Short exposures to tunicamycin induce apoptosis in SV40-transformed but not in normal human fibroblasts

When SV40-transformed fibroblasts (line 90VAVI) were exposedto tunicamycin, an inhibitor of N-linked glycosylation, an extensivecell death occured compared with untransformed fibroblasts.A considerable cell loss was obtained within 24 h after tunicamycinaddition, and after 72 h there were hardly any virus-transformedcells alive. A 2-h pulse treatment with tunicamycin was foundto be almost as effective as a continuous 48-h treatment inkilling the cells. Even such a short exposure as 7 min resultedin a drastically decreased cell viability (54%). The morphologyof the dying tunicamycin-treated 90VAVI cells suggested thatthey were undergoing apoptosis. This was also supported by theappearance of nuclear condensation, as assayed by propidiumiodide uptake, which was detectable within 2 h after tunicamycinaddition. Furthermore, analysis of DNA from tunicamycin-treated90VAVI cells by field inversion gel electrophoresis revealedDNA degradation into 50 kbp fragments within 2 h, and conventionalagarose gel electrophoresis showed ‘DNA laddering’,indicating internucleosomal DNA cleavage, detectable after 36h. Together with the finding that tunicamycin within secondscaused an elevation of [Ca²⁺]₁, a well documented early featureof apoptosis in many experimental systems, these results stronglysuggest that tunicamycin-induced cell death in 90VAVI is dueto apoptosis. The short tunicamycin exposure required to triggercell death in 90VAVI indicates that the apoptotic process isirreversibly induced soon after its addition. It seems unlikelythat the pool of one or several specific N-linked glycoproteinscould be depleted during such a short period. Instead the overallaccumulation of unglycosylated proteins in ER might contributeto the apoptotic response in 90VAVI. Tunicamycin also killedand induced DNA degradation in the breast cancer cell line MDA-231.     

Nerve potentials and afferent conduction velocities in the differential diagnosis of amyotrophy of the hand

Nerve action potentials recorded over the elbow after stimulation of the wrist were studied in patients with hand amyotrophy of different origin. In amyotrophic lateral sclerosis the amplitude of nerve action potentials does not change significantly even with extreme muscle wasting and loss of motor units.     

PBRM1 and VHL expression correlate in human clear cell renal cell carcinoma with differential association with patient’s overall survival

Objective

To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression.

Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer

AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocar-cinoma suspected of local recurrence and metastatic disease.The results were compared with conventional diagnostics.RESULTS:Immunoscintigraphic investigation was done in 53 patients.Tumor recurrence occurred in 38 patients,and was confirmed by other diagnostic modalities in 35.I...     

Assessment of hemostatic disturbances in women with established rheumatoid arthritis

Clinical Rheumatology - This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity....     

Pdx1- and Ngn3-Cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism

Pleomorphic adenoma gene-like 1 (PLAGL1) has been linked to transient neonatal diabetes mellitus. Here, we investigated the role of the related pleomorphic adenoma gene 1 (PLAG1) in glucose homeostasis. PLAG1 transgenic mice in which expression of the PLAG1 transgene can be targeted to different organs by Cre-mediated modulation were crossed with Pdx1-Cre or Ngn3-Cre mice, resulting in double transgenic P1-Pdx1Cre or P1-Ngn3Cre mice, respectively. P1-Pdx1Cre and P1-Ngn3Cre mice developed hyperplasia of pancreatic islets due to increased β- and δ- but not α-cell proliferation. In young P1-Pdx1Cre mice (less than 15 weeks) there was a balanced increase in the pancreatic content of insulin and somatostatin, which was associated with normoglycemia. In older P1-Pdx1Cre mice the pancreatic somatostatin content far exceeded that of insulin, leading to the progressive development of severe hypoglycemia beyond 30 weeks. In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic. In conclusion, forced expression of PLAG1 under the control of the Pdx1 or Ngn3 promoter in murine pancreas induces different degrees of endocrine hormone imbalances within the pancreas, which is associated with hypoglycemia in P1-Pdx1Cre mice but not P1-Ngn3Cre mice. These results suggest that once stem cell-derived islet transplantations become possible, the appropriate balance between different hormone-producing cells will need to be preserved to prevent deregulated glucose metabolism.     

Hand preference is selectively related to common and internal carotid arterial asymmetry

This study documents relationships between handedness and carotid arterial asymmetries. The article is divided into two sections, considering first geometric (n?=?195) and then haemodynamic (n?=?228) asymmetries. In the geometric study, diameters, lengths, and angles of the common carotid arteries in left and right-handed participants were measured using computed tomography angiography scans. Resistance to blood flow was calculated according to Poiseuille’s formula. In the haemodynamic study, peak systolic and end-diastolic velocity, vessel diameter, and volume flow rate of the common, internal, and external carotid arteries were measured in left and right-handed participants, using Doppler ultrasonography. The findings reveal for the first time that the extracranial arteries supplying the cerebral hemispheres are asymmetrical in a direction that increases blood flow to the hemisphere dominant for handedness. Significant handedness interactions were identified in arterial length, diameter, resistance to blood flow, velocity and flow volume rate (p?相似文献