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Mahmoud Lotfy

Molecular Cell biology and 

Immunology, Molecular and

Cellular Biology Department,

Genetic Engineering and

Biotechnology Research

Institute (GEBRI), Minufiya

University, Sadat City, Minufiya,

Egypt

&

Department of Applied Medical

Sciences, Jouf University,

Saudi Arabia.
mlotfy2000@yahoo.com
Dr. Mahmoud Lotfy, Ph.D

Dr. Lotfy is an associate professor of molecular cell biology and immunology, molecular and cellular

biology department, genetic engineering and biotechnology research institute (GEBRI), Minufiya

University, Sadat City, Minufiya, Egypt and department of applied medical sciences, Jouf University,

Saudi Arabia. GEBRI and National Liver Institute (NLI) are prominent centers in Minufiya University,

Egypt. Jouf University is a recent promising university in KSA, it was established as an extension

of the well-known King Saudi University, KSA. Now Jouf University included many of the faculties

and also research centers. The research interests of Dr. Lotfy are concerned mainly with the

molecular, cellular and immunologic backgrounds of the GIT diseases such as cancers, viral

hepatitis and schistosomiasis. He completed and published many of these relevant studies.

He is a peer reviewer of many international journals with high impact factor and his biography is

included in who is who in medicine and healthcare.

