Nonspecific Impairment Research Articles

Anxiolytic drugs selectively increase preferred duration of rewarding brain stimulation in a shuttlebox test

In the shuttlebox self-stimulation test described by Atrens, rewarding brain stimulation is independently initiated and terminated by rats. It has been hypothesized that gradually accumulating aversiveness of stimulation motivates the rat to terminate the rewarding stimulation train. In aggreement with this view, optimal doses of the known anxiolytics, pentobarbital (5 and 10 mg/kg) diazepam (1 and 2.5 mg/kg), chlordiazepoxide (3 and 5.4 mg/kg) and CL 218,872 (3, 10 and 30 mg/kg) preferentially increased the latency to terminate stimulation (the OFF latency), as compared with the latency to initiate stimulation (the ON latency). Higher doses increased both latencies in a nonselective fashion, suggesting nonspecific performance impairment. The shuttlebox self-stimulation test constitutes a potentially useful measure of experimental approach-avoidance conflict, with the OFF latency indicating anticonflict activity and the ON latency providing a control for performance variables.

Evidence for vagal involvement in the eating elicited by adrenergic stimulation of the paraventricular nucleus

We examined the role of the vagus nerves in mediating the eating and preprandial drinking seen after injection of norepinephrine (NE) into the region of the paraventricular hypothalamic nucleus of satiated rats. Complete subdiaphragmatic vagotomy (confirmed by gastric secretion tests) abolished the NE-elicited eating response, whether the diet used was lab chow, milk, or a milk-chow misture, and attenuated, by 38%, the NE-elicited drinking response. These effects occurred independently of changes in body weight or daily food intake imposed by vagal surgery. The vagotomized rats retained the capacity to rapidly increase eating in response to food deprivation or insulin injection challenges, indicating that the effect of vagotomy on NE-induced eating was not due to some non-specific impairment. Efferent vagal blockade of intact rats with systemic injections of atropine methyl nitrate (0.4 mg/kg) prior to central NE infusions yielded similar results. Finally-selective section of the coeliac branch of the vagus produced a 49% reduction of NE, elicited eating, as compared with a 29% reduction in water intake, while selective section of the gastric plus hepatic vagal branches, leaving only the coeliac branch intact, did not significantly affect either ingestive response. Both of these selectively vagotomized groups displayed an unimpaired capacity to increase food intake in response to systemic insulin injections. These results suggest participation of efferent vagal mechanisms in the adrenergic feeding, and, to a lesser extent, drinking phenomena and are consistent with a particular role for some function under coeliac vagal control (perhaps insulin secretion) in modulating the effects of NE on feeding behavior.

Polymorphic 4-hydroxylation of debrisoquine in chronic discoid psoriasis.

1. The 4-hydroxylation of debrisoquine was measured in 42 patients with chronic discoid psoriasis. 2. The proportion of poor metabolisers (4.8%) and the median metabolic ratio (0.5) in psoriatics were similar to that reported previously in a healthy British population. 3. We conclude that the abnormality of microsomal mono-oxygenase activity which we have found in the skin and other tissues of psoriatics is not due to a generalised (non-specific) impairment of microsomal oxidation and may be enzyme specific.

Graft-versus-host reactivity in F1 hybrid rats after pretreatment with parental strain lymphocytes and anti-lymphocyte serum

The pretreatment of F1 hybrid rats with both parental strain lymphocytes and anti-lymphocyte serum (ALS) enhanced the induction of nonspecific impairment of graft-versus-host (GVH) reactivity but inhibited the induction of donor-specific impairment of GVH reactivity. The results indicated that, in these experiments, these effects occurred as a result of the simultaneous intraperitoneal presence of the ALS and the lymphocyte pretreatment inoculum, suggesting that the interaction of the ALS and donor strain lymphocytes, possibly in association with recipient cells, was responsible.

Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis.

