Plasminogen activator inhibitor-1 messenger RNA expression is induced in rat hepatocytes in vivo by dexamethasone.

Plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of tissue plasminogen activator (tPA), plays a crucial role in the regulation of fibrinolysis. Both hepatocytes and endothelial cells have been implicated as major sources of plasma PAI-1. To study the relative contribution of these cell types to hepatic PAI-1 production, we have separated hepatocytes and hepatic sinusoidal endothelial cells by fractionation of freshly isolated rat livers using metrizamide density gradients and centrifugal elutriation. In untreated animals, PAI-1 messenger RNA (mRNA) was detected only in the purified endothelial cell fraction, and not in the hepatocyte fraction or in unfractionated liver. However, when the animals were treated with dexamethasone, PAI-1 mRNA expression was transiently induced in the liver. This induction paralleled the appearance of PAI-1 mRNA in purified hepatocytes, while PAI-1 expression in sinusoidal endothelial cells was unchanged. Four hours after dexamethasone treatment, plasma PAI-1 levels were increased approximately twofold over levels measured in animals treated with the diluent alone. These data suggest that PAI-1 production by hepatocytes may contribute to elevated plasma PAI-1 levels in the setting of acute injury and stress.     

Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P < 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies. Received: 7 August 1999 / Accepted: 8 November 1999     

Amazing results with hydroxyurea therapy in chronic hepatitis B: a preliminary report

Background and Aims

To introduce the possible role of hydroxyurea (HU), a well-characterized antineoplastic drug with established antiviral effects, in the treatment of chronic hepatitis B.

Methods

Four antiretroviral-naïve patients with chronic hepatitis B were enrolled in this limited pilot trial, and given 1000 mg/day of hydroxyurea for 4 weeks; then, the administration of the drug was suspended for 4 weeks. A clinical study and laboratory safety assessments and measurements of viral load were made at baseline, after drug therapy, and after one month suspension of the treatment

Results

All 4 patients showed a significant decrease in viral load after 4 weeks of hydroxyurea therapy and the viral load of 2 patients increased again after a 4-week suspension of hydroxyurea

Conclusions

Our data demonstrate that the old low-cost antineoplastic drug, hydroxyurea, efficiently blocks hepatitis B virus (HBV) replication. We suggest that HU will play an important role in the treatment of chronic hepatitis in the fore- seeable future. Further studies including those that evaluate optimal dosing in long-term use will continue to define the role of HU in the treatment of HBV infection alone or in combination with other antiviral drugs     

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.     

Health-related quality of life in primary antibody deficiency

Patients with primary antibody deficiencies (PAD) are susceptible to recurrent and chronic infections and a variety of complications. This study was performed to assess quality of life (QoL) of PAD patients who were under long term treatment and regular follow-up.Thirty six adults with proved diagnosis of PAD, who had received regular intravenous immunoglobulin replacement therapy, were enrolled in this study. The QoL of selected PAD patients was measured by Medical Outcomes Study 36-item Short-Form (SF-36) Health Survey questionnaire.The patients with PAD showed significantly reduced scores in physical component in comparison with healthy age-sex matched control subjects (60.2±20.1 vs. 85.5±4.7, P<0.001). Mental component score was also significantly decreased in the patient's group (59.8±19.5 vs. 72.3±3.4, P=0.002). There was a reverse association between SF-36 scores and number of infections episodes (r=-0.73 P=0.003). The patients with long delay diagnosis showed significantly lower SF-36 scores (r=-0.62, P=0.003).The patients with PAD who were diagnosed timely and managed appropriately seem to have lower complications and better QoL. However, the patients with severe phenotypes and long delay in diagnosis showed lower QoL, even in medical management.     

Transcatheter patch occlusion of ventricular septal defect in Down syndrome

Closure of perimembranous ventricular septal defects in patients with Down syndrome, either surgically or by Amplatzer occluders, carries a high risk of complete heart block. We report 5 closures using the transcatheter patch, a wireless bioabsorbable device without any reported heart block to date. The median defect size was 11 mm. Small devices were used in 4 patients and a medium size in 1. The patch was released after 48 hours in 3 patients and immediately in the other 2. Of the 5 patients, 3 were followed up for >5 years and 2 for 1 year. None of these patients had atrioventricular block during their follow-up. In conclusion, the transcatheter patch might be superior in terms of cardiac conduction system protection in patients with Down syndrome after ventricular septal defect closure.     

Effect of Alcohol Intake in Patients with Hypertension Currently on Medication Treatment

Regular alcohol use is a risk factor for hypertension and is associated with decreased rate of blood pressure control. The authors conducted a retrospective study of alcohol intake and number of hypertensive medications used in patients with hypertension visiting cardiology clinic from 2011 to 2012. The authors found that a history of alcohol consumption was not associated with number of antihypertensive medication or blood pressure control. However, diastolic blood pressure in normal-weighed drinker subgroup was higher than the nondrinker counterpart. Patients with higher body mass index and Black race tended to use more number of different classes of antihypertensive medication.     

Cardiac echinococcosis with negative serologies: a report of two cases

Cardiac involvement in hydatid cyst disease is uncommon, occurring in approximately 2% of hydatid cases. Two cases of cardiac hydatid cysts with negative serologic tests are reported herein. In Case 1, the patient underwent surgery to remove cysts from the liver and 10 years later presented with symptoms and signs of ischaemic heart disease. In Case 2, the patient first underwent surgery to remove cysts from the brain and 3 years later for cyst removal from the breast. In both cases the diagnosis was established by transthoracic two-dimensional echocardiography and then confirmed by surgery and histological examination. These cases are of particular interest because of the rarity of cardiac localisation as a new site of the hydatid cyst after one or more previous surgeries for hydatid cyst removal, and stress the need for frequent reevaluation to detect new hydatid cyst formation in the heart and elsewhere caused by the Echinococcosis organism.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.