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Biomedical subjects

K Mason

Publications and source records attributed to K Mason.

At least 19 recordsLinked to original sources

Increased levels of extracellular noradrenaline in the frontal cortex of rats exposed to naturalistic environmental stimuli: modulation by acute systemic administration of diazepam or buspirone.

In vivo microdialysis was used to investigate the effects of an IP injection of diazepam or buspirone (each at 3 mg/kg) on spontaneous efflux of noradrenaline in rat frontal cortex, and on changes in efflux induced by naturalistic stress. After drug administration, rats either remained in their home cages or were transferred individually to a novel cage, 1 h later. The novel cage was brightly lit (1500 lux) and contained another, unfamiliar rat. After transfer to the novel cage, noradrenaline efflux was lower in diazepam-injected rats than in their vehicle-injected counterparts. However, in both cases, stress caused a significant increase in efflux and the net increase was not affected by diazepam. Similarly, buspirone, which increased spontaneous efflux of noradrenaline, did not affect the net increase in efflux during stress. Neither compound modified locomotor activity in the novel cage. This suggests that any changes in noradrenaline efflux are unrelated to drug effects on non-specific arousal. It is concluded that generically unrelated anxiolytic agents can have different effects on spontaneous efflux of noradrenaline but do not modify the noradrenergic response to naturalistic stimuli.

Animals

Kinetics of the reaction of a myelin basic protein peptide with soluble IAu.

The kinetics of formation and dissociation of IAu-peptide complexes have been examined in the absence of detergent, using a glycosylphosphatidylinositol (GPI)-linked form of IAu. The GPI-linked form contains a lipid membrane anchor which can be specifically cleaved by phosphatidylinositol-specific phospholipase C to yield a water-soluble form of IAu. We find rapid binding of the myelin basic protein (MBP) peptide analogue Ac(1-14)A4C15 to IAu, as well as rapid dissociation of IAu-MBP peptide complexes at neutral pH in the absence of detergent. The reaction kinetics of the water-soluble and detergent-solubilized complexes are the same to within experiment error. In the presence of this MBP peptide, Ac(1-14)A4C15, cells transfected with native IAu as well as cells transfected with a GPI-linked form of IAu are functional in stimulating T-helper hybridoma cells.

Amino Acid Sequence

Myelin basic protein peptide complexes with the class II MHC molecules I-Au and I-Ak form and dissociate rapidly at neutral pH.

The acetylated N-terminal peptide of myelin basic protein (MBP) is the immunodominant T cell epitope in the induction of experimental autoimmune encephalomyelitis in the I-Au- and I-Ak-expressing mouse strains. We used a direct binding assay to examine the kinetics of binding and dissociation of a series of MBP peptide analogues with the affinity-purified class II MHC molecules I-Au and I-Ak. We observe much faster in vitro rates of binding and dissociation than has been reported previously for other immunogenic peptides at neutral pH. The kinetics also reveal inactivation of the peptide-free class II MHC molecules. These results are consistent with previously proposed mechanisms for tolerance escape and autoimmune disease.

Amino Acid Sequence

You can tell by the nose--judging sex from an isolated facial feature.

Measurements taken from the nose are among the most important physical variables which discriminate statistically between male and female faces, yet several investigators have claimed that it is difficult to judge sex on the basis of noses presented in isolation. Previous work on the isolated nose has, however, involved the use of frontal views only, which may have obscured important physical differences between the noses of males and females. An investigation of the accuracy of judgments of the sex of isolated noses observed in frontal, profile, and three-quarter views by male and female subjects is reported. Judgment of sex was performed significantly more accurately than chance in all cases except for frontal views of female noses, where judgment was significantly less accurate than chance. Analysis of variance demonstrated a significant interaction of sex of nose and view of nose, such that male noses were identified better in frontal and in profile views, but female noses better in the three-quarter view. It is suggested that one possible reason for the seemingly contradictory role of the nose in previous studies of sex judgment is that all noses look more male in frontal views. For a nose to be perceived as female, its distinctive shape must be made available to the perceiver; this is most likely from the three-quarter view.

Adolescent

Kinetics of the reactions between the invariant chain (85-99) peptide and proteins of the murine class II MHC.

The region comprising residues 83-107 of the extracytoplasmic domain of the class II MHC-associated invariant chain protein is essential for its functional interaction with MHC proteins. A nested set of peptides that encompass this region, designated the class II invariant chain-derived peptides (CLIP), bind to many MHC proteins and inhibit the binding of antigenic peptides. The kinetics of the reactions between CLIP and five different murine class II MHC proteins have been determined. Specificity of CLIP binding was confirmed by competition with antigenic peptides. Large differences in the reaction rates were observed. For example, half-times of dissociation ranged from 4.4 min to 17.5 h, a > 200-fold difference. These results demonstrate that CLIP bind to MHC heterodimers at a site that involves the polymorphic residues. These data support the hypothesis that the CLIP binding site is within the peptide binding groove. It is further suggested that these differences in kinetic stabilities of CLIP-MHC protein complexes might affect the diversity of endogenous peptides bound to class II MHC proteins.

