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PubMed1978

Functional properties of neurons in the monkey superior colliculus: coupling of neuronal activity and saccade onset.

One class of superior colliculus neuron was isolated which meets two criteria for participation in the initiation of visually elicited saccades. First, the pulse of spike activity recorded from these neurons was tightly coupled to saccade onset, preceding the onset of eye movements by approximately 20 msec. Secondly, if a visual stimulus sometimes elicited a saccade and sometimes failed to elicit a saccade, the occurrence of the spike pulse was highly correlated with saccade occurrence. For these neurons, there was a clear distinction between the most vigorous neuronal activity occurring in the absence of a saccade and the least vigorous activity accompanying appropriate saccades. These findings are consistent with views which attribute to the superior colliculus a role in the initiation of visually elicited saccades.

Animals↗

PubMed1986

The role of the subfornical organ in the drinking behavior of the pigeon.

Pigeons with radiofrequency lesions that damaged the subfornical organ (SFO) (n = 4) or that isolated it from adjacent structures (n = 5), but not sham-lesioned pigeons, were unresponsive to blood-borne (i.p.) ANG II (100 micrograms/pigeon) in the immediate postoperative period and for 60 days thereafter. These animals were less sensitive to hypovolemic challenge (20% PEG), but they responded normally to 24 h of water deprivation and to cellular dehydration. Despite their unresponsiveness to bloodborne ANG II, the lesioned pigeons drank normally to 10 ng of i.c.v. ANG II given as early as 10 days after surgery, and they drank reliably and vigorously but less in total volume to 100 ng i.c.v. They also drank quickly, vigorously, and in normal total volume to i.c.v. tachykinins and bombesins, and to the peripheral (i.p.) bombesins. Peripheral (i.m.) tachykinins produced only low volume and variable drinking in all birds tested regardless of brain damage. The SFO of the pigeon, like that of the mammal, is essential for drinking evoked by blood-borne ANG II and is not necessary for thirst aroused by ANG II acting from within the cerebral ventricles. Lastly, it does not mediate the dipsogenic effects of the tachykinins or the bombesins.

Angiotensin II↗

PubMed1984

Antibody-dependent cytolysis (ADCC) of tumor cells by activated murine macrophages is a two-step process: quantification of target binding and subsequent target lysis.

To analyze the antibody-dependent cell-mediated cytotoxicity (ADCC) reaction between tumor cells and activated murine macrophages in detail, it must be first determined if physical binding occurred between the two cell types. Over 15-20 min in vitro, antibody-coated HSB neoplastic targets became so firmly attached to the activated macrophages that they resisted removal with 4 vigorous washes. When a quantitative assay of binding was employed, attachment of tumor cells to activated macrophages was found to depend on the concentration of antibody and on the density of the macrophages. These two variables also determined the subsequent extent of cytolysis. Binding of antibody-coated targets by macrophages elicited with thioglycollate broth or activated by bacillus Calmette-Guerin (BCG) was comparable. Lysis by the activated macrophages, however, was far greater. Binding occurred at 4, 22, or 37 degrees C, while the subsequent lytic reaction occurred only at 37 degrees C. Thioglycollate broth effectively inhibited lysis but had no effect on binding. A porous filter placed between activated macrophages and targets resulted in abrogation of binding and lysis, even when antibody-coated targets were placed beneath the filters. When labeled, uncoated targets were added to cultures of macrophages in the presence of unlabeled antibody-coated targets, no lysis of the bystander (i.e., uncoated) targets was seen. The data suggest that ADCC is a multistep reaction, that vigorous physical binding of antibody-coated targets by activated macrophages is an initial and necessary step in ADCC, that such binding is not sufficient for ADCC, that such binding controls the selectivity of lysis in ADCC, and that the second step in ADCC results in target lysis.

Animals↗

PubMed1989

Generation of CD4+ blastoid T cells showing marked upregulation of CD4, class I and II MHC, and IL2 receptor molecules is required for the expression of potent encephalitogenicity.

