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Biomedical subjects

S Lal

Publications and source records attributed to S Lal.

At least 145 records · Page 8Linked to original sources

Construction of a hybrid plasmid capable of replication in Amycolatopsis mediterranei.

A new plasmid, pA387, has been isolated from "Amycolatopsis sp." (DSM 43387). This plasmid could be isolated from liquid culture as well as mycelium from agar plates by a modified procedure. Plasmid pA387 is about 29.6 kb and can be cured at low frequency by protoplasting and ethidium bromide and heat treatment. Hybridization experiments showed that this plasmid is present in free form and does not integrate into the chromosome. A hybrid plasmid was constructed by cloning a 5.1-kb fragment of pA387 into the Escherichia coli vector pDM10. This hybrid plasmid, termed pRL1, could be transformed into Amycolatopsis mediterranei and A. orientalis by electroporation. A transformation frequency of 2.2 x 10(3) transformants per micrograms of DNA at 12.5 kV/cm and a pulse duration of 10.8 ms was obtained in A. mediterranei, whereas 1.1 x 10(5) transformants per microgram of DNA were obtained at a field strength of 7.5 kV/cm and a pulse duration of 7.6 ms in A. orientalis. Plasmid pRL1 is the first hybrid plasmid which could be used successfully for the transformation of A. mediterranei. The plasmid has a rather high copy number, is genetically stable, and can be easily reisolated from A. mediterranei. Plasmid pRL1 will be useful for further construction of a shuttle vector for E. coli and A. mediterranei and becomes the basis for the development of gene cloning techniques in Amycolatopsis spp.

Cloning, Molecular↗

Effect of bromocriptine in patients with apomorphine-responsive erectile impotence: an open study.

An open pilot study was undertaken to investigate the therapeutic effect of the dopaminergic agent, bromocriptine (BC), in impotent patients who developed an erectile response to the dopamine receptor agonist, apomorphine. Eight out of 17 patients reported improvement in ability to obtain an erection; five of these 8 subjects were able to achieve penetration. The optimum dose of BC was 2.5 - 11.25 mg/day. A double-blind placebo-controlled study is merited.

Adult↗

Role of HLA-DR antigen on T-cell activation in visceral leishmaniasis.

Ability of peripheral blood monocytes in association with HLA-DR molecules to support T-cell activation in response to soluble Leishmania donovani antigen was investigated. Adherent cells were stained with monoclonal antibodies. The increased number of cells with DR expression was more efficient in presenting L. donovani antigen to sensitized T-cells. The results suggest that quantitative variation in monocytes with expression of DR molecules, correlates with their ability to support T-cell response to L. donovani antigen, in vitro, as assessed by migration inhibition factor (MIF). However, it is not clear whether this is due to only HLA-DR antigen on the surface or whether other factors are involved.

Cells, Cultured↗

Effect of some peptides on dopaminergic function in man.

Thyrotropin-releasing hormone (TRH) (200 micrograms iv) and 1-desamino-8-D-arginine vasopressin (DDAVP) (4 micrograms iv) antagonized the growth hormone (GH) response to apomorphine HCl (Apo) (0.5 mg sc) in 10 normal men. Apo had no effect on basal prolactin (PRL) levels but antagonized the PRL response to TRH. DDAVP plus Apo decreased PRL compared to placebo or DDAVP alone. These observations are compatible with (a) an inhibitory effect of TRH on hypothalamic and pituitary lactotrophe dopamine (DA) function (b) a facilitory effect of DDAVP on lactotrophe DA function and an inhibitory effect on hypothalamic DA function. Whether these are direct or indirect effects on DA mechanisms is unclear.

Adolescent↗

Red cell choline in spasmodic torticollis and in a monozygotic twin pair with Tourette's syndrome.

1. Alterations in cholinergic function may play a role in the pathophysiology of idiopathic spasmodic torticollis (ST) and Gilles de la Tourette's syndrome (GTS). We measured red blood cell (RBC) choline in (i) ST (n = 24) and paired controls matched for age and gender (ii) a 20-year old pair of monozygotic twins with GTS, one of whom was moderately affected (CV) and the other virtually recovered (DV) (iii) both parents of the GTS twins, using gas chromatography-mass spectrometry. 2. RBC choline decreased with age in control men (r = -0.76; p less than 0.01) but not in control women. 3. RBC choline (nmol/ml) was higher in control men (18.3 +/- 4.8, X +/- SD) vs control women (13.1 +/- 4.3) (p = 0.025). 4. There was no significant difference in RBC choline (nmol/ml) between ST patients (16.6 +/- 5.0) and controls (15.5 +/- 5.2). 5. The RBC choline values (nmol/ml) in the twins and parents were: 56.6 (CV), 58.3 (DV), 89.8 (father), 38.3 (mother) and in the controls (age 20-24) (n = 5) 18.2 +/- 3.6. 6. These data suggest (i) RBC choline is affected by age and gender (ii) RBC choline is unchanged in ST (iii) the regulation of RBC choline is under genetic control (iv) elevated RBC choline is not a state marker for GTS.

Adult↗

Androgen binding sites in human temporal cortex.

