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Biomedical subjects

S Lal

Publications and source records attributed to S Lal.

At least 163 records · Page 9Linked to original sources
PubMed1989

Early regulation of c-myc mRNA by 1,25-dihydroxyvitamin D3 in human myelomonocytic U937 cells.

The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 10 nmol/l) on the human monomyelocytic cell line U937 were investigated. Addition of 1,25-(OH)2D3 led to a decrease in cell proliferation which fell at 72 h to 67.8 +/- 4.3% (mean +/- S.E.M.) of control values. The presence of CD14, a surface marker found on mature monocytes/macrophages but not on U937 cells, was detectable as early as 18 h and peaked at 48 h, when 63.6 +/- 4.2% of the cells were positive. However, changes in c-myc mRNA levels were detected earlier, starting within 4 h of exposure to the hormone and being reduced to 38 +/- 8.2% of control values of 24 h. These effects were reversible after removal of the hormone, with the same sequence of events seen following addition of the hormone. There was first an increase in c-myc mRNA levels, starting within 2 h and reaching control values by 24 h. These changes were followed by loss of CD14 which became undetectable after 72 h. Proliferation recovered slowly and incompletely, since it was 81.7 +/- 0.7% of control after 72 h. A constant reciprocal relationship between c-myc mRNA and CD14 levels was found both in the presence and after removal of 1,25-(OH)2D3. Regulation of U937 cell proliferation and maturation by 1,25-(OH)2D3 is thus preceded by early modulation of c-myc mRNA.

Blotting, Northern↗
PubMed1989

Risk factors for heterotopic ossification in spinal cord injury.

Heterotopic ossification (HO) is a complication in 16% to 53% of spinal cord injured (SCI) patients. One third of these patients have moderate to severe HO that adversely affects function or health. Pharmacologic prophylaxis of HO for all SCI patients continues to be controversial. High-risk criteria for HO formation identified in total hip replacement patients are not applicable to SCI. A review of the literature did not reveal specific risk factors for HO with SCI. The charts of 100 randomly selected SCI patients, 50 with HO and 50 without HO, were reviewed retrospectively to learn if criteria which would predict high-risk patients could be identified. A total of 14 variables, seven demographic (age, sex, race, level of lesion, completeness of lesion, cause of injury, and geographic locus of patient) and seven medical (bladder stones, fractures, pressure sores, deep vein thrombosis, pulmonary embolism, spasticity, and urinary tract infections) were studied. Four of the 14 variables (age, completeness of lesion, presence of pressure sores, and spasticity) were significantly related to HO formation. The risk factors appear to be additive. When all were present, 92% of patients were found to have HO. Before the findings are applied clinically, it is suggested that a prospective study be conducted to confirm the risk predictive value of these factors in HO.

Adult↗
PubMed1989

[Morphology of 3,4,5,3',4'-pentachlorinated biphenyl-induced change in canine lung].

We investigated the light and electron microscopical changes of the lung in dogs treated with 3,4,5,3',4'-pentachlorinated biphenyl (PenCB). Beagle dogs were orally administered with 0.1 mg/kg of PenCB, and sacrificed 3, 5 and 7 weeks after the PenCB administration. Light microscopically, bronchiolar epithelial cells showed cytoplasmic vacuolization, which was most prominent 5 weeks after the PenCB administration. Electron microscopically, nonciliated bronchiolar epithelial cells (Clara cells) revealed degradation of glycogen particles, swollen, irregularly arranged smooth endoplasmic reticulum, and swollen mitochondria, while no significant change was found in other epithelial cells. The endothelial cells also showed no significant change except for increased number of cytoplasmic vesicles. This is a first report on halogenated hydrocarbon-induced degradation of glycogen particles in Clara cells.

Animals↗
PubMed1989

1,25-Dihydroxyvitamin D3, but not retinoic acid, induces the differentiation of U937 cells.

