Chloroquine resistance--discovering the missing link?

Toxicosis due to microcystin-containing blue-green algae has been sporadically reported in a variety of animal species. Most reports of intoxication involve algal blooms during periods of warm temperatures and abundant sunshine in the spring or early summer. A case of blue-green algae toxicosis with lesions attributable to toxins from Microcystis aeruginosa is described in 4 cattle from southern Georgia during November. The case was unusual in that characteristic hepatic necrosis was accompanied by severe mesenteric edema and peritoneal effusion. In addition, weather conditions and location were not expected to be conducive to algal blooms. Rapid diagnosis and identification of the probable source of intoxication allowed the owner to move the herd away from the affected pond. This action limited losses to only the 4 cattle.     

Hydroxyurea-induced fever and hepatitis

The Cdx2 gene is one of three murine homologues of the Drosophila homeobox gene caudal. Mice heterozygous for a null mutation in Cdx2 exhibit a variable phenotype including tail abnormalities, stunted growth and a homeotic shift of vertebrae. Most strikingly, however, 90% of heterozygous mice were reported to develop multiple intestinal adenomatous polyps, most notably in the proximal colon (Chawengsaksophak et al., 1997). These observations led us to propose that mutation of CDX2 may be involved in the genesis of some human colorectal tumours. A survey of DNA from 85 colorectal tumours revealed that one with extensive microsatellite instability (RER+ phenotype) has mutations in both alleles of CDX2. Both mutations occur in coding regions which contain repetitive elements and are consistent with those found in RER + tumours.     

Impact of sorghum processing on phytate,phenolic compounds and in vitro solubility of iron and zinc in thick porridges

This study focussed on the impact of process variables on levels of phytate and phenolic compounds, and in vitro solubility of iron (Fe) and zinc (Zn) in sorghum porridges, a major staple in semi‐arid tropics. The aim was to identify practices that enhance the mineral availability in this type of staple food. We studied the example of the West African porridge ‘dibou’ for which the processing methods involve grain cleaning, milling, sieving and cooking. Regional variations occur in the process, particularly in the cleaning which may be done wet or dry; sieving may be omitted in certain locations. Cleaning reduced the phytate content of the grain by 24–39%, while milling, sieving and cooking had no significant effect on phytate. Phenolic compounds measured as levels of reactive hydroxyl groups, remained constant after cleaning, milling and sieving, but significantly decreased by 38–65% after cooking. The Fe solubility tended to increase after cleaning but was drastically reduced due to cooking, and so was the soluble Zn. Levels of total phenolic compounds highly correlated with the Fe and Zn solubility (r² = 0.73 and 0.82, respectively). Phenolic reaction products formed during the cooking process are presumably related with the extensive browning phenomenon observed in the dibou porridge, and with the reduction observed in Fe and Zn solubility. Copyright © 2007 Society of Chemical Industry     

The effect of mersalyl on inositol trisphosphate receptor binding and ion channel function

A number of thiol-reactive agents induce repetitive Ca2+ spiking in cells by a mechanism thought to involve sensitization of the inositol 1,4,5-trisphosphate receptor (IP3R). To further define the basis of this interaction, we have studied the effect of several thiol-reactive agents on [3H]IP3 binding, IP3-gated channel activity, and conformation of the IP3R in membranes from hepatocytes, cultured WB rat liver epithelial cells, and cerebellum microsomes. At 4 degrees C, the organomercurial thiol-reactive agent mersalyl markedly stimulates (3-4fold) [3H]IP3 binding to permeabilized hepatocytes. The closely related molecule, thimerosal, has only a small stimulatory effect under these conditions, and GSSG or N-ethylmaleimide are without effect. The stimulatory effect of mersalyl was associated with a decrease in Kd of the IP3R with no change in Bmax. Mersalyl was without effect on detergent-solubilized hepatocyte binding sites or on the [3H]IP3 binding activity of cerebellum microsomes. In contrast to thimerosal, which potentiates IP3-mediated Ca2+ release, mersalyl blocked IP3-gated Ca2+ channels. Mersalyl pretreatment of WB membranes altered the pattern of immunoreactive receptor fragments generated upon subsequent cleavage of the receptor with proteinase K. This effect was not reproduced by thimerosal and was also not observed in experiments on cerebellum microsomes. We conclude that the WB cell and brain IP3 receptors are differently regulated by modification of thiol groups. Reaction of the WB cell IP3 receptor with mersalyl alters its conformation and modifies the accessibility of sites on the protein that are cleaved by proteinase K. In the presence of mersalyl, the receptor has high affinity for IP3 but is inactive as a Ca2+ channel. This contrasts with the high affinity receptor/active Ca2+ channel induced by thimerosal, suggesting that even closely related thiol agents may interact at different thiol groups.     

