The objective of this study is to evaluate the incidence of occult nodal micrometastases in N0 laryngeal squamous cell carcinoma using cytokeratin immunohistochemical analysis (CKIHA) and its influence on the overall occult metastatic rate. This is a prospective cohort study. A total number of 30 patients with N0 stage laryngeal cancer underwent 46 selective neck dissections for elective treatment of the neck. Nodes found to be negative using routine histopathological examination were evaluated for the presence of micrometastasis using CKIHA. The occult micrometastasis rate for all cases was 26.7 % which significantly increased the overall occult metastasis rate to 50 % (P = 0.014). The micrometastasis rate was 30.8, 25 and 20 % for glottic, supraglottic and transglottic tumors, respectively, which increased the overall occult metastasis rate to 53.8, 50 and 40 % but without statistical impact. The micrometastasis rate was 35.7 and 23.1 % in T3 and T4 tumors, respectively, and this increased the overall occult metastasis rate to 50 and 61.5 % with statistical influence in T3 tumors (P = 0.046). Micrometastasis upstaged the neck in 7 (23.3 %) patients with statistical impact on the PN stage (P = 0.007). The overall occult nodal metastasis rate in N0 laryngeal cancer is underestimated. Nodal micrometastasis may be missed during routine histopathological examination and can be detected using CKIHA.

The objective of this study is to evaluate the incidence of occult nodal micrometastases in N0 laryngeal squamous cell carcinoma using cytokeratin immunohistochemical analysis (CKIHA) and its influence on the overall occult metastatic rate. This is a prospective cohort study. A total number of 30 patients with N0 stage laryngeal cancer underwent 46 selective neck dissections for elective treatment of the neck. Nodes found to be negative using routine histopathological examination were evaluated for the presence of micrometastasis using CKIHA. The occult micrometastasis rate for all cases was 26.7 % which significantly increased the overall occult metastasis rate to 50 % (P = 0.014). The micrometastasis rate was 30.8, 25 and 20 % for glottic, supraglottic and transglottic tumors, respectively, which increased the overall occult metastasis rate to 53.8, 50 and 40 % but without statistical impact. The micrometastasis rate was 35.7 and 23.1 % in T3 and T4 tumors, respectively, and this increased the overall occult metastasis rate to 50 and 61.5 % with statistical influence in T3 tumors (P = 0.046). Micrometastasis upstaged the neck in 7 (23.3 %) patients with statistical impact on the PN stage (P = 0.007). The overall occult nodal metastasis rate in N0 laryngeal cancer is underestimated. Nodal micrometastasis may be missed during routine histopathological examination and can be detected using CKIHA.

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage. © 2003 Elsevier Inc. All rights reserved.

Bladder cancer is a common malignancy in developing countries in which bladder infection with the parasite Schistosoma haematobium is prevalent. Several epidemiological, histopathological, and clinical characteristics of schistosoma-associated bladder cancer suggest that it is distinct from bladder cancer seen in other places in the world. The aim of this study was to extend establishing the cytogenetic profile of this type of malignancy in advanced and metastatic cases, and to demonstrate its relation to the end results of systemic therapy. Fluorescence in situ hybridization was applied to interphase nuclei to detect numerical chromosome changes in 41 patients with bladder cancer. Numerical chromosome aberrations were detected in 27 of 41 cases (66%). In 17 (41%) cases, a gain of chromosome 7 was observed, while losses in chromosomes 9 and 17 were detected in 20 (49%) and 18 (44%) cases, respectively. Loss of chromosome Y was detected in 7 of the 32 male patients included in this study (22%). There was a statistically significant association between stage of the disease and overall survival; Bajorin score and time to disease progression and overall survival; and between response to systemic therapy and time to disease progression and overall survival. The only chromosomal abnormality that had a significant relationship with overall survival was the gain of chromosome 4. When the genetic basis of schistosoma-associated bladder cancer is fully understood, new diagnostic and therapeutic strategies could be developed, which in turn may promote better clinical management and survival.

Bladder cancer is a common malignancy in developing countries in which bladder infection with the parasite Schistosoma haematobium is prevalent. Several epidemiological, histopathological, and clinical characteristics of schistosoma-associated bladder cancer suggest that it is distinct from bladder cancer seen in other places in the world. The aim of this study was to extend establishing the cytogenetic profile of this type of malignancy in advanced and metastatic cases, and to demonstrate its relation to the end results of systemic therapy. Fluorescence in situ hybridization was applied to interphase nuclei to detect numerical chromosome changes in 41 patients with bladder cancer. Numerical chromosome aberrations were detected in 27 of 41 cases (66%). In 17 (41%) cases, a gain of chromosome 7 was observed, while losses in chromosomes 9 and 17 were detected in 20 (49%) and 18 (44%) cases, respectively. Loss of chromosome Y was detected in 7 of the 32 male patients included in this study (22%). There was a statistically significant association between stage of the disease and overall survival; Bajorin score and time to disease progression and overall survival; and between response to systemic therapy and time to disease progression and overall survival. The only chromosomal abnormality that had a significant relationship with overall survival was the gain of chromosome 4. When the genetic basis of schistosoma-associated bladder cancer is fully understood, new diagnostic and therapeutic strategies could be developed, which in turn may promote better clinical management and survival. © 2012 Elsevier Inc.

