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Biomedical subjects

A Mason

Publications and source records attributed to A Mason.

At least 19 recordsLinked to original sources

Purchaser-provider: the international dimension.

Purchaser-provider systems in health care are being implemented in several countries and are under consideration in many more. These new arrangements are described for the United Kingdom, Finland, New Zealand, and Australia, and in each case responsibility for funding, purchasing, providing, and ownership is identified. The four systems, along with managed care organisations in the United States, are also compared with regard to several important features. There is a fundamental similarity between these purchaser-provider arrangements but several key differences are well worth systematic study. This is a major challenge for academic bodies in Britain and other countries, and the opportunity to learn from each other should not be missed.

Australia

Contrast sensitivity and coherent motion detection measured at photopic luminance levels in dyslexics and controls.

Development dyslexics perform differently from controls on a number of low level visual tasks. We carried out three experiments to explore some of these differences. Dyslexics have been found to have reduced luminance contrast sensitivity at mesopic luminance levels. We failed to replicate this finding at photopic luminance levels. We also compared the (photopic) coherent motion detection thresholds of groups of child and adult dyslexics with those of age matched controls. Dyslexics were significantly less sensitive to motion. The results are discussed in relation to a recent suggestion that developmental dyslexia may be associated with a magnocellular visual deficit.

Adolescent

Immunohistochemical analysis of cathepsin D in prostate carcinoma.

Cathepsin D is a carboxyl protease that has been implicated as an important factor in tumor cell invasion. Sixty-nine cases of primary adenocarcinoma of the prostate were studied by the indirect immunoperoxidase method using a primary monoclonal anti-cathepsin D antibody. Immunoreactivity was graded from 0 (negative) to 4+ (intense reaction). The normal tubuloalveolar glands were, in general, negative. However, nine cases revealed focal staining of nonneoplastic luminal cells. Basal cells were negative except in areas of basal-cell hyperplasia, which were intensely positive. Thirty-nine of 78 carcinoma samples revealed 2+ or greater positive punctate lysosomal staining. In the 39 positive-stained cases, the reactivity was diffuse in three and focal in the remainder. The percentage of carcinoma cases whose worst lesions stained 2+ or greater showed a nonsignificant (P = 0.055) relation to Gleason grade but a significant (P = 0.031) relationship to pathologic stage. Thus, cathepsin D may prove to be a useful marker of prostate cancer progression.

Adenocarcinoma

Adjuvant psychological therapy for patients with cancer: a prospective randomised trial.

OBJECTIVE: To determine the effect of adjuvant psychological therapy on the quality of life of patients with cancer. DESIGN: Prospective randomised controlled trial comparing the quality of life of patients receiving psychological therapy with that of patients receiving no therapy, measured before therapy, at eight weeks, and at four months of follow up. SETTING: CRC Psychological Medicine Group of Royal Marsden Hospital. PATIENTS: 174 patients aged 18-74 attending hospital with a confirmed diagnosis of malignant disease, a life expectancy of at least 12 months, or scores on various measures of psychological morbidity above previously defined cut off points. INTERVENTION: Adjuvant psychological therapy, a brief, problem focused, cognitive-behavioural treatment programme specifically designed for the needs of individual cancer patients. MAIN OUTCOME MEASURES: Hospital anxiety and depression scale, mental adjustment to cancer scale, Rotterdam symptom checklist, psychosocial adjustment to illness scale. RESULTS: 156 (90%) patients completed the eight week trial; follow up data at four months were obtained for 137 patients (79%). At eight weeks, patients receiving therapy had significantly higher scores than control patients on fighting spirit and significantly lower scores on helplessness, anxious preoccupation, and fatalism; anxiety; psychological symptoms; and on orientation towards health care. These differences indicated improvement in each case. At four months, patients receiving therapy had significantly lower scores than controls on anxiety; psychological symptoms; and psychological distress. Clinically, the proportion of severely anxious patients dropped from 46% at baseline to 20% at eight weeks and 20% at four months in the therapy group and from 48% to 41% and to 43% respectively among controls. The proportion of patients with depression was 40% at baseline, 13% at eight weeks, and 18% at four months in the therapy group and 30%, 29%, and 23% respectively in controls. CONCLUSIONS: Adjuvant psychological therapy produces significant improvement in various measures of psychological distress among cancer patients. The effect of therapy observed at eight weeks persists in some but not all measures at four month follow up.

