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Biomedical subjects

S L Lightman

Publications and source records attributed to S L Lightman.

At least 361 records · Page 20Linked to original sources
PubMed1987

Selective mediation of kappa-opioid central cardiovascular effects by ascending noradrenergic pathways.

The role of ascending noradrenergic pathways in the mediation of central opiate-induced cardiovascular effects has been investigated. The effects of selective kappa- and delta-opiate agonists microinjected into the nucleus tractus solitarius (NTS) of urethane anaesthetized rats were compared following 6-hydroxydopamine lesions of either the dorsal (DNAB) or ventral (VNAB) noradrenergic bundles. In sham lesioned animals both opiates elicited a significant pressor effect and a variable but consistent bradycardia. The delta-agonist responses were not modified in lesioned rats. In marked contrast the pressor effect of the kappa-agonist was abolished in both DNAB and VNAB lesioned rats. The bradycardic response was not significantly modified. These findings are consistent with previous observations that the cardiovascular effects of kappa- and delta-opiates in the NTS are mediated via different mechanisms, and provide evidence for selective functional actions of endogenous opioids within brain nuclei.

Afferent Pathways↗
PubMed1987

Vasopressin-induced turnover of phosphatidylinositol in the sensory nervous system of the rat.

Vasopressin and oxytocin immunoreactivity (AVP-IR, OT-IR) have been detected in the trigeminal and dorsal root ganglia (TG, DRG) of the rat. We have investigated whether AVP or OT have any neurotransmitter role in these tissues by measuring the effects of the peptides on levels of intracellular second messengers. AVP and OT at concentrations up to 3 x 10(-6) M have no effect on the accumulation of cAMP. However, in tissue prelabelled with 3H-inositol, and in the presence of 10 mM Li+, AVP and OT cause an increase in the accumulation of inositol phosphates (IP), in a dose-dependent manner. AVP causes a maximum stimulation of 1.7 fold of control in TG, (p less than 0.01) and of 2.5 fold in DRG (p less than 0.01) at a concentration of 3 x 10(-7) M. OT causes a maximum stimulation of 1.3 fold of control in TG, (p less than 0.01), and of 1.75 fold of control in DRG, at a concentration of 3 x 10(-6) M. The stimulation of IP turnover by AVP in both tissues is inhibited by the specific V1-antagonist, (CH2)5Tyr(Me)AVP, at a concentration of 2 x 10(-5) M. The V2-agonist, DDAVP, has no effect on IP accumulation in either tissue at concentrations up to 3 x 10(-6) M. The response to exogenous AVP is still present in ganglia incubated in media without added CaCl2. We conclude that the rat TG and DRG contain receptors for AVP, and that these receptors have characteristics associated with the V1 subtype.

Animals↗
PubMed1987

Antigen-directed retention of an autoimmune T-cell line.

We have used the T-cell-mediated, organ-specific autoimmune disease model of experimental autoimmune uveoretinitis (EAU) in the Lewis rat to study antigen-directed retention of autoimmune T helper cells in the target organ. We have compared the migration into the eye of two T-helper-cell lines: ThS, specific for retinal S antigen (S-Ag), that is uveitogenic to normal syngenic recipients, and ThP, specific to purified protein derivative of tuberculin (PPD), that is non-uveitogenic. The retention of adoptively transferred 51Cr-labeled ThS and ThP was studied up to the stage of disease induction in unprimed animals, during the acute stage of EAU induced by active immunization with S-Ag, and during the acute stage of a uveitis induced by a nonocular antigen (bovine serum albumin, BSA). Low numbers of cells from the two lymphocyte lines were detected in the eyes of unprimed animals, with no obvious increase of ThS over ThP, despite induction of EAU in the recipient animals by the injected ThS cells. In S-Ag-induced EAU many more ThS accumulated in the eye than ThP. In BSA uveitis both T-cell lines accumulated in the eye to the same extent, but more than in control noninflamed eyes. These results demonstrate the presence of increased antigen-specific retention of circulating autoimmune T helper lymphocytes during the acute stage of an ocular antigen-specific, but not ocular antigen nonspecific, inflammation. Since detectable accumulation of ThS cells in the eye was not a prerequisite for the induction of EAU, this phenomenon appears to be the result, rather than the cause, of the autoimmune process.

Animals↗
PubMed1987

Oxytocin stress responses are dependent upon emotionality.

