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Biomedical subjects

A Mason

Publications and source records attributed to A Mason.

At least 55 records · Page 3Linked to original sources

Reevaluation of synaptic relationships of cerebellar terminals in the ventral lateral nucleus of the rhesus monkey thalamus based on serial section analysis and three-dimensional reconstruction.

Terminals of cerebellar afferents (CB) to different regions of the ventral lateral nucleus (VL) of the rhesus monkey thalamus were labeled with wheat germ agglutinin-horseradish peroxidase following injections into the dentate nucleus. Synaptic relationships of 17 CB with projection neuron dendrites (PNd) and local circuit neuron dendrites (LCNd) were analyzed in serial ultrathin sections from dorsal and ventral VL regions, which are known to differ cytoarchitecturally and functionally. Three terminals were reconstructed using three-dimensional (3D) computer image analysis techniques to obtain volumetric and planar measurements. CB in the ventral VL were often flat and elongated with synaptic vesicles arranged in clusters. Each CB was engaged with one PNd and one to four LCNd. A single bouton formed 8-50 synaptic contacts, with those on PNd outnumbering the ones on LCNd 4.1:1. Only some CB in the ventral VL were engaged in complex synaptic arrangements such as triads and serial synapses. Most CB in the dorsal VL displayed a roundish shape and numerous uniformly distributed synaptic vesicles. They formed 5-25 synaptic contacts with a 3:1 ratio of contacts on PNd compared with those on LCNd. CB in the dorsal VL participated in a variety of complex synaptic arrangements. Two types of triads were found: classic with CB, PNd and LCNd, and unconventional with CB and two LCNd. CB were also involved in serial synapses with two LCNd or LCNd and another PNd, and serial sequential synapses with two LCNd and a PNd. Three glomerulus-like structures were encountered in the dorsal VL. 3D reconstruction and volumetric measurements revealed that synaptic contacts formed by CB on PNd had varying shapes and sizes (0.022-0.274 microns2). Synapses formed on LCNd were larger (0.09-0.407 microns2). The total area of all active zones of a single CB on LCNd was either equal to or about 40% smaller than that of synapses on PNd. The entire active zone area comprised 1-1.6% of the total CB surface area and did not seem to correlate with the volume. Synaptic contacts formed by associated LCNd on PNd in complex arrangements were usually small (0.021-0.044 micron2). The results suggest that: synapses formed by CB on PNd and LCNd, and synapses formed by LCNd on PNd may differ in strength; a variety of different circuits participate in the processing of cerebellar afferent information in the primate VL; and these circuits differ in functionally different VL subdivisions.

Animals↗

HLA-C typing of eleven Papua New Guineans: identification of an HLA-Cw4/Cw2 hybrid allele.

HLA-C polymorphism of 11 individuals from Papua New Guinea was studied by serology and DNA typing (SSP ARMS-PCR). To resolve certain discrepancies HLA-C alleles were cloned and sequenced. Five alleles were identified by sequencing, four of which; Cw*0304, Cw*0401, Cw*12022 and Cw*1502 have been identified previously in other populations. The fifth allele, which was found in four individuals is a novel HLA-C allele. The new allele, called HLA-Cw*0403 is most similar to HLA-Cw*0401, differing by 10 nucleotides, 9 of which are located in the region from nucleotide 98 to 218. This region of Cw*0403 is identical to both HLA-Cw*0201 and Cw*02022. The 9 nucleotide differences between Cw*0401 and Cw*0403 result in 6 amino acid differences in the alpha 1 domain. These amino acids in Cw*0403 may contribute to the serological typing of some, but not all Cw*0403 expressing cells. The Final difference between Cw*0401 and Cw*0403 is a coding substitution at nucleotide 979 in exon 5. The guanine found in Cw*0403 is identical to all HLA-C alleles except HLA-Cw*0401, which has an adenine. The Cw*0403 allele was most likely formed by a gene conversion event between Cw*02 and Cw*04, involving a minimum of 121 to a maximum of 215 nucleotides.

Alleles↗

Accurate synapse regeneration despite ablation of the distal axon segment.

