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Biomedical subjects

A Wilson

Publications and source records attributed to A Wilson.

At least 397 records · Page 22Linked to original sources

Relationships between minute ventilation, oxygen uptake, and time during incremental exercise.

It has recently been reported that blood and muscle lactate increased exponentially during incremental exercise, casting some doubt upon the concept of 'anaerobic threshold'. To gain further insight into this controversy, we examined the relationships between minute ventilation (VE), time and oxygen uptake (VO2) in normal subjects during incremental exercise. During exercise, the relationship of VE to either time of exercise or to VO2 appeared curvilinear; VE was reliably described as an exponential function (y = axb + c) of both time of exercise (r2 = 0.96) and VO2 (r2 = 0.92). We also compared variables from 30-second incremental tests with variables obtained from quasi-steady-state incremental tests using cycle and treadmill ergometry. With the exception of heart rate, variables measured at maximum exercise were similar during short-duration and quasi-steady-state incremental tests. These data support the ideas that: there is no abrupt change in metabolism and oxygen availability during progressive exercise, and results of rapid incremental and quasi-steady-state exercise tests are generally comparable in normal individuals.

Adult↗

Parenteral nutrition via peripheral veins: a feasibility study.

Twenty patients who had undergone uncomplicated surgery of moderate severity were randomly allocated to two groups (both n = 10) who were fed using a peripheral vein for up to six days. Group I received, each day, a nutrient solution providing 10 grams of nitrogen as Perifusin (E Merck Ltd) and 1400 calories as dextrose and Intralipid (Kabivitrum Ltd) with an osmolality of 490 mosmol/kg. Group II received only 15 grams of nitrogen per day as Perifusin with an osmolality of 376 mosmol/kg. The mean (+/- s.e. mean) nitrogen balance over the study was similar in both groups, in Group I being -1.23 +/- 0.89, and in Group II being -1.05 +/- 1.08 g (P greater than 0.05 Mann-Whitney U test). The nutrient mixture given to Group I resulted in elevated levels of serum 3-hydroxybutyrate and lower levels of serum non-esterified fatty acids. These data suggest that lipolysis and ketogenesis were suppressed. There was no significant difference in serum lactate levels in either group. Venous thrombophlebitis at the infusion site was assessed daily using Maddox's criteria, with a minimal degree of inflammation occurring in either group. This preliminary study suggests that a total parenteral feeding regimen may be designed for peripheral vein infusion. Further studies are indicated.

Adult↗

Effects of ethanol on early potassium currents in Aplysia: cell specificity and influence of channel state.

The effects of ethanol (EtOH) on the early potassium current, IA, were examined in 3 identified neurons of Aplysia using voltage-clamp techniques. The primary effect of EtOH on this current was a pronounced increase in the time constant of decay. However, this effect was cell specific, being evident in cells MCC and R15 but not in cell B1. Other parameters of IA were not greatly affected in any of the cells, in comparison with the effects on decay time constant. Baseline parameters of IA were measured in each of the cells to determine whether subpopulations of IA channel might exist, and be differentially sensitive to EtOH. While differences did appear among cells, they were not consistent with an explanation of EtOH's actions based upon distribution of channel subtypes. The effect of EtOH on IA decay was dependent upon the voltage-clamp protocol used. When inactivation of IA developed at -20 mV, the slower development of inactivation noted above occurred. When inactivation without channel opening was produced by means of a prepulse to -40 mV, EtOH speeded up the development of inactivation. A number of possible explanations for these findings are discussed. Most of the effects of EtOH occurred within 1 min of application of the drug, suggesting relatively rapid access to the site of action. Effects continued to develop over succeeding minutes. This slower-developing effect may reflect either a delayed access to channels due to slower diffusion into or lateral movement within the lipid phase of the membrane, or it may indicate that channels are accessible to the EtOH molecule only when in certain states.

Animals↗

The red eye: a general practice survey.

A postal questionnaire was sent to all general practitioners registered in the United Kingdom enquiring about their experience, practice and attitudes regarding the red eye. Of the 31 500 questionnaires sent out 8742(28%) were returned. The doctors demonstrated a high level of anxiety about this condition combined with a low level of investigation. There was wide variation in the treatment of choice for non-specific conjunctivitis, with 10% of doctors choosing a steroid containing product. Diagnostic and therapeutic activity were more closely associated with the age of the doctor than with experience of ophthalmology. Further training at undergraduate or postgraduate level for general practice ophthalmology appears desirable.

Adult↗

Thrombin, unlike vasopressin, appears to stimulate two distinct guanine nucleotide regulatory proteins in human platelets.

