The efficiency of interference of Potato virus X infection depends on the target gene

RNA silencing is a natural defense response against viral infection. This phenomenon has been used to interfere with viral infections by exploiting fragments of viral genomes as sources of RNA silencing. Agrobacterium-mediated transient expression of a hairpin RNA derived from the TGBp1 gene of Potato virus X (PVX) induced RNA silencing of the TGBp1 gene and resulted in interference of PVX infection. The interference was induced in the infiltrated leaves but not in the upper non-infiltrated leaves. Transient expression of a CP hairpin RNA also induced interference of PVX. The TGBp1 hairpin RNA showed more efficient interference of PVX infection than the CP hairpin RNA.     

VAMP4 and its cognate SNAREs are required for maintaining the ribbon structure of the Golgi apparatus

Background

The Golgi apparatus is at a crossroads between anterograde and retrograde trafficking. It exhibits a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4) is a unique v-SNARE expressed exclusively in trans-Golgi networks (TGN), where it regulates retrograde trafficking from the early endosome to the TGN with its cognate SNARE partners Syntaxin 6, Syntaxin 16, and Vti1a.

Changes of acinar cells in the pancreato-biliary duct ligation with exocrine pancreatic stimulation model in rats; protective effects of a new potent protease inhibitor, ONO3307]

To evaluate the changes of pancreatic acinar cells in the pancreatic duct obstructed animals as well as the protective effects of a new potent protease inhibitor, ONO3307, we measured the serum amylase levels, pancreatic water content, histological changes, lysosomal fragility in in-vitro incubation, cathepsin B distribution in acinar cells, and cathepsin B and amylase output into pancreatic juice after short-termed (3 hrs) pancreatic duct obstruction with caerulein (0.2 micrograms/kg.hr) infusion in rats. Serum amylase levels, pancreatic water content, and lysosomal fragility in duct obstructed with caerulein infused animals were significantly increased compared with the control groups, and remarkable shift of cathepsin B from lysosomal fraction to zymogen fraction was observed in this group. These changes tended to continue 24 hours after removal of duct obstruction. But with infusion of ONO3307, these changes observed in duct-obstructed with caerulein infusion groups were significantly, almost completely attenuated. These results indicate the intimate relationship between the pathogenesis of acute pancreatitis and lysosomes and some known proteases which are inhibited by ONO 3307 and suggest the usefulness of such a kind of protease inhibitor in the treatment of acute pancreatitis.     

Off-Pump Coronary Artery Bypass Grafting in a Patient with Congenital Factor V Deficiency: Report of a Case

Congenital factor V deficiency is an uncommon bleeding disorder that necessitates hemostatic correction before surgery. We herein describe a patient with severe factor V deficiency who underwent successful off-pump coronary artery bypass grafting with a transfusion of fresh-frozen plasma.     

Adenosquamous carcinoma of the pancreas

A 58-year-old Japanese man was admitted complaining of abdominal pain. An abdominal computed tomography examination demonstrated a tumor in the head of the pancreas and multiple calcifications. A laparotomy was performed and the tumor was removed by Whipple's operation. Histologically, the neoplasm that invaded the duodenal wall and the papilla of Vater was composed of nests of malignant squamous cells with intercellular bridges and showed the formation of keratinized pearls with a small area of concurrently neoplastic glandular and squamous elements. On the basis of these features, the diagnosis of adenosquamous carcinoma of the pancreas was made. The patient died 18 months after the operation. The neoplastic behavior of this rare primary pancreatic carcinoma is similar to that of duct cell carcinoma as well as pure squamous cell carcinoma of the pancreas. As the pancreas can be the target of metastases of squamous carcinomas from other organs it is wise to be aware of this rare entity.     

Successful remission using metyrapone in an elderly patient with Cushing disease accompanied by generalized edema

An 82-year-old woman was referred to our hospital because of hypoalbuminemia and generalized edema. Hypercortisolemia was subsequently found as the levels of serum cortisol and plasma adrenocorticotropic hormone (ACTH) sampled in a fasting morning were 140 pg/mL and 41.9 μg/dL, respectively. These hormones were not suppressed after taking low-dose dexamethasone the previous night and increased to a mild extent in response to administration of corticotrophin-releasing hormone, suggesting presence of pituitary adenoma producing ACTH (Cushing's disease). However, intrasella localization of pituitary adenoma could not be determined by magnetic resonance imaging. Soon after administration of metyrapone was started in an attempt to reduce her cortisol levels, the patient suffered from severe pneumonia. The pulmonary infection and peripheral edema were improved with decreases in cortisol levels by continuing metyrapone administration with antibiotics and finally she was discharged from the hospital on foot. Metyrapone is a useful therapeutic choice to achieve a remission of cortisol levels in the elderly patients with Cushing's disease in association with serious hypercortisolemia impending severe infection.     