In each body ganglion of the leech Hirudo medicinalis there is a single S-cell. After an S-cell axon is severed, it regenerates along its surviving distal segment and reconnects with its synaptic target, the axon of the neighbouring S-cell. In approximately half the cases the regenerating axon forms a temporary electrical synapse specifically with the distal segment, which remains active and connected to the target, thereby functioning as a splice until regeneration is complete. To determine whether the distal axon segment is required for successful regeneration, distal segments of severed S-cell axons were ablated by intracellular injection of bacterial protease. Fifty-seven preparations were examined from 2 to 212 days after injection of the axon segment. The extent of S-cell axon regeneration was assessed electrophysiologically by intracellular and extracellular recording, and anatomically by intracellular injection of markers followed by light microscopy and electron microscopy. The S-cell axons regenerated successfully in almost 90% of animals examined after 2 weeks or more. In a further four animals the target S-cell was ablated in addition to the distal axon segment, permanently disrupting conduction along the S-cell pathway. Nevertheless, the regenerating axon grew along its usual pathway and there was no evidence that alternative connections were formed. It is concluded that, although the distal axon segment can provide a means for rapid functional repair, the segment is not required for reliable regeneration of the axon along its usual pathway and accurate formation of an electrical synapse.

Animals↗

Neuronal diversity in the subiculum: correlations with the effects of somatostatin on intrinsic properties and on GABA-mediated IPSPs in vitro.

1. We used intracellular current-clamp techniques to record from 33 ventral subicular neurons in slices or rat hippocampal formation. Presumed pyramidal neurons were characterized by their responses to depolarizing current pulses as either intrinsically burst firing (IB) or regular spiking (RS). Within the subiculum, IB cells were encountered most frequently in the deep cell layer, whereas RS cells were encountered most frequently in the superficial cell layer. IB cells had more depolarized resting potentials, lower input resistances, and more sag in their voltage responses to hyperpolarizing current pulses. 2. Somatostatin (5 microM) applied in the bathing medium caused a hyperpolarization and reduction in input resistance. These effects were of greater magnitude in IB cells. Somatostatin had no effect on sag in either cell type. These effects of somatostatin were unchanged in the presence of gamma-aminobutyric acid (GABA) receptor antagonists. 3. In a series of experiments conducted in RS cells only, somatostatin reduced the amplitude of the late but not the early component of evoked biphasic inhibitory postsynaptic potentials (IPSPs). 4. A second series of experiments was conducted in RS and IB cells. Somatostatin reduced the amplitude of pharmacologically isolated GABAA IPSPS in both cell types. In IB cells but not RS cells there was a correlation between this effect and the somatostatin-induced hyperpolarization. Somatostatin also reduced the amplitude of isolated GABAB IPSPS in both cell types, but more so in IB cells. 5. Somatostatin had no effect on the reversal potential of either IPSP in either cell type and no effect on the GABAA-mediated conductance in either cell type. In contrast, the GABAB-mediated conductance was reduced, especially in IB cells. 6. The effects of somatostatin on GABAA IPSPS are principally a result of membrane shunting and reductions in ionic driving force, but these mechanisms do not account for the reduction in GABAB IPSPS. 7. We suggest that the combined effects of somatostatin are likely to alter the balance between fast and slow inhibition and to do so more in IB cells than in RS cells.

Animals↗

Effects of somatostatin and related peptides on the membrane potential and input resistance of rat ventral subicular neurons, in vitro.

The effects of bath-applied somatostatin (SS), and related peptides on the membrane potential and input resistance of 117 ventral subicular neurons were investigated by intracellular recording in rat brain slices. Electrophysiological properties, which included burst-firing in response to depolarizing current pulses, indicated that the neurons studied were of the pyramidal type. For the 89 cells analyzed quantitatively, membrane potential was -69.1 +/- 0.3 mV (mean +/- S.E.) and input resistance was 23.9 +/- 0.5 megohms. SS (5 microM) caused a hyperpolarization of 3.4 +/- 0.3 mV (n = 9) and reduced input resistance by 16 +/- 3.1% (n = 6). SS D-Trp8, somatostatin, octreotide, CGP 23996 and MK 678 shared these effects, but somatostatin was inactive. SS effects persisted when bathing solutions contained tetrodotoxin, reduced calcium and elevated magnesium concentrations and when both of these treatments were combined. They were unaltered by antagonists at gamma-aminobutyric acid receptors or at ionotropic glutamate receptors. The effects of MK 678, SS, SS D-Trp8 and somatostatin were concentration-dependent, and these peptides were equipotent at 500 nM and at 5 microM. For MK 678, the EC50 was 316 nM for the hyperpolarization and 90 nM for the reduction in input resistance. We conclude that SS acts directly on pyramidal neurons of the rat subiculum to cause a hyperpolarization and a decrease in input resistance. We suggest that these effects are mediated by the SSTR2 receptor subtype.