The thrombin-stimulated GTPase activity of human platelets was additive with respect to the GTPase stimulation effected by prostaglandin E1, but not with that stimulated by adrenaline, vasopressin and platelet-activating factor (PAF). Treatment of platelet membranes with pertussis toxin partially inhibited the thrombin-stimulated GTPase, but had no effect on the vasopressin-stimulated GTPase activity, whereas cholera toxin treatment had no effect on either of these stimulated GTPase activities. Thrombin, adrenaline and PAF, but not vasopressin, inhibited the adenylate cyclase activity of isolated plasma membranes through the action of Ni only, this being inhibited by pertussis toxin. It is suggested that thrombin exerts effects through both the inhibitory guanine nucleotide regulatory protein Ni and through the putative guanine nucleotide regulatory protein, Np, involved in regulating receptor-stimulated inositol phospholipid metabolism. However, vasopressin appears to exert its effects solely through the putative Np.

ADP-Ribosylation Factors↗

Degradation of specificity in cytolytic T lymphocyte clones. The separate YAC-1-type (NK-like) and P815-type broad specificity killing patterns are both restricted to the larger cells within a clone but may be expressed independently in clones from different mouse strains.

Ly-2+ T cells cultured at limiting dilution with concanavalin A and irradiated spleen filler cells develop into clones of Ly-2+ cytotoxic T lymphocytes (CTL), which although initially specific, lyse a wide range of target cells by days 8 to 9. This anomalous nonspecific killing is now shown to be a function of the largest cells within the clone, with the majority of CTL behaving normally. Cold-target inhibition experiments demonstrate that two distinct recognition systems determine the broad-range killing, one being typified by a high affinity for P815 tumor cells, the other being typified by an affinity for YAC-1 tumor cells. Mouse strains differ in the probability that CTL in culture will demonstrate one or another of these killing patterns; some develop both, some one, and some neither. When both killing patterns develop, as in cultures of Ly-2+ cells from CBA mice, both are expressed in the same clone. High natural killer (NK) cell strains are those most likely to develop CTL clones with an ability to lyse the NK target YAC-1. The results have implications for the relationship of NK cells to T cells. They also suggest ways of avoiding the problem of anomalous T cell killing.

Animals↗

Platelet activating factor and U44069 stimulate a GTPase activity in human platelets which is distinct from the guanine nucleotide regulatory proteins, Ns and Ni.

Platelet-activating factor (PAF, 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine) and the stable thromboxane-receptor agonist U44069 (9 alpha, 11 beta-epoxymethanoprostaglandin H2) stimulated GTPase activity in platelet membranes in a dose-dependent fashion, yielding Ka values of 12 nM and 27 nM respectively. The degree of GTPase activation elicited by these agents was found to be additive with the GTPase activation due to either the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins when activated by prostaglandin E1 and adrenaline (+propranolol) respectively. Treatment of membranes with either cholera or pertussis toxins, which inhibited markedly the receptor-mediated stimulation of the GTPase activities of Ns and Ni respectively, had no or only a small effect, respectively, on the GTPase activity stimulated by PAF and U44069. It is suggested that PAF and U44069, which stimulate inositol phospholipid metabolism in platelets, exert actions through a guanine nucleotide regulatory protein which is distinct from Ns and Ni.

Blood Platelets↗

Clonal expansion of T cells: a cytotoxic T-cell response in vivo that involves precursor cell proliferation.

The response of peritoneal exudate lymphocytes to allogeneic tumor cells was used to determine whether the in vivo generation of cytotoxic T cells (CTL) involved the proliferation of precursor cells. Ten days post-injection, both cytotoxic activity and the formation of conjugates between lymphocytes and target cells were shown to be specific for the immunizing tumor alloantigens and to be effected by Ly-2+ cells. A cell-sorting-based procedure was developed to isolate specific conjugates between red-fluorescence-tagged CTL and blue-fluorescence-tagged tumor target cells. When [3H]thymidine was administered during the response, almost all isolated conjugate-forming CTL were 3H-labeled on autoradiography. Thus, the CTL were clearly products of dividing cells, a result that contradicts published data. Reassessment of a previously studied system, which suggested that CTL were not products of cell division, indicated that in that system many of the conjugate-forming cytotoxic cells studied were Ly-2- and nonspecific, and thus perhaps not T cells. We conclude that the clonal selection model is applicable to at least one in vivo T-cell response.

Animals↗

Evaluating bizarre-idiosyncratic thinking: a comprehensive index of positive thought disorder.

A summary of our method of assessing positive thought disorder, or bizarre-idiosyncratic thinking, from two short verbal tests is presented. This measure provides for standardized thought disorder assessments of: the overall presence and severity of thought disorder, and the type of disordered thinking shown. A definition and examples of bizarre-idiosyncratic thinking are provided, along with information on the reliability and validity of the scoring system. A method of establishing subject groups based on the severity of positive thought disorder also is presented--ranging from no thought disorder, to abnormal thinking, to severe formal thought disorder. This measure has been used to assess longitudinal changes in thought disorder symptoms over time and to evaluate relationships between thought disorder, other aspects of psychopathology (such as delusions), and adjustment in other areas of functioning across diagnostic groups.

