with emphysema. We studied a human alveolar macrophage-derived peptide messenger, the enzyme-releasing peptide (ERP), which causes neutrophils to secrete their enzymes. The secretion and synthesis of ERP was studied in human alveolar macrophages and in the macrophage-like cell lines THP-1, HL-60, and U937. All four cell types secrete an ERP-like peptide. THP-1 cells secrete a higher concentration of the peptide than do macrophages. The secretion of ERP by THP-1 is suppressed by the protein synthesis inhibitors actinomycin D and cycloheximide. While the macrophages secrete ERP, they do not synthesize it. These studies suggest that ERP is synthesized by an alveolar macrophage precursor and stored in the mature macrophage for later release. 12-O-tetradecanoylphorbol-13-acetate (TPA) suppresses ERP secretion by THP-1 cells, but it does not modify secretion in macrophages. Escherichia coli-derived lipopolysaccharide and dimethyl sulfoxide do not modify secretion in either cell type. The THP-1 cells secrete a high- and low-mass-ratio (Mr) form of ERP-like proteins. The low Mr but not the high Mr form stimulates neutrophils to secrete their granule enzymes. We conclude that human alveolar macrophages secrete ERP but do not synthesize it. It is likely that ERP is made by an alveolar macrophage precursor in a high Mr form that is cleaved prior to secretion by the macrophages.

Antibodies, Monoclonal↗
PubMed1991

Central auditory processing disorder: a case study.

We carried out extensive audiologic, electrophysiologic, and neuropsychologic testing on a young woman who complained that she had difficulty hearing in her educational environment. Conventional audiometric results, including pure-tone, speech, and immittance audiometry, were all within normal limits. The subject performed normally on tests involving the processing of rapidly changing temporal information, interaural time and intensity difference detection, and both absolute and relative sound localization. Early, middle, late and task-related auditory evoked potentials were essentially normal, although some asymmetry was observed in the middle latency (MLR) and late (LVR) responses. There was, however, a consistent left-ear deficit on dichotic sentence identification, on threshold and suprathreshold speech measures in the left sound field when various types of competition were delivered in the right sound field, and on cued-target identification in the left sound field in the presence of multitalker babble. Results suggest a central auditory processing disorder characterized by an asymmetric problem in the processing of binaural, noncoherent signals in auditory space. When auditory space was structured such that the target was directed to the left ear, and the competition to the right ear, unwanted background was less successfully suppressed than when the physical arrangement was reversed.

Acoustic Impedance Tests↗
PubMed1990

Activity level and auditory responsiveness in neonatal chickens.

The effects of prestimulus activity levels on auditory responsiveness were evaluated in newborn chickens. Rates of peeping were used as measures of prestimulus activity, and delays in the otherwise ongoing vocalizations were used as measures of responsiveness. Results show increased responsiveness to pure tones at intermediate levels of prestimulus activity. Responsiveness is reduced during periods of high and low activity. The effect is strongest just prior to the stimulus. Similar analyses could be useful in other studies that depend on the changing rate of repetitive responses, such as gross body movements, head turning, heart rate, and perhaps neural potentials. Some of the variability in the responses of young subjects can be controlled by measuring the subject's activity at the time a stimulus is presented.

Age Factors↗
PubMed1990

Development of temporal integration in newborn chickens.

The development of temporal integration was investigated in young chickens who momentarily delay their ongoing peeps when they hear a sound. An adaptive procedure was used to estimate absolute thresholds of pure tones and bands of noise between 10 and 460 ms in duration. Over 400 animals were tested at 0 and 4 days posthatch in a variety of conditions and controls. Thresholds decrease approximately 6 dB per doubling of duration. No difference in temporal integration was observed at low frequencies over this early postnatal period. Thresholds improved with age at higher frequencies, as expected, but only at long durations. This suggests that sensitivity may mature to long before short stimuli. A speculative hypothesis extends this idea and may explain data from chickens and humans.

Aging↗
PubMed1990

Aortic aneurysm surgery in the presence of a horseshoe kidney.

A review of three cases of aortic aneurysm in association with a horseshoe kidney is presented. Both the transperitoneal and retroperitoneal approaches to the aneurysm are detailed and the relative advantages and disadvantages outlined. The conventional approach of transection of the renal isthmus is not recommended because of the possibility of damage to the collecting system of the horseshoe kidney. The place of specialized investigations is outlined.