The relationship between surface molecule expression and encephalitogenicity of myelin basic protein (BP)-sensitized cells induced by three different sensitization protocols was studied using adoptive transfer in Lewis rats. (i) In BP/CFA sensitization, CD4+ blastoid T cells showing marked upregulation of CD4, class I and II MHC, and IL2 receptor molecules, but not CD5, CD8, or CD45, were generated after culture with BP. In this case, BP-cultured cells were strongly encephalitogenic in the recipients. (ii) In the case of BP/IFA sensitization, CD4+ T cells showed no remarkable change of cell size or surface molecule expression after culture with BP and were weakly encephalitogenic in the recipients. Vigorous proliferation of the cells induced by addition of recombinant IL2 to the culture with BP neither enhanced the encephalitogenicity nor produced CD4+ blastoid T cells showing marked upregulation of CD4, class I and II MHC, and IL2 receptor molecules. (iii) The sequentially transferred naive T cells showed no remarkable change of cell size or surface molecule expression, even after a second culture with BP, and were the least encephalitogenic. These data suggest that the generation of CD4+ blastoid T cells showing marked upregulation of CD4, class I and II MHC, and IL2 receptor molecules but not vigorous proliferation correlates closely with the potent encephalitogenicity in vivo.

Animals↗

PubMed1990

Effects of dopamine D1 and D2 receptor agonists and antagonists on bombesin-induced behaviors.

Central administration of bombesin elicits excessive grooming and locomotor activity in rats. This grooming activity is one characterised by vigorous scratching of the face, nape and body flanks. Pretreatment with the D1 receptor antagonist SCH 23390 inhibited the expression of bombesin-induced activity with grooming being more inhibited than locomotion. Blockade of D2 receptors with eticlopride significantly attenuated the behavioral responses to bombesin. When SCH 23390 and eticlopride were administered concurrently, it was apparent that D1 blockade had a greater effect on grooming and D2 blockade a larger effect on locomotion. Stimulation of D1 receptors by SKF 38393 elicited non-stereotyped locomotor activity and a form of grooming behavior characterised by vigorous washing of the face and ventral body surfaces. Co-administration of bombesin and SKF 38393 resulted in a form of grooming which resembled that elicited by SKF 38393 alone. The specific D2 agonist PPHT elicited a form of locomotion characterised by a downward oriented head posture and slow ambulatory activity around the cage perimeter. Co-administration of PPHT and bombesin resulted in a complete suppression of bombesin-induced behaviors and was largely indistinguishable from activity observed under PPHT alone conditions. These data implicate both D1 and D2 receptor based mechanisms in the modulation/mediation of the behavioral effects of bombesin. Part of the bombesin-induced behavioral effects may be explained by (indirect) activation of (a) dopamine system(s).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Babesia bovis: bovine helper T cell lines reactive with soluble and membrane antigens of merozoites.

Babesia bovis-specific T cell lines were established from cattle infected with either tick-derived or cultured parasites by stimulation of peripheral blood mononuclear cells with a crude parasite membrane fraction. Induction and enrichment of CD4+ T cells occurred over time. All cell lines responded vigorously and in a dose-dependent, MHC-restricted manner to intact merozoites, and to soluble and membrane fractions derived from merozoites by homogenization and high-speed centrifugation. Solubilization of the membrane fraction with nondenaturing zwitterionic or nonionic detergents yielded antigenic extracts which also stimulated the T cells. However, a differential response was observed, in that cell lines from one animal proliferated vigorously to the detergent extracts of the membrane fraction, whereas cell lines from a second animal proliferated only weakly to these extracts. SDS-PAGE analysis revealed common protein bands of 90 and 22 kDa in the various immunogenic fractions. Cell lines from the animal infected with cultured parasites also responded to parasite culture supernatant "exoantigens" and to the related parasite, Babesia bigemina. We conclude that antigens present in merozoite membranes and soluble parasite extracts preferentially stimulate CD4+ T cells from cattle immune to Babesia bovis. The differential pattern of response of T cell lines from different cattle suggests that more than one protein or epitope is immunodominant for T cells.

Animals↗

PubMed1984

Crowding or ACTH treatment of pregnant mice affects adult copulatory behavior of male offspring.

Sexual behavior of male offspring from female mice chronically crowded during Days 12-17 of pregnancy was investigated. In an 80-min test pairing with a sexually experienced female primed with estradiol and progesterone injections, males from crowded mothers displayed poorer copulation than controls: mount and intromission latencies were longer, number of mounts and intromissions lower, and ejaculations within the test period were abolished. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor in offspring from crowded mothers. A second series of experiments investigated the effects of ACTH treatment of females during the same period of pregnancy. A low dose rate (1 IU injected daily) had little effect but male offspring from females injected daily with 8 IU displayed longer intromission latency and fewer mounts and intromissions than controls. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor, although mount frequency remained depressed. The similarity of the effects on male offspring copulation of crowding their mothers during pregnancy or ACTH treatment during pregnancy suggest mediation by similar mechanisms, implicating involvement of maternal pituitary-adrenocortical secretions during pregnancy in the production of these behavioral deficits. Postnatal influences were minimized by fostering all litters at birth to untreated dams.

