Background: To determine the frequency and specificities of red blood cells -antibodies in multit... more Background: To determine the frequency and specificities of red blood cells -antibodies in multitransfused cancer patients. Methods: From total of 150 patients, 24 patients were diagnosed with haematological and 126 with non-haematological malignancies. Their medical records were reviewed and sorted by diagnosis, treatment medications, and past transfusion and/or treatment history. Only those patients were enrolled who had received at least five transfusions during the treatment. Antibody screening was performed by using commercial three-cell panel according to standardized methods. Allo-antibody was identified by using 11 cells panel. Results: Total patients with malignant disorders included 44 males and 106 females. Nine patients (6%) with non haematological malignancies possessed RBC allo-antibodies. The distribution of different allo-antibodies in positive patients was anti-D in 3 patients, anti-E in 2 patients while antiFya, anti Fyb, anti-Jka and anti-K were positive for 1 pat...
International Journal of Medical Research and Health Sciences, 2019
Objective: This kind of study was conducted first time in Pakistan. Its objective was to ascertai... more Objective: This kind of study was conducted first time in Pakistan. Its objective was to ascertain the associated clinical features and analyze the FANCA exon 28 and exon 29 mutations in Pakistani Fanconi anemia (FA) patients. Methods: A total of 38 patients with Fanconi anemia were recruited presenting in the Armed forces institute of pathology (AFIP) Rawalpindi Pakistan. They were enrolled in this study on the basis of comprehensive clinical evaluation and positive Diepoxybutane (DEB)/Mitomycin C Chromosomal breakage test. Genomic DNA was extracted from peripheral blood of patients and age and gender-matched controls. Mutation analysis of FANCA gene was done by conventional Polymerase chain reaction (PCR) and DNA sequencing. Various online tools and software were used for analysis of the obtained data and identification of the sequence alterations in FANCA gene in exon 28 and exon 29 of FA patients. Results and Discussion: The current study on screening of FANCA mutational analysi...
Background: To observe in vitro parameters of stored platelets in PAS as compared to plasma for 1... more Background: To observe in vitro parameters of stored platelets in PAS as compared to plasma for 10 days. Methods: A comparative study was carried out on 42 samples of random donor platelet concentrates (PC). They were divided into two groups of 21 samples each and stored in incubator at 22°C. In one group plasma was replaced with PAS. Sampling was done on day 0, 3, 5, 7, 8, 9 and 10. Bacterial cultures were carried out. All the samples,which showed contamination, were excluded from the study. Results: pH and glucose levels were reduced in both groups but they dropped more rapidly in PC stored in plasma than in PAS (p-value ≤ 0.001). However, the difference in LDH levels between two groups was not statistically significant. The mean values of PO2 were reduced whereas mean values of PCO2 were increased in both groups, but these changes were seen much less in PC stored in PAS (pvalue ≤ 0.001). The results showed that difference in all parameters between two groups was highly significan...
International Journal of Laboratory Hematology, 2020
IntroductionGlanzmann thrombasthenia (GT) is most common of inherited platelet disorders, resulti... more IntroductionGlanzmann thrombasthenia (GT) is most common of inherited platelet disorders, resulting from quantitative/qualitative defects in platelet surface integrin αIIbβ3, encoded by ITGA2B and ITGB3 genes. Little is known about clinical and molecular characteristics of GT patients from highly consanguineous Pakistani population.MethodsThis study analyzed the clinical and molecular spectrum of six GT patients from four unrelated but consanguineous families. Platelet surface expression of αIIbβ3 integrin was determined using flow cytometry analysis. ITGA2B and ITGB3 genes were screened for causative mutations by DNA sequencing. Detected mutations were characterized for their pathogenicity using a variety of in silico tools.ResultsGlanzmann thrombasthenia patients in this study generally presented early in life, had a severe course of clinical disease with transfusion dependency for management of bleeding episodes. Molecular analysis revealed 2 homozygous missense mutations in ITGB...
Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to b... more Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to be involved in clopidogrel high on treatment reactivity in ischemic heart disease (IHD) patients. Methods: A total of 240 patients with IHD were screened for CYP2C19 loss-of-function alleles (LOF; *2, *3) and PON-1 Q192R. Patients were classified as responders and nonresponders to clopidogrel based upon platelet aggregation studies. Genotyping of the CYP2C19 and PON-1 allele was carried out by PCR-RFLP. Results: Results showed that 14.3% of the patients were nonresponders, whereas 85.7% were responders to the clopidogrel therapy. CYP2C19*3 allele showed significant association with clopidogrel high on treatment reactivity in IHD patients. Conclusion: Result of our study demonstrate that IHD patients with CYP2C19*3 allele can face the problem of clopidogrel high on treatment reactivity in Punjabi Pakistani population.
Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children and forms a maj... more Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children and forms a major fraction of childhood malignancies in the developed countries. Numerous chromosomal aberrations have been observed in ALL including translocations which result in the production of fusion genes (BCR-ABL, TEL-AML1, and MLL-AF4). These chromosomal rearrangements have great prognostic and therapeutic significance. Amongst these, TEL-AML1 fusion gene represents a subgroup of ALL cases, which are associated with many clinically important parameters of good prognosis. The objective of this study was to detect the frequency of TEL-AML1 fusion oncogene in ALL and its association with already established prognostic factors such as age, WBC count and FAB subtype. Materials and Methods: Sixty-six patients with newly diagnosed ALL were studied and patients on chemotherapy and T-ALL were excluded. The data was analyzed by SPSS20 for prognostically important parameters such as age, sex, hemoglobin ...
Saudi Journal of Kidney Diseases and Transplantation, 2015
Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is... more Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient's response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 42 patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 ageand sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron and CRP were performed. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 ± 2.8 ng/mL and 8.5 ± 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 ± 2.4 ng/mL) while lower levels (16.9 ± 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as well as EPO resistance.
Background: Stored platelet concentrates (PC) are in increasing demand for transfusion to patient... more Background: Stored platelet concentrates (PC) are in increasing demand for transfusion to patients with thrombocytopenia or disordered platelet function with active bleeding. Platelets are difficult to preserve in vitro for longer period of time. Different platelet additive solutions (PAS) have been formulated which can increase the survival period of PC during storage. Study Design: Comparative study. Materials and Methods: The study was carried out to compare in vitro changes in platelet indices [platelet count and mean platelet volume (MPV)] and extent of swirling in stored PC with and without PAS stored for 10 day. Results: This study included 42 samples of random donor platelet concentrates, divided into two groups. In one group, PC were stored without PAS while in other group PAS was added to PC before storage. Changes in platelets count and MPV were monitored by using automated hematology cell analyzer, in both groups on day 0, 3, 5, 7, 8, 9, and 10. Bacterial cultures were also applied to detect bacterial contamination of PC. The results showed that mean platelet count of PC stored without PAS was 5.6 + 0.1 x 1010/L on day 0 and it was 5.5 + 0.5 x 1010/L in PC stored with PAS. The difference between the two groups started becoming statistically significant by day 7. Platelet count was significantly lower in PC without PAS as compared to the PC stored with PAS (P value ≤ 0.001). The difference in the mean platelet volume (MPV) between two groups was highly significant during 10 days storage (P value ≤ 0.001). Swirling was better seen in PC stored in PAS as compared to PC stored without PAS during 10 days storage. Blood cultures were applied on 42 samples on days 0, 5 and 10. Bacterial contamination occurred in few samples in both groups, those samples were not processed further. Conclusion: This study showed that the use of PAS in platelet concentrate storage bags increased the shelf life and viability of platelets as compared to those without PAS.
... Shahida Mohsin*, Maria Aslam*, Shabbir Hussain*, Shahla Suhail** *Department of Pathology, Un... more ... Shahida Mohsin*, Maria Aslam*, Shabbir Hussain*, Shahla Suhail** *Department of Pathology, University of Health Sciences, Lahore; ** Hemophilia Patients' Welfare Society, Lahore. ... 2008; 3 (1): 1-4. 3. Adil SN,Qureshi M A. Von Willebrand disease-an under diagnosed entity. ...
Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes... more Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes with approximately 24-h rhythmicity. Circadian genes and their protein products constitute the molecular components of the circadian oscillator that form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends from core clock genes to various clock-controlled genes that include various cell cycle genes. Aberrant expression of circadian clock genes, therefore, may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1) at mRNA level and determination of serum melatonin levels in peripheral blood samples of 37 CLL (chronic lymphocytic leukemia) patients and equal number of age- and sex-matched healthy controls in order to indicate association between deregulated circadian clock and manifestation of CLL. Results showed significantly down-regulated expression of Bmal1, Per1, Per2 and Wee1 and significantly up-regulated expression of Myc and Cyclin D1 (P < 0.0001) in CLL patients as compared to healthy controls. When expression of these genes was compared between shift-workers and non-shift-workers within the CLL group, the expression was found more aberrant in shift-workers as compared to non-shift-workers. However, this difference was found statistically significant for Myc and Cyclin D1 only (P < 0.05). Serum melatonin levels were found significantly low (P < 0.0001) in CLL subjects as compared to healthy controls whereas melatonin levels were found still lower in shift-workers as compared to non-shift-workers within CLL group (P < 0.01). Our results suggest that aberrant expression of circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL. Moreover, shift-work and low melatonin levels may also contribute in etiology of CLL by further perturbing of circadian clock.