Comparison of posterior pituitary responses to stress in rat strains with contrasting emotionality has revealed an inverse relationship between oxytocin (OT) responses and emotional reactivity. The plasma OT and arginine-vasopressin (AVP) responses to stress were determined in two psychogenetically selected strains of rat, Roman high avoidance (RHA) and Roman low avoidance (RLA), RLA's being more emotionally reactive than RHA's. Following 1 min immobilisation stress, plasma levels of OT were significantly higher in RHA's compared to RLA's. This finding correlates with the previous demonstration of a sex difference in the OT stress response, females having a higher response than males. Plasma levels of AVP were not significantly modified by immobilization in either strain of rat. However, control levels of AVP were markedly raised in both male and female RHA's.

Arginine Vasopressin↗
PubMed1987

Differential effects of beta-endorphin fragments on human natural killing.

The endogenous opiate peptide, beta-endorphin, has two effects on human natural killing (NK). Preincubation of effector lymphocytes with between 10(-7) and 10(-11) M beta-endorphin increases NK. Preincubation with lower concentrations results in a reduction in NK. Endorphin peptides containing an unmodified N-terminal sequence, and which are known to bind only to opiate receptors, increase NK. Sequences reported to bind only to nonopiate receptors reduce NK.

Cytotoxicity, Immunologic↗
PubMed1987

Reduced plasma renin activity in elderly subjects in response to vasovagal hypotension and head-up tilt.

The sympathoadrenal and renin-angiotensin systems play an important role in the cardiovascular responses induced by head-up tilt. In young people, hypotension and postural changes induced by tilt produce significant increases in plasma renin activity. The response of plasma renin activity to prolonged tilt and subsequent vasovagal hypotension has not been assessed in the elderly. Seventeen elderly subjects (10 with carotid sinus syndrome and seven age-matched controls) were studied during 45 minutes of recumbency and 120 minutes of head-up tilt to 40 degrees. Intra-arterial systolic blood pressure and heart rate were monitored continuously and plasma renin activity was measured at frequent intervals. Ten subjects developed vasovagal syncope during tilt (at 32 +/- 18 min). Systolic blood pressure and heart rate fell by 70 +/- 20 mmHg and 20 +/- 7 beats . min-1 (P less than 0.001 and P less than 0.01, respectively). Plasma renin activity did not change in syncopal subjects and remained unchanged up to 60 min after syncope. In seven subjects who completed 120 min of tilt without symptoms, heart rate rose during tilt but plasma renin activity remained unchanged. Plasma renin activity is not influenced by marked hypotension or prolonged head-up tilt in the elderly.

Aged↗
PubMed1987

Neuroendocrine control of vasopressin secretion and its effect on blood pressure in subjects with spinal cord transection.

The osmotic and cardiovascular control of arginine vasopressin (AVP) secretion, and the effect of this hormone on cardiovascular regulation were assessed both in normal controls and in subjects with tetraplegia. Infusion of hypertonic saline caused a marked rise in blood pressure in the tetraplegics but not in the normal controls. Head-up tilt resulted in a greater AVP response in the tetraplegics than in the controls because of the additional hypotensive response in the tetraplegics. Infusion of AVP itself at physiological concentrations had little effect on blood pressure in the normal subjects but resulted in a marked rise in blood pressure in the tetraplegics. Tetraplegics therefore show appropriate release of AVP to both osmotic and cardiovascular stimuli but increased sensitivity to the pressor effects of this hormone.

Adult↗
PubMed1987

Neurohypophyseal peptide function during early postoperative diabetes insipidus.

Neurohypophyseal function has been investigated in 11 children undergoing pituitary or suprasellar surgery. All had corticosteroid and thyroxine replacement; 9 developed diabetes insipidus (DI) within 1-12 h of operation. At the onset of DI, the plasma vasopressin (AVP) concentration was 3.9 +/- 1.2 pmol/l, considerably higher values usually associated with cranial DI (less than 0.9 pmol/l). AVP fell significantly to 1.1 +/- 0.2 pmol/l by the second day of DI. There was a similar change of levels of the AVP prohormone/carrier peptide, neurophysin I, but plasma oxytocin did not change significantly. High performance liquid chromatography of plasma at the onset of DI revealed a major peak that coeluted with synthetic AVP and two smaller peaks of AVP immunoreactivity. Seven patients required very large doses of desamino-8-D-arginine vasopressin (DDAVP) during the first day; 4 needed smaller doses on day 2. Water deprivation tests were performed on days 6 and 14 after operation in 5 patients with prolonged DI (2 with a triple response). There were no differences in plasma AVP on the two occasions but urinary AVP excretion rate was significantly higher on day 6 (2.4 +/- 0.8 pmol/h) than day 14 (0.7 +/- 0.3 pmol/h). It is concluded that early postoperative DI is not due to decreased levels of circulating AVP but may be related to the release of biologically inactive precursors from the damaged neurohypophysis. These may lead to renal refractoriness to AVP. There is a higher urinary AVP excretion rate on day 6 than day 14 after operation in both patients with a triple response and those with uninterrupted DI. Other factors may determine whether or not a transient resolution phase of DI occurs.

