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PubMed1992

Effect of ATG prophylaxis in sensitized and non-sensitized kidney graft recipients.

In our effort to find an optimum immunosuppressive protocol for kidney transplantation we introduced two forms of ATG prophylaxis: 1. high-dose single-bolus prophylaxis (9 mg/kg) in non-sensitized patients (PRA < 5%); and 2. low-dose 8-day prophylaxis (1.5-3.0 mg/kg) in sensitized patients (PRA > 5%). A total of 204 kidney graft recipients were included in this study and treated with a triple-drug therapy (TDT). In comparison with TDT-treated controls, in sensitized patients the 8-day ATG prophylaxis resulted in a reduced rate of rejection episodes (25.5% vs 47%), an improved 1-year graft survival (82% vs 71%) and patient survival (94% vs 90%). In non-sensitized patients the high-dose single-bolus ATG prophylaxis induced a T-cell lymphopenia lasting 4 to 5 days and, in comparison with the corresponding controls, resulted in a shortened hospital stay (31.2 days vs 36.7 days), a reduced rate of rejection episodes (25.5% vs 53%), an improved 1-year graft survival (92% vs 86%) and patient survival (100% vs 94%).

Antilymphocyte Serum↗
PubMed1985

The sensitizing capacity of Compositae plants. VI. Guinea pig sensitization experiments with ornamental plants and weeds using different methods.

Experimental studies in guinea pigs using ether extracts of 20 different species of the Compositae plant family were carried out with the open epicutaneous method (OET) and the guinea pig maximization test (GPMT). The results demonstrate that Cnicus benedictus (blessed thistle), Chrysanthemum leucanthemum (marguerite, ox-eye daisy) and Helianthus debilis (dwarf sunflower) are strong sensitizers while Helenium amarum (bitterweed), Gaillardia amblyodon (blanket flower), Artemisia ludoviciana (prairie sage), Ambrosia trifida (giant ragweed) and Solidago virgaurea (goldenrod) are medium sensitizers. Twelfe species revealed only a weak or no sensitizing capacity; among those were corn flower, wormwood, mugwort, coltsfoot and dandelion. Cross-reactivities were observed in a considerable number of the investigated plant species. The sensitizing power as well as the observed cross-reactions depend on the occurrence of sesquiterpene lactones which have an alpha-methylene group exocyclic to the lactone in common ("immunologic requisite"). As a practical consequence, patients suffering from allergic contact dermatitis due to Compositae species are strictly requested to avoid contact with the offending species and all related species to prevent recurrences of their skin lesions.

Allergens↗
PubMed1996

Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine.

Male Wistar rats (250-350 g) were injected (SC) daily with the putative selective dopamine D3 receptor agonist, 7-OH-DPAT (0.01, 0.10, or 1.0 g/kg) or vehicle for 10 days. Fifteen minutes after each injection, the rats were tested for locomotor activity in photocell arenas for 20 min or 2 h. In two experiments, following this subchronic treatment, all rats received a challenge injection of apomorphine (1.0 mg/kg, SC), or cocaine (10 mg/kg, IP) on day 11, and were tested for locomotor activity. In a third experiment, dopamine synthesis in striatal and mesolimbic (nucleus accumbens-olfactory turbercle) tissue was assessed following acute or chronic 7-OH-DPAT treatments by measuring the accumulation of dihydroxyphenylalanine (DOPA) after treatment with a DOPA decarboxylase inhibitor. Major findings were as follows: a) acute 7-OH-DPAT treatment produced a dose-dependent decrease in locomotor activity; b) when tested for 2 h, the 1.0 mg/kg dose of 7-OH-DPAT produced a progressively greater increase in activity across the 10 test days (i.e., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT did not result in cross-sensitization to either apomorphine or cocaine; d) acute treatment with the 1.0 mg/kg dose of 7-OH-DPAT significantly decreased dopamine synthesis in both striatal and mesolimbic regions; and e) chronic 7-OH-DPAT treatments did not affect basal dopamine synthesis in either brain region. Although the behavioral effects of 7-OH-DPAT were similar to the reported effects of the D2/D3 dopamine agonist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal dopamine synthesis. These results suggest that locomotor inhibition produced by low doses of 7-OH-DPAT is not related to dopamine autoreceptor stimulation, and the development of behavioral sensitization to high doses of 7-OH-DPAT is not due to the development of dopamine autoreceptor subsensitivity.

