Fibronectin inhibits endocytosis of calcium oxalate crystals by renal tubular cells

BACKGROUND: Fibronectin (FN; 230 kDa) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. We recently reported that FN has a protective effect against injury of renal tubular cells by exposure to oxalate and calcium oxalate (CaOX) crystals and inhibits the adhesion of CaOX crystals to renal tubular cells. In the study presented here, we investigated whether FN has inhibitory effect on crystal endocytosis by renal tubular cells. METHODS: The inhibitory effect of FN on endocytosis of CaOX crystals by MDCK cells was examined by using a radioactivity uptake assay. Also, crystal endocytosis by cells was morphologically assessed by means of transmission electron microscopy (TEM). RESULTS: FN had inhibitory effects on CaOX crystal endocytosis by MDCK cells. The morphological TEM study showed that few crystals were taken into cells when FN was added compared to the number of crystals when FN was not added. CONCLUSION: We found that FN had the inhibitory effects on the interaction between crystals and renal tubular cells, including the adhesion or endocytosis of crystals by cells.     

Prevalence of and risk factors for nocturia: Analysis of a health screening program

BACKGROUND: We examined the prevalence of and risk factors for nocturia in Kurashiki city and the surrounding area, a rural area in Japan. MATERIALS AND METHODS: We collected data on 6517 individuals (4568 men and 1949 women) who participated in a multiphasic health screening. We analyzed the relationships between nocturia assessed by a questionnaire (voiding twice or more during night) and other variables including age, hypertension, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus (DM), chronic renal failure, benign prostatic hyperplasia (BPH), smoking habit and alcohol intake. RESULTS: Overall, 1856 individuals (28.5%) answered that they arose to urinate at least twice during the night. This rate increased with age from 16.5% in individuals younger than 50 to 60.0% in those older than 69. Logistic regression analysis revealed that cohorts of subjects 50-59, 60-69, and 70 years old or over had, respectively, 1.75, 3.35, and 6.21 times the prevalence of nocturia of the 49 years or younger cohort. Hypertension (odds ratio [OR] 1.64) and DM (OR 1.70) were other independent positive risk factors for nocturia. On the other hand, current smokers who smoked 20 or more cigarettes per day were less likely to have nocturia than non-smokers (OR 0.72). In male individuals, BPH was another independent positive risk factor (OR 1.35). Gender was not associated with nocturia. CONCLUSIONS: Although population bias is an important limitation to this study, nocturia is associated with various factors suggesting that multiple approaches are needed to the treatment of patients with nocturia.     

Augmented Lung Adenocarcinoma Cytotoxicity by the Combination of a Genetically Modified Anti-Lewis Y Antibody and Antibodies to Complement Regulatory Proteins

Nine vervet monkeys ( Cercopithecus aethiops ) were infected intradermally with 8 × 10⁷ virulent L. donovani promastigotes. Four animals developed clinical visceral leishmaniasis and died over a period of 18 months. The remaining five animals have remained asymptomatic for a period of 3 years now. Attempts to isolate parasites from spleen and liver through biopsies were fruitless. Immunological respotises of these subclinically infected animals were examined. Enzyme-linked itnmunosorbent assay ( ELISA ) and western blot analyses demonstrated Leishmania specific antibodies in these animals, but the antibody titres were low. When proliferation of peripheral blood monocytes ( PBMC ) to Con-cunavalin A (Con A) of these animals was compared with control 'disease free animals' there were no significant differences iti response. However L. donovani antigen (fixed promastigotes) specific proliferation was demonstrated in the five subclinically infected animals. High and varying levels of interferon gamma (IFN-γ) were secreted in PBMC cultures from the five vervet monkeys when stimulated with either Con A or L. donovani antigens. In control animals, IFN-γ was only detected wheti PBMC were stimulated with Con A. Marked delayed-type hypersensitivity ( DTH ) responses were demonstrated in the five subclinically infected animals 48 h after injection with formalin fixed promastgotes.
It was concluded that the visceral Leishmania disease spectrum due to L. donovani observed in humans could be induced in vervet monkeys and that L. donovani asymptomatic/cryptic infected animals have competent humoral and cellular responses to homologous parasites.     

Randomized Clinical Trial of Endovascular Therapy for Acute Large Vessel Occlusion with Large Ischemic Core (RESCUE-Japan LIMIT): Rationale and Study Protocol

Endovascular therapy is strongly recommended for acute cerebral large vessel occlusion (LVO) with an Alberta stroke program early computed tomography score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of endovascular therapy for patients with a large ischemic core with an ASPECTS ≤5 (0–5) was not established. A multicenter, randomized, open-label, parallel-group trial was conducted to investigate the superiority of endovascular therapy over medical therapy without endovascular therapy for a large ischemic core with ASPECTS (3–5). Patients were randomly assigned to receive endovascular therapy or without endovascular therapy at a ratio of 1:1. The primary outcome was a moderate functional outcome, defined as a modified Rankin scale (mRS; scores ranging from 0 [no symptoms] to 6 [death]) ≤3 after 90 days. The secondary outcomes were defined as ordinal mRS, good functional outcome (mRS ≤2), excellent functional outcome (mRS ≤1), mRS shift analysis after 90 days, and early improvement of neurological findings at 48 hours. A total sample size of 200 was estimated to provide a power of 0.9 with a two-sided alpha of 0.05, for the primary outcome, considering a 15% dropout rate. This randomized clinical trial reported the applicability of endovascular therapy in patients with acute cerebral LVO with a large ischemic core.     

An immunohistochemical study of copper, zinc-containing superoxide dismutase detected by a monoclonal antibody in gastric mucosa and gastric cancer

The immunohistochemical localization of copper, zinc-superoxide dismutase (Cu,Zn-SOD) in human gastric mucosa and gastric cancer was studied using a monoclonal antibody. In gastric mucosa, parietal cells, pyloric glandular cells and foci of intestinal metaplasia showed positive staining in the cytoplasm and/or nucleus. The wide distribution of Cu, Zn-SOD in the gastric mucosa suggests cell function may be vulnerable to active oxygen species. In gastric cancer, 34 of 70 cases showed a positive reaction for Cu, Zn-SOD. There was a relationship between the grade of Cu,Zn-SOD immunoreactivity and the histological type of gastric cancer, well-differentiated types of gastric cancer being more frequently positive. The positive cases of poorly-differentiated adenocarcinoma were characterized by a pattern of diffusely infiltrative invasion. These results suggest that some types of gastric cancer are resistant to active oxygen species.     

Different susceptibility to the IL-3 induced-protective effects between Strongyloides ratti and Nippostrongylus brasiliensis in C57BL/6 mice

Repetitive administration of recombinant IL-3 induced protection against Strongyloides ratti but not against Nippostrongylus brasiliensis in C57BL/6 mice. Numbers of S. ratti were negligible from day 4 to day 6 post-infection in mice injected with IL-3, whereas N. brasiliensis burdens were almost equal from day 4 to day 6 between mice injected with IL-3 or with medium. Mice treated with IL-3 and then concurrently infected with S. ratti and N. brasiliensis were protected from intestinal S. ratti but not from N. brasiliensis. The numbers of intestinal mucosal mast cells were increased by the repetitive IL-3 treatment on one day after the final injection and was augmented by subsequent infection with both nematodes.