Vertebral osteomyelitis presenting with pleuritic chest pain and bilateral pleural effusions.
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Humans↗
Biomedical subjects
D Currie
Publications and source records attributed to D Currie.
Detection of cadmium exposure in rats by induction of lymphocyte metallothionein gene expression.
The induction of metallothionein (MT) gene expression in lymphocytes of rats was determined in order to detect exposure in vivo to cadmium. Both acute and chronic CdCl2 exposures resulted in the induction of the MT-1 gene in lymphocytes as measured by standard RNA Northern blot analysis. Twenty-four hours following an ip injection of 3.4 mg/kg CdCl2, a ninefold increase in MT gene expression was observed in lymphocytes, as well as five- and sevenfold increases in liver and kidney, respectively. Oral exposure of rats to 1-100 ppm CdCl2 via drinking water resulted in an approximate twofold enhanced MT signal in lymphocytes after 6 wk, and a threefold increase after 13 wk of exposure to 100 ppm Cd. No increases in lymphocyte MT gene expression were observed after 3 wk of Cd exposure. Liver MT gene expression was substantially induced following chronic Cd exposure, while kidney was not, although this organ had a higher basal expression of the MT-1 gene. Analysis of tissue Cd burdens demonstrated a dose-response Cd accumulation in liver and kidney, but only kidney burdens increased substantially with prolonged Cd exposure. These results demonstrate the utility of lymphocyte gene expression assays to detect in vivo toxicant exposure, and thus their applicability as molecular biomarker assays for human exposure assessment.
Animals↗
Dynamic demonstration of proximal vergence and proximal accommodation.
The complex interactions between accommodation and vergence have been described by dual interactive models which include influences of convergence accommodation and accommodative vergence. Using an SRI Eyetracker, we investigated changes in vergence and accommodation stimulated while looking through prisms or lenses, and while looking at real targets located at different distances. Our results suggest that both proximal accommodation and proximal vergence are stimulated when looking from a distant to a near real target. We suggest that models of convergence and accommodation interactions include proximal accommodation and proximal vergence before the crosslinks.
Accommodation, Ocular↗
Central effects of the calcium antagonist, nifedipine.
1. Central effects of the calcium antagonist, nifedipine retard (10, 20 and 40 mg) and nifedipine capsules (10 mg) were studied in 14 healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included. Medication was administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion, and recordings of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Nifedipine did not alter performance levels on any of the skills tested, while oxazepam (15 mg) increased the number of errors (P less than 0.01) and reduced accuracy at continuous attention (P less than 0.01). 4. Nifedipine (10 mg) reduced total power of the EEG in the frequency range (0.5-30 Hz), and nifedipine (20 mg) increased total alpha power (7.5-13 Hz) (P less than 0.05). Oxazepam reduced alpha and increased beta 1 power (13.5-21 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Convergence accommodation: laboratory and clinical evaluation.
The accommodation stimulated by convergence, CA/C, was measured under laboratory and clinical conditions. There was a small nonlinearity to the CA/C ratios measured under laboratory conditions for three of six subjects. We found that convergence accommodation decreases with decreasing accommodative amplitude but not as rapidly as has been reported in the literature. Our results suggest that convergence accommodation can contribute substantially to the near accommodative response for many patients.
Accommodation, Ocular↗
Central effects of the angiotensin-converting enzyme inhibitor, captopril. I. Performance and subjective assessments of mood.
1. Central effects of single doses of captopril (12.5, 25 and 50 mg) were studied in fourteen healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included, together with a single dose of atenolol (100 mg). The drugs were administered double-blind at 11.00 h, and performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Captopril did not impair performance on any of the tests, but improved short-term memory (P less than 0.05) and increased the number of letters cancelled (P less than 0.05). Oxazepam reduced the number of substitutions completed in the digit symbol test (P less than 0.01), accuracy on continuous attention (P less than 0.05), number of letters cancelled (P less than 0.05), and rate of finger tapping (P less than 0.05), and increased choice reaction time (P less than 0.001). Atenolol reduced the rate of finger tapping (P less than 0.05), but increased the number of letters cancelled (P less than 0.05). 4. No effects on mood or on subjective feelings were evident with captopril. Oxazepam reduced subjective alertness (P less than 0.05), and atenolol increased feelings of sleepiness (P less than 0.05). 5. Although these observations suggest that central effects may exist with captopril, no adverse consequences have been established on performance or on subjective assessment of mood. Captopril may, therefore, be an appropriate drug for hypertensive patients engaged in skilled activity.
Adult↗
Central effects of the angiotensin-converting enzyme inhibitor, captopril. II. Electroencephalogram and body sway.
