Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia.     

An outbreak of Shigella sonnei infection associated with consumption of iceberg lettuce

OBJECTIVES: This study compared the relative strength of the associations of a set of structural (social, economic, and political) variables and a set of health services variables with state-level infant, neonatal, and postneonatal mortality. It also examined whether health services mediate the relationships between structural variables and state-level infant, neonatal, and postneonatal mortality. METHODS: With the state as the unit of analysis, data for all 50 states were analyzed by means of multiple regression. RESULTS: Structural variables accounted for substantially more variance in infant, neonatal, and postneonatal mortality than health services variables, and health services variables were more strongly related to infant mortality than to neonatal or postneonatal mortality. When health services variables were controlled, the strengths of the associations between the structural variables and infant, neonatal, and postneonatal mortality were reduced but remained statistically significant. CONCLUSIONS: A substantial portion of the variance in state-level infant mortality is accounted for by states' structural characteristics, which are partially mediated by health services.     

Modeling individual’s aging within a bacterial population using a pi-calculus paradigm

We propose an aging mechanism which develops in artificial bacterial populations fighting against antibiotic molecules. The mechanism is based on very elementary information gathered by each individual and elementary reactions as well. Though we do not interpret the aging process in strictly biological terms, it appears compliant with recent studies on the field, and physically feasible. The root of the aging mechanism is an adaptation strategy based on a thresholding operation that derives from theoretical results on stochastic monotone games. The methods for implementing it denote their rationale in that they represent a sophisticated dialect of pi-calculus, a widespread computational paradigm for implementing dynamics of massive populations with bipolar reactions. As a result we may implement processes that explain some typical patterns of the evolution of the immunosystems.     

Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging

High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor binding was measured in the human hippocampal formation in a series of 57 cases aged between 24 weeks gestation and 100 years. Changes in nicotine receptor binding during development and aging were more striking than differences in alpha BT and muscarinic binding. Nicotine binding was higher at the late foetal stage than at any other subsequent time in all areas investigated. In the hippocampus a fall in binding then occurred within the first six months of life, with little or no subsequent fall during aging, whereas in the entorhinal cortex and the presubiculum the major loss of nicotine binding occurred after the fourth decade. alpha BT binding was significantly elevated in the CA 1 region, but in no other region of the hippocampus, in the late foetus, and there was also a fall in alpha BT binding in the entorhinal cortex during aging from the second decade. The modest changes in total muscarinic binding, which appeared to reflect those in M1 and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between the foetal stage and childhood and a tendency for receptors to fall with age in the hippocampus and subicular complex. These findings implicate mechanisms controlling the expression of nicotinic receptors to a greater extent than muscarinic receptors in postnatal development and aging in the human hippocampus.     

Oral mucositis with features of psoriasis: report of a case and review of the literature

There complete 18S ribosomal RNA gene sequences from the rumen ciliates, Entodinium caudatum (1,639 bp), Epidinium caudatum (1,638 bp), and Polyplastron multivesiculatum (1,640 bp) were determined and confirmed in the opposite direction. Trees produced using maximum parsimony and distance-matrix methods (least squares and neighbour-joining), with strong bootstrap support, depict the rumen ciliates as a monophyletic group. Entodinium caudatum is the earliest branching rumen ciliate. However, Entodinium simplex does not pair with En. caudatum, but rather with Polyplastron multivesiculatum. Signature sequences for these rumen ciliates reveal that the published SSrRNA gene sequence from En. simplex is in fact a Polyplastron species. The free-living haptorian ciliates, The Loxophyllum, Homalozoon and Spathidium (Subclass Haptoria), are monophyletic and are the sister group to the rumen ciliates. The litostomes (Class Litostomatea), consisting of the haptorians and the rumen ciliates, are also a monophyletic group.     

Native serotonin 5-HT3 receptors expressed in Xenopus oocytes differ from homopentameric 5-HT3 receptors

Efficacies of the 5-hydroxytryptamine (serotonin) 5-HT3 receptor (5-HT3R) agonists 2-methyl-5-HT, dopamine, and m-chlorophenylbiguanide on 5-HT3R native to N1E-115 cells and on homopentameric 5-HT3R expressed in Xenopus oocytes were determined relative to that of 5-HT. Efficacies of 2-methyl-5-HT and dopamine on 5-HT3R native to differentiated N1E-115 cells are high (54 and 36%) as compared with their efficacies on homopentameric 5-HT3R-A(L) and 5-HT3R-A(S) receptors expressed in oocytes (4-8%). m-Chlorophenylbiguanide does not distinguish between 5-HT3R in N1E-115 cells and in oocytes. The distinct pharmacological profile of 5-HT3R native to differentiated N1E-115 cells is conserved when poly(A)+ mRNA from these cells is expressed in oocytes. The results indicate that, apart from the known 5-HT3R subunits, N1E-115 cells express additional proteins involved in 5-HT3R function.     

Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.