Adolescent

Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance.

In this study, peripheral-blood mononuclear cells from patients with chronic hepatitis B and spontaneous or therapy-induced disappearance of HBsAg were examined for HBV DNA. Samples were evaluated by in situ hybridization and polymerase chain reaction both before and after clearance of HBsAg. By in situ hybridization, positive signals were observed in 2 of 13 samples collected after HBsAg loss, in 8 of 15 samples before HBsAg loss and in 0 of 4 control patients without serological markers of active or prior HBV infection. When polymerase chain reaction analyses were performed, HBV DNA was detected in 5 of 12 HBsAg-negative samples and 10 of 15 HBsAg-positive samples from the study group. Testing of mononuclear cells after disappearance of HBsAg revealed that two of eight patients were HBV DNA positive by in situ hybridization and by polymerase chain reaction, whereas two additional patients were positive by polymerase chain reaction alone. Mononuclear cell-associated HBV DNA was detected between 2 and 9 mo after the disappearance of circulating HBsAg by in situ hybridization and as long as 4 yr later by polymerase chain reaction. These data indicate that patients who have undergone HBsAg seroconversion may nonetheless harbor HBV DNA in their peripheral-blood mononuclear cells for prolonged periods.

Adult

Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen.

Polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA in the sera and livers of nine patients with chronic hepatitis B after treatment-induced or spontaneous loss of serum hepatitis B surface antigen. Patients were evaluated at intervals ranging from 3 to 67 months after disappearance of hepatitis B surface antigen. PCR was performed using primer pairs from the surface and core gene regions, and surface gene products were quantitated. Liver tissue was also evaluated by in situ hybridization to assess viral transcription. Five of the nine patients had viral DNA detectable in serum by PCR. Quantitation of polymerase chain reaction products in serum and liver showed that the DNA levels tended to decline progressively after antiviral therapy. Six of seven surface antigen-negative patients tested had detectable viral DNA in the liver, and four of the six DNA-positive patients were negative for DNA in serum by PCR. None had surface gene messenger RNA. Thus, it is concluded that hepatitis B virus DNA may be detectable by PCR in liver tissue years after the disappearance of hepatitis B surface antigen, even in the absence of detectable hepatitis B virus DNA in serum.

Alanine Transaminase

Effect of recombinant inhibin on luteinizing hormone and follicle-stimulating hormone secretion in the rat.

We investigated the effect of the iv injection of recombinant human (rh) inhibin on FSH and LH secretion in the female rat under various experimental circumstances. Rh inhibin caused dose-related decreases in mean plasma FSH, but not LH, levels in ovariectomized female rats 14 days old and older. The duration of this inhibition was proportional to the dose of rh inhibin, but no consistent changes in FSH secretion were observed until 4 h after treatment. Maximum suppression of FSH release was observed at about 15 micrograms rh inhibin/kg BW and lasted 8-10 h. Measurement of the area under the curve from 4-12 h after injection of inhibin indicated a dose-related decrease in total FSH secreted. When blood samples were withdrawn every 10 min to evaluate pulsatile gonadotropin release, analysis of FSH pulse parameters indicated that rh inhibin (25 micrograms/kg) interfered with pulse frequency, amplitude, and peak levels in both intact and ovariectomized rats. In contrast, pulsatile LH secretion was not measurably altered. These results demonstrate that rh inhibin acts primarily at the level of the pituitary to inhibit all parameters of FSH secretion and suggest that this effect is at least not entirely mediated by changes in GnRH receptors.

Aging

Effect of recombinant inhibin on gonadotropin secretion during proestrus and estrus in the rat.