Adolescent↗
PubMed1987

Enhanced vagal activity and normal arginine vasopressin response in carotid sinus syndrome: implications for a central abnormality in carotid sinus hypersensitivity.

The relation between arginine vasopressin and vagal activity in carotid sinus syndrome was studied in 10 patients and 17 age matched controls using head up tilt as a stimulus. Of the controls, seven had unexplained syncope and 10 were healthy elderly subjects with no previous history of syncope. Subjects were studied supine for 45 min and thereafter during 120 min head up tilt to 40 degrees. Phasic arterial pressure and heart rate were monitored throughout. Serum was sampled at frequent intervals to measure arginine vasopressin, noradrenaline, and adrenaline concentrations. Seventy per cent of carotid sinus patients had vasovagal syncope at (mean(SD)) 25(4) min after tilt compared with 43% of subjects with unexplained syncope and one healthy elderly control. The maximum (mean(SD)) fall in systolic blood pressure and heart rate was 70(20) mmHg and 20(7) beats.min-1 (p less than 0.001 and p less than 0.01 respectively). Arginine vasopressin, noradrenaline, and adrenaline concentrations rose significantly in syncopal subjects (p less than 0.001, p less than 0.01, and p less than 0.05 respectively). Changes in systolic blood pressure, heart rate, and hormone concentrations were similar for patients with carotid sinus syndrome and control subjects. For those who completed the tilt period without the development of symptoms, systolic blood pressure and arginine vasopressin and adrenaline concentrations were unchanged, whereas noradrenaline concentrations and heart rate rose significantly. Vasovagal activity is thus appreciably increased in carotid sinus syndrome. Furthermore, the afferent limb of the carotid sinus reflex appears to be intact in patients with carotid sinus syndrome since the pattern of arginine vasopressin release was not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

The plasma arginine vasopressin response to insulin-induced hypoglycaemia in children with short stature is related to age and the onset of puberty.

The plasma arginine vasopressin (AVP) response to insulin-induced hypoglycaemia was investigated in 27 children with short stature. None had diabetes insipidus. Six patients were excluded from further analysis because of hypothalamo-pituitary dysfunction. Of the remainder, 14 were prepubertal (Tanner 1) and seven were pubertal (Tanner 2-4). Both groups had similar height velocity retardation. There was a significant rise of AVP of 3.4 +/- 1.3 pmol/l at 30 min in the pubertal group (P less than 0.05) but no significant change in prepubertal patients. There was a significant relationship between chronological age and AVP response 30 min after insulin (r = 0.45, P less than 0.05) and a closer correlation between bone age and AVP response (r = 0.62, P less than 0.01). The data suggest that insulin-induced hypoglycaemia does not reliably stimulate AVP secretion in children and that this response is related to age and pubertal stage.

Adolescent↗
PubMed1987

Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer.

One hundred and four patients were randomised for the study. Fifty-five were entered into the D-Trp-6-LHRH group and 49 into the orchiectomy group. All pre-treatment patient characteristics were similar and testosterone levels at 1 month or later were in the castrate range in both groups. Forty-six patients (83%) in the D-Trp-6-LHRH group and 40 (82%) in the orchiectomy group had a partial remission or stable disease at 3 months or later. There was no significant difference between the groups for response or survival. Three patients in the D-Trp-6-LHRH group had a disease "flare" in the first 10 days of treatment. The flare symptoms resolved by the end of 4 to 8 weeks. The incidence of flushing, decreased libido and impotence was similar in both groups. Although there was less psychological morbidity in the D-Trp-6-LHRH group the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6-LHRH offers a safe and highly effective alternative to orchiectomy.

Clinical Trials as Topic↗
PubMed1987

Quantitative assessment of the permeability of the rat blood-retinal barrier to small water-soluble non-electrolytes.