Animals↗
PubMed1998

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats.

Sensory neuropeptides, released from the peripheral nervous system, might modulate glucose homeostasis by antagonizing insulin action. The effects of de-afferentation of functional small diameter unmyelinated C-fibres (sensory nerves) on in vivo insulin-mediated intracellular glucose metabolism were investigated by using euglycaemic insulin (6 and 18 mU/kg x min) clamps with [3-(3)H]-glucose infusion in 24 adult rats, treated neonatally with either capsaicin (CAP) (50 mg/kg) or vehicle (CON). Following the clamp, skeletal muscle groups, liver and adipose tissue were freeze-clamped. At plasma insulin levels of approximately 90 mU/l, CAP-rats showed a 21% increase in whole body glucose uptake compared with CON (24.4 +/- 1.6 vs 20.1 +/- 0.8 mg/kg min, p < 0.02), which was paralleled by a 20% increase in whole body glycolysis (12.6 +/- 0.8 vs 10.5 +/- 0.5 mg/ kg.min p < 0.05) (concentration of 3H2O in plasma). Whole body skeletal muscle glycogenesis was increased by 80% in CAP-rats (5.7 +/- 0.7 vs 3.1 +/- 0.7 mg/kg x min, p < 0.05) with increased muscle glycogen synthase activity. Whole body (muscle, liver and adipose tissue combined) de novo lipogenesis also was increased in CAP-rats compared with CON (0.69 +/- 0.10 vs 0.44 +/- 0.06 mg/kg x min, p < 0.05) (incorporation of [3-(3)H]-glucose counts into glycogen or fat). Hepatic glucose production was lower in CAP-rats compared with CON (0.6 +/- 0.6 vs 2.1 +/- 0.7 mg/kg x min, p < 0.05). Plasma glucagon, corticosterone, epinephrine and norepinephrine levels were reduced in CAP-rats: 43 +/- 2 compared with 70 +/- 6 pg/ml, 855 +/- 55 compared with 1131 +/- 138 nmol/l, 513 +/- 136 compared with 1048 +/- 164 pmol/l and 928 +/- 142 compared with 1472 +/- 331 pmol/l, respectively, p < 0.05. At plasma insulin levels of approximately 400 mU/l, CAP-rats showed no differences in peripheral and hepatic insulin action compared with CON. We conclude that the removal of endogenous sensory neuropeptides, by de-afferentation of capsaicin-sensitive sensory nerves, increases in vivo insulin sensitivity, but not responsiveness: 1) primarily through an increased sensitivity of skeletal muscle glycogen synthesis to insulin; 2) through a reduction in the levels of counter-regulatory hormones, thereby creating a milieu which favours overall in vivo insulin sensitivity with respect to glucose uptake, glucose production, glycolysis, glycogenesis and lipogenesis.

Afferent Pathways↗
PubMed1998

Sensitivity to cocaine and amphetamine among mice selectively bred for differential cocaine sensitivity.

Selective breeding of mice for differences in response to a drug offers a powerful means for testing hypotheses regarding underlying mechanisms and relationships between drug-induced behaviors. Starting from a heterogeneous stock of mice, we have selectively bred lines of mice for extreme differences in their locomotor response to 10 mg/kg cocaine HCl. Selection pressure has been maintained for 12 generations and has resulted in two cocaine sensitive (CAHI) and two cocaine insensitive (CALO) lines. Across the generations of selection, the CAHI lines showed progressively greater amounts of cocaine-induced locomotion, with mice from the S12 generation traveling over 21,000 cm/30 min. following 10 mg/kg cocaine. The CALO lines, in contrast, did not substantially diverge from control values until the S8 generation. By generation 12, however, the LO lines traveled no further following 10 mg/kg cocaine (7000 cm/30 min), than they did following an initial saline injection. Cocaine and amphetamine dose-response analyses were conducted on drug-naive mice from the tenth generation. The CAHI lines were extremely sensitive to the locomotor activating effects of all doses of cocaine, displaying from 2- to 6-fold greater amounts of cocaine-induced locomotion than the CALO lines. The CALO lines, in contrast, were completely insensitive to the psychomotor stimulant effects of cocaine. The CAHI lines were also more sensitive to the locomotor activating effects of amphetamine. Both lines showed dose-dependent amphetamine-induced locomotion that peaked at 3 mg/kg. However, at all doses, the CAHI lines showed a 2- to 4-fold greater amount of locomotion than CALO lines. Thus, the sensitivity to cocaine developed through selection using a single dose of cocaine has generalized to a range of doses of cocaine and to at least one other psychostimulant.