We have examined the effects of vitamin D3 metabolites and retinoic acid on the myelomonocyte cell line U937. Inhibition of proliferation, measured by incorporation of 125iodo-deoxyuridine was seen at 72 h with 1,25-(OH)2D3 but not 25(OH)D3 or 24, 25(OH)2D3 metabolites. CD14 molecules, not normally present on U937 cells, were induced on the cell surface. However, Class II major histocompatibility complex (MHC) molecules were not induced and Class I MHC molecules not increased in density as determined by flow cytometry. Retinoic acid inhibited proliferation but failed to induce CD14 molecules. These data suggest that both 1,25(OH)2D3 and retinoic acid act as an antiproliferation signal to U937 cells; only 1,25-(OH)2D3 induces the differentiation towards a more mature phenotype.

Calcitriol↗
PubMed1988

Glucocorticoid binding sites in human temporal cortex.

This work describes the presence of glucocorticoid binding sites in human temporal cortex obtained following partial lobectomy in two epileptic patients. Using [3H]dexamethasone as radioligand and cold cortisol or RU 28362 as competitor we found an apparent Kd of approximately 2.8 nM with a Bmax of approximately 34 fmol/mg protein. The order of potency of various unlabeled steroids to compete for [3H]dexamethasone binding was as follows: RU 28362 = RU 38486 = cortisol = dexamethasone greater than progesterone greater than spironolactone greater than estradiol. These data provide evidence for an intracellular mechanism by which circulating glucocorticoids might regulate neuronal function in the human cortex.

Adult↗
PubMed1988

Apomorphine in the evaluation of dopaminergic function in man.

1. Apomorphine (Apo), a short acting dopamine (DA) receptor agonist, stimulates growth hormone (GH) secretion, decreases prolactin secretion, induces yawning, penile erections and other physiological effects in man. An effect on behavior, movement disorders and alcoholism has also been described. 2. Apo-mediated responses are used to evaluate DA function in psychiatric and neurological disorders. Many of the studies in schizophrenia using the GH response to Apo as an index of central DA function are difficult to interpret because of failure to control for key variables. 3. The GH response to Apo is a useful system to evaluate the effects of various drugs including peptides which may not cross the blood brain barrier on DA function in man. 4. Apo is a potent sedative. Specific antimanic, antischizophrenic, and anticraving effects in alcoholics have not been convincingly demonstrated. Side effects of Apo and failure to use active placebo make double-blind studies difficult. 5. Apo improves parkinsonian symptoms and certain forms of reflex epilepsy but beneficial effects in other involuntary movement disorders requires further documentation. 6. Apo may be a useful agent to evaluate DA function in impotent patients and predict a therapeutic response to long-acting dopaminergic agents. 7. Impairment of DA function may play a role in diabetic impotence. 8. The development of a simple polygraphic method to monitor the yawning response to Apo may facilitate clinical studies on the basic physiology of yawning in man and the use of the yawning response as a measure of central DA function in schizophrenia and other clinical disorders. 9. The use of Apo with 18F-fluorodeoxyglucose positron emission tomography to examine regional DA function in man opens up a promising area of research. 10. Though long-acting orally active aporphine DA agonists and antagonists have been developed the problem of tolerance may limit their therapeutic potential.

Apomorphine↗
PubMed1988

Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum.

Recently, two research groups published numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomography (PET). One study appeared to confirm the increase of D2 receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient populations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop identified differences between the approaches of the two groups that could contribute to the divergent results, including age and chronicity of the patient samples, brain region selected for study, metabolism of the different radioligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop concluded that these initial efforts had made considerable progress in establishing the role of PET in the understanding of the biochemical processes underlying mental illness. In particular, the unique ability to quantify regional neuroreceptor density at different stages in the evolution of the disease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these apparent discrepancies.

Adult↗
PubMed1988

Effect of hydrocortisone on basal and apomorphine-induced growth hormone secretion in normal subjects.

The effect of hydrocortisone (HC) (200 mg, i.v. over 15 min) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg sc), and on basal prolactin (PRL) secretion was studied in 11 normal male volunteers. In addition, the effect of HC on 3H-spiperone binding to rat striatal membranes was investigated. HC alone increased basal GH secretion compared with placebo (p less than 0.02) commencing 90 min after injection (p less than 0.05). When HC was given before Apo the GH response to Apo was blunted (p less than 0.05), and the delayed HC-induced increase was absent (p less than 0.001). HC or Apo alone had no effect on PRL secretion but HC plus Apo significantly decreased PRL concentrations compared with placebo (p less than 0.01) or HC alone (p less than 0.001). HC (0.1-100 microM) had no effect on 3H-spiperone binding in vitro. The mechanisms involved in the effect of HC on GH and PRL are unclear. The ability of HC to both stimulate and antagonize GH secretion points to multiple sites of action within the hypothalamic-pituitary axis.

