Eighteen autopsy cases of adult T-cell leukemia (ATL) were investigated clinicopathologically. Thirteen of the patients had hypercalcemia during their clinical course. Nine of the thirteen had a high level of serum calcium at the terminal stage, even after extensive chemotherapy. Microscopic examination of the bone revealed proliferation of osteoclasts and bone resorption in eight patients. No osteoclast proliferation or bone resorption was found in the other nine normocalcemic patients. The infiltration of ATL cells was observed in only two patients--one was hypercalcemic and the other, normocalcemic. The factors affecting the serum calcium level were examined in two hypercalcemic patients. Hypercalcemia could not be accounted for by parathyroid hormone or prostaglandins E levels, which were in the normal range, or by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, which were low. Our findings are consistent with the mechanism proposed by several investigators, that the malignant T-lymphocytes produced an osteoclast-activating-factor-like substance that caused osteoclast proliferation and hypercalcemia.
Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor 1 (TGF1) pathway that is mediated by protein kinase C␦ (PKC␦). TGF1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKC␦, which is required for expression and activation of integrins. Increased expression of integrins ␣2 and ␣3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGF1 effects. Furthermore, TGF1 treatment and PKC␦ activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGF pathway, PKC␦ expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.
Background
Helicobacter pylori (HP) infection is considered to play a role in the pathogenesis of chronic spontaneous urticaria (CSU). However, the efficacy of HP eradication therapy on CSU symptom improvement has not been well established. This meta‐analysis was conducted to estimate the association between HP infection and CSU and to evaluate whether HP eradication therapy benefits patients with CSU.
Material and Methods
In October 2018, we searched databases for studies investigating the efficacy of HP eradication therapy for patients with CSU. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using random effects models.
Results
The meta‐analysis included 22 studies with a total of 1385 patients with CSU. When comparing the spontaneous remission of urticarial symptom in patients with HP‐positive to HP‐negative patients, HP‐negative patients showed significantly higher spontaneous remission of urticarial symptoms. (risk ratio 0.39; 95% confidence interval: 0.19‐0.81). Among HP‐positive CSU patients, remission of CSU was more likely shown in HP eradication therapy group compared to untreated group, aside from achieving HP elimination (risk ratio 2.10; 95% confidence interval: 1.20‐3.68). However, there was no significant difference in the remission of CSU whether antibiotic therapy was successful in eradication of HP or not (risk ratio 1.00; 95% confidence interval: 0.65‐1.54).
Conclusions
The results of this meta‐analysis show that HP might be associated with the occurrence and persistence of CSU. The effectiveness of HP eradication therapy in suppressing CSU symptoms was significant. Interestingly, we found that resolution of CSU was not associated with successful eradication of HP infection. CSU Patients who were undergone antibiotic therapy for HP eradication showed significant higher CSU remission with or without HP eradication. Further studies are recommended to evaluate the mechanisms associated with relation of HP with CSU.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.