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Biomedical subjects

Ahmed Ismail

Publications and source records attributed to Ahmed Ismail.

8 recordsLinked to original sources
PubMed2025

HER2 alterations across solid tumors: implications for comprehensive testing.

PURPOSE: ERBB2 (HER2) alterations (eg, overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial. METHODS: HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association. RESULTS: Of the 653 cases, HER2 IHC scores were distributed as 3+ (3.1%), 2+ (13.2%), and 1+ (19.8%), with 63.9% being IHC-negative. ERBB2 CN amplification was observed in 3.1%, with 75% exhibiting IHC3+. Pathogenic mutations were found in 3.1%, with low IHC3+ rates (5%). Among samples with ERBB2 mutations, only 3 had CN amplifications (1-positive, 2-intermediate). Somers'-D analysis revealed a strong association between CNV and IHC expression (D&#x2009;=&#x2009;0.73, P&#x2009;<&#x2009;.001). CONCLUSION: This study highlights ERBB2 alterations across diverse cancers, demonstrating their heterogeneity and clinical significance. ERBB2 mutation-carrying tumors are less likely to have HER2 protein 3+ expression or CN amplification, indicating the need for comprehensive genomic analysis to identify those patients. In the context of pan-tumor approval of T-DXd for HER2, findings support integrating genomic and phenotypic data to enhance diagnostic precision and inform therapeutic decision-making. Comprehensive ERBB2 (HER2) testing across tumor types is essential to expand access to HER2-targeted therapies.

Humans↗
PubMed2006

Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes.

BACKGROUND: Whereas the clinical manifestations and treatment of post-kala-azar dermal leishmaniasis (PKDL) have been adequately described before, the pathology received little attention, particularly the African form of PKDL which shows some clinical differences from the disease in India. Therefore, our aim was to characterize the pathology and the immunohistopathology in PKDL lesions and correlate the histopathological findings with the clinical features of the disease. METHODS: Biopsies of skin lesions were examined for histopathological changes in formalin-fixed tissues and for cell phenotypes and adhesion molecules by immunohistochemistry. RESULTS: The epidermis showed various changes in different combinations. The dermis was infiltrated by lymphocytes and macrophages, but plasma cells were scanty or absent. The majority of cells were CD3 T cells, with a preponderance of CD4 over CD8 cells. Degenerating basal keratinocytes expressed HLA-DR, ICAM-1 and Leishmania antigen and closely interacted with CD4 T cells. Regional lymph nodes showed hyperplasia of the B- and T-cell zones. CONCLUSIONS: The inflammatory reaction in PKDL lesions is in response to Leishmania parasites and/or antigen. The majority of cells are CD4 T cells. Degeneration of the basal keratinocytes is probably due to the action of cytotoxic CD4 T cells interacting with leishmania-expressing epidermal cells. Ismail A, Gadir AFA, Theander TG, Kharazmi A, El Hassan AM. Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes.

Adolescent↗
PubMed2005

Enantioselective determination of chiral toxaphene congeners in laying hens and eggs using multidimensional high-resolution gas chromatography.

A total of 22 chiral toxaphene congeners were analyzed in organ tissues and eggs of laying hens after they had been fed with food spiked with technical toxaphene. For the analysis, multidimensional high-resolution gas chromatography using a chiral column coated with randomly silylated heptakis(O-tert-butyldimethylsilyl)-beta-cyclodextrin, electron capture detection, and valveless "live column switching" technique was applied. The analytical results were additionally confirmed with mass spectral data, recorded in electron-capture negative ionization mode with selected-ion monitoring mass spectrometry. During both the feeding period of the laying hens with toxaphene-contaminated food (38 weeks, accumulation phase) and the following subsiding period without toxaphenes (another 14 weeks, decontamination phase), organs (liver, kidney, skin/fat), blood, meat, and eggs of the hens served as model matrices for toxaphene uptake. The enantiomeric ratios (ERs) of congeners 26, 31, 32, 40, 41, 42(a+b), 44, 50, and 62--known as the most important components of technical toxaphene occurring in the environment--could be analytically determined. Significant differences were observed with respect to their initial racemic ratios. On the basis of their chemical structures, the metabolic pathways of some congeners could be explained. Astonishingly, some of the toxaphenes applied as racemates could merely be found as single enantiomers at the end of the feeding program, for example, congener 32 in blood and meat samples or congener 44, especially in organ tissues, which showed ERs of zero or infinity. The findings of this study impressively emphasize that it is essential to isolate and analyze individual toxaphene enantiomers in food and biota tissues to be capable of evaluating their toxicity and metabolization more specifically.

Animal Feed↗
PubMed2005

Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres.

In recent years, the acylation of peptides during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres has been described in the literature. To investigate whether insulin is prone to the covalent attachment of lactic or glycolic acid, insulin-loaded PLA and PLGA microspheres containing 5% bovine insulin were manufactured using a w/o/w multiple emulsion-solvent evaporation technique. Microspheres were characterized for their insulin encapsulation efficiency and release characteristics in phosphate-buffered saline (PBS) at pH 7.4 and 37 degrees C. Moreover, the stability of the peptide during 18 days of release was evaluated using HPLC and HPLC-MS techniques. The results showed that the insulin loading efficiencies of PLA and PLGA microspheres were 75.18% and 79.63%, respectively. The microspheres were spherical with relatively porous surfaces with an average diameter of 40 and 53 mum, respectively. Insulin release from the microspheres was characterized by an initial burst, which was attributed to the amount of protein located on or close to the microsphere surface. The total ion chromatogram (TIC) of insulin samples extracted after 18 days of erosion in phosphate buffer pH 7.4 at 37 degrees C revealed that deamidation was the major mechanism of instability. Surprisingly, no acylation products were found. Control experiments in concentrated lactic acid solutions confirmed a minimal reactivity of the peptide under these conditions.

