Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH)₂D₃from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma.</p> <p>Case presentation</p> <p>An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide.</p> <p>Conclusion</p> <p>Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH)₂D₃can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.</p

Increased prevalence of rotavirus among children associated gastroenteritis in Riyadh Saudi Arabia

The aim of this study is to assess the epidemiology along with the molecular structure of rotavirus causing pediatric diarrhea among Saudi patients. However, in this report we sited the epidemiological reflect coming from our project

NHR-49 Helps Germline-Less Worms Chew the Fat

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity

Association studies on 11 published colorectal cancer risk loci

Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. In total, germline mutations in known genes and moderate- and low risk variants are today suggested to explain 10-15% of the total genetic burden. Hence, predisposed genetic factor are still left to be found. The aim of paper I was to investigate if 11 published loci reported to be associated with an increased or decreased risk of colorectal cancer could be confirmed in a Swedish-based cohort. The cohort was composed of 1786 cases and 1749 controls that were genotyped and analyzed statistically. Genotype– phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumor location, was performed. Of 11 loci, 5 showed statistically significant odds ratios similar to previously published findings. Most of the remaining loci showed similar OR to previous publications. Four statistically significant genotype–phenotype associations were reported. The aim of paper II was to further study these 11 SNPs and their possible correlation with morphological features in tumors. We analyzed 15 histological features in 1572 CRC cases. Five SNPs showed statistically significant associations with morphological parameters. The parameters were poor differentiation, mucin production, decreased frequency of Crohn-like peritumoral reaction and desmoplastic response. The aim of paper III was to identify new CRC loci using a genome wide linkage analysis. We used 121 non-FAP/LS colorectal cancer families and genotyped 600 subjects using SNP array chips. No statistically significant result was found. However, suggestive linkage was found in the parametric analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2) and one on 17p13.2 (LOD/HLOD=2.0). Our linkage study adds support for the previously suggested region on chromosome 9 and suggests three additional loci to be involved in colorectal cancer risk. It is debated whether CRC is a single entity or two different entities, colon- and rectal cancer. Studies have recognized their molecular differences. The aim of paper IV was to identify novel colon- and rectal loci. We performed a genome wide linkage analysis using 32 colon- and 56 rectal cancer families. No LOD or HLOD score above three was observed. However, results close to three could be demonstrated. A maximum HLOD= 2.49 at locus 6p21.1-p12.1 and HLOD= 2.55 at locus 18p11.2 was observed for the colon- and rectal cancer families respectively. Exome sequencing was done, on colon and rectal patients, in these regions of interest. We report 25 variants mutated in family members on chromosome 6 and 27 variants on chromosome 18. Further studies are ongoing to elucidate the importance of these variants

High spatial resolution analysis of ferromanganese concretions by LA-ICP-MS†

A procedure was developed for the determination of element distributions in cross-sections of ferromanganese concretions using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The effects of carrier flow rates, rf forward power, ablation energy, ablation spot size, repetition rate and number of shots per point on analyte intensity were studied. It is shown that different carrier gas flow rates are required in order to obtain maximum sensitivities for different groups of elements, thus complicating the optimisation of ICP parameters. On the contrary, LA parameters have very similar effects on almost all elements studied, thus providing a common optimum parameter set for the entire mass range. However, for selected LA parameters, the use of compromise conditions was necessary in order to compensate for relatively slow data acquisition by ICP-MS and maintain high spatial resolution without sacrificing the multielemental capabilities of the technique. Possible variations in ablation efficiency were corrected for mathematically using the sum of Fe and Mn intensities. Quantification by external calibration against matrix-matched standards was successfully used for more than 50 elements. These standards, in the form of pressed pellets (no binder), were prepared in-house using ferromanganese concentrates from a deep-sea nodule reference material as well as from shallow-marine concretions varying in size and having different proportions of three major phases: aluminosilicates, Fe- and Mn-oxyhydroxides. Element concentrations in each standard were determined by means of conventional solution nebulisation ICP-MS following acid digestion. Examples of selected inter-element correlations in distribution patterns along the cross-section of a concretion are given

Molecular Mechanisms of Fiber Differential Development between G. barbadense and G. hirsutum Revealed by Genetical Genomics

Cotton fiber qualities including length, strength and fineness are known to be controlled by genes affecting cell elongation and secondary cell wall (SCW) biosynthesis, but the molecular mechanisms that govern development of fiber traits are largely unknown. Here, we evaluated an interspecific backcrossed population from G. barbadense cv. Hai7124 and G. hirsutum acc. TM-1 for fiber characteristics in four-year environments under field conditions, and detected 12 quantitative trait loci (QTL) and QTL-by-environment interactions by multi-QTL joint analysis. Further analysis of fiber growth and gene expression between TM-1 and Hai7124 showed greater differences at 10 and 25 days post-anthesis (DPA). In this two period important for fiber performances, we integrated genome-wide expression profiling with linkage analysis using the same genetic materials and identified in total 916 expression QTL (eQTL) significantly (P<0.05) affecting the expression of 394 differential genes. Many positional cis-/trans-acting eQTL and eQTL hotspots were detected across the genome. By comparative mapping of eQTL and fiber QTL, a dataset of candidate genes affecting fiber qualities was generated. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed the major differential genes regulating fiber cell elongation or SCW synthesis. These data collectively support molecular mechanism for G. hirsutum and G. barbadense through differential gene regulation causing difference of fiber qualities. The down-regulated expression of abscisic acid (ABA) and ethylene signaling pathway genes and high-level and long-term expression of positive regulators including auxin and cell wall enzyme genes for fiber cell elongation at the fiber developmental transition stage may account for superior fiber qualities

Burden of rotavirus gastroenteritis in the Middle Eastern and North African pediatric population

<p>Abstract</p> <p>Background</p> <p>Rotavirus gastroenteritis (RVGE) is the most common cause of severe childhood diarrhea worldwide. Objectives were to estimate the burden of RVGE among children less than five years old in the Middle East (Bahrain, Iran, Iraq, Israel, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Syria, UAE, Yemen), North Africa (Algeria, Egypt, Libya, Morocco, Tunisia) and Turkey.</p> <p>Methods</p> <p>A comprehensive literature search was conducted in major databases on the epidemiology and burden of rotavirus among children less than five years old between 1999 and 2009. Data from each country was extracted and compared.</p> <p>Results</p> <p>The search identified 43 studies. RVGE was identified in 16-61% of all cases of acute gastroenteritis, with a peak in the winter. RVGE-related hospitalization rates ranged from 14% to 45%, compared to 14%-28% for non-RVGE. Annually, RVGE caused up to 112 fatalities per 100,000 in certain countries in the region. Hospitalization costs ranged from $1.8 to$4.6 million annually, depending on the country. The most recent literature available showed that G1P[8] was the most prevalent genotype combination in 8 countries (range 23%-56%). G2P[4] was most prevalent in 4 countries (26%-48%). G9P[8] and G4P[8] were also frequently detected.</p> <p>Conclusions</p> <p>RVGE is a common disease associated with significant morbidity, mortality, and economic burden. Given the variety and diverse rotavirus types in the region, use of a vaccine with broad and consistent serotype coverage would be important to help decrease the burden of RVGE in the Middle East and North Africa.</p

Culex pipiens, an Experimental Efficient Vector of West Nile and Rift Valley Fever Viruses in the Maghreb Region

West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 107.8 and 108.5 plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14–21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans