ORCID Profile
0000-0001-8252-5190
Current Organisation
Washington University in St. Louis
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Publisher: Cambridge University Press (CUP)
Date: 05-06-2018
DOI: 10.1017/S0031182018000239
Abstract: Sarcocystis spp. are intracellular coccidian parasites which infect domestic and wild animals and birds, resulting in considerable economic losses in production animals, and public health concerns worldwide. Sarcocystis spp. have an indirect life cycle where wild and/or domestic canine species primarily serve as definitive hosts and several domestic and wild animals (such as camels) act as intermediate hosts. In Northern Africa, the Middle East, Central Asia and China, camel meat is preferred due to cultural and religious traditions as well as its lower cholesterol/fat content than other red meat. However, camel meat quality could be downgraded by the presence of sarcocysts. To date, two Sarcocystis spp. have been reported from camels, including Sarcocystis ippeni (forms microscopic sarcocysts) and Sarcocystis cameli (forms both macroscopic and microscopic sarcocysts). Sarcocystosis is usually asymptomatic, though significant pathogenic effects have also been reported in camels. Despite the high occurrence of sarcocystosis in camels, little is known about various aspects of the disease in these animals. This paper provides a comprehensive review of the existing knowledge on the taxonomy, pathogenesis, epidemiology and diagnosis of Sarcocystis spp. infecting camels and it also highlights areas for further research that could enhance our understanding about sarcocystosis in camels.
Publisher: Springer Science and Business Media LLC
Date: 15-05-2009
DOI: 10.1038/JA.2009.37
Abstract: Escherichia coli are one of the leading causes of infection in wounds. Emerging multiple drug resistance among E. coli poses a serious challenge to antimicrobial therapy for wounds. This study was conducted to ascertain a baseline profile of antimicrobial resistance in E. coli isolates infecting surgical wounds. A total of 64 pus s les from hospitalized patients were screened and 29 (45.3%) were found to have E. coli, which were identified biochemically and confirmed by molecular methods. Using the disc diffusion method, antimicrobial resistance was observed toward tetracycline (100%), cefradine (100%), nalidixic acid (93.1%), icillin (86.2%), gentamicin (86.2%), cefixime (82.8%), ceftriaxone (82.8%), aztreonam (82.8%), ciprofloxacin (75.9%), streptomycin (72.4%), cefoperazone (65.5%), chlor henicol (58.6%) and amikacin (58.6%). In an effort to find relevant genes, 11 different genes were targeted by PCR. Among these, the mutated gyrA gene was found to be the most prevalent (82.8%), followed by the TEM (72.4%), catP (68.9%), catA1 (68.9%), tetB (62.1%), blt (58.6%), bla(CTX-M-15) (27.6%), bla(TEM) (20.7%), bla(OXA) (17.2%), tetA (17.2%) and aadA1 (13.8%) genes. The presence of integrons was also studied among these isolates. The prevalence of class 1 integrons was the highest (44.8%), followed by class 2 (27.6%). Three (10.3%) isolates carried both class 1 and class 2 integrons (first report from E. coli infecting wounds). The high incidence of integrons points toward their facilitation for carriage of antimicrobial resistance genes however, in nearly 37% isolates, no integrons were detected, indicating the significance of alternative mechanisms of gene transfer. Another salient finding was that all isolates were multidrug-resistant E. coli.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2019
Publisher: Springer Science and Business Media LLC
Date: 18-02-2018
DOI: 10.1007/S00436-018-5790-1
Abstract: Hepatozoon canis is a tick-borne pathogen of canids, which is distributed worldwide. However, very little is known about this protozoan parasite in Pakistan. This study provides the first molecular evidence of H. canis from farm dogs from three agro-ecological zones of Punjab, Pakistan. A conventional PCR targeting the 18S rRNA gene was used to characterize H. canis from farm dogs from three districts, namely Kasur, Rawalpindi, and Muzaffargarh, in Punjab. Of 341 blood s les tested, 155 (45.5%) were positive for H. canis, 73 (61.3%) from Kasur, 46 (42.5%) from Rawalpindi, and 36 (31.5%) from Muzaffargarh. Phylogenetic analyses revealed that 18S rRNA sequences of H. canis from this study clustered in three clades with those of H. canis from previously published studies to the exclusion of all other Hepatozoon spp. included in the analysis. This study provides the first insight into H. canis from farm dogs in Pakistan. Furthermore, it lays a foundation for future studies of the parasite to assess the impact of canine hepatozoonosis in dogs from various agro-ecological zones in Pakistan where pet ownership of dogs is increasing.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2022
DOI: 10.1038/S41467-022-34724-5
Abstract: Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK) however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8 + and CD4 + T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1 Y18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, ( R )- 9b , recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.