This work investigated the ability of recombinant human (rh) inhibin A or the GnRH antagonist [Ac-D2Nal1, delta Cpa2, delta 3Pal3, Arg5 delta 5-(p-methoxyphenyl)5-oxo-2-aminopentanoic acid6, delta Ala10]GnRH to alter plasma immunoreactive LH and FSH levels in cycling female rats. In a first series of experiments, rh inhibin A (25 micrograms/kg) was injected iv between 0800 and 0830 h, or at 0800 and 1200 h, on proestrus, and plasma hormone levels were measured from 1200-1900 h. Both regimens of administration significantly (P less than or equal to 0.01) lowered mean plasma FSH levels but did not mask the primary FSH surge. This treatment also lowered the overall amount of LH released, although the difference between control and inhibin-treated rats only reached statistical significance (P less than or equal to 0.05) after two injections of the protein. Measurement of the number of tubal ova shed on the next estrus showed no difference between rats injected with the vehicle or inhibin at 0830 h. Finally, it was shown that administration of the GnRH antagonist (100 micrograms/kg) at 1200 h interfered with the primary surges of both LH and FSH. In a second series of experiments, rh inhibin A (25 micrograms/kg) was injected once at 2000 h on proestrus. In these animals, inhibin significantly (P less than or equal to 0.01) decreased mean plasma FSH levels between 2000 h on proestrus and 0500 h on estrus and totally suppressed the secondary FSH surge. LH secretion remained low in control animals, and no measurable changes were observed after inhibin treatment. Flushing of the ova 5 days later (i.e. during estrus of the subsequent cycle) showed no difference between control and inhibin-treated rats. Injection of the GnRH antagonist (100 micrograms/kg) at 2000 h on proestrus decreased the total amount of FSH secreted during late proestrus and early estrus. However, FSH secretion showed an increase at between 0100 and 0400 h of estrus despite blockade of GnRH receptors. These results indicate that administration of rh inhibin A interferes with both the primary and secondary FSH surges. In contrast to its inability to alter LH release by ovariectomized rats, inhibin also blunted LH secretion during the afternoon of proestrus. Whether these results represent differential effects of inhibin on LH secreted by intact and gonadectomized animals, or whether the documented changes in pituitary responsiveness to GnRH during proestrus are accompanied by an increased sensitivity to inhibin, needs further investigation.

Animals

Primary structure and biological activity of human brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a 27-kDa basic protein of noncovalently linked 13.5-kD subunits related to nerve growth factor and is produced by the central nervous system (CNS). BDNF has been shown to promote the survival of neurons located in or directly connected with the CNS and is likely to function in adjusting the cell number within neuronal populations to the need of this projection field. Here we describe the primary structure of a human BDNF cDNA, the biological activities of pure recombinant human BDNF, and the tissue distribution of rat BDNF. BDNF mRNA can be found in some peripheral tissues as well as in the CNS, and recombinant human BDNF is a potent neurotrophic factor for primary peripheral sensory neurons.

Amino Acid Sequence

Effects in vivo of purified recombinant human activin and erythropoietin in mice.

Activin has been shown to act in vitro as an erythroid specific enhancing activity for erythropoietin (epo)-stimulated erythroid (BFU-E) and multipotential (CFU-GEMM) progenitor cells. To evaluate effects in vivo, purified recombinant activin-A and epo were administered s.c. to hypertransfused polycythemic mice for analysis of iron (59Fe) uptake, and to previously untreated mice for effects on reticulocyte release and proliferation of bone marrow (BM) and spleen (Spl) hematopoietic progenitors (CFU-GEMM, BFU-E, CFU-GM) and BM stem (CFU-S) cells. Activin alone had no effect in polycythemic BDF1 mice, but synergised with epo to significantly enhance 59Fe-incorporation into erythrocytes. In untreated C3H/HeJ mice, a single dose of activin enhanced reticulocyte release in 24 h to the level seen with epo. Activin plus epo did not further enhance reticulocyte release. Reticulocyte release was still apparent at day 4 in mice given epo twice a day for 3 days, but not in mice given activin twice a day for 3 days. Activin or epo each significantly enhanced the percent cells in S-phase of BM and Spl CFU-GEMM, BFU-E and CFU-GM in C3H/HeJ, W/Wv and Sl/Sld mice and BM CFU-S in BDF1 mice. The combination of epo plus activin did not further enhance proliferation. These results demonstrate activin's erythropoietic enhancing activities in vivo, and also activin and epo induction of enhanced proliferation of non-erythroid, as well as erythroid progenitors.

Activins

Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro.

