Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12

Human plasmacytoid dendritic cells (DC) (PDC, CD123+) and myeloid DC (MDC, CD11c+) may be able to discriminate between distinct classes of microbial molecules based on a different pattern of Toll-like receptor (TLR) expression. TLR1-TLR9 were examined in purified PDC and MDC. TLR9, which is critically involved in the recognition of CpG motifs in mice, was present in PDC but not in MDC. TLR4, which is required for the response to LPS, was selectively expressed on MDC. Consistent with TLR expression, PDC were susceptible to stimulation by CpG oligodeoxynucleotide (ODN) but not by LPS, while MDC responded to LPS but not to CpG ODN. In PDC, CpG ODN supported survival, activation (CD80, CD86, CD40, MHC class II), chemokine production (IL-8, IP-10) and maturation (CD83). CD40 ligand (CD40L) and CpG ODN synergized to activate PDC and to stimulate the production of IFN-alpha and IL-12 including bioactive IL-12 p70. Previous incubation of PDC with IL-3 decreased the amount of CpG-induced IFN-alpha and shifted the cytokine response in favor of IL-12. CpG ODN-activated PDC showed an increased ability to stimulate proliferation of naive allogeneic CD4 T cells, butTh1 polarization of developing T cells required simultaneous activation of PDC by CD40 ligation and CpG ODN. CpG ODN-stimulated PDC expressed CCR7, which mediates homing to lymph nodes. In conclusion, our studies reveal that IL-12 p70 production by PDC is under strict control of two signals, an adequate exogenous microbial stimulus such as CpG ODN, and CD40L provided endogenously by activated T cells. Thus, CpG ODN acts as an enhancer of T cell help, while T cell-controlled restriction to foreign antigens is maintained.     

Anterior segment evaluation of infants with retinopathy of prematurity

To understand the mechanisms of glaucoma in retinopathy of prematurity (ROP), anterior segment evaluation is essential. The authors prospectively examined the anterior segment of 27 eyes of 17 premature infants with stages IV and V ROP. Twenty-six eyes received no previous surgery or treatment. Schi?tz and applanation tonometry were performed. Structural evaluation of each anterior segment was conducted by biomicroscopy and Koeppe gonioscopy. In the 26 eyes, angle closure of greater than 180 degrees was noted in 3 (12%). The authors noted prominent Schwalbe's line in 4 eyes (15%), high iris convexity in 15 (58%), hypopigmentation of the iris root in 19 (73%), translucent matrix in the angles ("Barkan's-type" membrane) in 18 (69%), posterior synechiae in 16 (62%), visible iris or angle vessels in 12 (46%), and pigment clumping in the angle recess in 12 (46%). This study identified structural abnormalities in the anterior segment of ROP infants, including pathologic changes and anatomic features that could have a developmental origin.     

Pregnant adolescent and adult women have similarly low intakes of selected nutrients

OBJECTIVE: To examine the dietary intake of pregnant adolescents during the second and third trimester of pregnancy, and to compare their nutrient intake with that of pregnant adults. DESIGN: Two 7-day food records (14 days) from subjects participating in a larger randomized clinical calcium trial: the first at 19 to 21 weeks and the second between 29 and 31 weeks gestation. Intake of energy and selected nutrients were calculated and compared with dietary standards. SUBJECTS/SETTING: Fifty-nine pregnant adolescents and 97 pregnant adults recruited from prenatal clinics at a metropolitan university hospital. STATISTICAL ANALYSES: Two sample t tests, equality of variances, and repeated measures (analysis of variance). RESULTS: There was no difference in mean nutrient intakes between the second and third trimesters. Using two 7-day food records, we found mean intakes for energy, iron, zinc, calcium, magnesium, folate, and vitamins D and E to be below recommended standards in both groups. Other nutrients examined met or exceeded reference values. Total daily intakes for energy and 11 nutrients were significantly higher in the adolescent compared to the adult diets (P < .05). These differences were not evident when nutrient values were corrected for energy, indicating that increased energy intake in the teen-aged population was contributed by nutrient-dense foods. APPLICATIONS: This study indicates the need for continued dietary monitoring of pregnant adolescents and pregnant adults, including nutrition guidance that stresses food sources of calcium, magnesium, zinc, iron, fiber, folate, and vitamins D and E, the nutrients found deficient in their diets.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

The importance of free hydroxyl radicals to hypoxia preconditioning

Hypoxia preconditioning states that a sublethal hypoxia period will afford neuroprotection against a second harmful event. In our experiments, we carried out a procedure for the development of hypoxia preconditioning in adult male Wistar rats using hypoxic exposure (9% O(2); 91% N(2)) for 1 h. The protection against pentylenetetrazol (PTZ)-induced seizures was studied. For this, rats were tested by a single injection of PTZ (55 mg/kg i.p.) on days 1-21 after hypoxia exposure. The hypoxia exposure significantly prevented the development of acute PTZ convulsion at different times after hypoxia. The present study was designed to determine the effect of N-t-butyl-alpha-phenylnitrone (PBN), an electron-trapping agent and free radical scavenger, on hypoxia preconditioning against PTZ seizures 7 days after hypoxia exposure. PBN abolished the protective action of hypoxia exposure. The generation of free hydroxyl radicals in the brains of animals exposed to hypoxia was determined in a second experiment. For this purpose, the rats were i. p. pretreated with 30 mg/kg PBN and NaCl, respectively, 20 min before the start of hypoxia exposure. Forty-five minutes later the rats were i.p. injected with 300 mg/kg sodium salicylate and once again exposed to hypoxia for 15 min. Immediately after that the animals were decapitated and the free hydroxyl radicals and the salicylate content were estimated in the whole brain without cerebellum. Hypoxia preconditioned animals pretreated with NaCl showed a significantly higher extent of free hydroxyl radicals in the brain compared with PBN-injected preconditioned animals and with naive and sham exposed controls. The results pointed out that the generation of free reactive oxygen species under hypoxic conditions in the brain is involved in the development of the hypoxic preconditioning phenomenon.     

Complex fractures of the clivus: diagnosis with CT and clinical outcome in 11 patients

During a 20-month period, fractures of the clivus occurring after craniocerebral trauma were diagnosed with computed tomography (CT) in 11 patients. Five patients had longitudinally oriented fractures; these were fatal in four patients due to either vertebral-basilar artery occlusion, brain stem trauma, or both. Six other patients had transversely oriented fractures that extended through the carotid canal and petrous temporal bone. While less frequently contributing directly to mortality, transverse fractures were also associated with cerebrospinal fluid leaks (two patients) and a cavernous sinus-carotid fistula (one patient). They were not as frequently associated with Horner syndrome or cranial nerve deficits as suggested in the current literature. This retrospective evaluation reveals two distinct injury patterns that demonstrate a difference in related morbidity and mortality.     

Distal esophageal ballooning following Heller myotomy

Eccentric ballooning of the distal esophagus was observed radiographically in 11 of 23 patients (48%) who underwent Heller myotomy for achalasia. While, to the authors' knowledge, ballooning at the site of myotomy incision has not been described previously in the radiologic literature, it should be recognized as a normal and frequent postoperative finding. Radiologists should be aware of this finding so that it is not mistaken for postoperative abnormalities following esophagomyotomy or an epiphrenic diverticulum.