Effects of flurazepam on disturbed sleep in patients with AIDS

Polysomnograms were recorded of twelve patients with acquired immune deficiency syndrome (AIDS) during different stages in an open design. During the first night no hypnotics were administered, during the second night 30 mg flurazepam per os were given. Flurazepam affected mainly the NREM parameters. The times "awake" during the night were reduced, sleep stage 2 showed an increase, and the effective sleep time was also increased. The increase in sleep spindle density was remarkable, however, delta sleep and generation of K-complexes were not affected. Flurazepam did not affect REM sleep at all. The amount of REM sleep showed a slight increase. REM distribution during the night did not show the "bell shaped" increase and the decrease in the morning; the degree of the illness correlated with a flattening of REM distribution.     

Distribution of cerebral blood flow during deep isoflurane vs. pentobarbital anesthesia in rats with middle cerebral artery occlusion

While previous studies have identified a protective effect for barbiturate anesthesia during focal cerebral ischemia, no such effect has been demonstrated for isoflurane. To better understand the effects of these anesthetics on cerebral blood flow and metabolism that might have relevance to their respective potential for cerebral protection, fasted physiologically stable rats underwent autoradiographic determination of CBF and CMRglu during deep isoflurane or pentobarbital anesthesia (burst suppression of EEG). As expected, cerebral blood flow was significantly greater during isoflurane anesthesia (isoflurane = 157 +/- 18 and pentobarbital = 54 +/- 12 ml/100 g/min) while CMRglu values were nearly identical (isoflurane = 35 +/- 5 and pentobarbital = 33 +/- 4 mumol/100 g/min). Additional identically anesthetized rats underwent middle cerebral artery occlusion with CBF autoradiographically determined 1 h later. While the insult resulted in a significant reduction in the ipsilateral hemispheric and cortical blood flow in both anesthetic groups, flow remained at least twofold greater in isoflurane as opposed to pentobarbital-anesthetized rats. When regional flow was assessed, no difference between groups was observed with respect to the area of tissue with flow values falling between 0-10 ml/100 g/min. In contrast, isoflurane-anesthetized rats had significantly less hemispheric and cortical area with flow values in the ranges of 10-20 and 20-30 ml/100 g/min, respectively. These data, therefore, do not support the contention that isoflurane causes maldistribution of CBF during focal ischemia.     

Activity involvement, risk-taking, demographic variables, and other drug use: prediction of trying smokeless tobacco

Four activity participation variables (clubs, sports, church, and parties); two indices of "risk-taking" (preference for risk-taking, getting into trouble at school); three demographic variables (sex, ethnic group, socioeconomic status); and two drug use variables (trial of cigarettes and alcohol) were examined as correlates and prospective predictors of trial of smokeless tobacco in two cohorts of seventh graders in urban Los Angeles. The data were analyzed separately for males and females. Cross-sectional logistic regression analyses indicated that correlates of trying smokeless tobacco among the seventh-grade cohorts or among these same cohorts in the eighth grade (considering those persons who had not tried smokeless tobacco in seventh grade) generally included being white, trying cigarettes, risk-taking, and attending parties. Prospective logistic regression analyses with data from subjects who had not tried smokeless tobacco in the seventh grade indicated that predictors of subsequent trial of it generally included only being white and having tried cigarettes. Sports participation predicted onset only in one cohort of female subjects but not in males. Some activities that have been proposed as being predictive of smokeless tobacco use (e.g., sports participation) are generally irrelevant for a large sample of young adolescents in urban Los Angeles. White male cigarette smokers, regardless of the activities they have engaged in, are most likely to try smokeless tobacco.     

Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.     

Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice

Immune evasion by Lyme spirochetes is a multifactorial process involving numerous mechanisms. The OspE protein family undergoes antigenic variation during infection and binds factor H (fH) and possibly FHL-1/reconectin. In Borrelia burgdorferi B31MI, the OspE family consists of three paralogs: BBL39 (ErpA), BBP38, and BBN38 (ErpP). BBL39 and BBP38 are identical and therefore are referred to here as BBL39. The goals of this study were to assess the specificity of the antibody (Ab) response to the OspE paralogs and to identify the domains or determinants of OspE that are required for the binding of fH and OspE-targeting Abs that develop during infection. Here we demonstrate that at least some of the anti-OspE Abs produced during infection are paralog specific and that Ab binding requires conformational determinants whose formation requires both the N- and C-terminal domains of OspE. The binding of fH to OspE was also found to be dependent on conformational determinants. It is also demonstrated here that all of the OspE paralogs expressed by B. burgdorferi B31MI are capable of binding fH. The binding of fH to members of the OspF protein family was also assessed. In contrast to an earlier report, no binding of BBO39 or BBR42 to human fH was detected. Lastly, a series of competitive binding enzyme-linked immunosorbent assay analyses, designed to determine if fH and infection serum Abs bind to the same sites on OspE, revealed that these ligands interact with different regions of OspE.     

Taste bud development in the zebrafish, Danio rerio.

Taste buds are chemosensory endorgans consisting of modified epithelial cells. Fish and other vertebrates use their taste bud cells to sample potential food, either selecting or rejecting substances according to their edibility. The adult gustatory system in fish has been studied thoroughly, including regeneration experiments. Taste buds occur in the epithelia of the lips, the mouth cavity, the oropharyngeal cavity, and also in the skin of the barbels, the head, and sometimes even all over the body surface. Despite its importance for feeding, little is known about the ontogeny of the fish taste system. We examined the development of taste buds in the zebrafish on the light microscopical and the scanning and transmission electron microscopical levels. Taste buds develop later than the olfactory organ and the solitary chemosensory cells, two other chemosensory systems in aquatic vertebrates. The first few taste bud primordia are visible within the epithelia of lips and gill arches 3 to 4 days after fertilization, and the first few taste buds with open receptor areas appear on the lips and simultaneously on the gill arches 4-5 days after fertilization, which coincides with the onset of feeding. Taste buds in the mouth cavity, on the head, and on the barbels are formed later in development. As seen in other fish, zebrafish taste buds contain elongate dark and light cells, termed according to their electron density. Dark cells with a cell apex of many short microvilli appear first, followed by the light cells with one large microvillus. In addition, the zebrafish has a third fusiform cell type, which appears last. This cell type is low in electron density and has a brush-like apical ending with several small microvilli. This cell type has not been described previously. Furthermore, in zebrafish, the ontogenetic processes of taste bud formation differ from regenerative processes described in the literature.     

Acute promyelocytic leukemia: report of a variant translocation, t(1;17)

A 4-year-old female with acute promyelocytic leukemia (APL) was found to have a variant form of the 15;17 translocation, which is diagnostic of APL. The karyotype of the malignant cells was 47,XX,t(1;11)(q25;q21),t(1;17)(p36;q21), + 8. This case is additional evidence that the breakpoint of #17 at q21 is the characteristic chromosomal aberration of APL. The present case is also unusual because of the young age of the patient.     

Natural killer cell activity in the rat. Analysis of effector cell morphology and effects of interferon on natural killer cell function in the athymic (nude) rat

Athymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3? to 5?fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2- to 7-fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL-enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single-cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate-forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the target cell tested.     

Heterozygote detection in phenylketonuria

Phenylalanine loading was carried out on 105 parents of children with phenylalanine hydroxylase deficiency and 33 apparently normal individuals with no family history of phenylketonuria. The best discriminant was found to be the logarithmic transformation of the slope of the rise in serum tyrosine multiplied by the maximum serum tyrosine concentration over the maximum serum phenylalanine concentration obtained after an oral load with a pure solution of L-phenylalanine. The overlap between heterozygotes for phenylketonuria and normal homozygotes was 2.4%. The distribution of the discriminant values suggested three heterozygous phenotypes for phenylalanine hydroxylase deficiency, and the phenotypic combination of parents could be correlated to the phenotype of their affected offspring, i.e. classical phenylketonuria, mild phenylketonuria or hyperphenylalaninemia. The probability of heterozygosity for phenylketonuria was determined by means of the distribution of the discriminant values of the heterozygotes and that of normal homozygotes. The likelihood of being a heterozygote was corrected for the genetic background of the person requiring genetic counseling, and was finally expressed as the percentage probability of being a heterozygote for phenylketonuria.