Immunophenotypic characterization of the leukemic B-cells from Iranian patients with chronic lymphocytic leukemia : association between CD38 expression and disease progression

Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have hetero-geneous clinical courses, thus several biological parameters need to be added to the cur-rent clinical staging systems to predict disease outcome. Recent immunophenotypic stud-ies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL. Objectives: To investigate the expression pat-tern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between in-dolent and progressive groups. Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry. Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast ma-jority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and inten-sity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) pa-tients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients. Conclusion: Our results obtained in an Asian ethnic popula-tion confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.Tehran University of Medical Sciences and the Ministry of Health and Medical Education of Iran.Publishe

Immunophenotypic characterization of the leukemic B-cells from Iranian patients with chronic lymphocytic leukemia

Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have heterogeneous clinical courses, thus several biological parameters need to be added to the current clinical staging systems to predict disease outcome. Recent immunophenotypic studies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL. Objectives: To investigate the expression pattern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between indolent and progressive groups. Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry. Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast majority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and intensity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) patients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients. Conclusion: Our results obtained in an Asian ethnic population confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.Tehran University of Medical sciences, Tehran, IranPublishe

Comparative expression profile of orphan receptor tyrosine kinase ror1 in iranian patients with lymphoid and myeloid leukemias

It has recently been shown that ROR1, a member of the receptor tyrosine kinase family, is overexpressed in leukemic B cells of Chronic Lymphocytic Leukemia (CLL) and a subset of Acute Lymphoblastic Leukemia (ALL). In this comparative study the expression profile of ROR1 mRNA was investigated in Iranian patients with CLL and Acute Myelogenous Leukemia (AML) and the results were compared with those previously reported in our Iranian ALL patients. RT-PCR was performed on bone marrow and/or peripheral blood samples of 84 CLL and 12 AML patients. CLL samples were classified into immunoglobulin heavy chain variable region (IGHV) gene mutated (n=55) and unmutated (n=29) and also indolent (n=42) and progressive (n=39) subtypes. ROR1 expression was identified in 94% of our CLL patients, but none of the AML patients expressed ROR1. No significant differences were observed between different CLL subtypes for ROR1 expression. Taken together the present data and our previous results on ROR1 expression in ALL, our findings propose ROR1 as a tumor-associated antigen overexpressed in a large proportion of lymphoid (CLL and ALL), but not myeloid (AML) leukemias. Expression of ROR1 seems to be associated to lineage and differentiation stages of leukemic cells with a potential implication for immunotherapy.Tehran University of Medical Sciences and the Ministry of Health and Medical Education of Iran.Publishe

Indoor environment assessment of special wards of educational hospitals for the detection of fungal contamination sources: A multi-center study (2019-2021)

Background and Purpose: The hospital environment was reported as a real habitat for different microorganisms, especially mold fungi. On the other hand, these opportunistic fungi were considered hospital-acquired mold infections in patients with weak immune status. Therefore, this multi-center study aimed to evaluate 23 hospitals in 18 provinces of Iran for fungal contamination sources.Materials and Methods: In total, 43 opened Petri plates and 213 surface samples were collected throughout different wards of 23 hospitals. All collected samples were inoculated into Sabouraud Dextrose Agar containing Chloramphenicol (SC), and the plates were then incubated at 27-30ºC for 7-14 days.Results: A total of 210 fungal colonies from equipment (162, 77.1%) and air (48,22.9%) were identified. The most predominant isolated genus was Aspergillus (47.5%),followed by Rhizopus (14.2%), Mucor (11.7%), and Cladosporium (9.2%). Aspergillus(39.5%), Cladosporium (16.6%), as well as Penicillium and Sterile hyphae (10.4% each), were the most isolates from the air samples. Moreover, intensive care units (38.5%) and operating rooms (21.9%) had the highest number of isolated fungal colonies. Out of 256 collected samples from equipment and air, 163 (63.7%) were positive for fungal growth.The rate of fungal contamination in instrument and air samples was 128/213 (60.1%) and 35/43 (81.2%), respectively. Among the isolated species of Aspergillus, A. flavus complex (38/96, 39.6%), A. niger complex (31/96, 32.3%), and A. fumigatus complex (15/96, 15.6%) were the commonest species.Conclusion: According to our findings, in addition to air, equipment and instrument should be considered among the significant sources of fungal contamination in the indoor environment of hospitals. Airborne fungi, Hospital, Indoor air, Equipment, Sources of fungal contamination in the indoor environment of hospitals

Umbelliprenin from Ferula szowitsiana Activates both Intrinsic and Extrinsic Pathways of Apoptosis in Jurkat T-CLL cell line

Umbelliprenin is a prenylated compound, which belongs to the class of sesquiterpene coumarins. It is extracted from dried roots of Ferula szwitsiana collected from the mountains of Golestan forest (Golestan Province, north of Iran). Induction of apoptosis in Jurkat T-CLL cells has been previously shown. In this study, effect of umbelliprenin on proapoptotic caspases (caspase-8 and -9) and antiapoptotic Bcl-2 family protein was studied. Jurkat cells were incubated with umbelliprenin. Cells were then lysed and activation of proteins was studied by Western blot analysis. In this study, we showed that umbelliprenin activates intrinsic and extrinsic pathways of apoptosis by the activation of caspase-8 and -9 respectively. Inhibition of Bcl-2 was also shown. In conclusion, umbelliprenin induced apoptosis in Jurkat cells through caspase-dependent apoptosis pathway