Books

2011

Journal articles

2012
Yousery El-Sayed Sherif, Ahmed Abdel-Hamid El-Asmy, Mahmoud Lotfy (2012)  4-Hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (EX15) and its Cu(II) Complex as New Oxicam Selective Cyclooxygenase-2 Inhibitors   Croatica Chemica Acta 85: 1. 19-26  
Abstract: 4-Hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (EX15) as nonsteroidal antiinflammatory drug (NSAIDs) of oxicam family has been synthesized bearing high se-lectivity for cyclooxygenase-2 (COX-2) inhibition and high ability to chelate with Cu(II) ions. The EX15-Cu(II) complex, and [Cu(EX15)(OAc)(H2O)2], were synthesized and characterized by using elemental analysis, spectral (UV-Vis, IR), conductance, thermal and magnetic studies. Two equations were predicted using quantitative structure activity relationship (QSAR) and regression analysis for the COX-2 and COX-1 selectivity (microsomal assay) with a regression correlation (R) close to unity. Two techniques were used to investigate the validity of these equations; macrophage cell line (in vitro) selectivity and collagen-adjuvant arthritis model in rats (in vivo) which showed a significant antioxidant, analgesic and antirheumatic effect for 4-hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide and its Cu(II) complex, [Cu(EX15)(OAc)(H2O)2]. (doi: 10.5562/cca1802)
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2011
Yousery E Sherif, Mahmoud Lotfy, Elsayed A Elmorsy (2011)  Structure and quantitative structure-activity relationship (QSAR) for Caffeic acid amides as potential anti-platelet aggregation and anti-oxidative agents   Der Pharma Chemica 3: 1. 156-166  
Abstract: Cardiovascular diseases are the leading cause of morbidity in many countries worldwide. Antiplatelet therapy has been successful in reducing mortality and morbidity in cardiovascular diseases. Because inflammation is central to atherothrombosis, agents with both antiinflammatory and antithrombotic properties may be critical to preventing the considerable morbidity and mortality associated with atherothrombotic vascular disease including acute coronary syndrome (ACS), ischaemic stroke, transient ischaemic attack (TIA). The purpose of developing a QSAR model is to reduce the cost of the target designing by modifying the molecular structures for achieving the desired molecule with the proposed property, without experimental measurement. In the current study, we extend a published work that had been investiged the caffeic acid amides as antiplatelets aggregation and free radicals scavenging agents. In this report, four equations were generated to predicate the biological activities of these amide derivatives. Moreover, the biological activity for these molecules that was obtained experimentally is compared with the calculated ones from QSAR output. Newly postulated compounds were predicted as caffeic acid derivatives and their biological activity was deduced using QSAR. The results showed that many of newly fourteen postulated compounds showed prominent biological activities compared to the compounds investigated previously. Moreover, QSAR equations were useful in predicating the biologic activity of the old and postulated molecules. Thus the newly caffeic acid derivatives remain to be synthesized and investigated experimentally for their antiplatelet aggregation and antioxidation properties. Finally, our results may be exhibited a potential interest for investigators attempting to find new antiplatelets aggregation and free radicals scavenging agents.
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I H El-Sayed, Mahmoud Lotfy, M Moawad (2011)  Immunodiagnostic potential of mucin (MUC2) and Thomsen-Friedenreich (TF) antigens in Egyptian patients with colorectal cancer.   Eur Rev Med Pharmacol Sci 15: 1. 91-97 Jan  
Abstract: Colorectal cancer (CRC) is more common in developed countries and is the third most common cancer among both men and women. CRC provides an attractive model of tumour biology with normal mucosa to adenoma to carcinoma sequence. The TF-antigen (Thomsen-Friedenreich) can be identified by galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with CRC. TF antigen is expressed in the neoplastic mucosa and not expressed in colonic mucosa of normal subjects. Apomucins play important role in cell signalling and their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins including MUC2 is contributing in mucus formation to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and TF antigens in patients with adenoma and CRC.
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W A Nasif, M Lotfy, M R Mahmoud (2011)  Protective effect of gum acacia against the aspirin induced intestinal and pancreatic alterations.   Eur Rev Med Pharmacol Sci 15: 3. 285-292 Mar  
Abstract: The current study was carried out to examine the influence of aspirin (400 mg/kg of body weight) and gum acacia (one g/day) and their combination on pancreatic, intestinal mucosal enzymes, intestinal tissue iron and zinc after 21 days of treatment on experimental rats.
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Abdul-Zaher M Khattab, Wesam A Nasif, Mahmoud Lotfy (2011)  MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis.   Med Oncol 28 Suppl 1: S207-S213 Dec  
Abstract: Apomucins play important biological roles in cell-cell and cell-extracellular matrix interactions, in cell signaling, and in biological properties of cancer cells. Their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins, gel-forming components of viscoelastic mucus gels protecting the epithelia, includes mucins MUC2 and MUC6. Their principle function is to contribute in mucus formation by forming a tridimensional network via oligomerization domains to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and MUC6 in patients with gastric carcinoma. MUC2 and MUC6 expressions were detected immunohistochemically in gastric cancer biopsies using specific monoclonal antibodies. The results showed that in our gastric carcinoma cases, MUC2 expression was detected in 78.6% of cases. MUC2 expression is increased from well differentiated to moderately differentiated to poorly differentiated gastric adenocarcinoma. On the other hand, MUC6 was detected in 32% of cases. The expression of MUC2 is increasing, which is accompanied by an altered expression of MUC6 in gastric cancer. Therefore, it is concluded that the expression pattern of secreted mucins including MUC2 and MUC6 is altered apparently in gastric carcinoma.