Expression of nuclear lectin carbohydrate-binding protein 35 in human immunodeficiency virus type 1-infected Molt-3 cells

The nuclear carbohydrate-binding protein 35 (CBP35), a beta-galactoside-specific lectin with an M(r) of 35,000, has been identified in nuclear ribonucleoprotein complexes (RNPs) from a variety of mammalian tissues and cells. Here we determined that the expression of CBP35 mRNA greatly increases after infection of Molt-3 cells with human immunodeficiency virus type 1 (HIV-1), concomitantly with the onset of expression of the viral regulatory gene tat, and then declines. The increase in CBP35 mRNA level results in an enhanced synthesis of CBP35, as evidenced in nitrocellulose filter binding assay using radiolabeled, sugar-specific neoglycoprotein. Immunoblotting experiments showed that CBP35 is present in the 40S heterogeneous nuclear RNP complex from HIV-1-infected Molt-3 cells. CBP35 could also be detected using a novel photoreactive alpha-D-galactose probe designed for the specific detection of CBP.     

Meeting the needs of young adults

As they mature and become sexually active, more young people face serious health risks. Most face these risks with too little factual information, too little guidance about sexual responsibility, and too little access to health care. Meeting young adults' diverse needs challenges parents, communities, health care providers, and educators. Despite urgent needs, program efforts have been slight and slowed by controversy.     

Xanthobacter tagetidis sp. nov., an organism associated with Tagetes species and able to grow on substituted thiophenes

Members of the marigold genus of flowering plants (the genus Tagetes), which synthesize and accumulate thiophene compounds in their roots, were investigated as potential sources of bacteria able to degrade substituted thiophenes. Batch and continuous enrichment cultures inoculated with compost from root balls of Tagetes patula and Tagetes erecta reproducibly produced the same predominant type of bacterium when they were supplied with thiophene-2-carboxylate (T2C) or thiophene-2-acetate (T2A) as a carbon and energy substrate. This organism was a yellow-pigmented, neutrophilic, mesophilic, gram-negative, pleomorphic, rodshaped bacterium, which we classify as a new species of the genus Xanthobacter, Xanthobacter tagetidis; strain TagT2C (= DSM 11105) is the type strain. Strain TagT2CT (T = type strain) grew on simple thiophenes, such as T2C, thiophene-3-carboxylate, and T2A, on analogs of these compounds (pyrrole-2-carboxylate and furan-2-carboxylate), and on the condensed thiophene dibenzothiophene. X. tagetidis was facultatively autotrophic, fixing carbon dioxide by means of ribulose bisphosphate carboxylase, and was able to grow on hydrogen, thiosulfate, or sulfide as an energy substrate. It also grew on a wide range of other heterotrophic, chemolithotrophic, and methylotrophic substrates. Its growth on T2C was optimal at 28 to 31 degrees C and pH 7.6 to 7.8, and the maximum growth rate in batch culture was 0.22 h-1. The DNA base composition of X.tagetidis is 68 mol% G + C. A 16S ribosomal DNA sequence analysis of strain TagT2CT showed that this organism represents a distinct lineage within the Aquabacter-Azorhizobium-Xanthobacter cluster of the alpha-2 subclass of the Pro-teobacteria. Discrimination of X. tagetidis from the other genera in this group and from other Xanthobacter species is discussed.     

Synthesis of racemic 6,7,8,9-tetrahydro-3-hydroxy-1H-1-benzazepine-2,5-diones as antagonists of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors

The synthesis and pharmacological properties of several racemic 6,7,8,9-tetrahydro-3-hydroxy-1H-1-benzazepine-2,5-diones (THHBADs) are described. Synthesis was accomplished via a Schmidt reaction with 5,6,7,8-tetrahydro-2-methoxynaphthalene-1,4-diones (THMNDs) followed by demethylation. THMNDs were prepared via a Diels-Alder reaction with 2-methoxybenzoquinone (5) or 2-bromo-5-methoxybenzoquinone (14) and substituted 1,3-butadienes. The pharmacology of THHBADs was characterized by electrical recordings in Xenopus oocytes expressing rat brain NMDA and AMPA receptors. THHBADs are antagonists of NMDA and AMPA receptors with functional potency being dependent upon the substitution pattern on the tetrahydrobenzene moiety. The 7,8-dichloro-6-methyl (18a) and 7,8-dichloro-6-ethyl (18b) analogs are the most potent THHBADs prepared and have apparent antagonist dissociation constants (Kb values) of 0.0041 and 0.0028 microM, respectively, for NMDA receptors and 0.51 and 0.72 microM, respectively, for AMPA receptors.