Amino Acid Sequence

Short-lived complexes between myelin basic protein peptides and IAk.

Kinetic rate constants and the equilibrium dissociation constant have been determined for the reaction between an affinity-purified class II major histocompatibility complex molecule IAk and a myelin basic protein analogue peptide, fluorescein-labeled Ac(1-14)A4C15. Under the experimental conditions used, the lifetime of the peptide-free IAk molecule with respect to inactivation is 3.1 hr. The equilibrium dissociation constant, 3.3 +/- 1.7 microM, is determined from measurements of the kinetics of peptide inhibition of IAk inactivation. The measured peptide dissociation halftime is relatively short, 30 min, and the deduced association rate is 100 M-1.s-1. The rate constants and the equilibrium constant are similar to those characteristic of kinetic intermediates in reactions of peptides and class II proteins that lead to long-lived terminal complexes.

Amino Acid Sequence

The value of routine chest roentgenograms on admission for rehabilitation after traumatic spinal cord injury.

The value of routine chest roentgenograms has come under increasing scrutiny in the medical literature. In this retrospective study we investigated the value of routine chest radiographs obtained on admission to a rehabilitation unit after an acute spinal cord injury. The charts of all patients admitted for rehabilitation after a traumatic spinal cord injury during a 1-year period were reviewed and 79 patients fulfilled criteria for inclusion into the study. Of the 79 patients, 12 had findings on routine admission films, 9 of which were felt to be significant (11.4%). All 9 patients with abnormal admission films had experienced cardiopulmonary complications during their acute hospitalization (P < 0.001). Fourteen patients with normal chest roentgenograms on admission had repeat films performed during their rehabilitation stay, 4 of which were abnormal. All 4 had experienced cardiopulmonary complications during their acute hospitalizations (P < 0.01). Our findings would support the selective use of admission chest roentgenograms in spinal cord-injured patients with clinical indications or a history of cardiopulmonary complications during their acute care stay.

Adult

A cladistic analysis of the evolutionary relationships of the members of the tyrosinase gene family using sequence data.

Recently, DNA sequence data have been published on tyrosinase and tyrosinase-related proteins (TRPs) in a wide variety of vertebrates ranging from Rana to Homo. These proteins are in turn members of a larger family of binuclear copper-binding proteins, which all contain two highly conserved copper-binding domains. This gene family also includes tyrosinases from fungi and bacteria as well as arthropodan and molluscan hemocyanins. Parsimony-based alignment and tree construction algorithms (Malign, v1.85 and PAUP, 3.1.1) were used to analyze the diversification of both the evolutionarily conserved copper-binding domains in copper-binding proteins in general as well as the diversification of the vertebrate tyrosinase gene family more specifically. These analyses show that the diversification of the vertebrate tyrosinase gene family minimally predates the diversification of vertebrates. Vertebrate tyrosinases proper first diverged from an ancestral tyrosinase-related protein (TRP) that then subsequently diverged to form tyrosinase-related protein-1s (TRP-1s) and tyrosinase-related protein-2s (TRP-2s).

Algorithms

Reliability of notification data for childhood bacterial meningitis.

This study reports the notification rates over ten years (1980-1989) for 232 children with documented bacterial meningitis in Nottingham District Health Authority. The average notification rate was approximately 50 per cent of known cases. It was higher for meningococcal infections (57/84, 68 per cent) than for any other type (45/148, 30 per cent), and lower in neonates (1/29, 3 per cent) than in any other age group (101/203, 50 per cent). The results show that the notification rates required to be adjusted during the decade of the study (1980-1989). The achievement of better notification rates may now be more feasible since implementation of the recommendations of the Committee of Inquiry into the Future Development of the Public Health Function for the control of communicable diseases. This paper provides a baseline upon which to measure the impact of such changes.

Adolescent

Post-herniorrhaphy urinary retention: a randomized prospective study.

Urinary retention is a known complication of inguinal herniorrhaphy. Bladder distension due to vigorous fluid administration is believed to contribute to this problem. Our hypothesis is that fluid restriction will lower the incidence of urinary retention, post-herniorrhaphy. From January 1989 through March 1991, 113 male patients entered the study. Sixty patients (Group I) received unlimited iv fluids (1294 +/- 58 ml) and 9 patients (15%) developed urinary retention. Fifty-three patients (Group II) received 500 ml or less by protocol (485 +/- 2 ml) and 5 of these patients developed retention (9%). Thus, fluid restriction lowered the incidence of urinary retention post-herniorrhaphy but the difference did not reach statistical significance. In addition age over 60 years approached significance as a risk factor for postoperative urinary retention.