1. The passive permeability of the blood-retinal barrier (b.r.b.) to the water-soluble non-electrolytes, sucrose and mannitol, was determined using a multiple time point-graphical approach as has been used in the assessment of blood-brain barrier (b.b.b.) permeability. 2. The calculated permeability surface area product for the b.r.b. for sucrose was 0.44 (+/- 0.081 S.E. of mean) X 10(-5) ml g-1 s-1 (n = 20) and for mannitol was 1.25 (+/- 0.30) X 10(-5) ml g-1 s-1 (n = 18). These values are similar and comparable to those found for the capillaries in the brain (P greater than 0.05) and significantly different from zero (P less than 0.01). 3. Data on the concentrations of sucrose in different parts of the eye show that the permeability of the blood-retinal barrier, rather than the more permeable blood-aqueous barrier permeability, was being measured by our technique.

Animals↗
PubMed1987

Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor mRNA stimulation in the rat.

1. Cryostat sections were cut through the hypothalamus of rats which had been given a 2% (w/v) NaCl solution to drink for up to 12 days. 2. In situ hybridization histochemistry was performed on these sections using synthetic oligonucleotide probes against part of the precursor sequence for vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor (CRF). 3. Drinking 2% NaCl solution resulted in a progressive increase of vasopressin, oxytocin and dynorphin mRNAs hybridized in the magnocellular neurones of the supraoptic (s.o.) and paraventricular (p.v.) nuclei. No enkephalin mRNA was detected in the magnocellular areas of the control animals although small quantities of probe did hybridize after 12 days of salt loading and after the stress of I.P. hypertonic saline. 4. Ten-day-lactating female rats were also studied. They had a very marked increase in oxytocin mRNA with smaller increases of vasopressin and dynorphin mRNAs. No detectable enkephalin mRNA was hybridized in the magnocellular s.o. or p.v. nuclei and CRF mRNA was unchanged in both the s.o. nucleus and the p.v. nucleus.

Animals↗
PubMed1987

Controlled acute trial of a thyrotrophin releasing hormone analogue (RX77368) in motor neuron disease.

Twenty five patients with motor neuron disease completed a double blind randomised cross over trial of RX77368, a stabilised TRH analogue, iv over 2 hours against saline. Temporary improvement in bulbar symptoms including speech, respiratory parameters, tongue movements and swallowing were seen. Fasciculations increased and spasticity decreased. Change in muscle force with drug was different from placebo but both increase and decrease in force were seen and did not result in detectable changes in function. Side effects were clinically significant in 50% of the patients and cleared within 12 hours. Prolonged rise of thyroxine and an increase in plasma levels of prolactin, thyroid stimulating hormone and growth hormone were seen and followed characteristic patterns.

Adult↗
PubMed1987

Elevated cerebrospinal fluid vasopressin in motor neuron disease.

CSF vasopressin levels were significantly elevated in eight patients with motor neuron disease (2.5 +/- 0.4 pmol/l) compared with controls (0.7 +/- 0.1 pmol/l). CSF oxytocin and plasma vasopressin concentrations were similar in the two groups. This finding may be a primary part of the disease process or an epiphenomenon related to increased autonomic and descending pathway activity secondary to abnormal function and/or loss of anterior horn cells.

Aged↗
PubMed1987

Effects of endogenous atrial natriuretic peptide released by rapid atrial pacing in dogs.

The relationships between the hemodynamic, renal, and endocrine changes induced by rapid atrial pacing were studied in seven chloralose-anesthetized greyhounds paced from the right atrial appendage for 60 min at 250 beats/min. Pacing increased mean pulmonary wedge pressure, decreased cardiac output, and decreased mean arterial pressure. Systemic vascular resistance did not change significantly. Coronary sinus atrial natriuretic peptide (ANP) concentrations rose maximally within 5 min of commencing pacing. The corresponding increase in arterial ANP concentrations during this time was only 44% of its maximum value after 30 min of pacing. Plasma concentrations of arginine vasopressin were unchanged. Plasma renin activity decreased during pacing and showed a marked rebound increase at 60 min postpacing. Plasma norepinephrine levels did not change significantly during pacing. Urine flow increased during the latter 30 min of pacing. There was no significant change in sodium clearance despite high sustained concentrations of ANP. The lack of significant natriuretic and systemic vasodilator effects in association with high arterial plasma concentrations of endogenous ANP, in the absence of antagonistic mechanisms, suggests that the natriuretic and vascular effects of ANP may not be its major physiological actions.

Animals↗