Drug Stability↗
PubMed2003

Development of mortality statistics at governmental hospitals, Egypt.

Mortality statistics are of crucial importance to epidemiological research. Sources of mortality data in Egypt are many. The first records are hospital records, which submit its data to health office records and lastly civil register office records. Hospital records include hospital death notification certificate and hospital mortician register. Health office records include mortality register, death certificate and death notification report to civil register office. The latter is designed to have a coded data and cause of death according to ICD-10. It is supposed that the death notification report that originates from the hospital is the source of data for the rest of records and registers. So, all these data for the same dead person must be the same. Quality of the original data will reflect itself on the rest of data. This study aims at establishment and assessment of automated system for management of mortality data at (hospital 1, affiliated to Ministry of Scientific Research) and comparing this system and its output with another one (hospital 2, affiliated to the Ministry of Health). The tools of this study are review of the above mentioned records and registers and personal interviews. Death certificate itself is not reviewed, as it is not found in the health office. One-year data sample was chosen for the study. Development of the system at hospital 1 is based on system analysis, design, implementation, and evaluation. Results showed that automated system of hospital1 have the values of automation as timely retrieval and decreasing the error of transcription. Epi-Info software package gives easy statistical analysis and the potential for record linkage. Comparison between hospital death notification certificate that originated from the hospital and health office register showed 97.4% matching for words or expressions in hospital 1 and 50.0% in hospital 2. Comparing hospital death notification report with that originated from health office to related civil office, showed 100.0% matching for hospital1 and 86.7% for hospital 2. As regards correctness of reporting the cause of death, 97.4% of deaths in hospital1, and 29.9% in hospital 2 showed non-specific cause of death reported as circulatory and respiratory distress, that is the actual cause of death is not reported. It is concluded that, unification and automation of the systems is a requirement. Record linkage between different locations of mortality data is recommended. Training on reporting and coding the cause of death is also recommended.

Data Collection↗
PubMed2002

Stereoselective protein binding of alprenolol in the renal diseased state.

The investigation was undertaken to study the stereoselective protein binding of alprenolol in renal disease patient sera, compared to that in the sera of healthy volunteers. The in vitro stereoselective protein binding of beta-blockers was determined in undiluted serum and in isolated alpha(1)-acid glycoprotein (AGP) solutions by ultrafiltration. The stereoselctive serum protein binding of alprenolol, a beta-adrenergic blocking agent, in healthy volunteers was significantly altered in renal disease patients. We investigated the effects of AGP concentration and endogenous substances, including uremic toxins, on the stereoselective protein binding of alprenolol in renal disease patients. A good correlation between the unbound (R)/(S) ratio (F(R)/F(S) ratio), an apparent index of stereoselectivity in alprenolol serum binding and AGP concentration in serum, was found. However, stereoselective protein binding was not influenced by endogenous substances. This result can be explained by the difference in binding affinities of (R) and (S)-isomers of alprenolol to AGP. We conclude that the stereoselective protein binding of alprenolol in healthy volunteers and renal disease patients varies as a result of changes in AGP concentration. Accordingly, these findings might be useful in alprenolol therapy in renal disease patients.

Alprenolol↗
PubMed2002

Humoral and cellular immune responses to glucose regulated protein 78 -- a novel Leishmania donovani antigen.

The recently cloned glucose regulated protein 78 (GRP78) of Leishmania donovani has been suggested as a new and promising Leishmania vaccine candidate. We assessed antibody and T-cell reactivity to GRP78 in an enzyme-linked immunosorbent assay (ELISA) and in lymphoproliferative assays. Serological evaluation of plasma samples obtained in Sudan revealed that 89% of patients with visceral leishmaniasis (VL), 78% with post kala-azar dermal leishmaniasis (PKDL), and 85% with cutaneous leishmaniasis (CL) had antibody reactivity to this Leishmania antigen. Plasma from healthy Sudanese individuals living in an area endemic for malaria but free of leishmaniasis and plasma from healthy Danes was negative in the assay. GRP78 antibody was detected in 10% and 5% of plasma samples from Sudanese and Ghanaian malaria patients, respectively, whereas 35% of plasma samples from otherwise healthy Sudanese individuals with a positive leishmanin skin test showed antibody reactivity to recombinant GRP78 (rGRP78). In lymphoproliferative assays, 9 of 13 isolates of peripheral blood mononuclear cells (PBMC) from individuals previously infected with L. donovani and one of three individuals previously infected with L. major showed a response to rGRP78, whereas PBMC isolates from Danish control individuals did not respond. These findings, in addition to our previous observations in experimental CL (Jensen et al. 2001), confirm GRP78 as a possible vaccine antigen.

Animals↗