The ubiquitination of proteins can signal their degradation, modify their activity or target them to specific membranes or cellular organelles. Here, we show that monoubiquitination regulates the plasma membrane abundance and function of the potassium channel, ROMK. Immunoprecipitation of proteins obtained from renal cortex and outer medulla with ROMK antibody revealed that this channel was monoubiquitinated. To determine the ubiquitin binding site on ROMK1, all intracellular lysine (Lys) residues of ROMK1 were individually mutated to arginine (Arg), and a two-electrode voltage clamp was used to measure the ROMK1 channel activity in Xenopus oocytes. ROMK1 channel activity increased from 8.1 to 27.2 microA only when Lys-22 was mutated to Arg. Furthermore, Western blotting failed to detect the ubiquitinated ROMK1 in oocytes injected with R1K22R. Patch-clamp experiments showed that biophysical properties of R1K22R were identical to those of wild-type ROMK1. Although total protein expression levels of GFP-ROMK1 and GFP-R1K22R in oocytes were similar, confocal microscopy showed that the surface fluorescence intensity in oocytes injected with GFP-R1K22R was higher than that of GFP-ROMK1. In addition, biotin labeling of ROMK1 and R1K22R proteins expressed in HEK293 cells showed increased surface expression of the Lys-22 mutant channel. Finally, expression of R1K22R in COS7 cells significantly stimulated the surface expression of ROMK1. We conclude that ROMK1 can be monoubiquitinated and that Lys-22 is an ubiquitin-binding site. Thus, monoubiquitination of ROMK1 regulates channel activity by reducing the surface expression of channel protein. This finding implicates the linking of a single ubiquitin molecule to channels as an important posttranslational regulatory signal. 相似文献
We present the autopsy case of an 82-year-old Japanese woman with a mucin-producing adenoma accompanied by pancreas divisum
and a hepatic hilar carcinoma. She had suffered from a cholangiocellular carcinoma at the hepatic hilus for 2 months, which
was treated with radiation and chemotherapy. She did not complain of any abdominal pain. Obstructive jaundice deteriorated
despite percutaneous transhepatic bile duct drainage, and she died of hepatic insufficiency. At autopsy, a hepatic tumor was
confirmed to have caused severe obstructive jaundice. Histological examinations showed moderately to poorly differentiated
cholangiocellular adenocarcinoma with squamous metaplasia, probably due to radiation. A yellowish mucinous tumor was found
in the head of the pancreas near the minor papilla. It consisted of multiple rice-sized cystic lesions with thin septa. Although
it had no capsule, its margin was clear. Neither a wide opening of the major or minor papilla nor mucous drainage was observed.
Gross examinations revealed unfused pancreatic ducts. The slightly dilated dorsal duct and a branch of the mildly dilatated
ventral duct showed tumor involvement. Histological examinations showed mild atypia of the epithelia, and this pancreatic
tumor was diagnosed as branch duct-type mucin-producing adenoma with postradiation dysplasia. The combination of a mucin-producing
tumor and pancreas divisum is rare, and this is only the third reported case. 相似文献
A 47-year-old patient presented with jaundice. Laboratory examinations confirmed cholestasis. The patient had a long history of chronic pancreatitis. Subsequently, cholecystectomy and a duodenumpreserving resection of the pancreatic head (Frey's surgery) had been performed. Endoscopic retrograd holangiography was done. The endoscope was inserted the normal way to the untouched papilla vateri. After injection of contrast medium, only the side-to-side choledocho-jejunal anastomosis but not the common bile duct could be visualized because the catheter spontaneously slipped into the jejunum via the side-to-side choledocho-jejunal anastomosis.
After introducing a catheter percutaneously into the intrahepatic bile duct system, a long stenosis of the common bile duct could be visualized. It was possible to overcome the stenosis with a wire, but the wire also dislocated into the jejunum via the side-to-side choledocho-jejunal anastomosis and could not be placed through the papilla into the duodenum.
The problem was solved in a tricky way: A wire was introduced into the common bile duct via the papilla and placed into the duodenum. A loop was brought in percutaneously and was also placed in the jejunum. With the loop, the wire was grabbed and taken out percutaneously. Now a biliary metal stent could be positioned correctly over the wire to expand the stenosis.