1. Effects of single doses of captopril (12.5, 25 and 50 mg) on the electroencephalogram (EEG) and on body sway were studied in fourteen healthy male subjects. Oxazepam (15 mg), as an active control, and two placebos were included in the study, together with a single dose of atenolol (100 mg). Medication was administered double-blind at 11.00 h, and assessments made before and at 2 and 4 h after drug ingestion. 2. There were no changes in the EEG with captopril. Oxazepam reduced the circadian rise in alpha activity, while atenolol decreased beta power. Delta activity was modified by both oxazepam and atenolol. 3. A reduction in lower frequencies of body sway (0.05-1 Hz) occurred with captopril, while the spectra were unaffected by oxazepam. Atenolol increased (P less than 0.05) activity in the frequency range 0.75-2.75 Hz. 4. These observations suggest that captopril is free of central effects such as sedation that may occur with beta-adrenoceptor antagonists. Reduced body sway with captopril could reflect improved integration of central and peripheral control of posture.
Atenolol↗
Nasal potential difference: a clinical diagnostic test for cystic fibrosis.
Patients with cystic fibrosis (CF) demonstrate a markedly more negative potential difference (PD) across respiratory epithelia than normal or "diseased" controls. A technique is described for the measurement of nasal PD in both children and adults. 145 non-CF subjects showed a mean PD of -19.0 mV (range -2 to -36) in comparison to 60 patients with cystic fibrosis with mean of -46.0 mV (range -32 to -77). Amongst the latter group those with more severe disease had a more negative PD. Measurement of nasal PD is easily learnt and rapidly performed and may provide an additional means of diagnosis for CF.
Adolescent↗
Activation of the K-ras oncogene in liver tumors of Hudson River tomcod.
Adult Atlantic tomcod collected from the Hudson River slightly north of New York City have an extremely high incidence (55-90%) of histologically defined hepatocellular carcinomas, whereas tomcod from control sites in Maine or Rhode Island exhibit little evidence of this condition. Genomic DNA was isolated from Hudson tomcod tumors and from normal Hudson and Saco River, Maine tomcod livers and tested for transforming activity in the NIH3T3 transfection assay. Six out of nine tumors (66%) tested proved positive. Southern blot analysis of all primary (6/6) transfectant and nude mouse tumor DNAs revealed evidence of an exogenous tomcod K-ras gene, while no activation of the H-ras gene was observed. These studies demonstrate that an outbred population of fishes and inbred mammals suffer genetic alternations at the same oncogene loci and suggest that similar pathways to neoplasia may be operative in both systems. Oncogene activation in naturally exposed feral populations may prove a particularly sensitive marker of environmental degradation in aquatic systems.
Animals↗
The effect of inhaled sulfur dioxide and systemic sulfite on the induction of lung carcinoma in rats by benzo[a]pyrene.
In a previous study at this Institute, inhaled sulfur dioxide (SO2) was shown to enhance the induction by inhaled benzo[a]pyrene (BaP) of squamous cell carcinoma (SQCA) of the respiratory tract of rats (S. Laskin, M. Kuschner, A. Sellakumar, and G. V. Katz, 1976, In "Air Pollution and the Lung," pp. 190-213). We attempted to confirm and extend this finding by using an experimental protocol intended to illuminate the role of SO2. Rats were treated with BaP by 15 consecutive weekly intratracheal instillations. Some of these rats were simultaneously exposed either to SO2 by inhalation or to sulfite/bisulfite anions that accumulated systemically from endogenous generation in rats with induced sulfite oxidase deficiency. The total treatment period spanned 21 weeks, after which the rats were observed for the development of tumors. BaP-treated rats began to die with SQCA of the respiratory tract at approximately 200 days after the first BaP treatment and at 2 years after the first treatment nearly all rats in the BaP-treated groups had died, most with SQCA. Survival in the control groups was excellent and the health of all groups (aside from pulmonary SQCA in BaP-treated groups) was also excellent. The probability of dying with a pulmonary SQCA in the experimental groups treated with BaP, BaP plus inhaled SO2, and BaP plus systemic sulfite/bisulfite was calculated by the logrank analysis. The data sets of SQCA probability from these groups were not statistically different (i.e., P greater than 0.05) by the chi 2 test indicating that, in this experiment, neither inhalation exposure to SO2 nor systemic exposure to sulfite/bisulfite anions affected the induction of SQCA of the lung by intratracheally instilled BaP. We conclude that the results of this study do not support an etiological role for either SO2 or sulfite/bisulfite anions in the induction of SQCA of the respiratory tract by BaP.
Administration, Inhalation↗
Central effects of beta-adrenoceptor antagonists. I--Performance and subjective assessments of mood.
