Overshadowing and latent inhibition counteract each other: support for the comparator hypothesis

In 4 conditioned lick suppression experiments with rats, the combined effects of latent inhibition treatment followed by overshadowing treatment were assessed as a test of the comparator hypothesis's (R.R. Miller & L.D. Matzel, 1988) explanations of overshadowing and latent inhibition. Experiments 1 and 2 confirmed the prediction of the comparator hypothesis that combined latent inhibition and overshadowing treatments attenuate the response deficit produced by either treatment alone. Furthermore, consistent with the comparator hypothesis, posttraining changes in the associative status of the putative comparator stimulus altered responding to the target conditioned stimulus (Experiment 3), and switching contexts between latent inhibition and overshadowing treatments (Experiment 4) eliminated the interaction between the latent inhibition and overshadowing treatments.     

Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.     

CD4 cell counts of 200 x 10(6)/1 or below in natural history studies and surveillance: is one enough or are two better?

A retrospective cohort study was performed to examine the extent and clinical significance of misclassification associated with using the current United States AIDS case defining category of an initial CD4 count < or = 200 cells x 10(6)/l (< or = 200) compared with a definition requiring two consecutive counts below this level. The main outcomes examined were the probability of subsequent CD4 counts > 200 x 10(6)/l (> 200) and progression times to AIDS and death. Of the 2025 predominantly male homosexual HIV-positive patients attending two hospital based HIV clinics with initial CD4 cell counts < or = 200, 1524 (75%) subsequently had consecutive counts < or = 200, but only half did so at the next CD4 count. Ten per cent had either no further or only non-consecutive counts < or = 200, and 15% had only one CD4 count available for analysis. The cumulative proportion of patients with a CD4 count > 200 at one year after a first count of < or = 200 was about twice (39%) that observed among the subgroup with at least two consecutive counts < or = 200 (19%). The times from the initial counts of < or = 200 to AIDS and death were also shorter by six months and two months, respectively, in the subgroup with two or more consecutive counts < or = 200. A significant proportion of patients will be prematurely classified as having a CD4 cell count < or = 200 if a single CD4 count below this level is accepted. A definition of two consecutive counts < or = 200 should be adopted in preference to a single count < or = 200 for natural history studies and clinical trials, in which precise estimates of the time to or from a defined CD4 threshold are important. In surveillance programmes, however, such an approach may be impractical because of missing or infrequent serial CD4 counts, although adjustments can be made based on these estimates of premature misclassification.     

Myelination in cerebellar slice cultures: development of a system amenable to biochemical analysis

Myelin deposition and maintenance are critical to proper function of the mammalian nervous system. Previous investigations of myelination in the central nervous system (CNS) were hampered by the lack of an in vitro system that can faithfully reproduce in vivo events yet is amenable to biochemical investigation. We have developed a procedure, based on organotypic cultures, which permits efficient preparation of large numbers of cerebellar slice cultures that can be easily manipulated. Cultures have been examined to document myelination biochemically (by incorporation of [35S]sulfate into sulfolipids), immunohistochemically (by labeling the myelin components myelin basic protein and galactocerebroside), and morphologically (by both light and electron microscopy). We tested the effects of biologically active peptides and antibodies on myelination in the thin slices. The results indicate that the cultures provide an in vitro system that can be used to examine specific cellular events that occur during CNS myelination.     

The effect of promethazine hydrochloride on bilirubin metabolism in the rat

The effect of 21 days of promethazine-HC1 administration on hepatic bilirubin metabolism and transport was studied in adult rats. A significant increase in mean cumulative hepatic bilirubin uptake (84.5 +/- 7.6 (SE) mug/100 g/min in controls vs. 110.0 +/- 4.3 in treated rats), mean hepatic glucuronide conjugation (1,330 +/- 86 (SE) mug bilirubin conjugated/g liver/40 min in controls vs. 1.713 +/- 61 in treated rats), and mean maximal hepatic excretion (47.2 +/- 4.9 (SE) mug/100 g/min vs. 63.5 +/- 2.7) was observed in treated animals. Mean total liver weight and total hepatic protein also increased significantly. These observations suggest that promethazine is an inducer of protein and enzyme synthesis in rat liver and is capable of significantly stimulating the three major steps in hepatic disposal of bilirubin.     

The effect of parenteral alimentation fluid, undiluted with saline or fresh sera, on the growth of Candida albicans in vitro at 37 degrees C

Parenteral alimentation is often complicated by Candida albicans infection which may be fatal. This study investigated the effect of alimentation fluid (Aminosol) on C. albicans' growth in vitro. It was found that concentrated Aminosol (1400 millisomoles) maintained C. albicans in a viable state but inhibited replication. Dilution of alimentation fluid to physiological concentrations (300 milliosmoles) with either saline or aged pooled normal sera promoted in vitro growth of C. albicans which was equivalent to that obtained in BHI broth and was slightly less than that obtained in Sabouraud's broth. The effects of fresh sera with full complement activity were also investigated. In fresh sera appropriately diluted with physiological saline, some clumping of the yeasts was observed and all formed germ tubes. Growth as defined by budding or the formation of hyphae was inhibited. When Aminosol was diluted to 300 milliosomoles with fresh sera, all yeasts were noted to be in clumps with germ tubes as well as continually growing hyphae. Growth was approximately equal to that seen in Aminosol similarly diluted with saline.     

Immunohemostatic mechanisms in the development of primary open-angle glaucoma

The charts of 247 allergic patients (all ages) who were receiving immunotherapy were studied retrospectively. They belong to a private setting at the city of Santa Ana Chiautempan, Tlax (Mexico). We looked at whether they were compliant or noncompliance. Compliance was considered as those who did not stop immunotherapy during a 18-month period, and shorter periods s noncompliance. One hundred and fifty two (62%) were compliant and 95 (38%) were not. Noncompliance causes were: 29 patients felt better soon, 19 claimed high costs, 8 changed to alternative medicine. 6 felt worse because of immunotherapy, 6 moved to other cities, 2 preferred other allergists and 25 did not answer the questionnaire. Forty six per cent stopped during the first 2 to 6 months and 56% within 8 and 14 with a median of 5.4. Eighty per cent from those who were compliant claimed they felt much better and 18% only slightly better. The average length-compliance was 29.7 months.     

Addison-Biermer disease combined with chronic posthemorrhagic iron-deficiency anemia (dimorphic anemias)

The paper reports 7 cases of dimorphic anemia, development of Addison-Biermer disease in preexisting chronic posthemorrhagic anemia. The authors consider some diagnostic and therapeutic aspects. It is thought valid to discontinue iron preparations prior to vitamin B12 therapy and to start them again upon the arising reticulocytic crisis.