Studies on the role of glycosylation for human corticosteroid-binding globulin: comparison with that for thyroxine-binding globulin

The role of glycosylation on the secretion and the stability of human corticosteroid binding globulin (CBG) was studied. Cells of the human hepatoma line were labeled by [35S]methionine in presence of or absence of tunicamycin (TM). Media or cells were harvested at 0, 3, 6, and 20 h after the addition of excess unlabeled methionine. Media and cell lysates were incubated with anti-CBG serum and immune complexes were precipitated with Staphylococcus aureus protein A (Pansorbin). Immunoprecipitates were analyzed by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoprecipitation of T4-binding globulin (TBG) was also carried out with anti-TBG serum. Fluorographic analysis revealed three forms of CBG: CBG1, a glycosylated, mature, and secretory form with apparent mol wt of 70 K; CBG2, a glycosylated precursor which due to incomplete carbohydrate processing has an apparent mol wt of 54 K; and CBG3, a nonglycosylated form consisting of the 40 K core protein. In absence of TM, CBG1 was observed in media and CBG2 was detected in cell lysates. The proportion of CBG1 increased during the chase, whereas that of CBG2 decreased, indicating that CBG was secreted after processing of the oligosaccharides on CBG2. In presence of TM, CBG3 was found both in media and cell lysates. The sum of CBG3 in the medium and the cell lysate decreased during the chase, whereas that of CBG1 and CBG2 remained unchanged. Similar to CBG, TBG1 (mature form, 60 K) and TBG2 (partially processed glycosylated form, 54 K) were observed in media and cell lysates, respectively, in absence of TM. However, TBG3 (nonglycosylated, 44 K) was not detected in medium. These results indicate that glycosylation is not a key factor for the secretion of CBG but is important for its stability. On the other hand the glycosylation is indispensable for the secretion of TBG.     

The prevalence and clinical predictors of atherosclerotic renal artery stenosis in patients undergoing coronary angiography

Renal artery stenosis is an important cause of secondary hypertension as well as ischemic nephropathy. The purpose of this study was to determine the clinical predictors in patients with renal artery stenosis in a population referred for coronary angiography. From March 1998 to July 1999, 1459 patients undergoing coronary angiography for various indications were routinely screened for renal artery stenosis by undergoing abdominal aortography. Coronary angiography, carotid angiography, and abdominal aortography was performed via either the radial or the femoral approach. The data were analyzed retrospectively. Out of 1459 patients undergoing abdominal aortography, 158 (10.8%) were found to have significant renal artery stenosis with 24 of the patients having bilateral stenosis. Significant coronary artery diseases were found in 994 of the 1459 study population (68.1%), with 134 (13.5%) of these patients having concomitant renal artery stenosis. Multivariate logistic regression showed that extracranial carotid artery stenosis odds ratio [(OR) 4.89 (95% confidence interval 2.57–9.33), P < 0.001], peripheral artery disease [OR 4.64 (2.65–9.33), P < 0.001], renal insufficiency [OR 2.68 (1.43–5.02), P = 0.002], significant coronary artery disease [OR 2.01 (1.12–3.59), P = 0.019], hypercholesterolemia [OR 1.92 (1.07–3.43), P = 0.028], hypertension [OR 1.85 (1.16–2.95), P = 0.010], and old age (>60 years) [OR 1.64 (1.01–2.64), P = 0.044] were significant clinical predictors of renovascular disease. The prevalence of indolent atherosclerotic renal artery stenosis is relatively high in selected groups of patients with high clincial risk factors for this underdiagnosed disease. Renal artery stenosis should be highly suspected in patients who have these risk factors because early detection of this disease may reverse the progression to chronic renal failure and end-stage renal disease.     

TIMP-2 disrupts FGF-2-induced downstream signaling pathways

We have previously reported that tissue inhibitor of metalloproteinases-2 (TIMP-2), an endogenous inhibitor of matrix metalloproteinase, modulates angiogenic responses through the MMP inhibition-independent activity. In this study, we investigate the molecular mechanisms of TIMP-2-mediated growth inhibition in response to fibroblast growth factor-2 (FGF-2). Pre-treatment with a protein tyrosine phosphatase inhibitor orthovanadate or expression of a dominant negative Shp-1 mutant fails to induce TIMP-2 inactivation of FGF-2 signaling pathways in human microvascular endothelial cells. We also show that TIMP-2 inhibition of FGF-2-induced p42/44(MAPK) activation and cell proliferation is associated with TIMP-2 binding to integrin alpha3beta1 on endothelial cell surfaces, as demonstrated by use of anti-integrin alpha3 or beta1 blocking antibodies, or disruption of integrin alpha3 expression by siRNA. Collectively, our results indicate that TIMP-2 inhibits FGF-2 signaling pathways through association with integrin alpha3beta1 and Shp-1-dependent inhibition of p42/44(MAPK) signaling, which in turn, results in suppression of FGF-2-stimulated endothelial cell mitogenesis.     

