Soheir S. Mansy

CD133+ human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis

Elkhafif N, El Baz H, Hammam O, Hassan S, Salah F, Mansour W, Mansy S, Yehia H, Zaki A, Magdy R. CD133+ human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis. APMIS 2010.

Agarose cell block: innovated technique for the processing of urine cytology for electron microscopy examination.

Easy manipulation and preservation of cells in suspension through the different steps of sample processing for electron microscopy examination is essential for proper diagnosis. The author used agarose gel as an embedding media for processing cells in suspension for electron microscopic examination. The AgarCyto cell block procedure of Kerstens et al. (J Histochem Cytochem. 2000; 48: 709—718) was used to begin electron microscopic processing of exfoliated urothelial cells in voided urine or cells in suspension. Processing of agarose cell block simultaneously for light and electron microscopic examination represents a great advantage offered by this innovated technique.

Value of the Innovated Technique Agarose Cell Block in Improving the Sensitivity of Urine Cytology in Cases of Bladder Carcinoma

Proper handling and processing of urine sample can greatly improve diagnostic sensitivity. This work investigates the value of agarose cell block technique in processing urine samples simultaneously for light and electron microscopic examination, with the prospect to enhance the quality of diagnosis. The material of this study consisted of 45 voided urine samples, processed for the performance of Papanicolaou-stained urine smears, agarose cell blocks paraffin sections stained with hematoxylin & eosin, and electron microscopy-contrasted ultrathin sections. The studied technique increases the sensitivity of urine cytology and opens a new prospect for cytomorphological study.

Hepatic Stellate Cells and Fibrogenesis in Hepatitis C Virus Infection: An Ultrastructural Insight

An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation to hepatic fibrosis, apoptotic cellular changes, intracellular fat deposition, circulating inflammatory cells in the sinusoids, and the necroinflammatory activity in liver specimens of 33 patients proven to be positive for hepatitis C virus (HCV)-RNA by polymerase chain reaction with the intention that electron microscopy may throw more light on the role of HSCs in the complicated process of fibrogenesis. A detailed review concerning these parameters and observed evidence suggesting the potential properties of HSCs to recycle cellular debris into collagen fibers are reported.

Homing of transplanted bone marrow cells in livers of Schistosoma mansoni-infected mice

Elkhafif N, Voss B, Hammam O, Yehia H, Mansy S, Akl M, Boehm S, Mahmoud S, El Bendary O, El Fandy G. Homing of transplanted bone marrow cells in livers of Schistosoma mansoni‐infected mice. APMIS 2010; 118: 277–87.

Value of reelin for assessing hepatic fibrogenesis in a group of Egyptian HCV infected patients

Abstract Background: Development of non-invasive markers that can predict the stages of hepatic fibrosis without resorting to repeated liver biopsies is still an important goal to evaluate the effectiveness of antifibrotic treatment. The present work investigates the value of the assessment of peripheral circulating reelin, in which the liver represents its prime source, as a marker for monitoring hepatic fibrogenesis. Methods: Seventy-four cases with chronic hepatitis positive for serum HCV RNA and 15 healthy volunteers were enrolled in this study. Assessment of reelin in the harvested serum and in 64 corresponding liver biopsies using immunofluorescence technique was done. The results were evaluated in relation to the stages and quantitative morphometric analysis of hepatic fibrosis as well as the serum levels of the validated biomarker hyaluronic acid. Results: Significant correlation was detected between the levels of serum reelin and the semiquantitative assessment of reelin immunoreactivity in liver tissue, the stages of hepatic fibrosis, the morphometrically determined collagen and serum hyaluronic acid with a correlation coefficient of 0.675, 0.623, 0.479, 0.772, respectively with p<0.001. The sensitivity and the specificity of reelin for the determination of advanced (F2+F3) and significant fibrosis (F2–F4) were nearly comparable to the result of hyaluronic acid. In addition the area under curve (AUC) were 0.859, 0.871 for the reelin versus 0.878, and 0.891 for the hyaluronic acid. Conclusions: In conclusion serum reelin may be considered an additional useful parameter for monitoring the progression of hepatic fibrosis in HCV-infected patients specially in those with active rheumatological conditions which result in an increase in serum hyaluronic acid.