Amphetamine↗
PubMed1998

Experiential constraints on the development of tolerance to amphetamine hypophagia following sensitization of stereotypy: instrumental contingencies regulate the expression of sensitization.

In previous research, sensitization of stereotypy induced by injections of 2.5 mg/kg amphetamine did not interfere with subsequent tolerance development to the hypophagic effect of 2 mg/kg. This study examined the effect of a higher sensitizing dose. Rats given intermittent injections of 5 mg/kg amphetamine and then challenged with various doses of amphetamine showed focused head scanning at 2 mg/kg and oral stereotypy at 4 mg/kg. In contrast, saline controls showed diffuse sniffing and head scanning at 2 and 4 mg/kg. Subgroups from each condition were then given daily injections of either amphetamine (2 mg/kg) or saline and access to milk for 30 min. Dose-response tests revealed that both drugged groups learned to suppress stereotypy in order to feed at 2 mg/kg, but only the non-sensitized group could do so at 4 mg/kg. These results demonstrate that (1) rats learn to suppress only those stereotyped movements that they experience in the context of feeding and (2) instrumental contingencies can influence the expression of behavioral sensitization.

Animals↗
PubMed1991

Uptake characteristics of the InsP3-sensitive and -insensitive Ca2+ pools in porcine aortic smooth-muscle cells: different Ca2+ sensitivity of the Ca2(+)-uptake mechanism.

We have investigated the Ca2(+)-uptake characteristics of the InsP3-sensitive and -insensitive non-mitochondrial Ca2+ pools in permeabilized cultured porcine aortic smooth-muscle cells. The InsP3-sensitive Ca2+ pool, which was also GTP sensitive, had a high Ca2+ affinity and was highly oxalate permeable. The InsP3-insensitive Ca2+ store, which was also GTP insensitive, had a much lower Ca2+ affinity and presented a low oxalate permeability. The loading of both pools decreased at high free [Ca2+], although these cells did not have a Ca2(+)-induced Ca2+ release mechanism. This decreased loading of the InsP3-sensitive Ca2+ pool at higher free [Ca2+] must be taken into consideration when investigating a possible Ca2(+)-inhibition of the InsP3-induced Ca2+ release. Part of the Ca2+ uptake into the InsP3-insensitive Ca2+ pool was not affected by the Ca2(+)-pump inhibitors vanadate, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone.

Animals↗
PubMed1977

Characteristics of dopamine and beta-adrenergic sensitive adenylate cyclases in the frontal cerebral cortex of the rat. Comparative effects of neuroleptics on frontal cortex and striatal dopamine sensitive adenylate cyclases.

Homogenates of frontal cerebral cortex of the rat were prepared from microdiscs punched out in areas rich in dopaminergic terminals. Under optimal assay conditions, dopamine (10-4 M) stimulated an adenylate cyclase present in these homogenates by 80-100%. This stimulation reached 200% when microdiscs were punched out from the medial part of the frontal cerebral cortex, adjacent to the forceps minor. Dopamine interacted with an homogeneous population of receptor sites which had an apparent affinity (KD) of 3.8 +/- 0.9 x 10-6 M (N = 4). The dopamine receptor was blocked by fluphenazine and phentolamine but had no affinity for pindolol, propranolol or L-isoproterenol. The affinities of several neuroleptics having different chemical structures were simultaneously determined on striatal and on frontal cerebral cortex dopamine sensitive adenylate cyclases. Fluphenazine was more potent in blocking the striatal than the frontal cerebral cortex dopaminergic receptors. In contrast, in all experiments, haloperidol had an higher affinity for the cerebral frontal cortex than for the striatal dopaminergic receptors. Thus, haloperidol was less effective than fluphenazine in blocking the striatal dopaminergic receptors, and equally potent than fluphenazine in inhibiting the frontal cerebral cortex dopamine sensitive adenylate cyclase. Chlorpromazine, thioridazine and clozapine had the same affinity for the two dopaminergic adenylate cyclase systems. L-isoproterenol interacted with an homogeneous population of beta-adrenergic receptor sites (KD = 3 +/- 2 X 10-7 M; N = 4) coupled with an adenylate cyclase distince from the dopamine sensitive adenylate cyclase. This beta-receptor had no affinity for dopamine or fluphenazine but was blocked by propranolol or pindolol. L-Norepinephrine was shown to stimulate both the dopamine (KD = 1.8 +/- 1 X 10-5 M; N = 4) and the beta-adrenergic (KD = 8 +/- 3 X 10-7 M; N = 4) sensitive adenylate cyclases. Thus, the L-norepinephrine effect was totally blocked in the combined presence of fluphenazine and pindolol.