Adrenocorticotropic Hormone↗

PubMed1990

Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome.

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.

Dumping Syndrome↗

PubMed1987

Dissociation of secretory responses to low-calcium and beta-adrenergic stimulation in primary hyperparathyroidism.

We have used a parathyroid cell perifusion system to evaluate the secretory responses to low-calcium and beta-adrenergic stimuli in series of 13 adenomatous human parathyroid tissues. In cells from all chief cell adenomas PTH secretion could be influenced by changes in extracellular calcium concentrations (either an increase in response to lower calcium concentrations or a decrease following an increase in calcium levels). However, there was marked heterogeneity in the PTH secretory response to adrenergic stimulation. In most instances, adenomatous parathyroid tissue also responded quickly and vigorously to beta-adrenergic agents (mean increase in secretion 322% +/- 52 (SEM) over baseline), although five of the 13 tissues clearly showed no PTH secretory response. Furthermore, there was a dissociation between the responses to adrenergic and low-calcium stimulation in that the presence or magnitude of the response to one type of stimulus could not be used to predict the nature of the response to the other. Studies of cells from an oxyphil adenoma revealed a very vigorous response to adrenergic stimulation (1,400% over baseline), but no response to changes in extracellular calcium concentrations. These results indicate that human parathyroid tissue is capable of a marked secretory response to adrenergic stimulation. The dissociation between secretory responses to low-calcium conditions and adrenergic agents suggests that the mechanisms of secretion by low-calcium and adrenergic stimuli in adenomatous human parathyroid tissue are to some degree independent. Furthermore, aberrancies in the neoplastic parathyroid process apparently may affect either of these two secretory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMedDate not supplied

Adult respiratory distress syndrome as a complication of acute pyelonephritis during pregnancy.

Two cases of ARDS as a complication of acute pyelonephritis during pregnancy are presented. The severity of the clinical condition necessitated treating both patients by mechanical ventilation with high positive-end expiratory pressure. The review of the only six other similar cases already reported (only one needing vigorous respiratory treatment) as well as the two cases presented in this report show that the pyelonephritic aetiology of ARDS in pregnancy is very rare. Nevertheless, any septic condition could be complicated by respiratory failure in pregnancy. ARDS must be suspected in those patients suffering from urinary tract infection in which signs of hypoxia appeared during the third trimester of pregnancy. Early recognition of the syndrome, closed monitoring and vigorous treatment can prevent maternal complications and/or fetal distress.

Acute Disease↗

PubMed1975

Ingestion in the satiated rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation.

Anterior perifornical hypothalamic injection of l-norepinephrine in satiated rats elicits a brief, vigorous drinking response followed within a minute or two by a vigorous feeding response. These adrenergically elicited responses, which bear striking similarities to a rat's naturally motivated ingestive behaviors, were examined in the present series of experiments. It was found that: (1) Both responses could be elicited by perifornical hypothalamic injection of l-epinephrine, which was actually found to be more potent than l-norepinephrine. In contrast, only feeding could be elicited by the alpha-stimulant metaraminol, and neither feeding nor drinking could be elicited by hypothalamic injection of d-norepinephrine. l-isoproterenol, or dopamine. (2) The threshold doses of l-epinephrine for eliciting reliable ingestive responses were quite low, namely, 0.8 nmole (0.15 mug) for drinking and 0.2 nmole (0.04 mug) for feeding. (3) Pharmacological analysis of the ingestive behaviors induced by l-norepinephrine or l-epinephrine indicated that the eating response was mediated by alpha-adrenergic receptors, whereas the drinking response involved the synergistic action of both alpha- and beta-adrenergic receptors. No evidence for the involvement of dopaminergic or cholinergic (muscarinic) receptors was obtained. (4) A third adrenergically elicited phenomenon, namely, a suppression of drinking, was observed during and after the period of induced feeding. Analysis of this effect revealed its dependence solely upon alpha-adrenergic receptor activity.