1 Forde K, Mason C, Mathias M. Prolonged bleeding after exfoliation of a deciduous tooth in a pat... more 1 Forde K, Mason C, Mathias M. Prolonged bleeding after exfoliation of a deciduous tooth in a patient with Glanzmann’s thrombasthenia. Haemophilia 2012; 18: e58–9. 2 Di Minno G, Coppola A, Di Minno MND, Poon M-C. Glanzmann’s thrombasthenia (defective platelet integrin aIIb-b3): proposals for management between evidence and open issues. Thromb Haemost 2009; 102: 1157–64. 3 Mathew P, Young G. Recombinant factor VIIa in paediatric bleeding disorders– a 2006 review. Haemophilia 2006; 12: 457–72. 4 Poon M-C, d’Oiron R, Von Depka M et al. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann’s thrombasthenia: results of an international survey. J Thromb Haemost 2004; 2: 1096–103. 5 NovoSeven® SmPC 2011. European Medicines Agency website. Available at http:// www.ema.europa.eu/docs/en_GB/document_ library/EPAR_-_Product_Information/human/ 000074/WC500030873.pdf. Last accessed March 12, 2012). 6 Fiore M, Firah N, Pillois X, Nurden P, Heilig R, Nurden AT. Natural history of platelet antibody formation against aIIbb3 in a French cohort of Glanzmann thrombasthenia patients. Haemophilia 2012; 1–9. doi: 10.1111/j.1365-2516.2011.02744.x.
Introduction: Patients with end stage renal disease (ESRD) develop increased bleeding ten-dency... more Introduction: Patients with end stage renal disease (ESRD) develop increased bleeding ten-dency, which is characterized by defective interaction of platelets with damaged sub endothelium due to impaired platelet functions. This study was carried out to ...
JPMA. The Journal of the Pakistan Medical Association, 2017
TTo measure levels of platelet-derived microparticles and soluble P-selectin in patients of acute... more TTo measure levels of platelet-derived microparticles and soluble P-selectin in patients of acute myocardial infarction and their comparison with healthy controls. This case-control study was conducted in Department of Haematology, University of Health Sciences Lahore from April to September 2013, and comprised patients of acute myocardial infarction in group 1 and healthy controls in group 2. Platelet-derived microparticles and soluble P-selectin were measured by enzyme-linked immunosorbent assay. SPSS21 was used for data analysis. Of the 80 participants, 50(62.5%) were patients and 30(37.5%) were controls. The mean levels of platelet-derived microparticles and soluble P-selectin were significantly higher in group 1 compared to group 2 (45.70±10.30 vs 10.60±0.96, and 51.46±9.30 vs 9.16±1.04, respectively) (p<0.001). There was no significant difference in levels of platelet-derived microparticles and soluble P-selectin in three intervals after acute myocardial infarction (p>0....
Background: To determine the frequency and specificities of red blood cells -antibodies in multit... more Background: To determine the frequency and specificities of red blood cells -antibodies in multitransfused cancer patients. Methods: From total of 150 patients, 24 patients were diagnosed with haematological and 126 with non-haematological malignancies. Their medical records were reviewed and sorted by diagnosis, treatment medications, and past transfusion and/or treatment history. Only those patients were enrolled who had received at least five transfusions during the treatment. Antibody screening was performed by using commercial three-cell panel according to standardized methods. Allo-antibody was identified by using 11 cells panel. Results: Total patients with malignant disorders included 44 males and 106 females. Nine patients (6%) with non haematological malignancies possessed RBC allo-antibodies. The distribution of different allo-antibodies in positive patients was anti-D in 3 patients, anti-E in 2 patients while antiFya, anti Fyb, anti-Jka and anti-K were positive for 1 pat...