Evaluating the effect of main factors in determining speed bump location based on Taguchi design of experiments

Use of speed bumps as a traffic-calming technique is a key issue to a safe and smooth traffic flow. Lack of consideration on finding the best location for speed bump installation before stop points, such as traffic junctions, has provided the motivation to conduct this study. This paper investigates the influence of some main factors on determining bump location and to optimize the distance from bump to stop point in order to obtain the minimum speed at this point. A robust design was used whereby the effect of environmental noises on the parameters was investigated using the Taguchi design of experiments. A 2-level L8 inner array and an L4 outer array design is used to evaluate and analyze the results. The results suggested that the linear models effectively explain the performance indicators within the ranges of the factors. It can be concluded that the optimum setting suggested is at the most influential levels of the design parameters which yields a robust and insensitive design for speed bump installation after considering the effect of environmental noises. The car speed before bump has the greatest influence and also the most robust factor in terms of signal-to-noise ratio and mean analysis

Otomycosis in the South of Iran with a High Prevalence of Tympanic Membrane Perforation: A Hospital-Based Study

Introduction Otomycosis is a superficial infection of the external ear caused by fungal pathogens. The genera Aspergillus and Candida are considered the main fungal causative agents, with the predominance of Aspergillus section Nigri. The present study aimed to evaluate the clinical symptoms of patients with otomycosis and predisposing factors and to identify fungal etiological agents using molecular approaches. We also present an overview of published papers on tympanic membrane perforation (TMP) secondary to otomycosis. Materials and Methods An otorhinolaryngologist collected specimens from external ear canals of patients with suspected otomycosis based on the patient’s history and clinical examinations. The specimens were collected using sterile swabs. Fungal isolates were confirmed in clinical specimens by direct microscopy and culture methods. Fungal isolates were identified based on molecular approaches. Results In total, specimens from 211 patients with suspected otomycosis were examined. The presence of fungi was confirmed in about 51% of patients based on fungal elements in direct microscopy and culture-positive fungi. Aspergillus tubingensis was the most commonly isolated species (52.77%), followed by Aspergillus niger (25.92%). Otomycosis due to infection with Candida species was observed in 16% of cases. Of note, in 36.11% of cases, otomycosis was associated with TMP. Conclusion A mycological examination is indispensable for a correct diagnosis in patients with otitis extern. TMP should be considered in patients with otomycosis, as it appears to be relatively common in this population

(A) Immunoprecipated (IP) ROR1 from CLL cell lysates probed with serum from 4 non-progressive (NP) and 4 progressive (P) CLL patients as well as 4 control donors. Bands of 105 and 64 kDa could be seen. The blots were also probed with a goat anti-human ROR1 antibody, anti-CD20 MAb and an isotype control MAb. (B) CLL cells immunoprecipitated using anti-CD20 and isotype control MAbs. No ROR1 bands could be detected. (C) Patients’ sera were adsorbed with a pool of CLL cell lysate (n = 10). The 105 and 64 kDa bands disappeared or were significantly reduced. (D) Patients’ sera were absorbed with a pool of normal PBMC lysate (n = 5). The 105 kDa and 64 kDa ROR1 bands did not disappear.

<p>(A) Immunoprecipated (IP) ROR1 from CLL cell lysates probed with serum from 4 non-progressive (NP) and 4 progressive (P) CLL patients as well as 4 control donors. Bands of 105 and 64 kDa could be seen. The blots were also probed with a goat anti-human ROR1 antibody, anti-CD20 MAb and an isotype control MAb. (B) CLL cells immunoprecipitated using anti-CD20 and isotype control MAbs. No ROR1 bands could be detected. (C) Patients’ sera were adsorbed with a pool of CLL cell lysate (n = 10). The 105 and 64 kDa bands disappeared or were significantly reduced. (D) Patients’ sera were absorbed with a pool of normal PBMC lysate (n = 5). The 105 kDa and 64 kDa ROR1 bands did not disappear.</p

(A) Serum concentrations (ng/ml) of anti-ROR1 antibodies (ELISA) against a full length ROR1 protein and (B) a ROR1 KNG protein in CLL patients (n = 23): (●) non-progressive (n = 15) and (x) progressive (n = 8) CLL patients and (○) control donors (n = 20). Dotted line represents mean+2SD of controls. ***p<0.0001. (C) Reactivity of sera from CLL patients with a recombinant CEA protein. The results are shown as OD values at 450 nm for 1:50 and 1:100 serum dilutions. (D) Relation between conc. of antibodies against a full length ROR1 protein and ROR1 KNG protein in 23 CLL patients.

<p>(A) Serum concentrations (ng/ml) of anti-ROR1 antibodies (ELISA) against a full length ROR1 protein and (B) a ROR1 KNG protein in CLL patients (n = 23): (●) non-progressive (n = 15) and (x) progressive (n = 8) CLL patients and (○) control donors (n = 20). Dotted line represents mean+2SD of controls. ***p<0.0001. (C) Reactivity of sera from CLL patients with a recombinant CEA protein. The results are shown as OD values at 450 nm for 1:50 and 1:100 serum dilutions. (D) Relation between conc. of antibodies against a full length ROR1 protein and ROR1 KNG protein in 23 CLL patients.</p