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Biomedical subjects

Ahmed Hassan

Publications and source records attributed to Ahmed Hassan.

6 recordsLinked to original sources

Isoform-Level Analysis Reveals Reproducible Early Changes in Transcript Usage During Human Vaccine Responses.

Vaccine-induced transcriptional responses have been extensively characterized at the gene level, but whether vaccination also alters transcript isoform usage remains largely unexplored. Here, we reanalyzed longitudinal whole-blood RNA-seq data from a discovery cohort of mRNA COVID-19 vaccine recipients using the IsoformSwitchAnalyzeR framework and validated the findings in an independent cohort. Key findings were validated by full-length RNA long-read sequencing and extended to four additional vaccine cohorts covering distinct platforms and pathogens. mRNA vaccination induced a rapid and transient wave of differential transcript usage, peaking at 24 h post-vaccination with 131 isoforms significantly altered across 107 genes, before largely resolving by Day 14. Isoform switching events were reproducible across independent cohorts and confirmed by full-length RNA long-read sequencing. Structural annotation of switching transcripts, including RMI2, WARS1, and NT5C3A, revealed changes affecting predicted protein domains and signal peptides. Notably, highly concordant isoform switching patterns were observed across MVA-based SARS-CoV-2, influenza, and Ebola vaccine cohorts and showed dose-dependent modulation. Overall, differential transcript isoform usage is a rapid and transient feature of the early human immune response to vaccination that was observed across multiple vaccine platforms. These findings reveal an underappreciated layer of transcriptional regulation that complements conventional gene-level analyses and warrants integration into future vaccine immunogenicity studies.

Humans↗

Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression.

AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression. METHODS: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and II) by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls. RESULTS: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases. On the other hand, HCV viremia was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive in 55% of HCC cases, 65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RII (P<0.001), and TNF-RI (P>0.05), but lower TNFalpha (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). CLD patients had higher IL-2R, TNF-RI, and TNF-RII (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls. CONCLUSION: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Th1 and Th2 cytokines. IL-2R, TNF-RI, and TNF-RII could be used as potential markers.

Adult↗

HLA alleles in Egyptian HCV genotype-4 carriers.

Risk factors affecting asymptomatic HCV carriers as well as intrafamilial HCV transmission are not completely known. We hypothesized that immunological factors related to HLA profiles may affect the intrafamilial transmission. We investigated the possible association between HLA class I & II genes and the presence of HCV infection, as well as their possible role in intrafamilial tramsmition. One hundred forty five individuals comprising 40 families were recruited from bone marrow transplantation (BMT) unit at the National Cancer Institute, Cairo University. Serologic class I and generic class II MHC alleles were determined. Hepatitis C virus was detected by enzyme immunoassay (EIA) and confirmed by INNO-LIA. Detection of viral RNA was also confirmed by RT-PCR and HCV genotyping was done by immunoblotting (INNO-LiPA) and direct sequencing by TrueGene kit. Out of the 145 serum samples, 33 were positive for HCV antibodies by EIA and confirmed by both immunoblotting techniques and RT-PCR. Twenty-eight of them were eligible for HCV typing. The genotypes detected were 4, 2a, 1a and 1b. A mixed infection by more than one genotype was detected in 9 cases. Six families had 2 or more members reactive for HCV antibodies. Intrafamilial transmission was confirmed by HCV-sequence in 3 families. HLA class I & II alleles A28, A29, B14 & DR7 were significantly encountered in HCV positive than negative cases (p=0.040, 0.003, 0.001 & 0.010 respectively). In addition, two cases showed evidence of viral clearance, both expressed B50 (21) allele. We conclude that, there is a possible impact of both class I and class II alleles on HCV infection, resistance, clearance and intrafamilial transmission.

Adult↗

Optic nerve calcification after trauma.

Two patients with remote histories of severe optic nerve trauma displayed profound intraorbital optic nerve calcification on imaging studies. The presumed mechanism is optic nerve hemorrhage. Although calcification is known to occur long after brain hemorrhage, no comparable cases have been previously reported.

Adult↗

Traumatic chiasmal syndrome: a series of 19 patients.

PURPOSE: To present a clinical series of 19 patients with traumatic chiasmal syndrome. METHODS: A retrospective study was performed. This included all patients with traumatic chiasmal syndrome seen in the neuro-ophthalmology clinic at the Royal Adelaide Hospital between January 1970 and January 2000. RESULTS: Of the 19 study patients, most were young males involved in motor accidents. Two-thirds had skull fractures. Three-quarters of patients had a final visual acuity of 6/12 or better in at least one eye. Ten patients had a complete optic nerve palsy. The incidence of diabetes insipidus in this study was 37%. The incidence of cranial nerve lesions, hypopituitarism, carotid cavernous fistula, and other deficits were documented. Magnetic resonance imaging and surgical findings were consistent with known mechanisms of chiasmal injury. CONCLUSIONS: Trauma is a rare cause of chiasmal syndrome. Patients with bitemporal field defects should be questioned about prior head injury. In the acute setting, magnetic resonance imaging is the most useful investigation. The treating practitioner should anticipate and treat associated endocrine, ocular motility, and other disorders. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis. These mechanisms should not be considered mutually exclusive. Unilateral temporal hemianopia with a fellow blind eye is not necessarily the result of chiasmal disruption.

Adolescent↗

Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura.

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 x 10(9)/L, while mean platelet count at day 4 was 158 x 10(9)/L. At the end of 6 cycles 3 patients maintained a platelet count of >150 x 10(9)/L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.

Adolescent↗