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2010
Faris Q Alenzi, Eman M El-Nashar, Saad S Al-Ghamdi, Mohammed Y Abbas, Abubaker M Hamad, Osama M El-Saeed, Richard K H Wyse, Mahmoud Lotfy (2010)  Original Article: Investigation of Bcl-2 and PCNA in Hepatocellular Carcinoma: Relation to Chronic HCV.   J Egypt Natl Canc Inst 22: 1. 87-94 Mar  
Abstract: Bcl-2 family members can be functionally divided into anti-apoptotic and proapoptotic groups. The balance between these two groups may determine the fate of tumor cells. In hepatocellular carcinoma (HCC), this balance is often tilted towards the anti-apoptotic members in tumor cells, leading to resistance to cell death and rapid proliferation.
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Faris Q Alenzi, Mahmoud Lotfy, Richard Wyse (2010)  Swords of cell death: caspase activation and regulation.   Asian Pac J Cancer Prev 11: 2. 271-280  
Abstract: Apoptosis represents a crucial process in modulating organ development in the embryo, in organ homeostasis in the adult, and in fostering appropriate immunological function. Caspases represent two central classes of molecules that are either involved with the stimulation of the apoptotic cascade (initiator caspases), or the various sequential biological pathways required for its execution (effector caspases). With an eye towards therapeutic opportunities, this review discusses in detail the lineage of initiator and effector caspases, how they are each activated, their substrates, their regulation, and maps out how they interact throughout the process from initiation of the first apoptotic signal to the final consequential breakdown of cellular integrity.
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Faris Q Alenzi, Mahmoud Lotfy, Waleed G Tamimi, Richard K H Wyse (2010)  Review: Stem cells and gene therapy.   Lab Hematol 16: 3. 53-73 Sep  
Abstract: Both stem cell and gene therapy research are currently the focus of intense research in institutions and companies around the world. Both approaches hold great promise by offering radical new and successful ways of treating debilitating and incurable diseases effectively. Gene therapy is an approach to treat, cure, or ultimately prevent disease by changing the pattern of gene expression. It is mostly experimental, but a number of clinical human trials have already been conducted. Gene therapy can be targeted to somatic or germ cells; the most common vectors are viruses. Scientists manipulate the viral genome and thus introduce therapeutic genes to the target organ. Viruses, in this context, can cause adverse events such as toxicity, immune and inflammatory responses, as well as gene control and targeting issues. Alternative modalities being considered are complexes of DNA with lipids and proteins. Stem cells are primitive cells that have the capacity to self renew as well as to differentiate into 1 or more mature cell types. Pluripotent embryonic stem cells derived from the inner cell mass can develop into more than 200 different cells and differentiate into cells of the 3 germ cell layers. Because of their capacity of unlimited expansion and pluripotency, they are useful in regenerative medicine. Tissue or adult stem cells produce cells specific to the tissue in which they are found. They are relatively unspecialized and predetermined to give rise to specific cell types when they differentiate. The current review provides a summary of our current knowledge of stem cells and gene therapy as well as their clinical implications and related therapeutic options.
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Samir El-Masry, Mahmoud Lotfy, Mona Samy, Shadin Moawia, Ibrahim H El-Sayed, Islam M Khamees (2010)  Pattern of matrix metalloproteinases-9, P53 and BCL-2 proteins in Egyptian patients with pulmonary Mycobacterium tuberculosis.   Acta Microbiol Immunol Hung 57: 2. 123-133 Jun  
Abstract: Matrix metalloproteinases (MMPs) constitute a large family of enzymes that degrade extracellular matrix proteins (ECM). MMPs are implicated in different pathological conditions such as cancer. Bcl-2 and P53 are key controllers of programmed cell death (PCD) or apoptosis. The aim of the present study was to determine the MMP-9, P53 and Bcl-2 levels in Egyptian patients with Mycobacterium tuberculosis (MTB) (Group I) compared with healthy control individuals (Group II). The concentrations of serum MMP-9 were determined quantitatively using enzyme immunoassay (EIA). P53 and Bcl-2 levels were assayed by flow cytometric analysis using specific monoclones. MMP-9 level was significantly higher in MTB patients compared with healthy control. Similarly, P53 and Bcl-2 levels were increased in MTB patients compared with healthy ones. These data reflect the alteration of MMP-9 level during the course of MTB infection, accompanied with apparent dysregulation of cellular apoptosis as indicated by P53 and Bcl-2 over-expression.
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Mahmoud Lotfy, Ayman El-Meghawry El-Kenawy, Mohamed M Abdel-Aziz, Ibrahim El-Kady, Ayman Talaat (2010)  Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.   Asian Pac J Cancer Prev 11: 5. 1263-1266  
Abstract: Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.
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Gamal Badra, Mahmoud Lotfy, Amany El-Refaie, Moanis Obada, Elhamy Abdelmonem, Samia Kandeel, Amr Fathy (2010)  Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients.   Acta Microbiol Immunol Hung 57: 1. 29-42 Mar  