Clinical resistance to the induction of experimental allergic encephalomyelitis was observed in a closed colony of Lewis (designated Le-R) rats. Disease susceptibility in randomly bred animals appeared to increase with increasing age. In the small group of young Le-R rats, which were susceptible, disease onset was delayed, severity of symptoms was reduced, and duration of clinical signs was abbreviated compared to conventional Lewis rats. The severity of histologic neural tissue lesions correlated with clinical observations. Breeding experiments indicated that most Le-R rats were resistant to disease induction regardless of whether their ancestors had been selected for susceptibility or resistance. The F3 generation of resistant lineage was uniformly resistant at all ages tested. Virtually all (Lewis X Le-R)F1 rats of either sex were resistant when challenged at 7-8 wk of age indicating that resistance was a dominant autosomal trait. Approximately half of (F1 X Lewis) backcross rats developed paralytic EAE whereas one-fourth were entirely resistant, suggesting that disease resistance may be mediated by one or two genes. Le-R rats shared at least some of the Lewis rat major histocompatibility antigens. Resistance apparently did not reflect a nonspecific impairment of cellular immune responsiveness. Le-R rats, which had been challenged with myelin basic protein, developed antigen-reactive cells specific for basic protein or its encephalitogenic fragment. Spleen cells obtained from basic protein-sensitized Le-R rats did not adoptively transfer disease into Lewis rats. In contrast, spleen cells obtained from basic protein-sensitized Lewis rats readily transferred disease into both Lewis and Le-R recipients. These data suggest that disease resistance may be a result of an immunologic deficit (or suppressor cell activity) expressed during the differentiation of antigen-reactive cells into disease-inducing effector cells.

Donor-specific and nonspecific impairment of graft-versus-host reactivity in F 1 hybrid rats after pretreatment with parental strain lymphocytes

The relative contribution of donor-specific and nonspecific impairment of graft-versus-host (GVH) reactivity in F 1 hybrid rats pretreated with graded doses of parental strain lymphocytes was investigated, over a wide dose range, using the popliteal lymph node assay. Donor-specific and nonspecific impairment were shown to follow completely different dose/response curves peaking at widely different pretreatment doses. After pretreatment with certain doses of parental strain lymphocytes donor-specific and nonspecific impairment were induced simultaneously and the impairment of GVH reactivity in response to the pretreatment strain then appeared to be due to the combined effect of both. The possibility that donor-specific and nonspecific impairment might be induced by different lymphocyte populations in the pretreatment inoculum is discussed.

Effects of carrageenan on spontaneous and antibody-dependent cell-mediated cytotoxicity

We examined the effect of carrageenan on in vitro antibody-dependent cell-mediated cytolysis (ADCC) and spontaneous cell-mediated cytolysis (SCMC) in cultures of human peripheral blood mononuclear cells (PBL). Carrageenan, when present in the assay, nonspecifically reduced ADCC and SCMC against both Chang and chicken erythrocyte (CRBC) target cells. This reduction in cytotoxicity could not be attributed entirely to the macrophage toxic and complement-inhibitory properties of carrageenan because neither removal of complement nor macrophage depletion prevented the dose-dependent inhibition. In contrast, pretreatment of effector PBL, with carrageenan followed by removal of Carrageenan by washing did not alter ADCC or SCMC against Chang cells, which are mediated by nonphagocytic cells, but reduced both ADCC and SCMC activity against CRBC targets, which are mediated in part by macrophages. Thus, Carrageenan, when present in in vitro cell-mediated cytotoxicity assays, causes a nonspecific impairment of cytotoxicity that is independent of its anticomplement or macrophage-toxic properties.

IN VITRO RESPONSE OF INTESTINAL SEGMENTS OF MICE WITH HEREDITARY MUSCULAR DYSTROPHY TO VARIOUS PHARMACOLOGIC AGENTS.

SummaryThe influence of several pharmacologic agents on the contractile activity of intestinal segments from dystrophic (dy/ dy), heterozygous (Dy/dy) and wild-type (Dy/Dy) mice has been examined in an in vitro tissue bath system. There appears to be a non-specific impairment to the ability of intestinal smooth muscle from dystrophic animals to respond to stimulation by auto-nomic or myotrophic drugs. No consistent differences could be detected between the responses of segments from wild-type and from heterozygous animals.

Studies of thought disorder in schizophrenia. I. Chapman's tests of distractibility and associative intrusion in schizophrenia and organic brain disease.

Investigations of performance on cognitive tasks usually result in the findings that normal subjects achieve the highest mean scores, schizophrenic subjects are intermediate, and subjects with organic brain disease perform most poorly. The range of performance of schizophrenic patients is usually quite broad, overlapping with that of good normal subjects, at one extreme, and with that of poor-performing patients with organic disease, at the other. However, the pattern of error scores of the schizophrenic subjects does not distinguish their performance from that of these other clinical groups. It seems likely, therefore, that such data reflect only nonspecific impairment of cognitive function. The degree of such impairment is usually less in randomly chosen groups of schizophrenic subjects than that found in similarly chosen groups of patients with organic brain disease. * Since cognition in these patient groups grossly differs in many respects, one must conclude