Adenylyl Cyclases↗
PubMed1983

Functional correlations between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rat.

The effects of glucose injection into the hepatic portal vein on neural activity of the lateral hypothalamic area (LHA) were studied in rats. A majority of identified glucose-sensitive neurons in the LHA were inhibited by portal injection of glucose. This was found to be mediated through the alpha-noradrenergic pathways. Most of the glucose-insensitive neurons did not respond to the same procedure. Portal injection of hypertonic saline increased neural activity of some glucose-insensitive neurons but no glucose-sensitive neurons responded. Convergence of hepatic vagal afferent glucose-sensitive units on LHA glucose-sensitive neurons was clarified by this study.

Afferent Pathways↗
PubMed1991

pH sensitive liposomes provide an efficient means of sensitizing target cells to class I restricted CTL recognition of a soluble protein.

Exogenous antigens are normally endocytosed and enter the class II pathway of processing and presentation. It had been shown earlier that soluble antigen could be introduced into the class I pathway of processing and presentation by osmotic loading. In this report, we have demonstrated that OVA containing liposomes that destabilize on exposure to low pH, referred to as pH sensitive liposomes, could sensitize target cells to lysis by class I MHC-restricted OVA-specific CTL. However, OVA-containing pH insensitive liposomes, native OVA, or OVA subjected to the same protocol as was used to make the liposomes, failed to sensitize targets to OVA-specific CTL lysis. The pH sensitive liposomal approach was less toxic and more efficient (about 20-fold) in delivering than the osmotic loading approach. The pH liposome approach may prove valuable to study CTL recognition characteristics of less available proteins such as viral proteins.

Animals↗
PubMed1993

Sensitivity to inhibitors of type II topoisomerases from mouse L5178Y lymphoma strains that are resistant or sensitive to X-radiation.

Sensitivity to topoisomerase II inhibitors was tested at the cellular and enzyme level for two strains of mouse L5178Y lymphoma cells: resistant (LY-R) and sensitive (LY-S) to X-radiation. Differences in the susceptibility to inhibitors between LY-R and LY-S cells depended on the inhibitor used and were observed for adriamycin and VP-16, but not for mitoxantrone. On the other hand, isolated enzymes displayed the same sensitivity to all inhibitors tested regardless of the cell line. These results exclude the presence of altered topoisomerase II in LY-S cells as a possible reason for the collateral sensitivity of LY-S cells to X-radiation and topoisomerase II inhibitors.

Animals↗
PubMed1982

Sensitivity losses in a long wavelength sensitive mechanism of patients with retinitis pigmentosa.

the foveal vision of certain patients afflicted with retinitis pigmentosa may be mediated solely by a long wavelength sensitivity (lws) mechanism, because (1) increment threshold data could always be fitted to a single template curve with unity slope, (2) test and field sensitivities differ only by a proportionality constant over the visible spectrum, (3) intense background fields have additive (quantum catch) effects on thresholds, and (4) wavelength differences of bipartite foveal stimuli could not be distinguished. Both test and field sensitivities were appreciably lower than the lws sensitivity values for unaffected deuteranopes. The action spectrum was similar (but not identical) to estimates of the erythrolabe absorption spectrum. The results provide a better understanding of the photopic vision of patients with retinitis pigmentosa and further evidence that their effective optical density of residual cones is reduced.

Adult↗
PubMed1984

Temporal modulation sensitivities of red- and green-sensitive cone systems in dichromats.

