The effect of glutaurine on thyroid hormones in the rat

Glutaurine (gamma-L-glutamyl taurine), a proposed hormone isolated from parathyroid gland oxyphil cells, was examined for its effect on circulating thyroid hormones in the rat. In acute experiments performed over a 24 hr. period, glutaurine depressed plasma triiodothyronine (T3) levels in a dose-dependent manner; however, thyroxine (T4) levels were not affected significantly. In chronic experiments performed over a 2 wk. period, glutaurine significantly increased T3 levels, but, as with acute studies, the effect of T4 levels was not significantly altered. Following acute glutaurine administration, TSH levels were elevated above control. The increased T3 observed following chronic glutaurine administration may be due to a secondary increase in TSH levels. These data support the hypothesis that glutaurine aids in peripheral thyroid hormonal regulation. Observed differences between acute and chronic glutaurine action are though to result from the effect of glutaurine on the negative feedback inhibiting action of TSH.     

Adjuvant perioperative hepatic arterial mitomycin C and floxuridine combined with surgical resection of metastatic colorectal cancer in the liver

Twenty patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant perioperative therapy that included hepatic arterial mitomycin C and floxuridine (FUDR). The median survival for all 20 patients was 51 months: 10 are still alive with a median postoperative follow-up of 49 months; 6 are disease-free with a median postoperative follow-up of 43 months. Among 10 patients in whom the surgical margins of the specimen contained tumor cells, the median survival was 52 months. This survival was comparable to that among 10 patients in whom the surgical margins were tumor free (P = 0.22). Neither the number of metastatic liver deposits nor the disease-free interval between the primary diagnosis of colorectal carcinoma and the development of liver metastases significantly affected survival. A transient chemical hepatitis which resolved before the next scheduled treatment was associated with 50% of arterial chemotherapy cycles (approximately 70% of the patients). Gastric or duodenal ulcerations occurred in 23% of the patients. Surgical complications were either pulmonary such as pleural effusion or atelectasis, or wound infections and subphrenic abscesses. Although these results compare favorably with the results in previously published series, this aggressive adjuvant chemotherapy appears to be particularly justified in patients with tumor positive surgical margins or those with multiple tumor masses and, therefore, are characterized by a poor prognosis.     

Interleukin-4 downregulates interleukin-6 production in human peripheral blood mononuclear cells

We report that recombinant human interleukin-4 (IL-4) downregulates interleukin-6 (IL-6) production by human peripheral blood mononuclear cells (PBMC). PBMC were preincubated for up to 24 hr in the presence of IL-4 (100 U/ml) and then activated with lipopolysaccharide B Escherichia coli 026:B6 (LPS, 10 micrograms/ml), recombinant human tumor necrosis factor-alpha (TNF-alpha, 200 U/ml), or Concanavalin A (Con A, 10 micrograms/ml). Although all these signals induced IL-6 production, IL-4-treated cells produced significantly reduced levels of IL-6 protein. This effect was dose and time dependent. We conclude that IL-4 is a potent downregulatory modulator of IL-6 expression in human PBMC.     

Automated, quantitative cytopathic effect reduction assay for interferon.

A rapid, cytopathic effect reduction assay for human interferon (IFN) is described. Dilutions of IFN were made with an automated diluter in 96-well microtiter plates. Total incubation time was 26 h. IFN titers were calculated from optical density readings of crystal violet-stained monolayers in an automated spectrophotometer, which required less than 1 min to read each plate.     

Assessment of IgE-mediated sensitivity during immunotherapy: comparison of the RAST with and without adsorption of IgG to titrated prick skin tests

The effect of specific IgG induced by allergy immunotherapy on specific IgE binding in the RAST was assessed by removal of the IgG with staphylococcus protein A bound to Sepharose. In sera from those patients with the highest titers of specific IgG, RAST binding was increased 8% following adsorption of the post-immunotherapy sera while in sera obtained from the same patients before immunotherapy adsorption increased binding only 3%. The effect of allergy immunotherapy on the titrated prick skin test was compared to the effect on the RAST to the same allergen. In nine patients who received the highest dose of grass extract, the area of the titrated prick skin tests was reduced following immunotherapy by 75%. Staphylococcus protein-A adsorption of sera from these patients drawn before immunotherapy resulted in an increase in RAST binding of 2.7% compared to an increase of 6% in sera obtained after immunotherapy, suggesting suppression of RAST binding of only 3% by specific IgG. It is concluded that RAST levels are affected less than prick skin tests by the immunologic response to allergy immunotherapy. Some interference in RAST binding is produced by specific IgG antibody in high titers, but for many critical purposes the degree of interference is not significant.     

Longitudinal study of Plasmodium falciparum polymorphic antigens in a malaria-endemic population.

Plasmodium falciparum merozoite surface antigens MSP1 and MSP2 and an exported antigen, Exp-1, exhibit allelic polymorphism in natural populations. To explain this, one hypothesis is that antigen polymorphisms are maintained by frequency-dependent immune selection. An expectation of the hypothesis is that rare variants have an advantage over common variants because of a lower level of acquired immunity against them and thus increase in frequency until an equilibrium is attained. To test this hypothesis, the frequencies of polymorphic epitopes of MSP1, MSP2, and Exp-1 were determined among isolates from malaria patients in an urban area of The Gambia, during different periods of one transmission season (1988) and in different years (1982, 1983, 1988, and 1989). The frequencies remained very stable throughout the period of study, alternative epitope variants remaining either rare or common, without shifts in relative frequencies. These results are discussed with reference to the immune-selection hypothesis, with the conclusion that frequencies of the major dimorphic serological classes of MSP1 are probably not maintained by immune selection.     

Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate "relapse" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT1A, 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models. Neurochemical, neuroanatomical, and neuropharmacological studies indicate innate differences exist between the high alcohol-consuming and low alcohol-consuming rodents in various CNS limbic structures. In addition, reduced mesolimbic DA and 5-HT function have been observed during alcohol withdrawal in common stock rats. Depending on the animal model under study, abnormalities in the mesolimbic dopamine pathway, and/or the serotonin, opioid, and GABA systems that regulate this pathway may underlie vulnerability to the abnormal alcohol-seeking behavior in the genetic animal models.     

Quadricuspid aortic valve and single coronary ostium

We describe an autopsy patient in whom a rare congenital anomaly of quadricuspid semilunar aortic valve and coronary arteries originating from a single orifice of one aortic sinus occurred. To the best of our knowledge, this combination of cardiac anomalies has not been reported.     

Stimulus range influences intensity and hedonic ratings of flavour

Five concentrations of an artificial orange drink were presented for sensory evaluation in three overlapping concentration ranges. Three sensory panels, each of 30 subjects, rated the concentrations for intensity of flavour (intensity scale), relation to ideal flavour intensity (ideal-point scale), and pleasantness (hedonic scale). Except for the two extreme concentrations, neither of which was presented in more than one range, in all three response tasks the mean rating for a given concentration varied with the concentration range in which it was presented. However, the mean ratings showed good correspondence across response tasks (e.g. the concentration perceived as "moderately sweet" on the intensity scale was perceived as "just right" on the ideal-point scale and of maximal pleasantness on the hedonic scale), suggesting a link between the intensity and hedonic dimensions of sensory experience.