Anti-heparan sulfate antibody and functional loss of glomerular heparan sulfate proteoglycans in lupus nephritis.

Background The purpose of this study was to evaluate the features of heparan sulfate proteoglycans (HSPGs) as agrins of the glomerular basement membrane (GBM) and circulating anti-heparan sulfate (HS) antibodies in lupus nephritis, comparing titers among the following groups: lupus nephritis (LN), non-renal lupus, non-lupus nephritis, and healthy controls. Methods The stage of nephritis was determined based on the kidney biopsy. Alcian blue staining and immunohistochemical (IHC) staining for agrin were performed for histological evaluation of GBM HSPGs in normal glomeruli, non-lupus membranous glomerulonephritis (MGN), and lupus MGN. The results were used for measurement of the serum anti-HS antibody titers using an enzyme-linked immunosorbent assay (ELISA) in the following groups: 38 healthy controls, 38 non-lupus nephritis, 37 non-renal lupus, and 38 LN. Results Glomerulus HSPGs were stained bluish-green along the GBM with Alcian blue. However, IHC staining against agrin was almost completely negative in the lupus MGN group compared with the normal and non-lupus MGN groups, which showed brown staining of GBM. A higher level of anti-HS IgG was detected in LN compared with other groups, respectively. Higher titers were associated with the presence of SLE and nephritis. A higher degree of proteinuria normalized to glomerular filtration rate (eGFR) was observed in association with higher anti-HS antibody titers in LN. Conclusion This study demonstrated a functional loss of GBM HSPGs and higher levels of circulating anti-HS antibodies as a characteristic feature of lupus nephritis, suggesting their involvement in the pathogenesis of lupus nephritis and proteinuria.

Lack of association between LTA and LGALS2 polymorphisms and myocardial infarction in Japanese and Korean populations.

To investigate the recently reported associations of polymorphisms in lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) with myocardial infarction (MI), we analyzed a single nucleotide polymorphism of LTA (LTA 252A>G in LTA intron 1) and that of LGALS2 (LGALS2 3279C>T in LGALS2 intron 1) in Japanese and Korean populations. Although significant associations with MI were not observed in either population, we found that LTA 252GG was significantly associated with the severity of the disease for both the Japanese and Korean populations (P=0.017 and P=0.001, respectively). On the other hand, the polymorphism of LGALS2 was not associated with the severity of coronary atherosclerosis. These observations showed that, while the LTA 252GG genotype might modify the development of coronary atherosclerosis, the relation of LTA and LGALS2 to MI itself remained much less certain.

Cell-type specific regulation of thrombospondin-1 expression and its promoter activity by regulatory agents.

Thrombospondin-1 (TSP-1), a multifunctional protein that is able to function as a negative regulator of solid tumor progression and angiogenesis, is normally present at a very low level but rapidly elevated in pathological tissues. To understand the cellular regulation of TSP-1 expression, the mode of it's expression in Hep3B, SK-HEP-1, and porcine aortic endothelial (PAE) cells was examined in the presence of all-trans retinoic acid (ATRA), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or phorbol 12-myristate 13-acetate (PMA). ATRA or IL-6 induced a dose-dependent increase of TSP-1 protein and mRNA levels in PAE cells, while they negatively regulated TSP-1 expression in the Hep3B and SK-HEP-1 cells. In contrast, PMA showed just the opposite effects on the TSP-1 expression in the same cells. IFN-gamma had little effect on TSP-1 level in Hep3B and PAE cells. The TSP-1 expression in SK-HEP-1 cells by these agents showed a close resemblance to that of liver cells rather than that of the endothelial cell line. Possible TSP-1 promoter-mediated responses by ATRA, IL-6, IFN-gamma, or PMA in Hep3B and PAE cells examined with luciferase activity of TSP-LUC reporter plasmid showed that levels of TSP-1 promoter activity were lower than that of the expressed TSP-1 protein and mRNA levels. Transfection of c-Jun and/or RARalpha expression vectors into Hep3B and PAE cells resulted in the enhanced TSP-1 promoter activity as well as the increments of of its protein and mRNA level. These results suggest that regulatory agents-induced TSP-1 expression may be attributed to mRNA stability and/or translational activation in concert with transcriptional activation and TSP-1 expression may be independently controlled via each signal pathway stimulated by PMA or ATRA.

Nongenomic stimulation of nitric oxide release by estrogen is mediated by estrogen receptor alpha localized in caveolae.

Acute administration of 17beta-estradiol (E(2)) exerts antiatherosclerotic effects in healthy postmenopausal women. The vasoprotective action of E(2) may be partly accounted for by a rapid increase in nitric oxide (NO) levels in endothelial cells (ECs). However, the signaling mechanisms producing this rise are unknown. In an attempt to address the short-term effect of E(2) on endothelial NO production, confluent bovine aortic endothelial cells (BAECs) were incubated in the absence or presence of E(2), and NO production was measured. Significant increases in NO levels were detected after only 5 min of E(2) exposure without a change in the protein levels of endothelial NO synthase (eNOS). This short-term effect of estrogen was significantly blunted by various ligands which decrease intracellular Ca(2+) concentration. Furthermore, plasma membrane-impermeable BSA-conjugated E(2) (E(2)BSA) stimulated endothelial NO release, indicating that in the current system the site of action of E(2) is on the plasma membrane rather than the classical nuclear receptor. The partial antagonist tamoxifen did not block E(2)-induced NO production; however, a pure estrogen receptor alpha (ERalpha) antagonist ICI 182,780 completely inhibited E(2)-stimulated NO release. The binding of E(2) to the membrane was confirmed using FITC-labeled E(2)BSA (E(2)BSA-FITC). Western blot analysis showed that plasmalemmal caveolae possess ERalpha in addition to well-known caveolae-associated proteins eNOS and caveolin. This study demonstrates that the nongenomic and short-term effect of E(2) on endothelial NO release is Ca(2+)-dependent and occurs via ERalpha localized in plasmalemmal caveolae.

Intussusception into the enteroanastomosis after Billroth II gastric resection; diagnosed by gastroscopy.

A case of retrograde intussusception (acute type) of efferent limb into Braun side-to-side jejuno-jejunal anastomosis is presented. Intussusception, though infrequent, is well recognized complication after gastric surgery. Patient was 50 year old man who was admitted with epigastric pain and abdominal mass for 6 hours. Patient had a history of total gastrectomy 2 years before admission due to stage II gastric cancer. Seven hours after admission, hematemesis developed. Emergency fiberopticgastroscopy revealed type 4 jejunogastric intussusception. Segmental resection with end-to-end reanastomosis was performed.