Detection of genetic alterations in primary bladder carcinoma with dual-color and multiplex fluorescence in situ hybridization

Cytogenetic studies of bladder cancer have shown several nonrandom aberrations. Numerical aberrations of both sex chromosomes were investigated in 32 primary bladder tumors with bicolor fluorescence in situ hybridization (FISH). Loss of chromosome Y and overrepresentation of chromosome X were observed in subgroups of male patients. Chromosome X was represented normally in female patients. Two of the above primary bladder tumors, a transitional cell carcinoma (TCC) and an adenocarcinoma, were further analyzed with both multiplex FISH (24-color M-FISH) and G-banding. Both cases exhibited 1) common breakpoints on 5q11 approximately q12 and 15q24; 2) involvement of the pericentromeric area of chromosome 13; 3) structural abnormalities of chromosomes 8 and 17, with loss of material on the short arm; 4) structural abnormalities involving chromosome 11; and 5) loss of chromosome Y. The TCC case also exhibited structural abnormalities of chromosome 9, resulting in loss of 9q. The combined G-banding and M-FISH findings could help reveal regions potentially involved in bladder tumorigenesis.     

Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody

The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence.     

CASE REPORT: Light Chain Deposition Disease of the Liver Without Renal Involvement in a Patient with Multiple Myeloma Related to Liver Failure and Rapid Fatal Outcome

We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie stage III) who developed jaundice and severe cholestasis after a first cure with systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound and CT scan showed mild hepatomegaly without evidence of extrahepatic or intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive amorphous substance. Immunohistochemistry showed positivity for kappa-light chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD immunoglobulins as well as for AA and AL proteins and for amyloid P component. A diagnosis of light chain deposition disease (LCDD) of the liver was made. The patient developed rapid deterioration of liver function, leading to a multisystem dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5% and myeloma is the underlying disease in two thirds of patients with LCDD. The kidneys are involved in almost all cases of LCDD and renal dysfunction usually reveals the disease. Only three patients with LCDD of the liver without overt renal involvement have been reported so far. This is the first observation of LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis of high tumor mass myeloma, without overt renal involvement, leading rapidly to the patient's death.     

KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential

AIM： To study the association of the frequency and pattern of KIT and PDGFRA mutations and clinicopathological factors in a group of patients with gastrointestinal stromal tumors （GIST）. METHODS： Thirty patients with GIST were examined. Exons 9, 11, 13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing. RESULTS： KIT or PDGFRA mutations were detected in 21 of the 30 patients （70%）. Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant （P 〈 0.05）. Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour （P 〈 0.003）. GISTs with PDGFRA mutations located in stomach showed a mixed cell phenotype and were classified as of very low or low moderate malignant potential. CONCLUSION： Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.     

ConfidenHT™ System for Diagnostic Mapping of Renal Nerves

Purpose of Review

To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented.

Recent Findings

There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches. In both animals and humans, RNS is safe and results in an increase of blood pressure (BP) while the effect on heart rate varies. In this context, the ConfidenHT? system constitutes an integrated solution for effective RNS in humans.

Summary

Due to the diversity of renal nerve anatomy in humans, arterial areas for more effective renal denervation cannot be homogenously defined. The concept of mapping of renal nerves can improve completeness of renal denervation therapies by means of integrated RNS solutions such as the ConfidenHT? system.

     

Translocation (X;12)(p11;p13) as a sole abnormality in biphenotypic acute leukemia

A reciprocal t(X;12)(p11;p13) was found as the sole clonal abnormality in biphenotypic leukemia with myeloid and B-lymphoid differentiation. With fluorescence in situ hybridization analysis, the ETV6 gene (previously TEL) was found to be translocated intact to the derivative X chromosome; no MLL and BCR/ABL rearrangements were found. The patient achieved complete remission after induction chemotherapy. To our knowledge, this cytogenetic aberration has not been reported previously as a sole abnormality in hematological malignancies. Its presence may suggest an important role in the pathogenesis of biphenotypic leukemia.     

2015 Evidence Analysis Library Systematic Review on Advanced Technology in Food Production

In the late 20th century, plant breeders began using molecular biology techniques such as recombinant DNA, also known as genetic engineering, along with traditional cross-breeding. Ten plant and one animal food have been approved for commercialization in the United States. Today, foods and ingredients from genetically engineered (GE) crops are present throughout the food supply, which has led to varying levels of acceptance. Much discussion exists among consumers and health professionals about the believability of statements made regarding benefits or risks of GE foods. The aim of this systematic review was to examine the evidence on the association of consumption of GE foods and ingredients derived from them on human health, specifically allergenicity, food safety, pesticide consumption, nutrient adequacy, inflammation, and antibiotic resistance. An expert panel conducted a systematic review on advanced technology in food production. The 30 developed questions focused on effects of human consumption of GE foods and the effects of human consumption of foods containing pesticide residues on human health. Primary research published from 1994 to 2014 were identified using PubMed and Agricultural Online Access databases. Additional studies were identified by searching references of review articles. Twenty-one studies met the inclusion criteria. Relevant research addressed five of 30 questions. Four questions focused on food allergenicity, the fifth on nutrient adequacy, and all received a Grade III (limited/weak) rating. No human studies addressed 25 questions on the consumption of foods produced using genetic engineering technologies on gene translocation, cancer, food safety, phenotype expression, inflammation and inflammatory markers, or antibiotic resistance. These questions received a Grade V (grade not assignable). Evidence from human studies did not reveal an association between adverse health effects and consumption of foods produced using genetic engineering technologies. Although the number of available human studies is small, they support that there are no clear adverse health effects—as they relate to allergenicity and nutrient adequacy—associated with consumption of GE foods. The present systematic review is aligned with a recent report by the National Academy of Sciences that included human and animal research.     

Statin therapy and risk of diabetes in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia

Objective

Controversial findings exist regarding potential influence of statin therapy on diabetic incidence. Aim of this study was to investigate the role of long duration statin treatment on diabetes mellitus (DM) incidence of Heterozygous Familial Hypercholesterolemia (hFH) and Familial Combined Hyperlipidemia (FCH) patients.

Methods

Study population consisted of 212 hFH and 147 FCH patients that visited Lipid Outpatient Department (mean follow up of 11 and 10 years respectively). Several clinical data such as history of DM, cardiovascular disease, thyroid function, metabolic syndrome, glucose levels, lipid profile and lifestyle data were obtained. In order to compare the effects of different doses of different types of statins, a “statin treatment intensity product” was used.

Results

14% of FCH and only 1% of hFH patients developed DM during follow up. Although univariate analysis showed a statistical trend (p = 0.06) in the association between new onset DM and statin treatment intensity (STI) in the FCH subgroup of patients with normal baseline glucose levels, this was no longer significant after adjusting for several confounders. Furthermore, the type of statins used did not seem to play a role in the development of DM either in hFH or FCH patients.

Conclusion

Long duration of high STI does not seem to be associated with diabetic risk in hFH patients. High STI used in the FCH population is not associated with increased risk of new onset DM compared to low STI. Further studies are required in order to clarify the potential diabetogenic effects of statins in these high risk populations.