Aged

The haematology of homozygous sickle cell disease after the age of 40 years.

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Adult

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent

Effect of interleukin 1, inflammation, and surgery on the incidence of adhesion formation and death after abdominal irradiation in mice.

There is clinical evidence that prior surgery and inflammation can increase the risk of the chronic complications of radiotherapy delivered to the pelvic/abdominal region. We have established a murine model to study this interaction using as end points mortality and late gut-associated peritoneal adhesion formation. A single dose of 16 Gy of total abdominal irradiation (TAI) was used. This gave no early deaths (less than 1 mo) and a relatively low mortality over the period 1 to 6 mo after TAI. The incidence of adhesions, which is the most serious complication 2 to 6 mo after TAI, was also low. Injection of lipopolysaccharide (50 micrograms, i.p.) or human recombinant interleukin 1 (IL-1) in doses as low as 100 units prior to TAI greatly enhanced both radiation-induced adhesion formation and death. Prior surgery also increased radiation-induced mortality, so much so that adhesions could not be accurately quantified. The timing of administration of lipopolysaccharide and IL-1 and of surgery relative to TAI was important in determining the outcome. For example, IL-1 enhanced adhesion formation and death if given from 3 days before to 1 day after, but not 4 days or 4 wk after, TAI. If given 20 h or less before TAI, there was a dramatic increase in early mortality 1 to 3 wk later, which was not seen if IL-1 was given at other times. These early deaths were not caused by bone marrow or gut stem cell depletion and may be a result of fluid leakage. We propose that surgery, bacterial invasion, or other inflammatory signals might act through a common mechanism of stimulating IL-1 production to enhance radiation-induced adhesion formation and the early and late morbidity and mortality associated with abdominal irradiation. If this is the case, blocking IL-1 production might inhibit the development of these late complications.

Abdomen

Fitting the linear-quadratic model using time of occurrence as the end-point for quantal response multifraction experiments.

A statistical technique is given for fitting the linear-quadratic model to experimental quantal response multifraction data using the time of the response as the end-point. The analysis used is based on the Cox Proportional Hazards model. The technique is useful for late effects where the time of occurrence of the response is dose dependent. The technique is compared to logistic regression analysis and the advantages and disadvantages are discussed. Both methods are applied to a lung pneumonitis experiment and a kidney experiment.

Animals

Cardiopulmonary complications after major surgery: a role for epidural analgesia?

Improvement in postoperative pulmonary mechanics with epidural analgesia has been described. Data on the hemodynamic effects of this technique are absent from the surgical literature. To provide such data we have evaluated two groups of patients undergoing aortic reconstruction: group I (n = 25), general anesthesia and group II (n = 6), general anesthesia with adjunctive epidural analgesia. The groups were comparable preoperatively as judged by the incidence of cardiac history, preoperative ejection fraction, and measured hemodynamic parameters. Postoperatively there were no significant differences in the pressure-related parameters; however, rate-related factors including heart rate and double product were significantly decreased in group II with no reduction in cardiac index. Postoperative increases in total body oxygen consumption were also markedly attenuated by epidural analgesia. Epidural analgesia reduces the hemodynamic demands on the heart after major surgery and is a useful adjunct, especially in patients with coronary artery disease.

Aged

Alpha thalassemia and the hematology of homozygous sickle cell disease in childhood.

alpha Thalassemia modifies the hematologic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and bilirubin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of children with SS disease has afforded an opportunity to study the hematologic indices in nine children homozygous for alpha thalassemia 2 (two-gene group), 90 children heterozygous for alpha thalassemia 2 (three-gene group), and 167 children with a normal alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for alpha thalassemia status at birth.

Age Factors

The pharmacodynamic properties of lorazepam and methylphenidate drugs on event-related potentials and power spectral analysis in normal subjects.

The effect of lorazepam and methylphenidate on the ERPs and power spectral analysis was studied. Lorazepam caused prolonged latency and decreased amplitude of N200 and P300. This result suggests that lorazepam affects the neural processing of cognitive function. The drowsiness induced by lorazepam correlated inversely with alpha frequency power, but had no direct correlation with fast activity. On the contrary, when methylphenidate was given, there was no change in ERPs. There was an increase in percent alpha frequency correlated with the alertness of the subjects. An analysis of variance involving the factors of drug and time of rating showed that subjects showed a significant (p less than 0.0001) decrease in alertness over time while receiving lorazepam, and a significant (p less than 0.05) increase in alertness over time while receiving methylphenidate.

Adolescent