Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.     

Increased CD45RO CD62L CD4 T-cell subpopulation responsible for Th2 response in Kimura’s disease

Kimura’s disease is characterized by subcutaneous masses, eosinophilia, and markedly elevated serum immunoglobulin E, suggesting that T helper (Th)2 cells may play a role in the pathogenesis. We investigated Th2 cytokine synthesis by mononuclear cells and possible Th1/Th2 subpopulations in Kimura’s disease. Peripheral blood samples were obtained from seven patients with Kimura’s disease and CD4⁺ T-cell subpopulations separated by CD45RO and CD62L were isolated. Purified cells were stimulated with PHA or anti-CD3 mAb, and the cytokine levels were measured by Cytometric Bead Array kit. Peripheral blood mononuclear cells in the majority of the patients produced Th2 cytokines such as interleukin (IL)-3, IL-4, IL-5, IL-13 or GM-CSF higher than those of controls. The ratio of CD45RO⁺ CD62L⁺ cells in CD4⁺ T cells was increased in six out of seven patients compared to age-matched controls. Especially, patient 1 had remarkably increased levels of CD45RO⁺ CD62L⁺ population in CD4⁺ T cells. In addition, IL-4 production levels by CD45RO⁺ CD62L⁺ CD4⁺ T cells of patients 1 and 2 were higher than those of their CD45RO⁺ CD62L⁻ CD4⁺ T cells, in the same manner as those by a normal control. Taken together, the synthesis of Th2 cytokines and CD62L-positive subpopulation in CD45RO⁺ CD4⁺ T cells, which may represent characteristics of Th2, are increased in patients with Kimura’s disease, suggesting that deviation to Th2 may involve in pathogenesis of the disease.     

Both G3BP1 and G3BP2 contribute to stress granule formation

Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress‐induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules called stress granules (SGs). SGs are storage sites for the many mRNAs released from disassembled polysomes under these stress conditions and are essential for the selective translation of stress‐inducible genes. Ras‐GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG‐positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo‐multimer and a hetero‐multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.     

Disseminated intravascular coagulation in acute lymphoblastic leukemia at presentation and in early phase of remission induction therapy

 A high frequency of disseminated intravascular coagulation (DIC) in adult acute lymphoblastic leukemia (ALL) has been reported; however, its clinical relevance and characteristics have not been fully determined. We studied 67 adults with newly diagnosed ALL between 1982 and 1996 to clarify these questions. DIC was diagnosed in ten of 64 patients (16%) who underwent coagulation study at presentation and in 14 of 40 patients (35%) screened for DIC within 7 days after starting remission induction therapy. Overall, 24 of 67 patients (36%) had DIC during this period. Hemorrhagic symptoms were generally mild, while two patients required red blood cell transfusions. Patients who developed DIC had higher white blood cell counts and more frequently a palpable spleen than those who did not. There was no difference in age, French-American-British subtype, karyotype, immunophenotype, lactate dehydrogenase level, percentage of blasts in bone marrow, or frequency of lymphadenopathy or hepatomegaly between patients who had DIC and those who did not. Fibrinolysis tended to be milder in DIC complicating ALL than in that complicating acute promyelocytic leukemia; however, there was no difference in other coagulation parameters between these two subtypes. An etiological link between CD34 expression in common ALL patients and DIC was suggested. Received: December 8, 1997 / Accepted: March 13, 1998     

Inhibitory mechanism of human platelet aggregation by nafamostat mesilate

We found that nafamostat mesilate (NM) inhibits platelet aggregation induced by all agonists tested, including ADP, collagen, arachidonic acid, thromboxane A analog, A23187, phorbol 12-myristate 13-acetate (PMA), NaF and thrombin. The IC50 values were in the range of 9.3-17.8 microM. NM inhibited agonists-induced aspirin-treated platelet aggregation at >10 microM, suggesting that the action site lies beyond thromboxane (TXA)2 formation. However, NM inhibited thrombin (0.5 IU/ml)-induced TXB2 formation (IC50 = 1.9 +/- 0.6 microM, mean +/- SD). Intracellular Ca2+ mobilization was also inhibited only when platelets were challenged by thrombin, but the effect was found at NM concentrations >50 microM. This finding suggests that NM reduces the responses to thrombin by inhibiting its proteolytic activity on the platelet thrombin receptor (PAR1). NM did not affect the intracellular cAMP concentration or A-kinase activity. Agonists-induced surface expression of activated glycoprotein (GP)IIb-IIIa was inhibited by 10 microM NM and was completely inhibited by 50 microM NM. Since this inhibitory effect was parallel to the inhibition of platelet aggregation, the main inhibitory mechanism of NM against platelet aggregation seemed to be the suppression of activated GPIIb-IIIa expression, which makes it able to bind fibrinogen.     

Development of invasive adenocarcinoma in a long-standing diverted ileal J-pouch for ulcerative colitis

We report a case of a 50-year-old male with ulcerative colitis who developed well-differentiated adenocarcinoma in the ileal J-pouch, which had been defunctioning for 18 years. The extension of the carcinoma in the pouch suggested that it had recently appeared in the pouch. Monitoring by endoscopic examination and biopsy or pouch excision seems to be an appropriate action if a pouch is out of the fecal stream.     

Has Helicobacter pylori eradication for peptic ulcer been overrated?

Discovery of Helicobacter pylori has changed the life cycle of peptic ulcer disease (PUD). However, PUD does not completely disappear after elimination of H. pylori. Some ulcers recur even after successful eradication of H. pylori in non-users of non-steroidal anti-inflammatory drug (NSAID). In addition, the incidence of H. pylori-negative, non-NSAID PUD (idiopathic PUD) is reported to increase with time. Moreover, H. pylori-positive ulcers are not always H. pylori-induced ulcers because there are two paradoxes of the H. pylori myth: the existence of H. pylori-positive non-recurring ulcer and recurring ulcer after cure of H. pylori infection. Taken together, H. pylori is not the only cause of peptic ulcer disease. Therefore, it is still necessary to seriously consider the pathophysiology and the management of the ulcers, which may exist after elimination of H. pylori.     

Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized,parallel-group, multicenter,extension clinical trial

A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.     

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)