Fighting AIDS on the streets.
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Biomedical subjects
Publications and source records attributed to R Mason.
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The Interventional Radiology Group of the Royal College of Radiologists sent a questionnaire to major hospitals in the United Kingdom in 1982 and 1987 in order to assess the impact of the introduction and growth of interventional procedures on patient management over the 5-year period and to consider the implications of these data for the future staffing and equipment requirements of radiology departments. In the 194 hospitals correctly completing the most recent survey, a total of 30,794 interventional procedures were performed in a 12 month period, representing an overall increase of 116% since the previous survey of 1982.
Hypokalaemia (HK) is a risk factor for development of clinical arrhythmias, and epinephrine (Epi), released after myocardial infarction, may itself induce HK. The effects of selective beta 1- and beta 2-blockade with metoprolol (M) and ICI 118551 (I), respectively, and non-selective blockade with propranolol (P) against early ischaemia-induced arrhythmias were therefore compared in normokalaemic (NK) and dietary-induced HK rats. Plasma Epi, norepinephrine (NE), and K+ levels were also measured. All three blockers [5-10 mg/kg intravenously (i.v.)] were antifibrillatory in NK rats, whereas I and P (2-10 mg/kg) additionally reduced the number of ventricular premature beats. Coronary artery ligation increased plasma Epi levels in both NK an HK rats, but plasma NE increased further in HK rats. HK was also associated with an increased arrhythmia severity and negation of the antifibrillatory action of M. In contrast, I and P retained antiarrhythmic and antifibrillatory effects in HK animals and increased survival. Both I and P increased plasma K+ levels in both NK and HK animals whereas M did not. We concluded that beta 2-receptor-mediated HK after coronary occlusion may play a substantial role in arrhythmogenesis. Protection afforded by beta 2-blocking agents may be due to alleviation of HK in HK rats or to induction of hyperkalaemia in NK rats.
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The rationale and technique for preoperative retraction of a protrusive premaxilla in the bilateral complete cleft lip and palate patient are presented. Two types of pinned intraoral appliances are presented that can expand the palatal shelves while retracting the premaxillary segment. Findings from lateral cephalometric x-ray studies of eight appliance patients and six control patients with bilateral clefts but no appliance treatment are presented at age 15. The data indicate that the cephalometric values at age 15 are within the normal range for most patients. Incisor angulation was quite varied among the subjects.
We measured the concentrations of vitamin D-binding protein (DBP), total 25-hydroxyvitamin D, total 1,25-dihydroxyvitamin D [1,25-(OH)2D], and free 1,25-(OH)2D in sera of 107 patients with histologically proven chronic liver disease. Bone density measurements and dynamic skeletal histomorphometry were also performed. Osteoporosis, as defined by arbitrary criteria, was found in 42 patients (39%), while no patient had osteomalacia. Serum concentrations of vitamin D-binding protein, 25-hydroxyvitamin D, total 1,25-(OH)2D, and free 1,25-(OH)2D were reduced in patients with cirrhosis, but not in the noncirrhotic patients. Bone formation rates, which were low in 55 patients (51%), were correlated with liver functions, but not with the concentrations of either vitamin D metabolite. A subgroup of 44 patients with low serum 1,25-(OH)2D concentrations and low bone formation rates failed to show an appropriate increase in serum bone Gla protein after 1,25-(OH)2D3 administration even though serum concentrations of 1,25-(OH)2D rose normally. These data suggest that the bone disease in patients with hepatic disorders is not related to the serum concentrations of vitamin D metabolites or the effect of these metabolites on osteoblast function.
Indications of membrane alterations in vascular muscle cells of spontaneously hypertensive rats (SHR), compared to their Kyoto-Wistar normotensive controls (WKY), have led to further investigation of calcium channels. Previous work from this laboratory had shown the increased probability for opening of the longer-lasting (L-type) calcium channels in SHR, suggesting differences in number or modulation. These experiments have been carried out on the azygos vein of neonatal rats because that preparation has been characterized electro-physiologically, pharmacologically, and by contractile parameters. Divalent (inward) ion currents through the L-type calcium channels are more readily carried by barium than by calcium, a characteristic that is not true for the transient (T) channels. Because there is an increased ratio of L to T calcium channels in SHR, the substitution of barium for calcium is more apparent for inward current amplitude in SHR than in WKY. This increase in the sustained L-type calcium currents, appearing without increased blood pressure on the venous side in newborn animals, is suggestive of a genetic membrane alteration that could contribute to vascular muscle membrane changes important in the development of increased blood pressure. Description and differentiation of the ribbon shaped vascular muscle cells from cardiac muscle cells, and the potential for confusion of the two in older animals, was addressed. The predominance of T-type calcium currents in these azygos vein cells, which is likely to correlate with the predominance of rapid spontaneous contractions, offers a compelling reason for selection of azygos veins in Ca2+ channel comparisons to establish etiologic factors at the cell level in hypertension.