Adult↗
PubMed1987

Coexistence of central and peripheral benzodiazepine binding sites in the human pineal gland.

The pineal gland and particularly its major hormone, melatonin, may participate in several physiological functions, including sleep promotion, anticonvulsant activity and the modulation of biological rhythms and affective disorders. These effects may be related to an interaction with benzodiazepine receptors, which have been demonstrated to be present in the pineal gland of several species including man. The present study examined the characteristics of benzodiazepine binding site subtypes in the human pineal gland, using [3H]flunitrazepam and [3H]PK 11195 as specific ligands for central and peripheral type benzodiazepine binding sites respectively. Scatchard analysis of [3H]flunitrazepam binding to pineal membrane preparations was linear, indicating the presence of a single population of sites. Clonazepam and RO 15-1788, which have a high affinity for central benzodiazepine binding sites, were potent competitors for [3H]flunitrazepam binding in the human pineal, whereas RO 5-4864 had a low affinity for these sites. Analyses of [3H]PK 11195 binding to pineal membranes also revealed the presence of a single population of sites. RO 5-4864, a specific ligand for peripheral benzodiazepine binding sites was the most potent of the drugs tested in displacing [3H]PK 11195, whereas clonazepam and RO 15-1788 were weak inhibitors of [3H]PK 11195 binding to pineal membranes. Overall, these results demonstrate, for the first time, the coexistence of peripheral and central benzodiazepine binding sites in the human pineal gland.

Aged↗
PubMed1987

Nicotine exposure and tardive dyskinesia.

The prevalence of tardive dyskinesia (TD) in chronic psychiatric outpatients was significantly higher in smokers (46/85) than in nonsmokers (18/69) (p less than 0.001). This increased prevalence was associated with a significantly greater prescribed dose of neuroleptics in women, but not in men. Nicotine increases the synthesis and release of dopamine in the nigrostriatal pathway of animals. Such a mechanism may contribute to the higher prevalence of TD in smokers. The present findings suggest that smoking is a risk factor for the development of TD. A statistically significant association between smoking and TD, however, does not necessarily imply a cause-effect relationship. Treatment of TD with mecamylamine or other central nicotine antagonists merits investigation.

Dyskinesia, Drug-Induced↗
PubMed1987

Bioconcentration and metabolism of DDT, fenitrothion and chlorpyrifos by the blue-green algae Anabaena sp. and Aulosira fertilissima.

Anabaena and Aulosira fertilissima showed a marked ability to accumulate DDT, fenitrothion and chlorpyrifos. Although the maximum accumulation of DDT was almost the same in both organisms, there were significant differences in their abilities to accumulate fenitrothion and chlorpyrifos. Patterns of uptake of DDT under different treatments were also similar in both Anabaena and Aulosira, but there were significant differences in the patterns of accumulation of fenitrothion between these two organisms. In Aulosira the maximum accumulation of fenitrothion was observed on the second day, whereas, in Anabaena, maximum accumulation was noticed on the first day. A completely different pattern of accumulation of chlorpyrifos was observed in Aulosira, which continued to accumulate chlorpyrifos throughout the experimental period. Bioconcentration of DDT in Anabaena and Aulosira ranged from 3 to 1568 ppm (microg g(-1)) and 6 to 1429 ppm, respectively. Bioconcentration of fenitrothion and chlorpyrifos in Anabaena varied from 53 to 3467 ppm and 7 to 6779 ppm, respectively. In Aulosira the bioconcentration varied from 100 to 6651 ppm and 53 to 3971 ppm for fenitrothion and chlorpyrifos, respectively. Anabaena and Aulosira metabolised DDT to DDD and DDE. Amounts of these DDT metabolites detected in the organisms were dependent on the concentration of treatment. DDD was the major, and DDE the minor, metabolite. These organisms were not able to metabolise the organophosphorus insecticides, fenitrothion and chlorpyrifos.

Journal Article↗
PubMed1987

A simple method for the study of yawning in man induced by the dopamine receptor agonist, apomorphine.