Synaptic transmission between pairs of neurons in layer 2/3 of in vitro slices from the rat visual cortex was studied by dual intracellular recording. The intrinsic electrophysiological properties of these neurons suggested that they were pyramidal cells. More than 1/3 of the total number of synaptically connected neurons were stained by intracellular iontophoresis of biocytin, and all had pyramidal morphology. Postsynaptic potentials (PSPs) were evoked by single action potentials (elicited by current injection) in presynaptic cells. Measurements of PSP latency, amplitude, and shape were made on spike-triggered averages. Forty-eight synaptic connections were found out of a possible total of 549, equivalent to a probability of about 0.09. For these 48 connections, the distance between the 2 impalement sites ranged from 50 to 340 microns. All PSPs were depolarizing at rest (-74 +/- 5 mV, mean +/- SD), and all 14 of the PSPs that were also recorded with the postsynaptic cell depolarized to around action potential threshold (about -55 mV) remained depolarizing. PSPs had short latencies (1.2 +/- 0.6 msec, mean +/- SD), suggesting that they were mediated by monosynaptic pathways. Peak amplitudes of the averaged PSPs varied widely (range, 0.05-2.08 mV), but the majority were less than 0.5 mV. PSPs decayed exponentially with time constants that were correlated with, but slightly longer than, the membrane time constants of the postsynaptic cells measured using injected current pulses. Four cell pairs were connected reciprocally, and 6 examples of convergent input were found in which a single cell was postsynaptic to more than 1 presynaptic cell. Trial-to-trial fluctuations in PSP amplitude were analyzed for 16 synaptic connections. The amplitude of the PSP evoked by a presynaptic action potential fluctuated more than could be accounted for by the background noise.

Action Potentials

Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. I. Establishment of cell classes.

The purpose of this study was to determine whether different classes of neocortical pyramidal neurons possess distinctive electrophysiological properties. Neurons were assigned to classes on the basis of their somadendritic morphology as revealed by intracellular HRP injection. The electrophysiological features of each class are compared in the following paper (Mason and Larkman, 1990). Coronal slices were prepared from the visual cortex of the albino rat and maintained in vitro. Pyramidal neurons from layers 2/3 and 5 were impaled with electrodes containing HRP. After intracellular recording, the cells were injected, reacted to visualize the enzyme, and examined in the light microscope. The 18 neurons from layer 2/3 showed an underlying similarity of somadendritic morphology and were considered to constitute a single cell class, although some features varied with the depth of the soma in the cortex. The 22 layer 5 cells were more diverse and were divided into 2 main classes. Eleven cells had single, thick apical trunks which ascended to close to the layer 1 border then branched to form a terminal arbor. These cells were termed thick layer 5 cells, and were found mainly in the upper part of the layer. Ten layer 5 cells had single apical trunks which tapered to a fine diameter and terminated, without forming an obvious terminal arbor, near the top of layer 4 (3 cells) or in layer 2/3 (7 cells). These cells were termed slender layer 5 cells and were found throughout the layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. II. Electrophysiology.

The aim of this study was to determine whether the different morphological classes of pyramidal neurons in layers 2/3 and 5 of rat visual cortex (Larkman and Mason, 1990) have particular electrophysiological properties. Neurons in in vitro slices of rat visual cortex were impaled with glass micropipettes containing horseradish peroxidase (HRP) and studied using current-clamp techniques prior to pressure injection of HRP into the neurons. On morphological grounds, cells stained in layer 2/3 were placed into a single class whereas layer 5 cells were divided into 2 classes. Cells in one of these classes had thick apical dendrites which arborized in layer 1, whereas the apical dendrites of cells in the other class were thinner and did not reach layer 1 (Larkman and Mason, 1990). Despite variation between individual cells of a single class, significant differences were found in the time constants, current/voltage relations, and repetitive firing behaviors of the 3 classes. Burst firing responses to injected current pulses were confined to the layer 5 cells with thick apical dendrites. These results add to those from other areas of the brain demonstrating that the electrophysiological properties of pyramidal neurons are heterogeneous. Furthermore, we have shown that distinctive intrinsic membrane properties of pyramidal neurons in visual cortex are correlated with different morphologies.

Action Potentials