A case of hepatitis C-associated osteosclerosis that was improved with the combination therapy of peginterferon alfa-2b and ribavirin

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in skeletal mass in patients who are infected with hepatitis C virus (HCV). The clinical presentation is an acquired deep bone pain with increased serum alkaline phosphatase (ALP) activity. We present a case of a patient with HCAO who was treated with antiviral therapy. A 42-year-old Japanese man presented with severe, stabbing pain in his lower limbs. He was diagnosed with hepatitis C secondary to intravenous drug use 20 years earlier. Serum biochemical studies revealed markedly elevated ALP activity and osteocalcin levels. Skeletal radiographs showed diffuse bony sclerosis with marked cortical thickening in the long bones. The bony findings and clinical symptoms were attributed to HCAO. The HCV RNA viral load was high and the genotype was 2a. The patient was treated with peginterferon alfa-2b and ribavirin for 24 weeks. After 24 weeks of the combination therapy, the patient had a sustained virological response and clinical remission of bone pain and a decrease in the level of serum ALP. In conclusion, HCAO was improved by the combination therapy of peginterferon alfa-2b and ribavirin when the patient achieved sustained virological response. It was confirmed that HCAO was one of the extrahepatic manifestations of HCV.     

Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV1 Decline: A Longitudinal Cohort Study

BackgroundHeated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV₁) decline.MethodsParticipants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV₁ measurement in 2012–2014 and 2018–2019, and a worksite population (n = 722; mean age 49.3 years) without FEV₁ data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV₁ change between smoking groups were examined in the resident population.ResultsPrevalence of HTP-only and dual users in 2018–2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV₁ decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, −34 to 2 mL/year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV₁ decline as cigarette-only smokers.ConclusionsHTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV₁ decline. Tobacco policy should consider dual use as high-risk.Key words: heated tobacco products, electronic nicotine delivery devices, prevention, smoking caused disease     

QUANTITATIVE ANALYSIS OF LOW‐DOSE ASPIRIN‐ASSOCIATED SMALL BOWEL INJURY USING A CAPSULE ENDOSCOPY SCORING INDEX

Aim: The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low‐dose aspirin (LDA) using a CE scoring index. Methods: The CE score for small bowel mucosal injury was investigated to evaluate the severity of mucosal injury. Healthy volunteers and patients suspected of having small bowel disease were recruited for this study. The short‐term LDA group (V + S‐LDA group) consisted of volunteers who took low‐dose aspirin for 14 days; this group was then compared with healthy volunteers who did not receive LDA treatment (V‐Control group). The long‐term LDA group (L‐LDA group) consisted of patients with at least a 3‐month history of daily LDA use; this group was compared with non‐users of LDA (P‐Control group). Results: The CE score was significantly higher in the V + S‐LDA group than in the V‐Control group. In the V‐Control group, almost all the subjects were categorized as exhibiting a ‘normal’ change. ‘Mild’ changes were observed significantly more frequently in the V + S‐LDA group than in the V‐Control group. The CE score was significantly higher in the L‐LDA group than in the P‐Control group. ‘Mild’ or ‘moderate or severe’ changes were observed significantly more frequently in the L‐LDA group than in the P‐Control group. Conclusion: The CE scoring system was useful for evaluating LDA‐associated small bowel mucosal disease activity and for objectively scoring the small bowel inflammatory disease state.     

Effect of pregnane X receptor ligand on pharmacokinetics of substrates of organic cation transporter Oct1 in rats.

Because rat organic cation transporter 1 (Oct1, SLC22a1) is expressed mainly in the liver and mediates drug transport, its activity may determine the hepatic handling of cationic drugs. Here, we studied the regulation mechanism of the expression of Oct1, focusing on the nuclear receptors. In vitro studies using cultured hepatocytes indicated that expression of Oct1 was up-regulated by treatment with pregnenolone-16 alpha-carbonitrile (PCN) and by overexpression of rat pregnane X receptor (PXR). In addition, isolated rat hepatocytes exhibited an increase of 1-methyl-4-phenylpyridinium (MPP(+)) uptake on treatment with PCN. When rats were subcutaneously administered PCN, an increase of biliary excretion clearance and distribution volume was observed for drugs such as MPP(+), metformin, and tetraethylammonium, although the effects on pharmacokinetic parameters were variable among the tested drugs. In addition, the expression of Oct2 in kidney was increased by treatment with PCN. Thus, PXR ligands appear to regulate the expression of organic cation transporters in rats and thereby to influence the pharmacokinetic properties of cationic drugs. Because PXR ligands include various clinically used drugs, alterations of hepatic drug handling may arise from interactions between cationic drugs that are substrates of Oct1 and ligands of PXR.