Thirty male patients suffering from poor scholastic performance were enrolled in this study. The study and matched control groups underwent full pediatric and psychiatric assessment as well as chromosomal analysis and cytogenetic fragile X site detection. They were all in schools and had an IQ above 75. Exclusion included major dysmorphic features, visual or hearing impairment, ADHD, pervasive developmental disorder, tic disorder, anxiety and mood disorders. In addition the control group had at least an average scholastic performance as reported by parents and school grades and no history of any psychiatric disorder.
Results: 43.33% (n=13) of the study group had reading disorder or reading disorder &/or disorder of written expression; 13.33% (n=4) had mathematics disorder another 13.33% (n=4) had difficulties with mathematics not amounting to disorder, and 30% (n=9) qualified for the DSM IV TM category of academic problem (V62.3) where they presented with failing grades and significant underachievement despite their relative adequate intellectual capacity and absence of learning disorder. Chromosomal analysis detected 11 cases (36.67%) with chromosomal variations. These were interstitial deletion in chromosome 2(p22-p24) in one case; paracentric inversion chromosome 6 (p23 – p24) in one patient; paracentric inversion chromosome 9 (p21 – p24) in two patients; interstitial deletion in chromosome 15 (q22 – q23) in one patient; Chromosome 15(p +) ( duplication of the short arm) in two patients; supernumerary small marker chromosome in one patient; deletion of the heterochromatine of Y chromosome Y (q12) in two patients and break at X(q27) in folate deficient media in two patients (one had an additional 15p+). None of the control group was found to have an abnormal cytogenetic study. Conclusion: Poor academic performance could be added to the various phenotypes predicting genetic (chromosomal) abnormality.

MOTIVATION: High-dimensional mass cytometry (CyTOF) allows the simultaneous measurement of multiple cellular markers at single-cell level, providing a comprehensive view of cell compositions. However, the power of CyTOF to explore the full heterogeneity of a biological sample at the single-cell level is currently limited by the number of markers measured simultaneously on a single panel.

RESULTS: To extend the number of markers per cell, we propose an in silico method to integrate CyTOF datasets measured using multiple panels that share a set of markers. Additionally, we present an approach to select the most informative markers from an existing CyTOF dataset to be used as a shared marker set between panels. We demonstrate the feasibility of our methods by evaluating the quality of clustering and neighborhood preservation of the integrated dataset, on two public CyTOF datasets. We illustrate that by computationally extending the number of markers we can further untangle the heterogeneity of mass cytometry data, including rare cell-population detection.

AVAILABILITY AND IMPLEMENTATION: Implementation is available on GitHub (https://github.com/tabdelaal/CyTOFmerge).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cystinosis is the most common hereditary cause of renal Fanconi syndrome in children. It is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding for the carrier protein cystinosin, transporting cystine out of the lysosomal compartment. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. The kidneys are initially affected during the first year of life through proximal tubular damage followed by progressive glomerular damage and end stage renal failure during mid-childhood if not treated. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the disease. Several lines of treatment are available for cystinosis including the cystine depleting agent cysteamine, renal replacement therapy, hormonal therapy and others; however, no curative treatment is yet available. In the current review we will discuss the most important clinical features of the disease, advantages and disadvantages of the current diagnostic and therapeutic options and the main topics of future research in cystinosis.

The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis.

The involvement of the glomerulus in the pathogenesis of cystinosis, caused by loss-of-function mutations in cystinosin (CTNS, 17p13), is a matter of controversy. Although patients with cystinosis demonstrate glomerular lesions and high-molecular-weight proteinuria starting from an early age, a mouse model of cystinosis develops only signs of proximal tubular dysfunction. Here we studied podocyte damage in patients with cystinosis by analyzing urinary podocyte excretion and by in vitro studies of podocytes deficient in cystinosin. Urine from patients with cystinosis presented a significantly higher amount of podocytes compared with controls. In culture, cystinotic podocytes accumulated cystine compatible with cystinosin deficiency. The expression of podocyte specific genes CD2AP, podocalyxin, and synaptopodin and of the WT1 protein was evident in all cell lines. Conditionally immortalized podocyte lines of 2 patients with different CTNS mutations had altered cytoskeleton, impaired cell adhesion sites, and increased individual cell motility. Moreover, these cells showed enhanced phosphorylation of both Akt1 and Akt2 (isoforms of protein kinase B). Inhibition of Akt by a specific inhibitor (Akti inhibitor 1/2) resulted in normalization of the hypermotile phenotype. Thus, our study extends the list of genetic disorders causing podocyte damage and provides the evidence of altered cell signaling cascades resulting in impaired cell adhesion and enhanced cell motility in cystinosis.