International Journal of Medical Research and Health Sciences, 2019
Objective: This kind of study was conducted first time in Pakistan. Its objective was to ascertai... more Objective: This kind of study was conducted first time in Pakistan. Its objective was to ascertain the associated clinical features and analyze the FANCA exon 28 and exon 29 mutations in Pakistani Fanconi anemia (FA) patients. Methods: A total of 38 patients with Fanconi anemia were recruited presenting in the Armed forces institute of pathology (AFIP) Rawalpindi Pakistan. They were enrolled in this study on the basis of comprehensive clinical evaluation and positive Diepoxybutane (DEB)/Mitomycin C Chromosomal breakage test. Genomic DNA was extracted from peripheral blood of patients and age and gender-matched controls. Mutation analysis of FANCA gene was done by conventional Polymerase chain reaction (PCR) and DNA sequencing. Various online tools and software were used for analysis of the obtained data and identification of the sequence alterations in FANCA gene in exon 28 and exon 29 of FA patients. Results and Discussion: The current study on screening of FANCA mutational analysi...
Background: To observe in vitro parameters of stored platelets in PAS as compared to plasma for 1... more Background: To observe in vitro parameters of stored platelets in PAS as compared to plasma for 10 days. Methods: A comparative study was carried out on 42 samples of random donor platelet concentrates (PC). They were divided into two groups of 21 samples each and stored in incubator at 22°C. In one group plasma was replaced with PAS. Sampling was done on day 0, 3, 5, 7, 8, 9 and 10. Bacterial cultures were carried out. All the samples,which showed contamination, were excluded from the study. Results: pH and glucose levels were reduced in both groups but they dropped more rapidly in PC stored in plasma than in PAS (p-value ≤ 0.001). However, the difference in LDH levels between two groups was not statistically significant. The mean values of PO2 were reduced whereas mean values of PCO2 were increased in both groups, but these changes were seen much less in PC stored in PAS (pvalue ≤ 0.001). The results showed that difference in all parameters between two groups was highly significan...
International Journal of Laboratory Hematology, 2020
IntroductionGlanzmann thrombasthenia (GT) is most common of inherited platelet disorders, resulti... more IntroductionGlanzmann thrombasthenia (GT) is most common of inherited platelet disorders, resulting from quantitative/qualitative defects in platelet surface integrin αIIbβ3, encoded by ITGA2B and ITGB3 genes. Little is known about clinical and molecular characteristics of GT patients from highly consanguineous Pakistani population.MethodsThis study analyzed the clinical and molecular spectrum of six GT patients from four unrelated but consanguineous families. Platelet surface expression of αIIbβ3 integrin was determined using flow cytometry analysis. ITGA2B and ITGB3 genes were screened for causative mutations by DNA sequencing. Detected mutations were characterized for their pathogenicity using a variety of in silico tools.ResultsGlanzmann thrombasthenia patients in this study generally presented early in life, had a severe course of clinical disease with transfusion dependency for management of bleeding episodes. Molecular analysis revealed 2 homozygous missense mutations in ITGB...
Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to b... more Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to be involved in clopidogrel high on treatment reactivity in ischemic heart disease (IHD) patients. Methods: A total of 240 patients with IHD were screened for CYP2C19 loss-of-function alleles (LOF; *2, *3) and PON-1 Q192R. Patients were classified as responders and nonresponders to clopidogrel based upon platelet aggregation studies. Genotyping of the CYP2C19 and PON-1 allele was carried out by PCR-RFLP. Results: Results showed that 14.3% of the patients were nonresponders, whereas 85.7% were responders to the clopidogrel therapy. CYP2C19*3 allele showed significant association with clopidogrel high on treatment reactivity in IHD patients. Conclusion: Result of our study demonstrate that IHD patients with CYP2C19*3 allele can face the problem of clopidogrel high on treatment reactivity in Punjabi Pakistani population.
Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children and forms a maj... more Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children and forms a major fraction of childhood malignancies in the developed countries. Numerous chromosomal aberrations have been observed in ALL including translocations which result in the production of fusion genes (BCR-ABL, TEL-AML1, and MLL-AF4). These chromosomal rearrangements have great prognostic and therapeutic significance. Amongst these, TEL-AML1 fusion gene represents a subgroup of ALL cases, which are associated with many clinically important parameters of good prognosis. The objective of this study was to detect the frequency of TEL-AML1 fusion oncogene in ALL and its association with already established prognostic factors such as age, WBC count and FAB subtype. Materials and Methods: Sixty-six patients with newly diagnosed ALL were studied and patients on chemotherapy and T-ALL were excluded. The data was analyzed by SPSS20 for prognostically important parameters such as age, sex, hemoglobin ...
Saudi Journal of Kidney Diseases and Transplantation, 2015
Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is... more Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 42 patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 ageand sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron and CRP were performed. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 ± 2.8 ng/mL and 8.5 ± 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 ± 2.4 ng/mL) while lower levels (16.9 ± 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as well as EPO resistance.