Apomorphine (Apo), a dopamine (DA) receptor agonist, induces yawning by stimulating central DA autoreceptors. Few data are available on Apo-induced yawning in man. A simple method for recording and measuring Apo-induced yawning by measuring the displacement of the lower jaw using a pair of linearlized magnetometers with one sensor attached to the forehead just below the hairline and the other under the chin is described. The output of the magnetometers is fed into a DC amplifier and displayed on a strip chart recorder. Complete concordance between evaluators reading the tracings and between observed yawning and recorded yawns was found. Measuring Apo-induced yawning may provide a simple approach to evaluating DA autoreceptor function in normal subjects and in patients with psychiatric and neurological disorders. Preliminary data show that Apo-induced yawning is more marked in women than in men. This is in contrast to spontaneous and drug-induced yawning in animals which is predominantly a male phenomenon. Sleep appears to inhibit Apo-induced yawning.

Apomorphine↗
PubMed1987

Effect of apomorphine on melatonin secretion in normal subjects.

There is some evidence in animals that dopamine (DA) affects melatonin secretion. The effect of apomorphine (Apo), a selective DA receptor agonist, and placebo on day-time melatonin secretion was studied in six normal men. Apo HCl in a dose (0.5 mg sc) which increased growth hormone secretion in all subjects had no effect on day-time melatonin concentrations in plasma. In keeping with other clinical studies these data suggest that melatonin secretion is not regulated by a DA mechanism in man.

Adolescent↗
PubMed1987

Apomorphine-induced penile tumescence in impotent patients--preliminary findings.

Apomorphine (Apo), a short acting dopamine (DA) receptor agonist induces penile erections in normal subjects. The erectile response to one or more doses of Apo HCl (0.25, 0.5, 0.75, 1.0 mg sc) or placebo was investigated in eight impotent subjects and penile tumescence monitored using a mercury strain gauge and strip chart recording. Four patients showed a full erection with Apo and one a partial response. Distressing side effects (nausea, sweating) were associated with non-response or partial response. Three responders to Apo were treated with low doses of the long acting DA receptor agonist, bromocriptine (2.5-3.75 mg/d po); all three showed complete recovery of erectile function within two weeks. A subgroup of impotent patients may have impaired central DA function. Testing with Apo may provide a diagnostic and predictive test to identify such patients who may respond to treatment with low doses of bromocriptine or other DA receptor agonist.

Adult↗
PubMed1987

Muscarinic, benzodiazepine, GABA, chloride channel and other binding sites in frontal cortex in hepatic coma in man.

Alterations in several neurotransmitter systems in brain have been implicated in the pathophysiology of hepatic coma (HC). Studies on human autopsy material are few. We investigated 3H-quinuclidinylbenzilate (QNB), 3H-spiperone, 3H-imipramine, 3H-PN-200-110, 3naloxone, 3H-flunitrazepam, 3H-muscimol, 35S-t-butylbicyclophosphothionate and 3H-cyclohexyladenosine binding sites in frontal cortex from seven patients with HC and five controls. The density of 3H-QNB binding sites was significantly decreased and the affinity slightly increased in HC. The functional significance of these selective changes in muscarinic receptor binding sites is unclear. Further studies evaluating cholinergic function in HC are indicated. Acute studies in animals point to an increase in GABA and BZ binding sites in HC. The present results show that the BZ/GABA-receptor-chloride-ionophore complex is unchanged in HC in man. Serotonergic (5HT-2), adenosine (A-1), imipramine (5HT uptake sites), opiate (naloxone) and calcium channel antagonist binding sites are unchanged in HC.

Adenosine↗
PubMed1987

Effect of ascorbic acid on brain amphetamine concentrations in the rat.

Ascorbic acid is reported to have antiamphetamine effects in rodents. The effect of ascorbic acid (1 g/kg ip) on the half-life of amphetamine (10 mg/kg) in rat brain using 3H-amphetamine and on amphetamine-induced stereotyped behaviour was investigated. Ascorbic acid had no effect on amphetamine-induced stereotyped behaviour or on the half-life of amphetamine in brain. If ascorbic acid antagonizes amphetamine-induced behavioural responses this is unlikely to be a result of altering the pharmacokinetics of amphetamine.

Amphetamine↗