Trisomy 12 in Epstein-Barr virus-transformed lymphoblastoid cell lines of normal individuals and patients with nonhematologic malignancies

Karyotypes of 36 lymphoblastoid cell lines established by Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) of eight normal individuals and 28 patients with various nonhematologic malignancies were analyzed. In seven lines (19.4%), cells with trisomy 12 were noted, with clonality in two of these lines. In two of 11 metaphases with such trisomy, chromosome 12 was involved in structural rearrangements [t(8;12)(q12;p12) and t(12;12)(q11;q24)]. No cells with trisomy 12 were observed in phytohemagglutinin (PHA)-stimulated PBL cultures of these individuals. In 250 individuals (normal and with nonhematologic malignancies) examined in our laboratory in the last 5 years, extra copies of chromosome 12 in PHA-stimulated PBL cultures were observed in only five of 23,216 cells (0.02%). There were no cases of clonality in these samples. The frequency of an extra chromosome 12 was comparable to that of the other chromosomes except 21 and X, whose frequency of occurrence was 0.08% and 0.09%, respectively. These findings should be considered random events in PHA-stimulated PBL. On the contrary, in lymphoblastoid cell lines established by EBV transformation, trisomy of chromosome 12 was the most frequent numerical abnormality. It was observed in 64.7% of all cases with chromosome gains and therefore could not be considered a random occurrence. The specificity of this phenomenon for EBV transformation is supported by the results of cytogenetic analysis of eight lymphoblastoid cell lines established by an alternative procedure in our laboratory [1]. In 400 cells analyzed not a single cell with trisomy 12 was observed. We suggest that EBV transformation might either randomly induce formation of such cells in immortalized B-cell populations or show potentially blastomogenic cells or proneness to their formation in certain individuals who could be predisposed to develop lymphoproliferative diseases, especially chronic lymphocytic leukemia (CLL) in which trisomy of chromosome 12 is the most common alteration.     

Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.

INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1.     

Growing up in the shadow of Chornobyl: adolescents’ risk perceptions and mental health

Purpose  

Despite long-term research on risk perceptions of adults after ecological disasters, little is known about the legacy for the generation exposed to toxic elements as infants. This study examined Chornobyl-related risk perceptions and their relationship to mental health in adolescents raised in Kyiv in the aftermath of the accident.     

Urokinase-type plasminogen activator (uPA) decreases hepatic SR-BI expression and impairs HDL-mediated reverse cholesterol transport

Objectives

The aim of the present study was to investigate the effect of urokinase-type plasminogen activator (uPA) on the expression of the scavenger receptor class B type I (SR-BI) in hepatocytes, and its impact on the removal of HDL-cholesteryl ester (CE) in the liver.

Methods and results

Huh7 hepatoma cell lines were incubated with increasing concentrations of uPA. uPA dose-dependently decreased SR-BI protein expression, as determined by flow cytometry (FACS) and by Western blot assays, and down-regulated SR-BI gene expression. Functionally, uPA decreased both the cellular binding of HDL to Huh7 hepatocytes, and the selective uptake of CE from HDL, as determined by several methods including BODIPY staining, cellular cholesterol determination and chasing radio-labeled CE transfer from HDL to the cells. These results were further confirmed using primary rat hepatocyes. The effect of uPA on hepatic SR-BI expression was mediated via binding to the uPA receptor (uPAR). In vivo, SR-BI protein and gene expressions were found to be increased in hepatocytes derived from the uPAR-KO mice compared to C57Bl/6 mice, and in parallel HDL-cholesterol levels in plasma derived from uPAR-KO mice were decreased. Moreover, deficiency of uPAR significantly accelerated the plasma decay of injected HDL-[³H]CE.

Conclusions

The results of this study suggest that uPA decreases the removal of HDL-CE in the liver via suppression of the hepatic SR-BI expression. Impaired reverse cholesterol transport (RCT) may result in atherogenic dysfunctional HDL metabolism and may contribute to atherosclerosis development.     

Transthoracic parametric Doppler for bedside diagnosis of pulmonary embolism: A pilot study

Transthoracic parametric Doppler (TPD), unlike conventional ultrasonography, measures signals originating from movements of pulmonary blood vessel walls. In this pilot study, we tested TPD in 15 patients diagnosed with pulmonary embolism on computed tomography pulmonary angiography. Results were mapped to the upper, middle, and lower thirds of the right lung. In the lower third, TPD yielded 100% specificity and positive predictive value for acute pulmonary embolism. If validated in a larger series, this rapid bedside technique might obviate the need for computed tomography in specific cases. This could be advantageous in patients who are unstable, in intensive care, or have allergies to iodinated contrast material.     

Gouty flexor tenosynovitis of the digits: report of three cases

Gouty tenosynovitis in the hand is a rare entity. To date the limited cases described have involved predominantly extensor tendons in the fingers and flexor tendons in the palm or wrist. Flexor tendon involvement is less common and has been reported only twice to our knowledge distal to the palm. We report 3 cases of extra-articular gout presenting as tophaceous involvement of flexor tendons in the fingers. All cases were treated surgically. These cases are presented to heighten awareness of this rare entity and to provide a setting for a discussion of management.     

Residual deficits from concussion as revealed by virtual time-to-contact measures of postural stability.

OBJECTIVE: Traumatic brain injury (TBI), including mild traumatic brain injury (MTBI), commonly known as a "concussion", is still one of the most puzzling neurological disorders and least understood injuries facing sport medicine and the scientific community [Cantu R. Concussion assessment Ongoing controversy. In: Slobounov S, Sebastianelli W, editors. Foundations of sport-related brain injuries. New York: Springer Press; 2006. p. 87-111.]. It was our primary objective to assess the dynamic properties of postural control in subjects prior to and after sport-related MTBI using the traditional center of pressure (COP) and virtual time-to-contact (VTC) measures. METHODS: We assessed 12 student-athletes prior to and 30 days after they suffered sport-related MTBI on a number of standing still and dynamic postural tasks. All subjects were clinically asymptomatic at day 30 of testing and were cleared for full sport participation based upon neurological and neuropsychological assessments, as well as clinical symptoms resolution. RESULTS: The findings showed: (1) no significant differences for any of the standard COP-based measures of postural control (i.e., 90% ellipse COP area, COP velocity and Stability Index) as a function of testing day (prior to and 30 days post-injury, p>.05); (2) no differences in terms of VTC shape, distribution and nominal values before and after concussion during standing still postural tasks regardless of vision conditions, p>.05; and (3) there were significant alterations in VTC in terms of absolute values, range of VTC at the deflection points and mode at the day 30 post-injury. CONCLUSIONS: The deficits in VTC control are indicative of residual postural abnormality in subjects suffering from mild traumatic brain injuries and provide further evidence that VTC is used to regulate dynamic postural movement. SIGNIFICANCE: The results show that residual postural abnormalities in concussed individuals may be undetected using conventional research methods and the implications of this for clinical practice are discussed.