Abstract: Liver fibrosis (LF), where the chronic HCV infection is a major cause, is a characteristic of chronic liver diseases. LF results from chronic damage to the liver in conjunction with the accumulation of ECM proteins. Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are thought to play an essential role in the hepatic lesions. The available data concerning the circulating levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in chronic hepatitis C are not conclusive. Therefore, the present study was designed to seek the relationship between serum MMP-9, and TIMP-1 to liver status in chronic liver disease in fifty patients divided into three groups (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma). MMP-9 and TIMP-1 were analyzed by the enzyme linked immunosorbent assay (ELISA). The results showed that the lowest serum level of MMP-9 was found in chronic hepatitis patients compared to the control ( P < 0.05). Serum MMP-9 is decreasing during progression of chronic hepatitis to cirrhosis showing the least level in the cirrhotic group. Serum TIMP-1 was significantly higher in the cirrhotic group compared to chronic hepatitis ( P < 0.05) and controls ( P < 0.001). MMP-9 was negatively correlated to both TIMP-1 and the histological severity in chronic hepatitis. There was a positive correlation between TIMP-1 and the degree of fibrosis (r = 0.73, P < 0.001). Lastly, there was a statistically significant increase of MMP-9 ( P < 0.001) and TIMP-1 ( P < 0.05) in HCC patients compared with the other groups. In conclusion, these findings raise the possibility of using serum TIMP-1 as a non-invasive assay in liver fibrosis. Further, the altered balance between circulating MMP-9 and TIMP-1 during HCV infection may play an important role in aggravating liver injury progression in chronic liver diseases.
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Samir El-Masry, Mohamed El-Shahat, Gamal Badra, Mohamed F Aboel-Nour, Mahmoud Lotfy (2010)  Helicobacter pylori and Hepatitis C Virus Coinfection in Egyptian Patients.   J Glob Infect Dis 2: 1. 4-9 Jan  
Abstract: Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide. It has been shown that Helicobacter pylori (H. pylori) plays an important role in chronic gastritis, peptic ulcer disease and gastric malignancies, and its eradication has been advocated. The association between H. pylori infection and liver cirrhosis in patients with hepatitis C virus has been documented in different parts of the world; nevertheless, no conclusive data is available in Egypt.
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2009
Mohamed M Abdel-Aziz, Mahmoud Lotfy, Ibrahim M El-Kady, Mostafa Abozaid (2009)  Mutant p53 protein in the serum of patients with colorectal cancer: Correlation with the level of carcinoembryonic antigen and serum epidermal growth factor receptor.   Cancer Detect Prev 32: 4. 329-335 05  
Abstract: Enzyme-linked immunosorbent assay (ELISA) was used for analysis of serum mutant p53 protein, carcinoembryonic antigen (CEA), and epidermal growth factor receptor (EGFR). Serum samples were obtained from 48 patients with colorectal cancer (CRC) and a control group of twenty healthy individuals.
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Hasan Abusini, Khaled Abuelteen, Ali Elkarmi, Faris Q Alenzi, Mahmoud Lotfy (2009)  Investigation of Helicobacter pylori infection in Jordanian patients using six enzyme immunoassays for immunoglobulin G (IGG) and IGA testing.   Roum Arch Microbiol Immunol 68: 4. 240-245 Oct/Dec  
Abstract: Helicobacter pylori (H. pylori) is the etiologic agent of a variety of gastrointestinal disorders. The rationale of the current study is to evaluate six enzyme immunoassays for detection of anti-H. pylori immunoglobulin G (IgG) and IgA in Jordanian patients. Biopsy specimens and blood samples were obtained from patients underwent the endoscopy unit at Al-Bashir hospital in Jordan. The serum samples were investigated for the presence of anti-H. pylori IgG and IgA antibodies in patients with positive H. pylori biopsy samples. The results showed that IgG utilizing kits are more sensitive than of IgA kits and the IgA kits are more specific than of that IgG kits. Moreover, the biopsy is seemingly the gold standard for diagnosis of H. pylori is followed by H. pylori culture on brucella agar medium. An imperfect relation between the presence of H. pylori infection and the antibody response was existed that could be explained either because of the unsatisfactory sensitivities and specificities of the commercial kits used or because of weak immunological response in our patients to H. pylori antigens. Collectively, the H. pylori diagnosis that depends on the detection of anti-H. pylori antibodies in the hospital setting and in the screening programs should consider another test for confirmation the initial diagnosis.
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2007
Wesam A Nasif, Hoda M El-Emshaty, Mahmoud Lotfy, Khaled Zalata, Nabil G El-Hak (2007)  Apoptosis dysregulation in human gastric carcinomas: relationship to anti- and pro-apoptotic protein expression.   Asian Pac J Cancer Prev 8: 1. 45-50 Jan/Mar  
Abstract: Apoptosis and the genes regulating this process have recently become a focus of interest in the study of cancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performance of these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and protein expression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigated with gastric tumor samples of forty patients . DNA ploidy pattern was analyzed using flow cytometry and Bcl-2, Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serum Bcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed that the mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases (61.5+/-11.0 unit/ml) compared to the negative ones (47.5+/-3.5 unit/ml). Serum Bcl-2 protein positivity was detected in 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%, 68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked with the histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On the other hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002). In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer. Therefore, analysis of their expressions may add useful information concerning tumor behavior.
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Samir El-Masry, Ibrahim H El-Sayed, Mahmoud Lotfy, Lamiaa Mahmoud, Mohamed El-Naggar (2007)  Utility of slot-blot-ELISA as a new, fast, and sensitive immunoassay for detection of carcinoembryonic antigen in the urine samples of patients with various gastrointestinal malignancies.   J Immunoassay Immunochem 28: 2. 91-105  