Spotlight on the three main hepatic fibrogenic cells in HCV-infected patients: Multiple immunofluorescence and ultrastructure study

ABSTRACT The present work deals with the simultaneous ultrastructure and triple immunofluorescence study of the three main hepatic fibrogenic cells, hepatic stellate cell, myofibroblast (MF), and fibroblast, in a group of hepatitis C virus (HCV) RNA positive patients, as their exact interrelation behavior in vivo with the progress of hepatic fibrosis is still inadequate. In this study, for the first time, cells having the morphological characteristic of MF and not bone marrow fibrocytes were revealed in liver portal vessels. This necessitates the reevaluation of the available knowledge concerning bone marrow fibrocyte. Also, the distribution, cellular interrelations, and the fate of MF were highlighted.

Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV infected patients

ABSTRACT Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma (HCC). Although the early diagnosis of HCC is vital for successful curative treatment, the majority of lesions are diagnosed in an irredeemable phase. This work deals with a comparative ultrastructural study of experimentally gradually induced HCC, surgically resected HCC, and potential premalignant lesions from HCV-infected patients, with the prospect to detect cellular criteria denoting premalignant transformation. Among the main detected pathological changes which are postulated to precede frank HCC: failure of normal hepatocyte regeneration with star shape clonal fragmentation, frequent elucidation of hepatic progenitor cells and Hering canals, hepatocytes of different electron density loaded with small sized rounded monotonous mitochondria, increase junctional complexes bordering bile canaliculi and in between hepatocyte membranes, abundant cellular proteinaceous material with hypertrophied or vesiculated rough endoplasmic reticulum (RER), sequestrated nucleus with proteinaceous granular material or hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro-vesicular fat deposition. In conclusion, the present work has visualized new hepatocytic division or regenerative process that mimic splitting or clonal fragmentation that occurs in primitive creature. Also, new observations that may be of value or assist in predicting HCC and identifying the appropriate patient for surveillance have been reported. Moreover, it has pointed to the possible malignant potentiality of liver stem/progenitor cells. For reliability, the results can be subjected to cohort longitudinal study.

HCV has Transforming Potential to Retrovirus: An Ultrastructure Hypothesis

The present work highlights intracellular viral morphogenesis and virus–host cell interactions in patients proved to be infected with HCV. The material of this study consisted of 28 liver biopsies taken from patients positive for serum HCV-RNA by polymerase chain reaction. Liver biopsies were processed for light and electron microscopic examination. Ultrastructural findings of this work supported a new hypothesis for the turnover of HCV to retrovirus and described the presumed involved mechanism. This novel perception offers important insights that can explain the vague mechanisms of HCV behavior in the infected hepatocytes.

Immunohistochemical and electron microscopic morphometric image analysis of hepatocellular carcinoma in association of HCV infection

ABSTRACT Early detection of hepatocellular carcinoma (HCC) is crucial for successful therapy. The present work examined the value of ultrastructural morphometric image analysis of hepatocyte nuclei in patients with chronic hepatitis C virus (HCV) versus HCC cases with chronic HCV and the corresponding surgical tumor-free safe margins (TFMs), to highlight any early predictive signs of neoplastic cellular transformation. This work also performed an immunohistochemical assessment of cytokeratin 19 (CK19) and Ki-67-positive cells to visualize any associated proliferative activity in the examined groups. The results showed significant decrease in the hepatocyte nuclear surface areas in the HCC and TFMs versus those in the HCV cases. The hepatocyte nucleolar surface area was significantly increased in the HCC cases versus that in the HCV cases. This increase was associated with a significant increase in Ki-67-positive cells in the HCC cases compared to those in the other groups. Conversely, the mean number of CK 19-positive cells was significantly reduced in the HCC cases compared to the cell numbers in TFMs and HCV cases with severe hepatic fibrosis. Liver progenitor cells (LPCs) were discerned in the reactive ductules and canaliculo-ductular junctions that characterized TFMs. LPCs were sporadically distributed in the liver lobules and reactive bile ductules in the HCC samples. In conclusion, CK 19 represents an important marker for distinguishing between dysplastic and malignant liver nodules. Electron microscopic morphometric image analysis may be considered as adjunct factor for assessing hepatocyte malignant transformation. Wider scale studies are needed to authenticate these results.