Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production

The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-gamma) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.     

A twin-family study of self-report symptoms of panic-phobia and somatization

Self-report symptoms of anxiety are widely used in mental health and social science research as an index of current psychiatric state. Previous twin studies have suggested that genetic factors account for a significant proportion of the variance in these symptoms. To replicate and extend these findings, we examined self-report symtoms of panic-phobia and somatization in the “Virginia 30,000” twin-family sample. Model fitting applied to 80 unique relationships in the twin-family pedigree produced the following major results: (i) genetic effects were significant for both symptom factors, accounting for between 25 and 49% of the total variance, with the exception of symptoms of panic-phobia in females, where they accounted for 15–16% of the variance; (ii) familial environmental effects were absent for symptoms of somatization, while for symptoms of panic-phobia they accounted for a very small proportion of variance in males (≤1.2%) and a modest proportion in females (6–17%) (iii) spousal correlations were present for both factors, ranging from +0.05 to +0.20; (iv) genetic factors which influenced symptoms were generally the same in males and females, although their effect was greater in males; (v) heritability estimates were lower in the population-based than in the volunteer sample; and (vi) when test-retest reliability was included in the model, results suggest that genetic factors account for at least half of the stable variance for all symptom factors, except panic-phobia in females. Our results support the validity of previous twin studies of self-report symptoms of anxiety and suggest that genetic factors significantly influence these symptoms but familial-environmental factors play little or no etiologic role.     

Mature cystic teratoma of the ovary associated with complete colonic wall and mucinous cystadenoma

Mature cystic teratomas of the ovary frequently contain intestinal type epithelium, but they are rarely associated with complete intestinal wall. The association of mature cystic teratoma with mucinous cystadenoma is not unusual. However, the pathogenetic relationship between these two lesions remains unanswered. We report a mature cystic teratoma of the ovary in a 16-yr old female that contained a complete colonic wall in continuity with an endocervical-type mucinous cystadenoma. Both the mucinous cystadenoma and the colonic wall showed the typical histopathological and immunohistochemical patterns of classical mucinous cystadenoma (positive for CK7, negative for CK20) and normal colonic wall (positive for CK20, negative for CK7), respectively. The microscopic and immunohistochemical patterns of the epithelium from the transitional zone between colonic wall-like structure and mucinous cystadenoma demonstrated features of both types of epithelium, positive for both CK7 and CK20, and focally positive for a neuroendocrine marker, chromogranin, which is normally present in colonic mucosa. These results suggest that the mucinous cystadenoma originated from the colonic epithelium of the mature cystic teratoma.     

Does feeding regime affect physiologic and thermal responses during exposure to 8, 20, and 27° C?

Summary When the loss of body heat is accelerated by exposure to low environmental temperatures, additional substrates must be oxidized to provide energy to sustain temperature homeostasis. Therefore, the present investigation examined the relation between feeding regime [pre-experimental carbohydrate feeding (FED) vs a fast (FAST)], during 120 min of exposure to 8, 20, and 27° C in well-nourished men. The following were examined: tissue insulation (I; °C · m² · W^–1), rectal temperature (T _re; °C), and oxygen consumption ( O₂; ml · kg^–1 · min^–1). O₂, T _re, and I revealed no significant differences between treatments (FED vs FAST) at any temperature. At 27° C, I was less (P < 0.05) than at 20 and 8° C, and decreased (P < 0.05) as exposure time increased. At 8° C, O₂was higher (P < 0.5) than at 20 or 27°C, and O₂increased as time increased (P < 0.05). T _re decreased (P < 0.05) as time increased for all conditions. Respiratory exchange ratio (R) differed (P < 0.05) between treatments (FED vs FAST), temperature (8 vs 20° C), and across time. Values for R suggests that carbohydrate accounted for 56% and 33% of caloric utilization during the FED vs FAST conditions, respectively. At 8 vs 20° C, R represented 54% vs 30% of cabohydrate utilization. Across time, R demonstrated that in both conditions (FED vs FAST) there was a decreased reliance on carbohydrate utilization for energy provision. From these data it appears that while substrate utilization differed between dietary treatment and across time this did not differentially affect O₂or T _re during protracted exposure to 8, 20, and 27° C. The higher R in the 8° C condition for both dietary treatments demonstrates that carbohydrate utilization is increased in shivering cold-exposed humans. However, the reduction in R across time suggests that fat oxidation is also involved in metabolic heat production and core temperature maintenance during shivering in the cold.     

Adenoviral vectors expressing siRNAs for discovery and validation of gene function

RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts.     

Evaluation of two chromogenic agar media for recovery and identification of Staphylococcus aureus small-colony variants

To identify the most rapid and reliable technique for recovery and identification of Staphylococcus aureus small-colony variants (SCVs), the colonial appearance of 106 isolates representing SCVs and the normal phenotype were evaluated on two newly described chromogenic agar media. Although almost all of the SCVs grew on the chromogenic agar media, they did not exhibit a change of color. In comparison with conventional media, S. aureus ID agar (SAID; bioMerieux, La Balme Les Grottes, France) showed the most reliable results, with 49 of 53 SCVs tested growing either as an SCV colony or with a normal phenotype after only 24 h of incubation. Growth of SCVs was often not detected before 72 h of incubation on some of the media tested. In conclusion, the most accurate and rapid method to detect both the species S. aureus and the SCV phenotype is to inoculate specimens onto both Columbia blood agar and SAID.