Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell 1 dominant state

Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy. Using a C57BL/6 mouse model, OK-432 was found to induce multiple cytokines including the Th1 polarizing cytokine IL-12. Expression of IL-12 protein by murine splenocytes was restricted to macrophages and B cells and led to high levels of IFN-gamma production from both CD4+ and CD8+ T cells. Of the Th2 cytokines IL-4 and IL-10, only IL-10 protein was detected and originated primarily from the adherent cell population. Its expression was delayed relative to IL-12. A similar pattern of cytokine induction was observed from human PBMCs. OK-432-driven IFN-gamma production was inhibited by anti-IL-12 Ab, anti-IL-2 Ab, anti-TNF-alpha Ab, and anti-IL-2R alpha Ab, suggesting that IFN-gamma production from Th1 cells is induced by the cooperation action of these cytokines through the IL-2R alpha pathway. When compared with another widely used immunopotentiator bacillus Calmette-Guérin (BCG), OK-432 was a stronger IL-12 and IFN-gamma inducer. Furthermore, the mechanism of IFN-gamma induction by OK-432 differed from BCG in that coincident granulocyte-macrophage CSF and IL-1 expression played little to no role. These results suggest that OK-432 is a potent multicytokine inducer, specifically a strong inducer of IL-12, and that OK-432 may exert its antitumor effect by promoting a Th1-dominant state.     

Management of displaced lateral orbital wall fractures associated with visual and ocular motility disturbances

Impacted fractures of the lateral orbital wall are a type of orbital blow-in fracture that may be accompanied by decreased visual acuity and ocular motility limitations. Eleven patients who suffered this injury triad were retrospectively reviewed to determine the nature of the ophthalmologic injuries and the effect of fracture reduction on recovery of ophthalmologic functions. Two patients with decreased visual acuity owing to trauma to the globe recovered to subjective pretrauma levels following surgery. Nine patients were thought to have a traumatic optic neuropathy with varying degrees of visual loss. Patients with an injury to the intraorbital portion of the optic nerve and a presurgical visual acuity of 20/400 or better recovered to subjective pretrauma levels. Those with visual acuity of less than 20/400 or an injury to the intracanalicular portion of the nerve had responses ranging from no improvement to objective improvement with large field defects. Ocular motility improved in all patients, many in the immediate postsurgical period consistent with removal of a mechanical restriction. No patients had worsening of ophthalmologic deficits as a result of manipulation of fracture fragments. Our experience suggests that early surgical intervention facilitates recovery of vision and eye movement. The traumatic optic neuropathy that accompanies this fracture is distinct from the indirect type of optic nerve injury that may respond to steroids, and the ophthalmoplegia is distinct from the usual traumatic superior orbital fissure syndrome that resolves spontaneously. An understanding of the impacted lateral orbital wall fracture and its ophthalmologic implications is essential for any surgeon who desires to manage craniomaxillofacial injuries.     

Schizosaccharomyces pombe produces novel pyruvate-containing N-linked oligosaccharides

The large N-linked oligosaccharides released by endo-beta-N-acetylglucosaminidase H from Schizosaccharomyces pombe glycoproteins were analyzed for the presence of noncarbohydrate functional groups. No phosphate, sulfate, or acetate could be detected; however, approximately six molecules of pyruvic acid/molecule were found on 98% of the oligosaccharides. Pyruvate moieties were acetal (ketal)-linked to galactose residues in the R configuration to carbons 4 and 6. This is the first report of pyruvate functional groups being attached to N-linked oligosaccharides in yeast and appears only to be the second documentation of this sugar modification in eukaryotes.     

Folic acid supplementation--when and how

The periconceptional intake of 400 micrograms of folic acid can prevent 50-70% of neural tube defects. It is difficult to achieve this intake with diet alone, even with the recently approved levels for grain-food fortification. Therefore, a daily multivitamin with folic acid is recommended for all women of childbearing potential. Obstetrician-gynecologists should exercise every opportunity to educate their patients to this end. Although raised as a concern, the potential of masking the megaloblastic anemia of pernicious anemia is unlikely with these levels of supplementation, and considering the rarity of the disease in women of reproductive age.     

Nuclear magnetic resonance studies of D2O-substrate exchange reactions catalyzed by glutamic pyruvic and glutamic oxaloacetic transaminases

Nuclear magnetic resonance studies in D2O (greater than 90%) with glutamic pyruvate transaminase (GTP) (2.6.1.2) demonstrate that this enzyme catalyzes the rapid exchange of both the alpha and beta hydrogens of L-alanine, the exchange of only one alpha hydrogen of glycine, and the beta hydrogens of pyruvate and fluoropyruvate. When the beta hydrogens of L-alanine undergo the enzyme-catalyzed exchange, the product may have 1, 2 or 3 of beta hydrogens exchanged. The exchange is stimulated by the addition of catalytic amounts of copartner of transaminations reaction. A mechanism is proposed for an extension of the conjugated system to include the alpha and beta carbons to explain the labilization of the beta hydrogens.