Abstract: Carcinoembryonic antigen (CEA) is the most widely used clinical tumor marker. CEA immunoassay has found acceptance as a diagnostic adjunct in clinical diagnosis of gastrointestinal tumors (GIT). Several immunoassays have been established for detection of CEA in plasma, serum, tissue, feces, and urine of cancer patients using polyclonal or monoclonal antibodies raised against CEA. Some of these assays display both high sensitivity and specificity for the detection of CEA. However, these assays require special and highly expensive equipment and the procedures require long periods for their completion. In the present study, we established a Slot-Blot Enzyme Linked Immunosorbent Assay (SB-ELISA), based on anti-CEA monoclonal antibody (CEA-mAb), as a new, simple, fast, cheap, and non-invasive immunodiagnostic technique for detection of CEA in the urine of GIT patients. Urine and serum samples were collected from 248 GIT patients (58 with pancreatic cancer, 20 with hepatoma, 23 with ampullary carcinoma, 15 with hilar cholangiocarcinoma, 28 with gastric cancer, 14 with esophageal cancer, and 90 with colorectal cancer). Moreover, urine and serum samples were collected from 50 healthy individuals to serve as negative controls. The traditional ELISA technique was used for determination of CEA in the sera of GIT patients using anti-CEA monoclonal antibody. A comparison between the results of both techniques (ELISA and SB-ELISA) was carried out. The traditional ELISA detected CEA in the sera of 154 out of 248 GIT patients with a sensitivity of 59.8%, 51.7% positive predictive value (PPV) and 75.37% negative predictive value (NPV). In addition, it identified 15 false positive cases out of 50 healthy individuals with a specificity of 70%. The urinary CEA was identified by a Western blotting technique and CEA-mAb at a molecular mass of 180 Kda. The developed SB-ELISA showed higher sensitivity, specificity, PPV, and NPV (70.1%, 78%, 62.4%, and 82.13%, respectively) for detection of CEA in the urine of GIT patients. The semi-quantitative SB-ELISA showed a higher overall efficiency of 72.8% versus 63.4% in the case of the quantitative ELISA, for detection of CEA. In conclusion, SB-ELISA is more efficient for detection of CEA in gastrointestinal tumors. It is a simple, rapid, non-invasive, and sensitive assay. Moreover, all steps of the SB-ELISA are performed at room temperature, without the use of expensive equipment; this may enhance the application of this assay in field studies and mass screening programs.
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S El-Masry, Mahmoud Lotfy, W A Nasif, I M El-Kady, M Al-Badrawy (2007)  Elevated serum level of interleukin (IL)-18, interferon (IFN)-gamma and soluble Fas in patients with pulmonary complications in tuberculosis.   Acta Microbiol Immunol Hung 54: 1. 65-77 Mar  
Abstract: Mycobacterium tuberculosis can cause life-threatening complications in which the immune response plays an important role. This study was designed to evaluate the serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and soluble Fas (sFas) in cases with pulmonary tuberculosis due to confirmed M. tuberculosis infection. The study comprised 50 patients with M. tuberculosis classified to 13 complicated cases and 37 uncomplicated patients. A significant (P<0.05) increase was found in the serum levels of IL-18, IFN-gamma and sFas in patients compared to controls and also in complicated cases compared to uncomplicated ones. Moreover, a positive significant correlation was found between serum levels of sFas with IL-18 (r=0.532, P<0.001), and with IFN-gamma (r=0.37, P=0.008) and lastly between serum levels of IL-18 with IFN-gamma (r=-0.612, P<0.001). It is concluded from these results with the recent observations that IFN-gamma levels are elevated after successful MTB treatment, suggest the possibility of enhanced Fas expression and then stimulating the infected macrophages to show an increased FasL-induced apoptosis. Modulation of FasL system by M. tuberculosis might represent an escape mechanism to evade the effect of apoptosis. Moreover, the elevated serum levels of IL-18, IFN-gamma and sFas can be considered as pathognomonic markers suggesting pulmonary tuberculosis especially in complicated cases.
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Faris Q Alenzi, Richard K Wyse, Waleed G Tamimi, Mohammad S Bamaga, Mahmoud Lotfy (2007)  A close link between Fas, p53 and Apaf-1 in chronic myeloid leukemia.   Saudi Med J 28: 7. 1119-1121 Jul  
Abstract: In chronic myeloid leukemia (CML) proliferation is increased and resistance to apoptosis has been proposed as a mechanism accounting for myeloid cell expansion. There is still controversy on whether apoptosis plays an important role in the regulation of myelopoiesis. This study aims to investigate whether apoptosis-related proteins play a role in the evolution of CML and to identify, the relationship between Fas, p53 and apoptosis protease activating factor (Apaf-1) in CML. We found increased p53 and Apaf-1 messenger ribonucleic acid (mRNA) in patients with CML. However, one patient, who had a p53 point mutation, showed a massive elevation of p53 mRNA during blast crisis yet, conversely, a considerable reduction in Apaf-1 mRNA and Fas mRNA. Our results show an in-vivo linkage between Fas, p53 and Apaf-1 transcription regulation. This suggests that key genes involved in apoptosis are also involved in CML disease progression.
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Hassan Abdel-Hady, Ali Zaki, Gamal Badra, Mahmoud Lotfy, Carlo Selmi, Alessia Giorgini, Mohamed El-Sayed, Reda Badr (2007)  Helicobacter pylori infection in hepatic encephalopathy: Relationship to plasma endotoxins and blood ammonia.   Hepatol Res 37: 12. 1026-1033 Dec  
