Treatment of Gram-negative folliculitis with 13-cis-retinoic acid.
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Biomedical subjects
Publications and source records attributed to D H Jones.
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ULtrastructural examination was conducted on livers of young rats which were given (intraperitoneal injection) several methylated benzenes (73 mg/kg of body weight) for 3 consecutive days and on livers of aging rats (12 to 19 months old) which were fed methylated benzenes in the diet (200 mg/1,000 g of feed) for periods of 1, 2, 3, and 6 months. The young animals demonstrated white, raised, nodular lesions along the free margins of the liver. The lesions in young animals consisted of lipid droplets surrounded by macrophages and fibroblasts. Some fibroblasts in these lesions appeared to be active in collagen synthesis. Mast cells and eosinophils also occurred in the lesions. Hepatocytes in these young animals appeared morphologically normal. In contrast, hepatocytes in the aging rats developed 2 types of vacuoles. The 1st type of vacuole was bound by a double-unit membrane--the other unit membrane possibly derived from smooth endoplasmic reticulum; it contained a mottled, globular, electron-lucent material. The 2nd type of vacuole was peripherally located in hepatocytes, was single membrane-bound, and occasionally was observed opening into the space of Disse (spatium perisinusoideum). Our observations indicated that acute exposures (3 days) to at least some methylated benzenes does not cause ultrastructurally observable abnormalities in hepatocytes of young rats, but chronic oral ingestion of some can cause formation of vacuolar structures in aging rat hepatocytes.
Miniature Sinclair swine bearing cutaneous melanomas and nonmelanoma bearing littermate controls were tested for lymphocyte blastogenic response in a microculture assay. Lymphocytes were assayed for 3H-thymidine incorporation following stimulation with concanavalin A, phytohemagglutinin or pokeweed mitogen. Treatment with all mitogens revealed a significantly (p less than 0.05) reduced proliferative capacity in melanoma swine as compared to littermate controls. These results lend further support for the use of miniature Sinclair swine as a research model for human melanoma.
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The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in the Salmonella/mammalian microsome test. Urine samples obtained from hymenoxon-treated mice were found to be negative activity when tested directly and when incubated with beta-glucuronidase. Hymenoxon did not produce lethal DNA damage as measured in the Escherichia coli polA or Bacillus subtilis recombinational assays.
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Three sesquiterpene lactones (hymenoxon, helenalin, and tenulin) were tested for genotoxicity using six strains of Bacillus subtilis. Hymenoxon was found to produce lethal DNA damage in strains rec A8 and mc-1 while helenalin was lethal in strains mc-1 and rec E4. Tenulin did not produce lethal DNA damage in any of the strains tested.
Pretreatment of mice with the microsomal enzyme inducers, phenobarbital or polychlorinated biphenyl, or microsomal enzyme inhibitor, chloramphenicol, did not significantly alter the toxicity of hymenoxon. Pretreatment of mice with the hepatotoxin, carbon tetrachloride, provided significant protection against challenge dosages of hymenoxon. The LD50 of hymenoxon following carbon tetrachloride pretreatment was increased to 630 +/- 20.5 mg/kg as compared to the known oral LD50 of 241 +/- 10 mg/kg. These results suggest that a metabolite of hymenoxon may be responsible for the toxicity of this sesquiterpene lactone.
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Using techniques for enhanced microtubular preservation, including albumin pretreatment (Gray, 1975), occipital cortex of rats was studied electron microscopically at various ages of development. A close structural relationship was seen between microtubules, sacs of SER and the postsynaptic "thickening" in primordial spines and with the dense "plate" material of spine apparatuses. Stereoscopic preparations in addition show a more complicated substructure than previously described for the "plate". Microtubules may contribute to the formation of the "plate" of the spine apparatus which in turn is associated with the postsynaptic "thickening" of the mature spine. Possible functional correlates are discussed.
