Stimulation of melanotic expression in a melanoma cell line by theophylline

Theophylline, a phosphodiesterase inhibitor, was found to be a potent stimulator of melanogenesis in the RPMI 3460 hamster melanoma cell line. This stimulation was greater than that caused by either dibutyryl cyclic AMP (db-cAMP) or another phosphodiesterase inhibitor, papaverine. Theophylline and db-cAMP treatments also produced strikingly different morphologies in the monolayered cells. The theophylline effect on melanogenesis was diminished by db-cAMP, whereas simultaneous treatment of cells with db-cAMP and papaverine produced greater stimulation of melanotic activity than either agent acting alone. Theophylline, therefore, may have phenotypic effects that are at least partially independent of phosphodiesterase inhibition. Theophylline stimulated melanin biosynthesis, as measured by rates of 2- [2-¹⁴C] thiouracil incorporation, and also caused an increase in the level of tyrosinase (EC 1.10.3.1) activity. This melanotic stimulation was prevented by the presence of cordycepin or cycloheximide. Theophylline inhibited DNA synthesis and mitosis in the melanoma cell cultures but stimulated protein synthesis. However, inhibition of proliferation and the first appearance of induced melanotic activity did not bear an immediate direct relationship to one another.     

The dermatoglyphics of American Negroes

Digital and palmar dermatoglyphics of 184 male and 224 female normal American Negroes were evaluated for digital patterns, digital ridge counts, palmar patterns, palmar main line terminations, accessory triradii and palmar creases. All subjects were seven year olds examined and found free of chronic or other genetic diseases. The results were presented for the left and right hand for the most part comparable to those of the African and other American Negro groups reported earlier. The distributions of the various dermatoglyphic features among the Negroes taken as a group were compared to those of the other racial groups and their differences were discussed.     

Haptoglobin-ABO interaction: a possible explanation for the excess of Hp 1 among offspring of ABO incompatible matings.

The Hp1 frequency among ABO phenotypes varies in the Hutterite population as follows: O less than A less than B less than AB. Within group O, the Hp1 frequency is significantly lower than the Hp1 frequency among the other groups combined. The Hp1 frequencies among ABO genotypes, known by means of family pedigrees, vary as follows: OO less than AO less than BO less than AB less than AA less than BB. This holds for both main subjects of this isolate, although they have been reproductively isolated since World War I. The higher Hp1 frequency among type A, B, and AB individuals explains the observation of the higher Hp1 frequencies found among H-leut offspring who are incompatible with their mothers (mainly AO offspring of OO mothers) compared to offspring from the same matings who are compatible with their mothers.     

Combined metformin-salicylate treatment provides improved anti-tumor activity and enhanced radiotherapy response in prostate cancer; drug synergy at clinically relevant doses

BackgroundThere is need for well-tolerated therapies for prostate cancer (PrCa) secondary prevention and to improve response to radiotherapy (RT). The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro. The purpose of this study was to examine whether combined MET+SAL treatment could provide enhanced PrCa tumor suppression and improve response to RT.MethodsAndrogen-sensitive (22RV1) and resistant (PC3, DU-145) PrCa cells and PC3 xenografts were used to examine whether combined treatment with MET+SAL can provide improved anti-tumor activity compared to each agent alone in non-irradiated and irradiated PrCa cells and tumors. Mechanisms of action were investigated with analysis of signaling events, mitochondria respiration and DNL activity assays.ResultsWe observed that PrCa cells are resistant to clinically relevant doses of MET. Combined MET + SAL treatment provides synergistic anti-proliferative activity at clinically relevant doses and enhances the anti-proliferative effects of RT. This was associated with suppression of oxygen consumption rate (OCR), activation of AMPK, suppression of acetyl-CoA carboxylase (ACC)-DNL and mTOR-p70^s6k/4EBP1 and HIF1α pathways. MET + SAL reduced tumor growth in non-irradiated tumors and enhanced the effects of RT.ConclusionMET+SAL treatment suppresses PrCa cell proliferation and tumor growth and enhances responses to RT at clinically relevant doses. Since MET and SAL are safe, widely-used and inexpensive agents, these data support the investigation of MET+SAL in PrCa clinical trials alone and in combination with RT.     

Inhibitory Effects of Secondary Metabolites from the Red Alga Delisea pulchra on Swarming Motility of Proteus mirabilis

Abnormal, uncoordinated swarming motility of the opportunistic human pathogen Proteus mirabilis was seen when a crude extract of the Australian red alga Delisea pulchra was added to the medium. This occurred at concentrations at which growth rate, swimming motility, cell elongation, polynucleation, and hyperflagellation were not affected. One halogenated furanone from D. pulchra inhibited swarming motility at concentrations that did not affect growth rate and swimming motility. Other structurally similar D. pulchra furanones had no effect on swarming, suggesting considerable specificity in the effects of furanones on swarming motility by P. mirabilis.     

Identification and Localization of a Rickettsia sp. in Bemisia tabaci (Homoptera: Aleyrodidae)

Whiteflies (Homoptera: Aleyrodidae) are sap-sucking insects that harbor “Candidatus Portiera aleyrodidarum,” an obligatory symbiotic bacterium which is housed in a special organ called the bacteriome. These insects are also home for a diverse facultative microbial community which may include Hamiltonella, Arsenophonus, Fritchea, Wolbachia, and Cardinium spp. In this study, the bacteria associated with a B biotype of the sweet potato whitefly Bemisia tabaci were characterized using molecular fingerprinting techniques, and a Rickettsia sp. was detected for the first time in this insect family. Rickettsia sp. distribution, transmission and localization were studied using PCR and fluorescence in situ hybridizations (FISH). Rickettsia was found in all 20 Israeli B. tabaci populations screened but not in all individuals within each population. A FISH analysis of B. tabaci eggs, nymphs, and adults revealed a unique concentration of Rickettsia around the gut and follicle cells, as well as a random distribution in the hemolymph. We postulate that the Rickettsia enters the oocyte together with the bacteriocytes, leaves these symbiont-housing cells when the egg is laid, multiplies and spreads throughout the egg during embryogenesis and, subsequently, disperses throughout the body of the hatching nymph, excluding the bacteriomes. Although the role Rickettsia plays in the biology of the whitefly is currently unknown, the vertical transmission on the one hand and the partial within-population infection on the other suggest a phenotype that is advantageous under certain conditions but may be deleterious enough to prevent fixation under others.