Abstract: Background/Aim: Hepatic encephalopathy (HE) is frequently observed in patients with advanced liver disease and manifests a wide variety of neuropsychiatric signs and symptoms. Ammonia toxicity and bacterial endotoxins have been suggested as key determinants of HE onset whereas a role for Helicobacter pylori infection has not been established. We investigated the correlation between H. pylori infection and HE severity (evaluated through functional tests) in 60 outpatients with established liver cirrhosis and 20 non-cirrhotic controls. Methods: Fasting arterial blood ammonia, plasma endotoxins, and H. pylori infection status were investigated in all subjects. Results: H. pylori infection was documented in 35/60 (58%) patients and in 6/20 (30%) controls (P = 0.039). Significant differences were observed between patients with and withoutHE for age, presence of ascites, fasting arterial blood ammonia, plasma endotoxin, and H. pylori infection. Further, a significant increase in fasting arterial blood ammonia and plasma endotoxin was associated with H. pylori infection in cirrhotic patients. Last, medical treatment of H. pylori infection led to a significant decrease in HE severity and fasting arterial blood ammonia levels. Conclusion: In conclusion, we submit that H. pylori infection might, in fact, play a role in increasing the circulating levels of ammonia and endotoxins in cirrhotic patients, thus facilitating the onset of HE.
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2006
Gamal Badra, Imam Waked, Carlo Selmi, Saleh M Saleh, Ahmed El-Shaarawy, Mahmoud Lotfy (2006)  Serum islet cell autoantibodies during interferon alpha treatment in patients with HCV-genotype 4 chronic hepatitis.   Clin Dev Immunol 13: 1. 11-15 Mar  
Abstract: Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle Eastern countries. It is well established that interferon-a (IFNa) treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 +/- 6 years) with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32%) previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.
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Wesam A Nasif, Mahmoud Lotfy, Ibrahim H El-Sayed, Ayman El-Meghawry El-Kenawy, Mohamed El-Shahat, Nabil Gad El-Hak (2006)  Implications of CEA and p53 overexpression in the poor prognosis of colorectal cancer.   Med Oncol 23: 2. 237-244  
Abstract: Colorectal cancer (CRC) is one of the most frequent and aggressive types of cancer. Several clinicopathologic features have been studied to identify the prognostic factors that can provide information concerning the favorable or the poor outcome of colorectal cancer. In the present study, the relationship between serum CEA, p53 expression, and DNA index to the different clinicopathological characteristics of colorectal cancer patients was sought. Fifty patients with CRC were included in this study. p53 protein was detected immunohistochemically using specific monoclonal antibodies. Samples were investigated for DNA index using flow cytometry. In addition, the serum CEA was determined using ELISA. The results showed that 27/50 (54%) were positive for p53. Concerning CEA reactivity, it was found that 35/50 (70%) were reactive for CEA. These results indicate that CEA is more sensitive than p53 to detect colorectal cancer. There was a statistically significant difference between the recurrent and nonrecurrent groups in the CRC Duke's stages, survival time, serum CEA (p = 0.001, 0.016, < 0.001, respectively). Kaplan-Meier method and log-rank test showed that the mean survival time for cases positive for both p53 and CEA is significantly different from cases positive for CEA only, positive for p53 only, and negative for both p53 and CEA (p = 0.0002). Survival time was statistically significant with respect to sex, p53, CEA, and Duke's stages (p = 0.006, 0.024, 0.001, 0.017, respectively). Cox regression model showed that the prognosis of colorectal cancer is influenced by sex, p53, CEA reactivity, and CRC Duke's stages (p = 0.014, 0.006, 0.019, 0.014, respectively). In conclusion, the use of more than one tumor marker may successfully aid in the prediction of colorectal cancer prognosis.
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Samir El-Masry, Mahmoud Lotfy, Mohamed El-Shahat, Gamal Badra (2006)  Serum laminin assayed by Slot-Blot-ELISA in patients with combined viral hepatitis C and schistosomiasis.   Clin Biochem 39: 6. 652-657 Jun  
Abstract: Hepatic schistosomiasis and chronic hepatitis C virus (HCV) are the most prevalent agents causing hepatic fibrosis in humans. Laminin (LA) has been related to liver fibrosis and subsequent development of portal hypertension in chronic liver disease. There are no available data describing the pattern of laminin in combined HCV and schistosoma-infected patients, thus the rationale of this study was to assess the serum LA as an index of liver fibrosis in patients with schistosomiasis and/or chronic viral hepatitis C and to evaluate a developed Slot-Blot Enzyme-Linked Immunosorbant Assay (Slot-Blot-ELISA) as a method of estimation.
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Mohamed F Abouel-Nour, Mahmoud Lotfy, Abdelfattah M Attallah, Barbara L Doughty (2006)  Schistosoma mansoni major egg antigen Smp40: molecular modeling and potential immunoreactivity for anti-pathology vaccine development.   Mem Inst Oswaldo Cruz 101: 4. 365-372 Jun  
Abstract: The pathogenesis of Schistosoma mansoni infection is largely determined by host T-cell mediated immune responses such as the granulomatous response to tissue deposited eggs and subsequent fibrosis. The major egg antigens have a valuable role in desensitizing the CD4+ Th cells that mediate granuloma formation, which may prevent or ameliorate clinical signs of schistosomiasis.S. mansoni major egg antigen Smp40 was expressed and completely purified. It was found that the expressed Smp40 reacts specifically with anti-Smp40 monoclonal antibody in Western blotting. Three-dimensional structure was elucidated based on the similarity of Smp40 with the small heat shock protein coded in the protein database as 1SHS as a template in the molecular modeling. It was figured out that the C-terminal of the Smp40 protein (residues 130 onward) contains two alpha crystallin domains. The fold consists of eight beta strands sandwiched in two sheets forming Greek key. The purified Smp40 was used for in vitro stimulation of peripheral blood mononuclear cells from patients infected with S. mansoni using phytohemagglutinin mitogen as a positive control. The obtained results showed that there is no statistical difference in interferon-g, interleukin (IL)-4 and IL-13 levels obtained with Smp40 stimulation compared with the control group (P > 0.05 for each). On the other hand, there were significant differences after Smp40 stimulation in IL-5 (P = 0.006) and IL-10 levels (P < 0.001) compared with the control group. Gaining the knowledge by reviewing the literature, it was found that the overall pattern of cytokine profile obtained with Smp40 stimulation is reported to be associated with reduced collagen deposition, decreased fibrosis, and granuloma formation inhibition. This may reflect its future prospect as a leading anti-pathology schistosomal vaccine candidate.