The outcome of endoscopic treatment in bile duct injury after cholecystectomy]

BACKGROUND/AIMS: Bile duct injury is the most serious complication of cholecystectomy. The aim of this study was to evaluate the outcome of endoscopic treatment in bile duct injury after cholecystectomy. METHODS: We reviewed the results of endoscopic treatments in the patients diagnosed as bile duct injury after cholecystectomy on cholangiographic examinations, retrospectively. Endoscopic treatment included insertion of nasobiliary drainage catheter or plastic stent after endoscopic sphicterotomy. RESULTS: A total of twenty-two patients (9 male, 13 female; median age of 59 years) with bile duct injury were included. Endoscopic treatment was successfully performed in 12 of 13 patients with bile leak only. In patients with both bile leak and stricture, endoscopic treatment was successful in 2 of 3 patients. In 6 patients with complete obstruction of bile duct, endoscopic treatment failed and surgical approach was needed. In our series, transpapillary endoscopic treatment was not successful when proximal bile duct above the injured site was not visualized by endoscopic retrograde cholangiopancreatography (ERCP) and surgery was performed in all cases. Overall success rate of endoscopic treatment in 22 patients with bile duct injury was 64% (14/22). There was no complication associated with endoscopic treatment. CONCLUSIONS: ERCP is useful for the treatment of bile leakage after cholecystectomy and can be used for the treatment prior to surgery. Surgical intervention is needed in case of endoscopic treatment failure.     

A case of spontaneous dissection of the superior mesenteric artery treated by percutaneous stent placement]

Acute mesenteric ischemia can result from emboli, arterial and venous thrombi or vasoconstriction secondary to low-flow states. Isolated spontaneous dissection of the superior mesenteric artery is a rare cause of acute mesenteric ischemia. The mortality rates of acute mesenteric ischemia averages 71% with a range of 59-93%. Diagnosis before the occurrence of intestinal infarction is the most important factor in improving survival rate for patients with acute mesenteric ischemia. A 68-year-old female presented with postprandial epigastric pain, and a dissection of the superior mesenteric artery and a gallbladder polyp were shown in abdominal computed tomographic scan. After the percutaneous metalic stent placement and laparoscopic cholecystectomy, her symptoms improved. We report a case of spontaneous dissection of main trunk of the superior mesenteric artery which was successfully treated by percutaneous stent placement with a review of literature.     

Varix of the right atrium.

A 68-year-old female patient was referred for the evaluation of an incidentally detected asymptomatic cardiac mass. Imaging studies showed a 3.0 x 2.4 cm, well circumscribed, round, cystic mass with a calcified nodule that was attached to the lower rim of the fossa ovalis in the right atrium. Under cardiopulmonary bypass, the right atrium was opened to reveal a well circumscribed, dark bluish, pedunculated mass. Histologically, the specimen was a unilocular cyst lined by flattened endothelium, with peripheral fibrin clots and dystrophic calcification of the wall. Immunohistochemical staining of the lining cells was positive for cluster designation 34, which represents hematopoietic progenitor cell antigen. The final pathologic diagnosis was compatible with varix of the heart, which should be considered for a cystic mass with a calcified nodule located in the right atrium, near the lower rim of the fossa ovalis.     

A case of severe skin eruption caused by Lamivudine in a patient with chronic hepatitis B]

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.     

A case of polymyositis with concomitant diffuse alveolar damage following interstitial pneumonia]

A 68-year-old woman had been given a diagnosis of interstitial pneumonia (NSIP pattern) and followed up at our hospital for 3 years. She was admitted to our hospital because of dyspnea, lower limb edema and myalgia. On admission, serum CPK and CRP levels were elevated and an electromyogram suggested inflammatory myopathy. We diagnosed polymyositis (PM) with progressive interstitial pneumonia (IP). Although methylprednisolone pulse therapy and immunosuppressive agents were administered, pulmonary lesions became aggravated. The patient died due to respiratory failure as a result of the progress of IP. The autopsy lung revealed diffuse alveolar damage (DAD) at the both acute and fibrotic phases, suggesting that DAD could coincide with PM. We report here a rare case of polymyositis with diffuse alveolar damage (DAD).