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Biomedical subjects

S Lear

Publications and source records attributed to S Lear.

17 recordsLinked to original sources
PubMed1995

Relationship between balance system function and agoraphobic avoidance.

There is a striking similarity between the situations avoided by people with agoraphobia and the environments which provoke disorientation in people with organic balance disorders. This study investigated the possibility that agoraphobia might be linked to balance system dysfunction by comparing the results of balance system tests in 36 people with symptoms of panic and agoraphobia and 20 normal controls. A traditional battery of audiovestibular tests was supplemented with moving platform posturography, which assesses the postural instability induced by disorienting perceptual conditions. Subjects also completed questionnaire measures of somatic symptoms of dizziness and anxiety, agoraphobic cognitions, avoidance behaviour and state anxiety. Over 60% of the Ss with symptoms of panic and agoraphobia were destabilised by the disorienting perceptual conditions, compared with just 10% of the normal controls. Postural instability was strongly related to reported agoraphobic avoidance (r = 0.63, P < 0.01), even after controlling for symptoms, anxiety and agoraphobic cognitions. In our discussion we consider alternative interpretations of these findings, future directions for research, and implications for therapy.

Adult↗
PubMed1995

Effects of anxiety arousal and mental stress on the vestibulo-ocular reflex.

Although the subjective reports of patients suggest that anxiety may aggravate vertigo and imbalance, there has been little research into how anxiety might directly affect balance system functioning. We conducted two studies to examine the effect of anxiety and arousal on the vestibulo-ocular reflex (VOR). In the first study, pre-lest fear ratings were obtained from 20 normal subjects and 36 anxious subjects immediately prior to rotation and caloric testing. Fear ratings were significantly correlated with the maximum slow-phase velocity (SPV) of nystagmus induced by caloric testing. In the second study, we assessed the VOR response to rotation of 36 normal subjects under 3 task conditions: a) minimal alerting (counting backwards during rotation), b) physical arousal (induced by exertion prior to rotation); c) mental arousal (induced by performance of stressful mental tasks during rotation). Both the physical and mental tasks induced a significant increase in heart rate compared with the alerting condition. The maximum SPV of the nystagmus induced by rotation was significantly greater during performance of the mental task than in the other two conditions. These combined results indicate that anxiety may influence the gain of the VOR.

Adolescent↗
PubMed1992

cAMP activates the sodium pump in cultured cells of the elasmobranch rectal gland.

The inorganic ion content of rectal gland cells cultured from Squalus acanthias was studied by electron probe analysis in order to determine the effect of stimulation by cAMP. Cell sodium was reduced by 30% (P less than 0.01) at 8 min after exposure to dibutyryl cAMP and theophylline and remained low at 25 and 33 min. Chloride content also fell significantly with stimulation. Although cAMP may activate several transport sites, the results are consistent with a direct effect of stimulation to increase the activity of the sodium pump in shark rectal gland.

Animals↗
PubMed1991

Twenty percent of biopsy specimens from sun-exposed skin of normal young adults demonstrate positive immunofluorescence.

Fifty normal healthy adults, aged 18 to 41 years, without a history of systemic diseases, dermatoses, or photosensitivity and who were not receiving medication were studied. Paired 3-mm punch biopsy specimens were obtained from the sun-exposed and the non-sun-exposed skin. The data from the study revealed a bright continuous band of immunofluorescence (IF) along the dermoepidermal junction in 10 (20%) of 50 sun-exposed skin biopsy specimens, as compared with none from non-sun-exposed skin biopsy specimens with the use of polyvalent antisera. Fractionated monospecific immunoglobulin demonstrated a bright continuous band of IF composed of IgG alone in one patient, IgA alone in two patients, IgG and IgA in combination in two patients, and the combination of IgG, IgM, and IgA in five patients. There was a statistically significant increase in positive IF in men (seven of 15) vs women (three of 35). This information suggests that in the examination of a patient suspected of having lesions of cutaneous lupus erythematosus, positive IF from sun-exposed skin is nonspecific and adds little information to the clinical and histopathologic findings.

Adolescent↗
PubMed1990

Somatostatin mediates bombesin inhibition of chloride secretion by rectal gland.

The function of bombesin-like peptide, a neurotransmitter present in nerve fibers of elasmobranch rectal glands, is unknown. Since the principal activity of the rectal gland is to secrete chloride, the effects of bombesin on chloride secretion and the role of somatostatin in this response was studied. Bombesin failed to stimulate secretion in rectal glands perfused in the basal state. When added to glands stimulated by a constant infusion of vasoactive intestinal peptide (VIP), bombesin (8 x 10(-7) M) reversibly inhibited chloride secretion by 56 +/- 9.7% and at the same time evoked a 10-fold increase in the liberation of somatostatin into the venous effluent. Inactivation of somatostatin by the addition of cysteamine partially suppressed the inhibitory effect of bombesin on glandular secretion. The effect of bombesin to reduce chloride secretion was completely prevented by the calcium channel blocker nifedipine, which inhibits neurotransmitter release. These results suggest that bombesin inhibits the effect of VIP to stimulate chloride secretion by releasing somatostatin from neurosecretory nerve terminals within the rectal gland.