Animals↗

PubMed1990

Effect of clenbuterol on sexual behavior in male rats.

The intraperitoneal injection of clenbuterol, a beta-2 adrenoceptor agonist which readily penetrates into the brain, modified the copulatory pattern of male rats. In sexually vigorous rats, the acute administration of clenbuterol at the dose of 0.1 or 1 mg/kg reduced the number of mounts and/or intromissions and increased the postejaculation interval, while the repeated administration (7 days) of a dose of 0.1 mg/kg/day had no effect. In sexually sluggish rats, both the acute (0.01 or 0.1 mg/kg) and repeated (0.1 mg/kg/day x 7 days) administration of clenbuterol increased the percent of animals achieving ejaculation and succeeding in initiating a new copulatory series within the respective cutoff times, and reduced mount, intromission and ejaculation latencies, as well as the postejaculation interval. These data show that clenbuterol negatively affects the copulatory behavior of sexually vigorous male rats, but improves that of sexually sluggish ones, and provide further evidence that central beta-receptor activation produces behavioral effects.

Animals↗

PubMed1993

Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior.

Accumulating evidence indicates that neurokinins play a role in the neural regulation of male rat copulatory behavior. We have previously reported that injections of the neurokinin substance P into the medial preoptic nucleus facilitated male rat copulatory behavior. Recently, a number of other neurokinins, neurokinin K (neuropeptide K), neurokinin A (substance K), and neurokinin gamma (derived from the same gene as substance P), have been identified in the mammalian CNS. Therefore, in a series of experiments we examined the effects on male copulatory behavior following bilateral injections of different doses of neurokinin K (NkK), neurokinin A (NkA), or neurokinin gamma (Nk gamma) into the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BnST), or the caudate/putamen. Bilateral injections of NkK into the MPOA or BnST inhibited the expression of male copulatory behavior. The most marked effect was seen following bilateral injections of 0.25 and 0.52 nmol of NkK into the MPOA and the BnST. These injections produced a dramatic suppression of copulatory behavior in previously sexually vigorous male rats when compared to control injections. In contrast, bilateral injections of three different doses of NkA into the MPOA failed to affect any parameter of male copulatory behavior. Bilateral injections of 0.431 nmol of Nk gamma into the MPOA failed to affect the expression of copulatory behavior, but significantly delayed its initiation when compared to controls. Bilateral injections of 0.251 nmol of NkK into the caudate/putamen had no significant effect on copulatory behavior in sexually vigorous male rats when compared to control injections. The results of the present study provide further support for a role of neurokinins in the regulation of copulatory behavior in male rat. Taken together, these results suggest that the effects of neurokinins upon the expression of male copulatory behavior are site specific for brain regions in the sexually dimorphic vomeronasal pathway which includes the MeA, BnST, and MPOA.

Amygdala↗

PubMed1995

Maximal exercise and acute mood response in women.

The present study was designed to characterize and assess the reliability of acute mood responses to maximal exercise in women. All subjects (N = 22; age = 45 +/- 2.5 yr; BMI = 24.3 +/- 0.9 kg/m2) participated in two maximal walking tests spaced approximately one month apart. The abbreviated Profile of Mood States (POMS) questionnaire was administered immediately prior to and within 5 min following maximal exercise at both occasions. Maximal heart rate, rating of perceived exertion, and functional aerobic capacity responses indicated compliance to maximal exertion at both tests. Using repeated measures ANOVA, no significant (p < .05) differences were noted between the two tests for any of the POMS subscales. Significant pre to postexercise increases were noted for fatigue and self-esteem subscales while the tension and vigor affects significantly decreased. Because no interactions were found, these effects are concluded to be independent of the order in which the tests were performed. Additionally, intraclass correlations computed for each respective POMS subscale, ranged between 0.69 and 0.81 for fatigue, tension, vigor, self-esteem, confusion, and total mood disturbance. The anger and depression subscales were noted to have intraclass correlations of 0.29 and 0.43, respectively, and may have been influenced by a floor effect in this study population. It is concluded that the abbreviated POMS questionnaire may be reliably used to assess acute mood responses to maximal exercise in women and that even maximal exertion has the potential to acutely benefit mood by decreasing tension and increasing self-esteem.

Affect↗

PubMed1978

The hydrolysis of bile acid conjugates.