Publisher: Oxford University Press (OUP)
Date: 04-2017
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.HUMIMM.2019.06.001
Abstract: Mucin 1 is a cell-membrane associated mucin, expressed on epithelial and immune cells that helps protect against pathogenic infections. In humans, MUC1 is highly polymorphic, predominantly due to the presence of a variable number tandem repeat (VNTR) region in the extracellular domain that results in MUC1 molecules of typically either short or long length. A genetic link is known between these MUC1 polymorphisms and inflammation-driven diseases, although the mechanism is not fully understood. We previously showed that MUC1 on murine macrophages specifically restricts activation of the NLRP3 inflammasome, thereby repressing inflammation. This study evaluated the effect of MUC1 VNTR polymorphisms on activity of the NLRP3 inflammasome in human macrophages, finding that long MUC1 alleles correlated with increased IL-1β production following NLRP3 inflammasome activation. This indicates that the length of MUC1 can influence IL-1β production, thus providing the first evidence of an immune-modulatory role of MUC1 VNTR polymorphisms in human macrophages.
Publisher: Journal of Infection in Developing Countries
Date: 22-10-2009
DOI: 10.3855/JIDC.66
Abstract: Background: Drug resistance is a major problem in Escherichia coli isolated from surgical wound infections. In this study, we evaluated relationship between phylogenicity and drug resistance. Methodology: A total of 29 multi-drug resistant (MDR) E. coli isolates of known drug resistance genes and integron profile were selected for the present study. Triplex PCR was conducted for phylogenetic classification of these isolates into four established phylogenetic groups: A, B1, B2 and D. Statistical analysis was done to determine the association of different drug resistance genes and integrons with the phylogenetic groups. Results: Most of the isolates (44.8%) belonged to phylogenetic group A followed by group B2 and D (24.1% each) and group B1 (6.9%). Conclusions: There is a definitive relationship between drug resistance and various phylogenetic groups of E. coli infecting wounds. A shift towards phylogenetic group A might be observed with an increasing drug resistance profile.
Publisher: FapUNIFESP (SciELO)
Date: 12-2011
Publisher: Mary Ann Liebert Inc
Date: 2010
Abstract: The Shiga toxin-producing Escherichia coli (STEC) is an emerging foodborne pathogen. The proportion of cases attributed to STEC in an episode of diarrhea in the Faisalabad region of Pakistan was investigated. In addition, as increase in Shiga toxin (Stx) release after exposure to various antimicrobial agents is widely reported, we also elucidated the in vitro effects of three commonly used antibiotics ( icillin, gentamicin, and cefotaxime) on Stx release. Isolation and detection of STEC was done using enzyme-linked immunosorbent assay and polymerase chain reaction, followed by phenotypic characterization. In vitro Stx release from isolated STEC was determined using enzyme-linked immunosorbent assay, and Stx-induced verocytotoxicity was quantified using cytotoxicity detection assay. STEC was detected in 5 (21.7%) of 23 patients. Exposure to minimum inhibitory concentration (MIC) of icillin, gentamicin, and cefotaxime resulted in a considerable decrease in toxin release and level of cytotoxicity in most of the STEC isolates when compared with control (without antibiotic exposure). Exposure to sub-MIC of icillin resulted in a relative increase in Stx release and cytotoxicity (p <or= 0.05) in three of the four isolates tested, whereas a decreasing trend was observed in isolates exposed to sub-MICs of gentamicin and cefotaxime. Sub-MIC of gentamicin resulted in largest decrease in Stx release and a similar trend was observed with cefotaxime to a lesser extent. In conclusion, these in vitro observations suggested that sub-MIC of icillin may stimulate Stx release and level of cytotoxicity and therefore should be avoided. Gentamicin did not show such effects and therefore may be considered for STEC antimicrobial therapy.
Publisher: American Society for Microbiology
Date: 2018
DOI: 10.1128/JCM.01469-17
Abstract: Accurate and rapid diagnosis is crucial in combating parasitic diseases that cause millions of deaths worldwide. However, the scarcity of specialized diagnostic equipment in low- and middle-income countries is one of the barriers to effective management of parasitic diseases and warrants the need for alternative, inexpensive, point-of-care diagnostic tools. Due to their multiple built-in sensors, smartphones offer cost-effective alternative to expensive diagnostic devices. However, the use of smartphones in parasitic diagnoses remains in its infancy. This minireview describes various smartphone-based devices applied specifically for the diagnosis of parasitic diseases and discusses challenges and potential implications for their use in future.
Location: United States of America
No related grants have been discovered for Muhammad Azeem Saeed.