We have characterized putative androgen receptor binding sites in five separate biopsy samples of human temporal cortex from epilepsy patients using an in vitro exchange assay with soluble fractions and [3H]5 alpha-dihydrotestosterone as radioligand. The results revealed highly specific, saturable binding with an apparent affinity constant (Kd) of approximately 2 nM with a moderate capacity (Bmax) of approximately 50 fmol/mg protein. In competition studies, we found that only testosterone and 5 alpha-dihydrotestosterone competed effectively (i.e. at low nanomolar concentrations) for [3H]5 alpha-dihydrotestosterone binding sites. These data indicate the presence of androgen receptors in human cortex that are pharmacologically very similar to that previously described in rodent and infrahuman primate CNS, and suggest the existence of a possible mechanism whereby circulating androgens might influence neuronal events in human cortex.

Adolescent↗

Apparent absence of serotonin1B receptors in biopsied and post-mortem human brain.

In order to determine if post-mortem delays could account for the apparent absence of 5-HT1B sites reported in human brain, 5-HT1B binding parameters were determined in fresh and fresh-frozen cortical biopsies and compared to results obtained in post-mortem tissues. Binding parameters and in vitro receptor autoradiography were performed by using two different ligands which have been shown to label 5-HT1B sites, namely [3H]5-HT, in presence of 100 nM 8-OH-DPAT, and [125I]cyanopindolol, in presence of 10 microM (-)isoproterenol. No specific binding was detected with [125I] cyanopindolol in either fresh cortical biopsies or post-mortem tissues, suggesting that the apparent absence of 5-HT1B receptor sites reported earlier was not related to long post-mortem delays. Some specific labelling was seen with [3H]5-HT, in presence of 8-OH-DPAT. This binding, which is unlikely to be to the 5-HT1B type, could represent labelling to the 5-HT1D or 5-HT1E sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Apomorphine: clinical studies on erectile impotence and yawning.

1. The erectile response to the short-acting dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.25, 0.5, 0.75 and 1.0 mg sc), and placebo was evaluated in 28 impotent patients and penile circumference monitored using a mercury strain gauge and strip chart recording. 2. A full erection (increment in penile circumference greater than 2 cm and lasting at least one minute) occurred in 17 patients with Apo; no erection developed after placebo. An erection occurred in 6/8 patients with impaired glucose tolerance, 2/6 patients with diabetes mellitus and in both patients on lithium. 3. Nine patients who responded to Apo were treated in an open trial with bromocriptine; 6 reported improvement in potency. 4. Impairment in DA function may play a role in idiopathic impotence and in impotence associated with impaired glucose tolerance and diabetes mellitus. 5. An erectile response to Apo may predict therapeutic response to bromocriptine or other long acting dopaminergic agents. 6. Lithium, which inhibits DA-sensitive adenylate cyclase, does not prevent Apo-induced erections. This provides further support indicating that Apo induces erections by an effect on D2 receptors. 7. The yawning response to placebo and four doses of Apo HC1 (3.5, 5.0, 7.0, and 10.5 ug/kg sc) was evaluated in five normal men using a polygraphic technique. The yawning response was also assessed in normal young (less than 30 yrs; N = 16) and elderly (greater than 60 yrs; N = 12) volunteers. 8. Under experimental conditions of study, placebo induced spontaneous yawning. This was antagonized by 3.5 and 5.0 ug/kg Apo HC1 but increased by 7.0 ug/kg Apo HC1. These observations are compatible with the view that Apo HC1 in doses of 3.5-5.0 ug/kg stimulates presynaptic DA receptors whereas 7.0 ug/kg stimulates postsynaptic DA receptors. 9. Spontaneous and Apo-induced yawning were significantly decreased in the elderly which suggests that D2 receptor function declines with normal aging.

Adult↗

Improvement in spasmodic torticollis following treatment and withdrawal from high dose lorazepam--clinical observations.

1. Six consecutive patients with idiopathic spasmodic torticollis (ST) in whom initial amelioration with lorazepam was lost, improved following withdrawal from high doses of lorazepam (3 entered remission or virtual remission; 3 showed marked to moderate improvement). None of 12 control patients improved. 2. The possibility that benzodiazepine-receptor mechanisms play a role in the pathophysiology of ST is proposed to explain these findings.

Adult↗

Neuroleptic-induced marching-in-place.

Marching-in-place (MIP) was observed in 12 out of 133 (9%) chronically hospitalized psychiatric patients and in none of 60 hospital staff controls. The prevalence was similar in both sexes. MIP was associated with tardive dyskinesia or parkinsonism or both but did not occur alone. Counting the number of steps per minute provides a reliable method to quantify MIP and may permit a simple objective method for investigating the neuropharmacology of this phenomenon. Preliminary observations suggest that anticholinergic agents may improve MIP in some patients but worsen it in others.

Adult↗

Abnormal food-seeking behavior after surgery for craniopharyngioma.

Three patients are described in whom surgical removal of a craniopharyngioma was followed by extreme hyperphagia resulting in obesity and abnormal food-seeking behavior, including foraging for food, stealing food or stealing money for food. These behaviors resemble those seen in the Prader-Willi syndrome but contrast with those noted in bulimia. This deviant behavior was a major factor in the poor outcome of surgery. Attempts at rehabilitation were unsuccessful.

Adolescent↗

Methysergide-induced psychosis: case report with long-term follow-up.

Methysergide, a congener of LSD and potent serotonin (5-HT) antagonist, induced a florid transient psychosis resembling an LSD psychosis in a patient with spasmodic torticollis with a family history of schizophrenia. Thirteen years later he developed a major depression. A variety of other drug challenges and treatments for his torticollis had no psychotomimetic effect. Blockade of 5-HT receptors may subserve methysergide-induced psychosis.

Adult↗