Animals↗
PubMed1990

Prostaglandin E2 inhibits oxygen consumption in rabbit medullary thick ascending limb.

The effect of prostaglandin (PG) E2 on transport-dependent oxygen consumption (QO2) of rabbit medullary thick ascending limb (MTAL) cells was studied. Exogenous PGE2, at a concentration of 30 microM, inhibited ouabain-sensitive QO2 by 70%. Addition of either ouabain or bumetanide, after PGE2, further depressed QO2, whereas PGE2 had no effect when added after these transport inhibitors. There was no significant inhibition of QO2 by PGE2 in the absence of either Na or Cl. The QO2 of amphotericin-treated cells was inhibited by the addition of PGE2. Therefore the inhibitory effect of PGE2 was on the transport-dependent moiety of QO2 and was independent of Na entry. Other prostanoids had no significant effect on MTAL QO2. Suspensions of isolated MTAL cells accumulated PGE2 at about one-fifth the rate of outer medullary collecting duct cells. Finally, PGE2 caused an increase in intracellular adenosine 3',5'-cyclic monophosphate levels by approximately 100%. Although the precise mechanism of action is unclear, PGE2, which is synthesized by several cell types in the renal medulla, exerts an inhibitory effect on transport in rabbit MTAL.

Animals↗
PubMed1989

The effect of organotin compounds on chloride secretion by the in vitro perfused rectal gland of Squalus acanthias.

The effects of various organotins on membrane function and electrolyte transport were studied in the marine elasmobranch, Squalus acanthias. The isolated perfused rectal gland was used as a model of electrolyte transport. This gland can be stimulated to secrete chloride by atrial natriuretic peptide, veratrine, and vasoactive intestinal polypeptide although the mechanism of action of each secretagogue is different. By analysis of the inhibitory effect of an organotin in the presence of each secretagogue, the mechanism of inhibition can be inferred. Tributyltin (TBT) produced a reversible inhibition of epithelial transport at 10(-8) to 10(-7) M which resulted from inhibition of stimulus-secretion coupling in VIP-containing neurons within the gland. The transporting epithelial cells were unaffected at these concentrations. Trimethytin (TMT) produced inhibition at 10(-7) M which was not reversible and which affected primarily the transporting epithelial cells. Triethyltin and triphenyltin were without effect. The inhibitory effect of TBT and TMT was not affected by simultaneous administration of dithiothreitol. TBT also produced inhibition of oxygen consumption, Na+,K-ATPase, and proton ATPase in dispersed rectal gland cells. These results indicate that organotins are toxic to cell membrane functions which are intimately involved in the movement of electrolytes. This is the first evidence of toxicity to membrane transport functions in a marine species which is at risk from environmental exposure.

Animals↗
PubMed1987

Dibutyryl cyclic AMP inhibits transport dependent QO2 in cells isolated from the rabbit medullary ascending limb.

Because the medullary thick ascending limb of the loop of Henle is the target of several polypeptide hormones that stimulate adenyl cyclase in this nephron segment, we examined the effects of cyclic AMP on thick ascending limb of the loop of Henle cells isolated by enzymatic digestion and density gradient centrifugation from the outer medulla of the rabbit kidney. The functional parameter that was measured was transport dependent oxygen consumption. Oxygen consumption was measured using a polarographic oxygen electrode in a constant temperature chamber. We found that dibutyryl cyclic AMP inhibited oxygen consumption in a dose dependent way. Maximal inhibition was observed at a concentration of 10(-5) M. The effect of dibutyryl cyclic AMP was not present in the absence of either sodium, chloride or both implying that its effect is restricted to the sodium and chloride dependent oxygen consumption. The effect of dibutyryl cyclic AMP was additive to that of furosemide 10(-4) M while that of furosemide was not additive to that of cyclic AMP suggesting that the site of action of cyclic AMP is distal to that of furosemide. The effect of dibutyryl cyclic AMP was not additive to that of ouabain and was absent in cells where oxygen consumption was stimulated with amphotericin B in the absence of chloride indicating that it has no effect on Na-K-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP.

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. These include: perfusion with procaine (10(-2) M), perfusion with high Mg2+ (9.5 mM) and low Ca2+ (0.5 mM) concentrations, and addition to the perfusate of the calcium channel blockers nifedipine (10(-6)M), diltiazem (5 X 10(-5)M), or verapamil (10(-4)M). Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal gland nerves, into the venous effluent or perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhance local release of neurotransmitters.