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Ibrahim H El-Sayed, Mahmoud Lotfy, Om-Ali Y El-Khawaga, Wesam A Nasif, Mohamed El-Shahat (2006)  Prominent free radicals scavenging activity of tannic acid in lead-induced oxidative stress in experimental mice.   Toxicol Ind Health 22: 4. 157-163 May  
Abstract: Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues leading to biochemical and physiological dysfunction. The present study was designed to investigate the effect of tannic acid on some biochemical parameters in Swiss albino mice exposed to lead acetate. The levels of thiobarbaturic acid-reactive substances (TBARS) as an index of lipid peroxidation, nitric oxide (NO), and serum lead (Pb) were significantly increased following intragastric administration of 50 micromole lead acetate/kg body weight three times a week, every other day for three weeks, compared to the corresponding control values. On the other hand, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione content (GSH) and serum copper (Cu) and zinc (Zn) were significantly diminished relative to the control values. The administration of 20 mg tannic acid/kg body weight three times a week every other day for three weeks, enhanced the endogenous antioxidant capacity of the cells by increasing the activities of antioxidant enzymes (SOD, CAT, GSH-R, GST), GSH content and serum Cu and Zn levels. Compared to the lead acetate-exposed group, the levels of TBARS, NO and Pb were decreased in the lead acetate exposed group treated with tannic acid. These results afford evidence supporting the hypothesis that lead induces oxidative stress in hepatic cells. Moreover, tannic acid has a potential in sustaining global antioxidant effect in hepatic cells leading to decreased oxidative stress and cellular damage initiated through free radical production by lead acetate.
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M Lotfy, I M El-Kady, W A Nasif, A E El-Kenawy, G Badra (2006)  Distinct serum immunoglobulins pattern in Egyptian patients with chronic HCV infection analyzed by nephelometry.   J Immunoassay Immunochem 27: 1. 103-114  
Abstract: Hepatitis C has emerged as a major worldwide public health problem. The host immune response to HCV infection is composed of both a non-specific immune response, including interferon (IFN) production and natural killer (NK) cell activity, and a virus-specific immune response, including humoral and cellular components. Susceptibility to infection has been related to immunological disturbances. Several studies have provided experimental evidence of disorders of both cellular and humoral immunity. The present study was carried out to evaluate the serum immunoglobulins level (IgG, IgM, IgA) and IgG-subclasses (IgG1-4) in chronic hepatitis C patients in comparison with healthy control patients. This study included 50 patients with biochemical, serologic, virologic, and histologic evidence of chronic hepatitis C. Total IgG, IgA, and IgM were assayed by nephelometry. IgG subclasses were assayed using human IgG subclasses enzyme immunoassay. The results showed a significant increase of total serum IgG and IgM levels found in patients with chronic HCV compared with the healthy control patients (P < 0.001 for each). There was a statistically significant difference in the IgG subclasses (IgG1 to IgG4) between the patients and controls (P < 0.001 for each). On the other hand, no significant difference was found between patients and healthy controls in IgA level (P = 0.4). The normal total serum immunoglobulins pattern is apparently shifted in chronic hepatitis C infection in the Egyptian patients. This pattern may include an ethnic or biologic background and could be used in the differentiation of the patients with minimal liver disease.
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2005
I M El-Kady, M Lotfy, G Badra, S El-Masry, I Waked (2005)  Interleukin (IL)-4, IL-10, IL-18 and IFN-gamma cytokines pattern in patients with combined hepatitis C virus and Schistosoma mansoni infections.   Scand J Immunol 61: 1. 87-91 Jan  
Abstract: Schistosoma mansoni infection is characterized by a strong T-helper type 2 (Th2) cell-associated immune response, but in the case of viral infection, it is associated with interferon-gamma (IFN-gamma) increase and induction of Th1 immune response. Few data are available about the immune response of cases infected with combined hepatitis C virus (HCV) and schistosomiasis. Thus, the investigation of the cytokine pattern in patients coinfected with both HCV and Schistosoma mansoni was our rationale. This study included four patient groups: Group 1 included 20 patients infected with chronic HCV, Group 2 included 15 patients infected with schistosomiasis alone, Group 3 included 20 patients with chronic HCV and schistosomiasis and Group 4 included 15 healthy control individuals with matched age and sex. Serum levels of IFN-gamma, interleukin (IL)-4, IL-10 and IL-18 were measured in all groups by enzyme-linked immunosorbent assay. The results showed that the patients infected with HCV had significantly higher serum levels of IFN-gamma and IL-18 compared with the controls and with the patients with schistosomiasis and coinfection (P < 0.001). On the other hand, serum levels of IL-4 and IL-10 were significantly higher in patients with schistosomiasis and coinfection compared with the control group (P < 0.001 and 0.0001, respectively) and with the HCV patients (P < 0.05 and P < 0.001, respectively). A significant increase in serum levels of IL-4 and IL-10 was also found in HCV patients compared with the control (P < 0.05). Schistosomiasis appears to induce a Th2 cytokine profile, with increase in serum levels of IL-4 and IL-10, even in the presence of HCV coinfection. In conclusion, schistosomiasis may downregulate the stimulatory effect of HCV on Th1 cytokines and this may lead to the chronicity of HCV infection in coinfected patients.