Animals↗

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↗

Aspects of current and future inhibin research.

Inhibin was first isolated in 1985. Major progress has been made in defining various aspects of its structure and physiology, using a heterologous radioimmunoassay. Current research is aimed at characterizing the nature of the circulating forms of inhibin and is examining whether there are sex-specific roles for inhibins A and B. It has been recognized that various forms of epithelial and stromal ovarian cancer produce members of the inhibin peptide family but the precise nature of these products is not yet clear. The recognition that the inhibin subunits together with follistatin are expressed locally within the pituitary has lead to an investigation of their possible roles in intrapituitary regulation. It is clear that these peptides also have intragonadal roles. Of particular current interest is the nature of the signals that control the specificity of cellular peptide production and that determine whether a particular cell produces inhibin or activin. The inhibins are members of a complex family with many potential roles in physiology and pathophysiology. The role of the inhibins in feedback control of follicle stimulating hormone in the male, particularly, remains unclear. New applications for inhibin and related peptides are likely to be developed.

Female↗

Hypertensive and normal pregnancy: a longitudinal study of blood pressure, distensibility of dorsal hand veins and the ratio of the stable metabolites of thromboxane A2 and prostacyclin in plasma.

OBJECTIVE: By combining serial measurements of the circulating concentrations of thromboxane A2 and prostacyclin with measurements of venous distensibility (taken during the pregnancies of both normal women and those with pregnancy induced hypertension or pre-eclampsia), to test the following hypotheses: 1. that changes in the venous plasma ratio of thromboxane (TXB2) and 6-keto-PGF1 alpha would correlate with changes in the blood pressure of women developing and recovering from pregnancy induced hypertension or pre-eclampsia and 2. that changes in venous distensibility would correlate with changes in arterial blood pressure in pregnancy induced hypertension or pre-eclampsia. DESIGN: Prospective, longitudinal cohort study. SETTING: John Hunter Hospital clinic, Newcastle, Australia. SUBJECTS: One hundred and sixty primiparous women, recruited when presenting for their first routine antenatal visit, were investigated at, or close to, 19, 28 and 37 weeks of gestation; a subgroup was also studied in the postnatal period. The measurements of the patients who developed pregnancy induced hypertension or pre-eclampsia were compared with those of controls selected from the cohort. MAIN OUTCOME MEASURES: Serial measurements of the circulating concentrations of the stable metabolites of thromboxane A2 and prostacyclin (TXB2 and 6-keto-PGF1 alpha, respectively), venous distensibility and immediate (no rest) and resting (for at least 30 min) blood pressures. RESULTS: There was no significant difference between the subject and control groups at any time during or after the pregnancy in the concentrations of prostaglandin metabolites, their ratio or venous distensibility. In contrast, there was a significant difference between the groups at 19 weeks for immediate and resting readings of diastolic pressure (6 mmHg (95% CI 1.5 to 10.5) and 4 mmHg (95% CI 0.1 to 7.9), respectively). These differences increased through the pregnancy but mean postnatal readings for the groups were almost identical suggesting that the subjects were not intrinsically hypertensive compared with controls. Blood pressures for the subject group, both immediate and resting, were significantly different from the 19 week readings at 28 weeks (diastolic) and at 37 weeks (systolic and diastolic). The only significant change from first readings among controls was in postnatal systolic pressure which was significantly higher than 19 week values, probably reflecting the vasodilatation, with accompanying hypotension, of early, normal pregnancy. This difference was not observed in those who subsequently developed pregnancy induced hypertension or pre-eclampsia. CONCLUSIONS: Our study was unable to demonstrate differences in circulating metabolites or venous distensibility between normotensive women and those with pregnancy induced hypertension or pre-eclampsia. If pregnancy induced hypertension or pre-eclampsia in humans represents not so much the presence of abnormal constrictor influences as a process initiated by failure of normal vasodilatation in early pregnancy, studies carried out later may detect mainly adaptive and secondary changes.