Aged↗
PubMed1989

Hypoxic-reperfusion injury in the inflamed human joint.

A series of experiments showed that, on exercise of the inflamed human knee, intra-articular pressure rises above synovial capillary perfusion pressure, causing intra-articular hypoxia; and that, on cessation of exercise, there is oxidative damage to lipids and IgG within the joint. These findings are consistent with the hypothesis that persistence of synovial inflammation can be due to exercise-induced hypoxic-reperfusion injury mediated by reactive oxygen species.

Adult↗
PubMed1989

Isoflurane for refractory status epilepticus: a clinical series.

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Adolescent↗
PubMed1989

A novel C-terminal signal sequence targets Escherichia coli haemolysin directly to the medium.

Escherichia coli haemolysin (HlyA), a 107K (K = 10(3) Mr) protein, is secreted to the medium in an hlyB, hlyD-dependent process. Secretion, however, depends on neither an N-terminal signal sequence nor on SecA, which is part of the normal cellular export machinery for periplasmic and outer membrane proteins. In contrast, HlyA contains a novel C-terminal secretion signal encompassing the last 27 amino acids and possibly some additional residues immediately upstream. This region is characterized by a 16 residue 'aspartic acid box' composed largely of small amino acids which we propose constitutes an important element in recognition of the membrane translocation complex constituted by HlyB and HlyD. This feature is also found at the C-terminus of the adenyl cyclase and leukotoxin A molecules and resembles a recently identified eukaryotic C-terminal signal for targeting to glycosomes. A domain of the HlyB component of the haemolysin transport system is also similar to a domain widely distributed in nature, apparently acting as an ATP-dependent transport protein for a wide variety of molecules. Secretion of haemolysin, however, is the first example of a protein translocation system involving an HlyB-like molecule. This suggests that a major role of HlyB or at least its C-terminal domain is the coupling of energy to translocation of the haemolysin. It is more likely therefore that HlyD is more involved in the actual translocation through the membrane. On the basis of genetical and biochemical studies we propose that the haemolysin is translocated directly to the medium bypassing the periplasm. We further propose that HlyB and HlyD together constitute a membrane-bound translocator specific for molecules bearing the HlyA targeting sequence, and that the organization of this complex (conceivably involving other E. coli membrane proteins) must somehow straddle the inner and outer membranes. Finally, the HlyA C-terminal domain has been successfully used to promote the secretion to the medium of a number of heterologous polypeptides, in an HlyB,D-dependent manner.

Amino Acid Sequence↗
PubMed1989

Automated enhanced latex agglutination assay for rheumatoid factors in serum.

This improved assay of rheumatoid factors in serum, described here for use with the Baker "Encore" centrifugal analyzer, is efficient, with 250-sample throughput per hour; reproducible, with between-batch CV = 5% and within-batch CV = 2% (mid-assay range); and results correlate well (r = 0.9) with those by other methods. The method is fully quantitative and automated, involves no predilution steps, and can be adapted for use in a wide range of systems. It has a sensitivity of 96% and specificity of 80% in diagnosing rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Handgun regulations, crime, assaults, and homicide. A tale of two cities.

To investigate the associations among handgun regulations, assault and other crimes, and homicide, we studied robberies, burglaries, assaults, and homicides in Seattle, Washington, and Vancouver, British Columbia, from 1980 through 1986. Although similar to Seattle in many ways, Vancouver has adopted a more restrictive approach to the regulation of handguns. During the study period, both cities had similar rates of burglary and robbery. In Seattle, the annual rate of assault was modestly higher than that in Vancouver (simple assault: relative risk, 1.18; 95 percent confidence interval, 1.15 to 1.20; aggravated assault: relative risk, 1.16; 95 percent confidence interval, 1.12 to 1.19). However, the rate of assaults involving firearms was seven times higher in Seattle than in Vancouver. Despite similar overall rates of criminal activity and assault, the relative risk of death from homicide, adjusted for age and sex, was significantly higher in Seattle than in Vancouver (relative risk, 1.63; 95 percent confidence interval, 1.28 to 2.08). Virtually all of this excess risk was explained by a 4.8-fold higher risk of being murdered with a handgun in Seattle as compared with Vancouver. Rates of homicide by means other than guns were not substantially different in the two study communities. We conclude that restricting access to handguns may reduce the rate of homicide in a community.

British Columbia↗