1. Central effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) were studied in 12 healthy male subjects. Two placebo ingestions and an active control (oxazepam 15 mg) were included. Single doses were administered double-blind at 11.00 h, and assessments of performance and subjective feelings were made before, 2 h and 4 h after ingestion. 2. Performance was measured using letter cancellation, digit symbol substitution, continuous attention, choice reaction time, finger tapping, short term and immediate memory, critical flicker fusion and two flash fusion. Subjective feelings were assessed using twelve visual-analogue scales. 3. Oxazepam impaired performance at letter cancellation (P less than 0.001), digit symbol substitution (P less than 0.05), continuous attention (P less than 0.001), immediate recall (P less than 0.05) and finger tapping (P less than 0.05), but neither of the beta-adrenoceptor antagonists affected these measures. Propranolol (40 and 160 mg) also impaired short term memory (P less than 0.05), though it was not possible to establish this effect with atenolol. 4. Subjective alertness was reduced by oxazepam (P less than 0.01) and atenolol (P less than 0.05), while propranolol (40 mg) reduced anxiety (P less than 0.01) and propranolol (80 mg) impaired ability to concentrate (P less than 0.05). 5. The results suggest that both lipophilic and hydrophilic antagonists modify the central nervous system, though impairment may be difficult to establish with conventional tests. The observations on memory and alertness suggest that the central effect of beta-adrenoceptor antagonists may be subtle.
Adrenergic beta-Antagonists↗
Central effects of beta-adrenoceptor antagonists. II--Electroencephalogram and body sway.
1. Effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) on the electroencephalogram and on body sway, were studied in 12 healthy male subjects. The study was double-blind, and included two placebos and an active control, oxazepam (15 mg). Medication was ingested at 11.00 h, and assessments were made before, and at 2 h and 4 h after ingestion. 2. All doses of both beta-adrenoceptor antagonists modified the electroencephalogram, and the changes reported were statistically significant at probability levels of less than 5%. The circadian rise in alpha activity was reduced by both beta-adrenoceptor antagonists as well as by oxazepam. Atenolol also decreased beta activity. 3. Body sway was modified by atenolol and oxazepam (P less than 0.05). The increase with oxazepam was most marked in the low frequency component (0.05-2.25 Hz) of the spectrum, while atenolol modified only the component of higher frequency (2.25-4.0 Hz). 4. These observations suggest that propranolol and atenolol have a sedative effect, and that hydrophilic antagonists are unlikely to be free of central activity. The changes in body sway could imply that peripheral mechanisms may be modified at least with atenolol.
Adrenergic beta-Antagonists↗
Zygomaticotemporal approach to the basis cranii and basilar artery.
When using the zygomaticotemporal approach, one removes the whole of the zygomatic bone with its attachment to the masseter muscle, allowing a lower and more anterior approach to the interpeduncular cistern along the inferomedial surface of the temporal lobe. Minimal brain retraction is required to give an excellent view of the bifurcation of the basilar artery and of the suprasellar region.
Basilar Artery↗
Establishment of a rat nasal epithelial tumor cell line.
A new cell line designated NAS 2BL has been established from a rat nasal tumor induced by inhalation of the direct-acting carcinogen methylmethane sulfonate. The cells are epithelial in morphology, have a generation time of 34 h, require 10% fetal bovine serum for optimal growth, and exhibit keratinization at confluence. The karyotype is aneuploid, with several marker chromosomes, and the cells are transformed by the criterion of nude mouse tumorigenicity.
Animals↗
Multiple respiratory tract stenoses associated with mucociliary dysfunction.
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Animals↗
Expression of the CYP1A1 gene in peripheral lymphocytes as a marker of exposure to creosote in railroad workers.
We have conducted a pilot study to assess levels of cytochrome CYP1A1 gene expression in human peripheral lymphocytes as a molecular biomarker assay for polycyclic hydrocarbon exposure. Basal and 3-methylcholanthrene-induced levels of gene expression were measured by standard slot-blot mRNA analyses in mitogen-stimulated cultures of peripheral blood lymphocytes from creosote-exposed railroad workers and unexposed control subjects. Dermal and inhalation exposure of workers to creosote may vary substantially as a function of working conditions related to temperature. Therefore, blood specimens were collected from separate groups during the winter, fall, and summer. Basal and induced CYP1A1 gene expression levels were not elevated in workers from any of the three seasonal studies. However, induced/basal (inducibility) CYP1A1 mRNA ratios from workers sampled in the summer (when actual exposures were greatest) were significantly higher when compared to those of controls (P < 0.01). These studies demonstrate the potential usefulness of specific gene expression assays in human peripheral lymphocytes for the assessment of carcinogen exposure in human populations.
Adult↗