6-Ketoprostaglandin F1 alpha↗

Colonic preparation with Picolax: patient tolerance and approaches to fluid replacement.

Sodium picosulphate (Picolax) is widely used for bowel preparation prior to colonic investigation or surgery. The most troublesome side effect reported is headache, which has been thought to be due to dehydration. In a prospective randomized study we investigated the incidence of adverse effects in patients given Picolax prior to barium enema examination, and assessed the incidence of adverse effects with different oral fluid regimens. A total of 197 outpatients were allocated to one of five fluid regimens on the day prior to the enema: (a) 4 pints of Dioralyte (glucose and electrolyte solution); (b) 4 pints of half-strength Dioralyte; (c) 4 pints of water; (d) 6 pints of water; and (e) free fluids. In a questionnaire, 36% of patients had no headache (graded 0/5), while 38% had a significant headache (graded 3/5 or greater). Sixteen per cent had significant abdominal pain, 42% had dry mouths, 43% thirst and 34% tiredness or irritability. There was no correlation between headache and fluid regimen. Furthermore, we have found no evidence of dehydration. None of the five fluid regimens was shown to offer any advantage, and we therefore recommend that patients be allowed to drink according to thirst when taking Picolax.

Abdominal Pain↗

Integrated specialty and operational system for diabetes management in south west England.

The management and control of diabetes throughout South West England has been assisted by the use of a networked computerised information system which is totally integrated with hospital and community information systems. The objectives of the diabetes system are to produce an aid to diabetes management, which includes the creation of a district diabetes register accessed and maintained by clinicians based in both the hospital and in the community, whilst at the same time providing auditable information.

Delivery of Health Care, Integrated↗

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↗

Electrophysiology and burst-firing of rat subicular pyramidal neurons in vitro: a comparison with area CA1.

Intracellular recordings were made from subicular and CA1 neurons in slices of the ventral hippocampal and parahippocampal region of the rat. All of the subicular cells that were stained by intracellular injection of biocytin were pyramidal in form. Although most electrophysiological properties were similar in the two areas, in response to depolarising current injection, the majority of subicular cells displayed a distinctive pattern of burst-firing which was rarely seen in CA1 cells. Burst-firing was voltage sensitive but was not abolished by blocking excitatory synaptic transmission, suggesting that it is an intrinsic membrane property of subicular pyramidal cells.

Action Potentials↗

Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection.

Hepatitis B virus-specific nucleic acid sequences and proteins have been detected in extrahepatic tissues of acutely and chronically infected patients. However, apart from peripheral blood mononuclear cells and bone marrow cells, little is known about the specific cell types that permit viral replication. In this study, we assessed the extrahepatic tissues of four patients who died with chronic hepatitis B virus infection and two uninfected controls by means of in situ hybridization and immunohistochemical study. Three of these patients had diffuse extrahepatic distribution of the virus. Hepatitis B virus nucleic acid sequences and proteins were detected in the lymph nodes, spleen, bone marrow, kidney, skin, colon, stomach, testes and periadrenal ganglia. The following cell types were found to be positive for hepatitis B virus: endothelial cells, macrophages/monocytes, hematopoietic precursors, basal keratinocytes, mucosal epithelial cells, stromal fibroblasts and sustentacular and neuronal cells. It is probable that these cells could support viral replication because hepatitis B virus DNA replicative intermediates, viral transcripts and HBsAg and HBcAg proteins were detected in most. These findings may be relevant to the initiation of extrahepatic syndromes associated with chronic hepatitis B virus infection such as vasculitis, glomerulonephropathy, neuropathy and dermatitis.

Adult↗