The intestinal epithelium forms a first line of innate host defense by secretion of proteins with antimicrobial activity against microbial infection. Despite the extensive studies on the antimicrobial host defense in many gastrointestinal tracts, little is known about the antimicrobial defense system of the stomach. The potent antimicrobial peptide buforin I, consisting of 39 aa, was isolated recently from the stomach tissue of an Asian toad, Bufo bufo gargarizans. In this study we examined the mechanism of buforin I production in toad stomach tissue. Buforin I is produced by the action of pepsin isozymes, named pepsin Ca and Cb, cleaving the Tyr39-Ala40 bond of histone H2A. Immunohistochemical analysis revealed that buforin I is present extracellularly on the mucosal surface, and unacetylated histone H2A, a precursor of buforin I, is localized in the cytoplasm of gastric gland cells. Furthermore, Western blot analysis showed that buforin I is also present in the gastric fluids, and immunoelectron microscopy detected localization of the unacetylated histone H2A in the cytoplasmic granules of gastric gland cells. The distinct subcellular distribution of the unacetylated histone H2A and the detection of the unacetylated buforin I both on the mucosal surface and in the lumen suggest that buforin I is produced from the cytoplasmic unacetylated histone H2A secreted into the gastric lumen and subsequently processed by pepsins. Our results indicate that buforin I along with pepsins in the vertebrate stomach may contribute to the innate host defense of the stomach against invading microorganisms.

Microbial colonization and infection of placental tissues often lead to adverse pregnancy outcomes such as preterm birth, a leading cause of neonatal morbidity and mortality. The fetal membranes of the placenta, a physical and active barrier to microbial invasion, encapsulate the fetus and secure its intrauterine environment. To examine the innate defense system of the human placenta, antimicrobial peptides were isolated from the fetal membranes of human placenta and characterized biochemically. Two salt-resistant antimicrobial host proteins were purified to homogeneity using heparin-affinity and reversed-phase HPLC. Characterization of these proteins revealed that they are identical to histones H2A and H2B. Histones H2A and H2B showed dose-dependent inhibition of the endotoxin activity of LPS and inhibited this activity by binding to and therefore blocking both the core and lipid A moieties of LPS. Consistent with a role for histones in the establishment of placental innate defense, histones H2A and H2B were highly expressed in the cytoplasm of syncytiotrophoblasts and amnion cells, where the histone proteins were localized mainly to the epithelial surface. Furthermore, culturing of amnion-derived WISH cells led to the constitutive release of histone H2B, and histones H2A and H2B contribute to bactericidal activity of amniotic fluid. Our studies suggest that histones H2A and H2B may endow the epithelium of the placenta with an antimicrobial and endotoxin-neutralizing barrier against microorganisms that invade this immune-privileged site.

This study aims to ascertain the incidence of cancer in patients with systemic lupus erythematosus (SLE) in comparison with that in the general population in Korea, and to identify the cancer-types, the organ involvement, and the association with immunosuppressive therapy. The study subjects were consecutive SLE patients evaluated at Kangnam St. Mary's hospital between 1997 and 2007. The incidence rate of cancer was calculated and was analyzed in comparison to that of age- and sex-matched cohort obtained from the Korea National Cancer Registry. Nine hundred fourteen patients were observed for a total of 5,716 person-years. A total of 16 cases of cancer occurred. The average age at the diagnosis of cancer and the mean disease duration were 43 years and 11 years, respectively. The standardized incidence ratio (SIR) of all cancers was 1.45 (95% CI 0.74-2.16); The SIRs for the three most frequent cancers were 3.42 for cervix cancer (CI 0.00-7.26), 15.37 for non-Hodgkin's lymphoma (NHL; CI 2.90-37.68), and 43.55 for bladder cancer (CI 8.21-106.78). There were significant differences in the hematologic and renal involvement between SLE patients with cancer and without. Cyclophosphamide therapy, especially with cumulative dose more than 6 g (p = 0.017), seemed to contribute to the increased risk of cancer. Long disease duration, damage, and hematologic involvement were associated with increased risk of cancer occurrence. SLE patients are at high risk for NHL and bladder cancer. Active cancer screening is required in SLE patients with long disease duration and damage who are treated with high dose cyclophosphamide.

Breast cancer has become the most common cancer in Korean women in recent years, with continuously increased incidence rates attributed to westernized lifestyles. Design: Retrospective case series evaluating the changing patterns of clinical characteristics in breast cancer during the last 15 years.