After the procedure jaundice was cured quickly. The further course was uneventful with complete recovery. 相似文献
Today, nearly 90% of common bile duct stones are extracted endoscopically. Problems are encountered if there are large stones or a duct stenosis. Extracorporeal piezoelectric lithotripsy (EPL) as well as intracorporeal electrohydraulic lithotripsy (EHL) serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed. A total of 35 patients with common bile duct stones in whom conventional endoscopic treatment had failed were selected on the condition that stone visualization through ultrasound was possible and that the papilla was within easy reach of the endoscope. Patients fulfilling the inclusion criteria were randomly treated either by EPL or EHL. The average age of our patients was 73 years. The main reasons for failure of conventional endoscopy were due to the large size of the stones (13 patients), impacted stones (16), or the presence of a biliary stricture (6). In the EPL group, visualization of the stones by ultrasound and ensuing treatment were possible in 16 of 18 patients (89%); stones could be fragmented in 15 patients. In 13 patients, the biliary tree could then be completely freed of calculi; the success rate was 72% for all the patients (13 of 18). On average, the patients had 2.3 treatments on the lithotripter, and 3870 shock waves were applied per treatment. In the EHL group stones were successfully fragmented in 13 of 17 patients (76.5%). The average number of treatments was 1.4. Comparing both therapies, there was no difference in stone-free rates. In both groups, additional endoscopic interventions were necessary to clear the bile duct. The mean number of lithotripsy sessions was less in the EHL group (1.4 vs 2.3). There were no major differences in average hospital stay, 30-day mortality was zero in both groups. Combined treatment including EPL, EHL, and intracorporeal laser lithotripsy was finally successful in 32 patients (91.5%). It is concluded that EHL might be the method of choice for smaller, single stones in the more proximal parts of the common bile duct. In these cases, complete duct clearance in one lithotripsy session can be achieved. Multiple and large stones are probably best accessible to EPL. With a combination of the methods described, the bile duct can be cleared of concrements in almost every instance. As a result, surgery for choledocholithiasis has become the absolute exception.This work was presented in part at the 1993 Annual Meeting of the american Gastroenterological Association in Boston and published in abstract form (Gastroenterology 104:A347, 1993). 相似文献
Infection with Salmonella enterica serotype Typhimurium sequence type (ST) 313 is associated with high rates of drug resistance, bloodstream infections, and death. To determine whether ST313 is dominant in the Democratic Republic of the Congo, we studied 180 isolates collected during 2007–2011; 96% belonged to CRISPOL type CT28, which is associated with ST313. 相似文献
Asian dust storms originating from arid regions of Mongolia and China are a well-known springtime phenomenon throughout East Asia. Evidence is increasing for the adverse health effects caused by airborne desert dust inhalation. Given that people spend approximately 90 % of their time indoors, indoor air quality is a significant concern. The present study aimed to examine the influence of outdoor particulate matter (PM) levels on indoor PM levels during Asian dust events under everyday conditions.
Methods
We simultaneously monitored counts of particles larger than 0.3, 0.5, 1, 2, and 5 μm using two direct-reading instruments (KC-01D1 airborne particle counter; Rion), one placed in an apartment room and another on the veranda, under everyday conditions before and during an Asian dust event. We also examined how indoor particle counts were affected by opening a window, crawling, and air purifier use.
Results
An Asian dust event on 24 April 2012 caused 50- and 20-fold increases in PM counts in outdoor and indoor air, respectively. A window open for 10 min resulted in a rapid increase of indoor PM counts up to 70 % of outside levels that did not return to baseline levels after 3 h. An air purifier rapidly reduced PM counts for all particle sizes measured.
Conclusions
It is important to account for occupant behavior, such as window-opening and air purifier use, when estimating residential exposure to particulate matter. 相似文献
Cardiovascular diseases (CVD) are major contributors to mortality and morbidity in South Asia. Chronic exposure to air pollution is an important risk factor for cardiovascular diseases, although the majority of studies to date have been conducted in developed countries. Both indoor and outdoor air pollution are growing problems in developing countries in South Asia yet the impact on rising rates of CVD in these regions has largely been ignored. We aimed to assess the evidence available regarding air pollution effects on CVD and CVD risk factors in lower income countries in South Asia. A literature search was conducted in PubMed and Web of Science. Our inclusion criteria included peer-reviewed, original, empirical articles published in English between the years 1990 and 2012, conducted in the World Bank South Asia region (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka). This resulted in 30 articles. Nine articles met our inclusion criteria and were assessed for this systematic review. Most of the studies were cross-sectional and examined measured particulate matter effects on CVD outcomes and indicators. We observed a bias as nearly all of the studies were from India. Hypertension and CVD deaths were positively associated with higher particulate matter levels. Biomarkers of oxidative stress such as increased levels of P-selection expressing platelets, depleted superoxide dismutase and reactive oxygen species generation as well as elevated levels of inflammatory-related C-reactive protein, interleukin-6 and interleukin-8 were also positively associated with biomass use or elevated particulate matter levels. An important outcome of this investigation was the evidence suggesting important air pollution effects regarding CVD risk in South Asia. However, too few studies have been conducted. There is as an urgent need for longer term investigations using robust measures of air pollution with different population groups that include a wider range of air pollutants and outcomes, including early indicators of CVD. These regions are facing burdens from increasing urbanization, air pollution and populations, generally weaker health infrastructure, aging populations and increased incidence of non-communicable diseases, included CVD. The extent to which the problem of air pollution and CVD will impact these countries will depend largely on the information available to inform policy and programs, which are still lacking, political will as well as social and economic development. 相似文献