Adenosine↗
PubMed1987

Sodium-potassium pump, ion fluxes, and cellular dehydration in sickle cell anemia.

We studied the role of the sodium-potassium pump in erythrocytes of 12 patients with sickle cell anemia (SS). Ouabain-binding sites per cell and pump-mediated Rb/K uptake were significantly higher in SS patients than in white or black controls. Ouabain-resistant Rb/K influx was also greater than in normal controls or patients with sickle cell trait. Deoxygenation of SS erythrocytes increased ouabain-sensitive Rb/K influx without altering ouabain binding, presumably as the consequence of an increase in the passive influx of sodium. Deoxygenation increased mean corpuscular hemoglobin concentration (MCHC) by 5.5%, and studies of the density distribution of SS cells indicated an increase in highly dense fractions known to contain sickled erythrocytes. Ouabain prevented the rise in MCHC and reduced the percentage of dense cells. These findings indicate a magnified role for the sodium-potassium pump in the pathophysiology of SS erythrocytes and suggest that its inhibition might prove useful in therapy.

Adolescent↗
PubMed1986

Cyclic AMP-dependent stimulation of Na,K-ATPase in shark rectal gland.

Scatchard analysis of 3H ouabain bound to isolated rectal gland cells as a function of increasing ouabain concentrations produced a concave curvilinear plot that was resolved into two specific sites with either a high (I) or low (II) affinity for ouabain. Cyclic cAMP/theophylline (+/- furosemide, 10(-4) M) increased the amount of 3H ouabain bound to the high-affinity site I. Vanadate, a phosphate congener which promotes formation of the ouabain-binding state of the enzyme, mimicked the effects of cAMP/theophylline at low concentrations of ouabain, suggesting that cAMP/theophylline increases binding to site I by enhancing the rate of turnover of resident enzyme. Enhanced 86Rb uptake seen following cAMP/theophylline administration was primarily associated with increased flux through the high-affinity ouabain site, and this stimulation was not obliterated by the co-administration of furosemide. A model was presented which suggested the presence of two noninteracting pools of enzyme or isozymes which exhibit either a high or low affinity for ouabain. Cyclic AMP both stimulated turnover via site I, and modified the kinetics of binding of 3H ouabain to site II. The (ave) Kd of 3H ouabain for site II was increased from 3.6 microM (controls) to 0.5 microM (cAMP/theophylline) and the Hill coefficient was modified from 0.45 (controls) to 1.12 (cAMP/theophylline), suggesting a transition from a negative- to a noncooperative binding state. While furosemide reversed the effects of cAMP/theophylline on site II kinetics, it did not obliterate cAMP/theophylline effects on site I. This suggests that cAMP may alter the intrinsic turnover rate of this particular pool of Na,K-ATPase in shark rectal gland.

Animals↗
PubMed1986

Atrial peptides inhibit oxygen consumption in kidney medullary collecting duct cells.

Atrial natriuretic peptides (ANP) stimulate renal Na+ excretion by poorly understood mechanisms, perhaps involving direct inhibition of Na+ transport in the kidney medulla. To examine the effects of ANP on renal cells directly, we prepared highly purified cell suspensions derived from inner and outer medullary collecting duct and thick ascending limb of rabbit kidney and monitored ouabain-sensitive oxygen consumption (QO2). Human ANP diminished QO2 by 27.4 +/- 1.6% (mean +/- SE) in inner medullary collecting duct cells but had no effect in cells derived from outer medullary collecting duct or thick ascending limb. The inhibitory effect of ANP was not additive with either amiloride or ouabain. ANP was without effect in the presence of amphotericin. These results indicate that ANP inhibited Na+ entry in inner medullary collecting duct cells. ANP-mediated inhibition of QO2 was dose dependent (Ki = 5.5 X 10(-10) M) and exhibited selectivity for peptide structure. These results suggest that atrial peptides enhance renal sodium excretion partly by direct inhibition of medullary collecting duct sodium transport.

Amiloride↗
PubMed1986

Isolated rectal gland cells: oxygen consumption and hormonal stimulation.

Cells isolated from rectal glands of Squalus acanthias, using collagenase and hyaluronidase digestion, retained normal morphological characteristics as judged by light microscopy of 1-micron plastic sections. Their oxygen consumption per unit weight was comparable to that of intact rectal gland studied either in situ, or by isolated perfusion, as well as that of rectal gland slices. Cellular respiration was stimulated by dibutyryl cyclic AMP and theophylline or by vasoactive intestinal peptide which stimulate secretion of chloride by the intact gland. Stimulated oxygen consumption was inhibited by ouabain and bumetanide and was proportional to the concentration of sodium or chloride in the incubation solution. The oxygen consumption of these cells parallels the secretory and metabolic behavior of the intact rectal gland, suggesting that it reflects energy demands for ion transport. The relative ease with which a homogeneous preparation of viable and active cells can be obtained and the apparent preservation of many of their key functional characteristics make this preparation a useful tool for the study of hormone-stimulated ion transport.