Studies were made of a) the relationship of bile acid structure and analytical recoveries (measured by 3-hydroxysteroid oxidoreductase) following vigorous alkaline hydrolysis of bile acid conjugates and b) the relationship of structure and hydrolysis time of taurine- and glycine bile acid conjugates in a reaction catalyzed by glycocholic acid hydrolase. Alkaline hydrolysis resulted in good recoveries of hydroxy and 7 and 12- oxo-bile acids but poor recoveries of 3-oxo-bile acids. Borohydride reduction of the 3-oxo-acids prevented these losses. Complete enzymatic hydrolysis of glycine conjugated bile acids was about five times more rapid than that of taurine conjugates. Hydrolysis of conjugates containing oxo groups was slow. Borohydride reduction of oxo-acids corrected this and did not inhibit enzymatic hydrolysis. It was concluded that both vigorous alkaline and enzymatic hydrolysis are satisfactory in bile acid assays if borohydride reduction is instituted before the hydrolytic step. However, due to the presence of possible enzyme inhibitors and solubility difficulties, strong alkaline hydrolysis is preferable to enzymatic hydrolysis in fecal bile acid determinations at this time.

Amidohydrolases↗

PubMed1982

Age-related changes in in vitro and in vivo survival of murine CFU-S and CFU-c.

Present evidence suggests that the proliferative potential of most cell types declines with age. An apparent exception to this is the erythroid and myeloid colony-forming cell (CFU-S) of the marrow. In an effort to reveal a latent proliferative defect in old marrow, CFU-S from the marrow of young and old B6AF1 mice were serially transplanted every 12 days into lethally irradiated young syngeneic hosts. Contrary to expectation, it was found that the number of CFU-S declined more slowly if the marrow had been obtained from old donors. Similarly, it was found that CFU-S, but not CFU-c, from old marrow replicated or were recruited more vigorously in long-term culture than CFU-S from young donors. The results obtained with anti-Thy 1.2 serum and complement treatment of old marrow cells suggest that CFU-S from old marrow replicate more vigorously because old marrow has more theta + helper cells or the old CFU-S is more responsive to theta + helper stimuli.

Aging↗

PubMed1991

Glomerular macrophage proliferation in experimental immune complex nephritis.

In immune complex nephritis, glomerular hypercellularity is known to result from the proliferation of intrinsic cells and from the infiltration of mononuclear cells, primarily macrophages. An immunohistochemical double-labeling procedure was used to determine whether macrophages were among the cells which may undergo mitosis within the glomerular tuft. The monoclonal antibody ED1 served as a macrophage marker; cells in the S-phase of mitosis were recognized by uptake of bromodeoxyuridine. Glomerular proliferation was studied in chronic serum sickness of LEW rats, an animal model of immune complex nephritis for which the relationship between immunopathology and pathophysiology has been well described. In normal glomeruli, resident mesangial macrophages accounted for an unexpectedly large proportion (greater than or equal to one-third) of the total mitotic activity. In immune complex glomerulonephritis, the rate of glomerular macrophage proliferation increased rapidly just at the onset of proteinuria and remained high throughout the remaining course of disease. Glomerular macrophages from rats with proliferative nephritis also divided more vigorously than normal in short term culture in vitro, while persistently expressing abnormal surface marker phenotypes. The proliferation of mesangial macrophages appears to be a prominent feature of the normal process of glomerular cell renewal. In hypercellular glomeruli, vigorous local proliferation could greatly amplify the potential of macrophages to cause damage.

Animals↗

PubMedDate not supplied

Mescaline treated rats attack immobile targets.

Rats were exposed to a series of targets in a shock induced aggression situation. Control rats fought most with moving targets, such as another normal rat, and did not attack immobile targets, such as a dead rat or a rat model. Rats treated with 15 mg mescaline/kg showed a similar pattern of target control though they bit frequently while controls did not bite. Rats treated with 50 mg/kg delivered vigorous biting attacks to a variety of targets but fought most with the immobile dead rat. They failed to attack only the rat model. Much of the data were consistent with the hypothesis that mescaline releases aggressive behavior from inhibitory control, leading to longer and more vigorous attacks on a wider variety of targets. This hypothesis, however, failed to explain why stationary targets were more effective for animals treated with 50 mg mescaline/kg while only moving targets were effective for controls.

Aggression↗