Humans↗

Analysis of heart rate and respiratory patterns in sudden infant death syndrome victims and control infants.

Retrospective analyses of patterns of breathing and heart rate variability obtained by visual inspection and spectral analysis of ECG and respiratory activity have provided markers associated with subsequent death in a referred population of infants at high risk for sudden infant death syndrome (SIDS). Such markers include breathing patterns characterized by excessive apneic pauses and periodic breathing, heart rate spectra characterized by increased low frequency oscillations, and respiratory activity spectra characterized by a widened "bandwidth" during regular breathing. To test whether such measurements could distinguish SIDS cases and randomly selected controls from a population study the data from 10 cases and 100 age-matched control subjects were analyzed blind. The code was disclosed after completion of the analysis. We found that none of the markers served to distinguish the SIDS cases from the controls in the population at large. This observation may indicate important physiological differences between infants destined to die in the referred high risk population and infants who die of SIDS at large. The possible reasons for our inability to identify the group of SIDS in the general population, as compared to the group of deaths in the referred high risk group are: (1) different disease processes in the two groups, (2) difference responses to the same disease process in the two groups, (3) a response reflecting the psychosocial setting of the referred high risk population, (4) methodological differences between this and previous studies. We conclude that these markers are not of value in screening the population at large.

Heart Rate↗

Intact ability to lower urine pH in nonacidotic adrenalectomized rats.

Distal acidification was assessed in adrenalectomized (ADX) rats in which the development of acidosis was prevented by oral supplementation with NaHCO3, with or without glucocorticoid replacement. Totally corticosteroid-deficient nonacidotic rats were capable of lowering their urine pH in response to Na2SO4 infusion from a baseline of 7.47 +/- 0.22 to 4.83 +/- 0.1 (p less than 0.001). A similarly intact ability to lower the urine pH was also demonstrated in glucocorticoid-replaced mineralocorticoid-deficient rats. Absolute ammonium excretion was lower in ADX animals compared to controls (0.79 +/- 0.08 vs. 0.46 +/- 0.06 microEq/min, p less than 0.01) but when corrected for the difference in GFR, ammonium excretion was the same in ADX and adrenal-intact rats. During bicarbonate loading and at similar blood and urine pH, and bicarbonate concentrations, the U-B pCO2 gradient was similar in mineralocorticoid-deficient and adrenal intact rats (44 +/- 5.1 vs. 36 +/- 2.6 mm Hg, respectively). Amiloride administration to mineralocorticoid-deficient rats led to a reduction in the U-B pCO2 gradient from 30 +/- 4.5 to 10 +/- 3.0 mm Hg (p less than 0.002). These results indicate that the ability to lower the urine pH and raise the urine pCO2 is intact in the nonacidotic ADX rat; ammonium excretion in this model is reduced in proportion to the observed reduction in GFR, and amiloride administration inhibits acidification in ADX rats. The data strongly suggest the presence of a major site of aldosterone-independent, sodium-dependent acidification mechanism likely located at the level of the cortical collecting tubule.

Acidosis↗

Degradation of specificity in cytolytic T lymphocyte clones: two broad specificity, H-2-independent recognition systems, one natural killer-like, develop during culture, in addition to the clonally distributed antigen-specific receptor.

Ly-2+ CBA mouse T lymphocytes stimulated with concanavalin A in limiting dilution culture produce clones of cytotoxic T lymphocytes (CTL) which, although initially specific, eventually lyse a wide range of target cells. The nature of the recognition system for this apparently "nonspecific" cytolysis was examined using a range of tumor cells as labeled targets and as cold target inhibitors. Most syngeneic and allogeneic murine tumor cells were lysed but the degree of lysis varied, even for different sublines of the same tumor. All tumor cells cold target inhibited their own lysis, and cross-inhibited lysis of other targets to varying degrees. The recognition stage of "nonspecific" cytolysis appeared to be independent of target cell H-2 expression; some H-2-negative murine target cells were lysed and some were not, but all gave cold target inhibition of "nonspecific" cytolysis. Xenogeneic tumor cells were resistant to lysis, but some nevertheless gave cold target inhibition of the "nonspecific" cytolysis of murine targets. A study of the specificity of cold target cross-inhibition revealed two distinct patterns of recognition which existed simultaneously in "nonspecific" CTL; one was like that of natural killer cells and was directed to targets such as YAC-1, the other was distinct from that of natural killer cells and was directed to targets such as P815. Thus, murine CTL may express three distinct receptors, the clonally distributed, H-2-restricted, antigen-specific T cell receptor and two different "broad-range" receptors common to most clones.

Animals↗