Adenosine↗
PubMed1985

Disparate mechanisms for hypoxic cell injury in different nephron segments. Studies in the isolated perfused rat kidney.

Hypoxic injury was evaluated morphologically in the proximal tubule and in the medullary thick ascending limb of isolated rat kidneys perfused for 90 min without O2 or with various metabolic inhibitors. Inhibition of mitochondrial respiration (with rotenone, antimycin, oligomycin) or of intermediary metabolism (with monofluoroacetate, malonate, 2-deoxyglucose) caused reduction in renal oxygen consumption, renal function, and ATP content comparable with those elicited by oxygen deprivation. Metabolic inhibition produced hypoxiclike injury in the first portions of the proximal tubule, S1 and S2 ("clubbing" of microvilli, mitochondrial swelling), and the extent of damage was correlated with the degree of ATP depletion. In the third portion of the proximal tubule, S3, hypoxiclike damage (cytoplasmic edema or fragmentation) occurred most consistently when both aerobic and anaerobic metabolism were inhibited simultaneously. In the medullary thick ascending limb, none of the metabolic or mitochondrial inhibitors used could reproduce the injury of oxygen deprivation. Thus, the proximal tubule and the thick ascending limb have markedly different responses to cellular energy depletion, suggesting disparate mechanisms for hypoxic injury along the nephron.

Adenosine Triphosphate↗
PubMed1983

De novo sterologenesis in the intact rat.

On the basis mainly of in vitro studies, the liver and, to a lesser degree, the small intestine are widely accepted as the major sites of de novo sterologenesis. Utilizing [3H]water, we have investigated de novo sterologenesis in intact rats. Greater than 80% of labeled nonsaponifiable lipids and more than 70% of the labeled cholesterol were localized to extrahepatic, extraintestinal tissues. Feeding cholesterol markedly suppressed hepatic sterologenesis but had little influence on extrahepatic sites of sterol synthesis. Similarly, partial hepatectomy, which greatly decreased sterol synthesis in the liver, also did not significantly affect the accumulation of labeled sterols in extrahepatic tissues; therefore, the transport of sterols from the liver did not account for a significant portion of labeled sterols in extrahepatic tissues. Cannulation of the thoracic duct demonstrated that transport of newly synthesized intestinal sterols to peripheral tissues also did not account for the large accumulation of labeled sterols in extrahepatic, extraintestinal tissues. The primary extrahepatic, extraintestinal sites of sterologenesis were the skin and remaining carcass. The lung, kidney, spleen, heart, ovary, brain, muscle and adipose tissue made minor contributions to de novo sterol synthesis. Therefore, tissues other than the liver and intestine, especially the skin and remaining carcass, are important sites of de novo sterologenesis in vivo.

Animals↗
PubMed1982

Intrapulmonary shunting during induced hypotension.

The effect of sodium nitroprusside (SNP) and nitroglycerin (TNG) on pulmonary shunting (Qs/Qt) in 14 consenting adults [nine with normal lung function and five with chronic obstructive pulmonary disease (COPD)] was studied under general anesthesia. Qs/Qt significantly increased (p less than 0.005) from 5.19% to 8.81%, whereas pulmonary arterial pressure (PAP) decreased from 18.5 to 8 torr (p less than 0.005) and pulmonary vascular resistance (PVR) decreased from 235 to 147.75 dynes . sec/cm5 (p less than 0.025) when SNP was administered to patients with normal lung function. Nitroglycerin increased Qs/Qt from 5.13% to 6.19% (p less than 0.005), whereas PAP decreased from 18 to 10 torr (p less than 0.005) and PVR decreased from 237 to 162.6 dynes . sec/cm5 (p less than 0.025) in these patients. In patients with COPD, SNP and TNG produced no significant changes in Qs/Qt, PAP, or PVR. Cardiac output remained unchanged in both groups of patients. Various mechanisms to explain these results can be postulated. When hypotension is induced in patients with normal pulmonary function. PAP decreases and the effect of gravity puts more blood through dependent areas where most of the shunt units are. In patients with COPD, destructive vascular changes increase PAP, preventing vasodilators from decreasing PVR. In addition, dilation of hypoxic pulmonary vasoconstriction (if present) by SNP and TNG will occur independent of the two previously mentioned mechanisms. These results provide evidence that SNP- and TNG-induced hypotension may cause significant impairment in pulmonary gas exchange in patient with normal lung function. In patients with COPD pulmonary gas exchange is not affected after deliberate hypotension with SNP or TNG.

Adult↗