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We have shown previously that ulcerogenic (type I) strains of Helicobacter pylori(Hp) retard their entry into macrophages. However, the signaling pathways that regulate Hp phagocytosis are largely undefined. We show here that Hp strongly activated class IA phosphoinositide3‐kinases (PI3Ks) in macrophages, coincident with phagocytosis, and endogenous p85 and active protein kinase Bα accumulated on forming phagosomes. PI3K inhibitors, wortmannin and LY294002, inhibited phagocytosis of Hp in a dose‐dependent manner, and blockade of engulfment correlated directly with loss of 3′‐phosphoinositides in the membrane subjacent to attached bacteria. During uptake of large immunoglobulin G (IgG)‐coated particles, PI3Ks regulate pseudopod extension and phagosome closure. In marked contrast, we show here that 3′‐phosphoinositides regulated actin polymerization at sites of Hp uptake. Moreover, Hp and IgG beads activated distinct PI3K isoforms. Phagosomes containing IgG‐coated particles accumulated 3′‐phosphatase and tensin homologue deleted on chromosome 10 and Src homology 2 domain‐containing inositol 5′‐phosphatase, yet Hp phagosomes did not. Finally, rapid uptake of IgG‐opsonized Hp or a less‐virulent type II Hp was PI3K‐independent. We conclude that Hp and IgG beads are ingested by distinct mechanisms and that PI3Ks regulate the actin cytoskeleton during slow phagocytosis of ulcerogenic Hp.

Botanical dietary supplements have a long history of use in Europe and Asia, but the use of these products is becoming increasing popular in the United States. Because these products are classified as dietary supplements, the U.S. Food and Drug Administration does not routinely monitor them for environmental contaminants. Ginseng served as a model botanical dietary supplement and was purchased from suppliers in the United States, Europe, and Asia. Samples were analyzed for metals (e.g., cadmium, nickel) and chlorinated pesticides (e.g., PCNB, DDT, and metabolites). Flame and furnace atomic absorption spectrophotometry were utilized for analysis of metals, while gas chromatography (GC) and GC-mass spectrophotometry were utilized for analysis of chlorinated pesticides. Because no formalized guidelines exist to determine risk of botanical dietary supplements, U.S. Environmental Protection Agency guidelines for protection of human health were used. Metals and chlorinated organics were found in Ginseng samples, but the concentrations posed no noncarcinogenic hazard; however, a 1000 mg/d dose for 350 d/yr resulted in 1 × 10-6 carcinogenic risk in 19% of the Ginseng samples analyzed. At a lower usage rate (42 d/yr), no samples exceeded 1 × 10-6 risk. Chlorinated organics, such as aldrin and heptachlor epoxide, accounted for the carcinogenic risk (1 X 10-6) in the Ginseng samples.

A family was studied in which two members died from leukemia, two died from cancer, and two others had hereditary telangiectasia. Slight immunoglobulin abnormalities and cytogenetic mosaicisms were found among their apparently normal relatives. The neoplastic potential of these findings can only be inferred from their previous association with similar malignancies. Their occult nature is compatible with the dearth of information concerning susceptibility toward malignant diseases. An analysis of the literature indicates that a possible predisposition toward familial leukemia is directed toward malignancy in the broad sense rather than toward any specific variety. Useful information about leukemogenesis may be forthcoming from further similar studies.

Because 2APC + 25 mg thalidomide or + 32 mg Codeine sulfate elevated the threshold to experimentally induced pain of 10 human subjects above threshold increments which followed placebos or no treatment while 2 APC alone did not, it is concluded that the analgesic potential of APC is enhanced by added compounds in the quantities employed.