Microtubules were shown to remain intact in brain slices and subfractions maintained at 0 degrees C for 1 h. Under the same conditions, microtubules isolated from brain by warm assembly-cold disassembly methods, disassemble into their constituent subunit proteins. No selective depletions of microtubules were seen when brain slices were incubated in homogenizing buffer at either 0 degrees C or 37 degrees C. The response of native microtubules in brain slices in incubation in other solutions showed that their properties were otherwise the same as those of assembled microtubules. The separated alpha and beta subunits of isolated cold labile and cold stable microtubules were compared by electrophoresis and isoelectric focusing and were shown to possess the same mobilities. The results suggest that native microtubules are temperature insensitive and that isolated microtubules are assembled from pre-existing pools of subunit proteins. The results further suggest that native microtubules possess a factor, lacking in isolated assembled microtubules, which confers temperature stability on the former.
1. Forearm venous plasma noradrenaline, heart rate and intra-arterial blood pressure were measured sequentially during and after upright bicycle exercise in five normotensive and six hypertensive patients. 2. Plasma noradrenaline increased significantly between 4 and 8 min during exercise. 3. On stopping exercise blood pressure and heart rate decreased rapidly whilst plasma noradrenaline increased in each subject to reach a maximum at a median time of 108 s after exercise. 4. Plasma noradrenaline decreased in five of six normotensive patients between the end of exercise and 2 min after exercise performed in the supine position. 5. Evidence in favour of a reflex increase in sympathetic activity after upright exercise is discussed.
1. The 24 h urinary excretion of free 4-hydroxy-3-methoxyphenylethylene glycol (HMPG), HMPG conjugated as glucuronide and HMPG conjugated as sulphate was determined in nine healthy volunteer subjects and six patients with phaeochromocytoma. In both groups of subjects most (97%) HMPG was in the conjugated form. 2. Although patients with phaeochromocytoma excreted five- to ten-fold the amounts of each of the forms of HMPG excreted by the control subjects the ratio of these different forms of HMPG to each other did not differ significantly between the groups. 3. In cerbrospinal fluid and brain about 80% of HMPG was free and of the conjugated HMPG in these two tissues most was in the glucuronide form. 4. In is concluded from these data that both HMPG sulphate and HMPG glucuronide have a substantial peripheral origin and that measurements of their urinary excretion cannot be used as an index of brain catecholamine turnover.
1. Erythrocyte catechol-O-methyltransferase was studied in a population sample of 147 subjects. 2. There was a wide interindividual variability of catechol-O-methyltransferase activity, which was not unimodally distributed. Catechol-O-methyltransferase activity was not influenced by blood pressure, age or sex, nor was it related to plasma noradrenaline or urinary catecholamines or metanephrines. 3. It is not likely that inactivation of noradrenaline by O-methylation at least by erythrocytes is an important mechanism determining plasma noradrenaline, let alone arterial pressure.
1. Chronic beta-adrenoceptor blockade with oxprenolol causes elevation of plasma noradrenaline levels, as compared with placebo, despite a significant fall in blood pressure and pulse rate. 2. The plasma noradrenaline concentration is not influenced by the frequency of administration or the formulation of the drug. 3. Plasma noradrenaline levels are not correlated with the plasma concentration of the drug. 4. The changes in plasma noradrenaline concentrations support a peripheral rather than central mechanism of action of beta-adrenoceptor blockers in man.
A case is cited in which hydrallazine was used in conjunction with volume expansion as a novel approach to the improvement of orthostatic symptoms in a patient with idiopathic postural hypotension.
With the more widespread use of sensitive specific methods of measurements of catecholamines and metabolites, more emphasis must be given to assessment of dynamic indices of catecholamine turnover. Wide inter-individual differences in noradrenaline clearance from plasma and in resting endogenous production rate, together with individual differences in responsiveness, frustrate simplistic attempts to relate plasma level of transmitter with turnover. To assess catecholamine function adequately plasma and urinary levels of catecholamine and the main metabolites should be determined together with an index of responsiveness. Central nervous catecholamine turnover cannot be easily assessed from measurement of urinary metabolite excretion Cerebrospinal fluid concentration of MHPG may provide an index of brain noradrenaline turnover.
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