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Mohamed El-Shahat, Samir El-Masry, Mahmoud Lotfy, Ayman El-Meghawry El-Kenawy, Wesam A Nasif (2005)  Relationship of Helicobacter pylori to Bcl-2 family expression, DNA content, and pathological characteristics of gastric cancer.   Int J Gastrointest Cancer 36: 2. 61-68  
Abstract: Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer has been well documented, the exact mechanisms of this association have not been fully elucidated. Scarce data on H. pylori infection and its relationship with the different pathological characteristics are available in Egypt.
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Khaled R Zalata, Wesam A Nasif, Si-Chun Ming, Mahmoud Lotfy, Nadia A Nada, Nabil Gad El-Hak, Stephen H Leech (2005)  p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt.   Cell Oncol 27: 4. 245-253  
Abstract: Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm).
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Ayman El-Meghawry El-Kenawy, Mahmoud Lotfy, Attalla El-Kott, Mohamed El-Shahat (2005)  Significance of matrix metalloproteinase 9 and CD34 expressions in esophageal carcinoma: correlation with DNA content.   J Clin Gastroenterol 39: 9. 791-794 Oct  
Abstract: Esophageal carcinoma is common in many countries, and it is characterized by poor prognosis and rapid clinical progression with a high frequency of lymph node metastasis and recurrence. The present study was carried out to evaluate the correlation between vascular endothelial cell marker (CD34), matrix metalloproteinase type 9 (MMP9), and DNA content in esophageal carcinoma.
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M F Abouel-Nour, M Lotfy, I El-Kady, M El-Shahat, B L Doughty (2005)  Localization of leucine aminopeptidase in the Schistosoma mansoni eggs and in liver tissue from infected mice.   J Egypt Soc Parasitol 35: 1. 147-156 Apr  
Abstract: Infection with Schistosoma mansoni causes hepatic granuloma formation and fibrosis in response to parasite eggs. The present work localized the leucine aminopeptidase (LAP) in S. mansoni eggs and in liver tissue sections from infected mice. Fresh eggs and livers obtained from infected hamsters were processed and stained with the L-leucine-7-amino-trifluoromethyl-coumarin specific substrate. The L-argnine-7-amino-trifluoro-methylcoumarin and Bestatin (leucine aminopeptidase inhibitor) were used to test the LAP substrate specificity and reactivity. The staining pattern for that enzyme in the egg and liver tissue reflects that the leucine aminopeptidase is a major egg constituent distributed in nearly all the egg except the spine. The control substrates confirmed the substrate broad specificity of LAP. In conclusion, the LAP enzyme is a major egg antigen and the target antigen for the antipathology vaccine development studies.
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2004
Gamal Badra, Yousry Mostafa, Mamdouh Morsy, Mahmoud Lotfy, Tarek Salem, Ahmed El-Shaarawy (2004)  Some immunological studies & HLA-DRB1 in hepatitis C virus related necrolytic acral erythema   Pan-Arab League of Dermatologists (PALD) 15: 1. 29-38  
Abstract: Necrolytic acral erythema (NAE) is unique in its acral location and strong association with hepatitis C virus (HCV) and altered immunological functions. The aim of the present work was to evaluate HLA DRB1* alleles, some parameters of immune system function (complements C3 & C4, anti-smooth muscle antibody (ASMA) and antinuclear antibody (ANA) and response of cutaneous lesions to low dose interferon alpha (3 million unit (MU)/week) and hydroxychloroquine in NAE patients. This study included 22 patients with HCV-related NAE (group I), 45 chronic hepatitis C without NAE (group II as pathological control) and 45 healthy subjects (group III, normal control). ANA was positive more in patients than normal control (18.2% vs 0%, P <0.003), however no significant difference was found between the two patients groups. ASMA was more significantly positive in patients with NAE than HCV patients, and in both patients groups than control 59.1%, 17.8% and 0%; P <0.001 and 0.0001, respectively). A significant decrease in C3 and C4 was found in NAE patients than HCV patients without NAE, (P <0.01) and in both patients groups than normal control (P < 0.001). NAE was associated with HLA- DRB1* 03, (72.7%, 16 of 22 vs 24.4%, 11 of 45 of normal control, Pc < 0.0009 and 35.6% 16 of 45 HCV patients without NAE, Pc = 0.03). clinical improvement and significant decrease in alanine amino transferase (ALT) (p < 0.001) were observed in NAE patients after two months of interferon alpha and hydroxychloroquine therapy. So, we can conclude that necrolytic acral erythema (NAE) appears to be an immune mediated response in chronic HCV patients, associated with, lower C3 & C4 and higher frequency of positive ASMA. The results suggest that the development of HCV related NAE is associated with HLA- DRB1* 03 marker and low dose interferon alpha (3 MU per week) and hydroxychloroquine are good treatment modalities for NAE.
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Mohamed El-Shahat, Mahmoud Lotfy, Lamiaa Fahmy, Mohamed F Abouel-Nour, Aymen El-Maghawry El-Kenawy (2004)  Prognostic value of microvessel density, matrix metalloproteinase-9 and p53 protein expression in esophageal cancer.   J Egypt Natl Canc Inst 16: 4. 224-230 Dec  
Abstract: Worldwide, esophageal carcinoma is one of the most aggressive cancers. It is relatively common in many countries and characterized by poor prognosis and rapid clinical progression.
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2001
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1994

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