Treatment of male Wistar rats with sodium selenate (2.24 mg Se/kg, s.c.) inhibited their body weight gain for 24 hr, after which the animals recovered. Intraperitoneal injections of sodium-2,3-dimercaptopropane-1-sulphonic acid (60 mg/kg), meso-2,3-dimercaptosuccinic acid (50.9 mg/kg) and calcium disodium ethylenediamine-tetraacetate (500 mg/kg) 15 min after Se had no protective effect, whilst 2,3-dimercaptopropanol (15 mg/kg) inhibited the recovery of the Se-treated animal. Sodium diethyldithiocarbamate (DDTC, 70 mg/kg, i.p.) reduced the Se-induced loss of body weight but had no effect on the tissue disposition of 75Se when injected 15 min, 3 hr or 6 hr after a s.c. injection of sodium [75Se] selenite (50 microCi, 17.4 micrograms Se/kg). The citrate salts of bismuth (2.5 and 5 mg Bi/kg, s.c.), antimony (1.5 and 3 mg Sb/kg, s.c.) and germanium (40 mg Ge/kg, s.c.) also reduced the selenate-induced loss of body weight, whilst germanium citrate (40 mg Ge/kg) and bis-carboxyethyl germanium sesquioxide (80, 200 and 400 mg Ge/kg) promoted significant dose-related increases in the 24 hr urinary excretion of 75Se when given 15 min after sodium [75Se] selenite (30 microCi, 0.5 mg Se/kg, s.c.).
Several studies have implicated the suprachiasmatic nuclei (SCN) as a target for the action of melatonin in its regulation of seasonal and circadian behaviour. Single-unit activity from the SCN and adjacent paraventricular area and anterior hypothalamus was recorded using the in vitro rat hypothalamic slice preparation. Neurones were tested for responses to iontophoresed or pressure ejected melatonin (n = 62) and serotonin (5-HT, n = 80). The majority (n = 24-26) of melatonin-sensitive SCN neurones were inhibited by melatonin in a dose-dependent manner during the latter portion of the projected light phase of the circadian light-dark cycle. A putative melatonin antagonist, N-acetyltryptamine, exhibited concentration dependent mixed agonist-antagonist effects on melatonin-evoked responses.
Rats were housed in either continuous lighting (LL), an extended photoperiod of 18 h light-6 h dark (LD 18:6) or a 12 h light-12 h dark (LD 12:12) lighting cycle. The effects of these various lighting regimens on the sensitivity of dorsal lateral geniculate neurones to iontophoresed noradrenaline and serotonin (5-HT) was examined. Exposure to either continuous lighting or to an extended photoperiod (LD 18:6) resulted in the development of an enhanced responsiveness to iontophoresed noradrenaline (alpha 1-adrenoceptor) and 5-HT. The development of light-induced noradrenaline and 5-HT supersensitivity resembles the changes obtained with antidepressant treatments.
The effect of histamine on the release of endogenous noradrenaline and 5-hydroxytryptamine (5-HT) has been examined in slices of rat cerebral cortex. Histamine was found to produce a marked release of both amines from rat cerebral cortex at concentrations between 0.1 and 1 mM. This response to histamine was relatively resistant to removal of calcium ions from the incubation medium when compared to the release evoked by depolarising potassium stimuli. The response to 1 mM histamine was not, however, significantly inhibited by the H1-antagonist mepyramine (1 microM) or the H2-antagonist cimetidine (100 microM). Furthermore, impromidine which is both a potent H2-agonist and a potent H3-antagonist was without effect on the basal and histamine-stimulated release of endogenous noradrenaline and 5-HT. The response to histamine was, however, significantly attenuated by nisoxetine, fluoxetine and imipramine which are inhibitors of the amine uptake systems. The results of this study show that high concentrations (0.1 to 1 mM) of histamine can produce a marked increase in the release of endogenous 5-HT and noradrenaline from rat cerebral cortex, apparently via a non-receptor mechanism. This effect will need to be borne in mind in interpreting biochemical and behavioral responses to histamine in this concentration range.
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This paper describes the technique of sequential endoscopy and biopsy of the intact rat stomach. It is recommended that this procedure be performed on fasted animals with access to water only, when a mortality of only 4% can be achieved.
Class II (Ia) molecules of the major histocompatibility complex are important in the presentation of antigen to T cells and in the regulation of the immune response. Recent studies have suggested that many epithelial cell types can express class II molecules. We examined rat alveolar type II epithelial cells, a cell which can synthesize and secrete pulmonary surface-active material, for the expression of class II antigens. Using an indirect immunofluorescent technique with a mouse anti-rat class II monoclonal antibody (OX-4), the majority of type II cells isolated from pathogen-free Sprague-Dawley rats expressed Ia antigens as determined by fluorescent microscopy and cell sorter analysis. In culture, the Ia expression was lost from type II cells. The addition of recombinant interferon-gamma to cultures of type II cells induced the expression of class II antigens. These findings suggest that class II antigen expression on type II cells may have relevance to immune responses occurring in the lung.
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Using iontophoretic techniques we observed that in vivo isapirone (TVX Q 7821), a selective ligand for the 5-HT1A binding site, at low ejection currents (5-30 nA) antagonised 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT)-induced suppression of hippocampal unit activity, with little effect on baseline firing rate itself. At higher ejection currents (20-100 nA) or following prolonged application, isapirone inhibited unit firing. Responses to GABA were unaffected by isapirone. These data demonstrate that isapirone is a 5-HT1A receptor antagonist with partial agonist properties on 5-HT sensitive neurones in the rat hippocampus.
The rate and pattern of neuronal discharge in the hamster suprachiasmatic nucleus (SCN) was studied using an in vitro hypothalamic slice preparation. The firing rate of hamster SCN neurones (n = 183 cells) exhibited a circadian variation similar to that reported in the rat. SCN neurones tested for responses to pressure ejection of neuropeptide Y (NPY) (n = 49) were either tonically excited (65%) or unresponsive (35%). There was a tendency for more NPY-responsive cells to be recorded during the light phase of the circadian light-dark cycle.