The temporal modulation sensitivities of protanopes, deuteranopes and normal observers were measured with sinusoidal grating patterns (of spatial frequency 2.5 c/deg) whose contrast was modulated sinusoidally in time. Contrast sensitivity functions obtained from the three types of observers are almost identical. If we accept that in each class of dichromat only one cone type (red-sensitive, R, or green-sensitive, G) supports threshold, and that post-receptoral filters in both classes of observers are the same, the results show that R and G cones have the same temporal properties.

Adult↗
PubMed1986

The spectral sensitivity of blue-sensitive pigeon cones: evidence for complete screening of the visual pigment by the oil-droplets.

The relative spectral sensitivity of blue-sensitive pigeon cones was determined using flicker-photometry based on mass ERG-responses from intact subjects during high-level light adaptation. The resulting spectral sensitivity curve can be mimicked by a P460 nomogram screened by an oil-droplet that absorbs 50% at 466 nm. Comparison of the curve with the nomogram indicates that on the average less than 10% of the light that excites the blue-sensitive cones is guided past or diffracted around their oil-droplets.

Adaptation, Ocular↗
PubMed1994

Ultraviolet vision in a passeriform bird: from receptor spectral sensitivity to overall spectral sensitivity in Leiothrix lutea.

A survey of recent results out of spectrophotometric, microspectrophotometric, and behavioral tests concerning the UV vision of the passeriform bird Leiothrix lutea is presented. In the spectrophotometric study it was shown that the ocular media of Leiothrix' eyes are highly transparent to the near UV with lambda T50 at 320 nm. The comparison of the microspectrophotometric and the behavioral data showed a good fit between the peaks of the four single cones' effective sensitivity spectra and the four peaks in the behavioral spectral sensitivity function. The relation further suggests that the behavioral function might be described as the "over-envelope" of the single cone sensitivities. Leiothrix lutea possesses a genuine UV cone type and reveals it's highest sensitivity in the behavioral test to UV light.

Animals↗
PubMed1988

Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma.

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction.

Adult↗
PubMed1990

The conformation-sensitive immunoassay: a membrane based ELISA system for identifying antibodies sensitive to alterations of protein conformation.

A Conformation-Sensitive Immunoassay (CSI) has been developed for identification of antibodies that are sensitive to alterations in protein conformation. The method involves covalently coupling proteins to an activated hydrophilic membrane support. The membrane bound proteins are then treated under conditions known to alter protein conformation, immobilized in a non-native state via additional covalent interactions with the support, and subsequently probed using conventional ELISA techniques. This method has been validated using several well characterized conformation-sensitive antibodies to horse cytochrome c and sperm whale myoglobin. A panel of monoclonal antibodies directed against bovine somatotropin (bSt) has been partially characterized using this validated CSI procedure. Each of these antibodies to bSt has been shown to detect conformational alterations of bSt structure. Data are also presented that demonstrates that the accuracy of CSI analysis is superior to that of Western blotting for characterizing conformation-sensitive antibodies.

Animals↗
PubMed2006

Anxiety sensitivity within the anxiety disorders: disorder-specific sensitivities and depression comorbidity.

The tendency to perceive anxious states as aversive and harmful is hypothesized to confer vulnerability to the development of anxiety disorders. The most commonly used measure of anxiety sensitivity, the Anxiety Sensitivity Index [ASI; Reiss, S., Peterson, R.A., Gursky, D.M., & McNally R.J. (1986). Anxiety sensitivity, anxiety frequency, and the prediction of fearfulness. Behavior Research and Therapy, 24, 1-8], is composed of multiple lower-order factors, assessing fear of physical symptoms, fear of publicly observable anxious symptoms, and fear of cognitive dyscontrol. This study examined the convergent validity of the lower-order anxiety sensitivity dimensions in DSM-IV diagnosed anxiety disorders. Participants with primary diagnoses of panic disorder with agoraphobia, social phobia, and generalized anxiety disorder (GAD) completed the ASI and measures of anxiety and depression severity. Support was found for the convergent validity of all ASI dimensions in reference to thematically related anxiety disorders and in the identification of patients presenting with and without secondary major depressive disorder (MDD). The ASI-fear of cognitive dyscontrol dimension displayed strong and nonredundant associations with GAD, dimensional depression scores, and secondary diagnoses of MDD. The conceptual implications of the shared importance of fear of cognitive dyscontrol in GAD and MDD are discussed.

Adult↗