Background: Stored platelet concentrates (PC) are in increasing demand for transfusion to patient... more Background: Stored platelet concentrates (PC) are in increasing demand for transfusion to patients with thrombocytopenia or disordered platelet function with active bleeding. Platelets are difficult to preserve in vitro for longer period of time. Different platelet additive solutions (PAS) have been formulated which can increase the survival period of PC during storage. Study Design: Comparative study. Materials and Methods: The study was carried out to compare in vitro changes in platelet indices [platelet count and mean platelet volume (MPV)] and extent of swirling in stored PC with and without PAS stored for 10 day. Results: This study included 42 samples of random donor platelet concentrates, divided into two groups. In one group, PC were stored without PAS while in other group PAS was added to PC before storage. Changes in platelets count and MPV were monitored by using automated hematology cell analyzer, in both groups on day 0, 3, 5, 7, 8, 9, and 10. Bacterial cultures were also applied to detect bacterial contamination of PC. The results showed that mean platelet count of PC stored without PAS was 5.6 + 0.1 x 1010/L on day 0 and it was 5.5 + 0.5 x 1010/L in PC stored with PAS. The difference between the two groups started becoming statistically significant by day 7. Platelet count was significantly lower in PC without PAS as compared to the PC stored with PAS (P value ≤ 0.001). The difference in the mean platelet volume (MPV) between two groups was highly significant during 10 days storage (P value ≤ 0.001). Swirling was better seen in PC stored in PAS as compared to PC stored without PAS during 10 days storage. Blood cultures were applied on 42 samples on days 0, 5 and 10. Bacterial contamination occurred in few samples in both groups, those samples were not processed further. Conclusion: This study showed that the use of PAS in platelet concentrate storage bags increased the shelf life and viability of platelets as compared to those without PAS.
... Shahida Mohsin*, Maria Aslam*, Shabbir Hussain*, Shahla Suhail** *Department of Pathology, Un... more ... Shahida Mohsin*, Maria Aslam*, Shabbir Hussain*, Shahla Suhail** *Department of Pathology, University of Health Sciences, Lahore; ** Hemophilia Patients&#x27; Welfare Society, Lahore. ... 2008; 3 (1): 1-4. 3. Adil SN,Qureshi M A. Von Willebrand disease-an under diagnosed entity. ...
Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes... more Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes with approximately 24-h rhythmicity. Circadian genes and their protein products constitute the molecular components of the circadian oscillator that form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends from core clock genes to various clock-controlled genes that include various cell cycle genes. Aberrant expression of circadian clock genes, therefore, may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1) at mRNA level and determination of serum melatonin levels in peripheral blood samples of 37 CLL (chronic lymphocytic leukemia) patients and equal number of age- and sex-matched healthy controls in order to indicate association between deregulated circadian clock and manifestation of CLL. Results showed significantly down-regulated expression of Bmal1, Per1, Per2 and Wee1 and significantly up-regulated expression of Myc and Cyclin D1 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) in CLL patients as compared to healthy controls. When expression of these genes was compared between shift-workers and non-shift-workers within the CLL group, the expression was found more aberrant in shift-workers as compared to non-shift-workers. However, this difference was found statistically significant for Myc and Cyclin D1 only (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Serum melatonin levels were found significantly low (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) in CLL subjects as compared to healthy controls whereas melatonin levels were found still lower in shift-workers as compared to non-shift-workers within CLL group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Our results suggest that aberrant expression of circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL. Moreover, shift-work and low melatonin levels may also contribute in etiology of CLL by further perturbing of circadian clock.
1 Forde K, Mason C, Mathias M. Prolonged bleeding after exfoliation of a deciduous tooth in a pat... more 1 Forde K, Mason C, Mathias M. Prolonged bleeding after exfoliation of a deciduous tooth in a patient with Glanzmann’s thrombasthenia. Haemophilia 2012; 18: e58–9. 2 Di Minno G, Coppola A, Di Minno MND, Poon M-C. Glanzmann’s thrombasthenia (defective platelet integrin aIIb-b3): proposals for management between evidence and open issues. Thromb Haemost 2009; 102: 1157–64. 3 Mathew P, Young G. Recombinant factor VIIa in paediatric bleeding disorders– a 2006 review. Haemophilia 2006; 12: 457–72. 4 Poon M-C, d’Oiron R, Von Depka M et al. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann’s thrombasthenia: results of an international survey. J Thromb Haemost 2004; 2: 1096–103. 5 NovoSeven® SmPC 2011. European Medicines Agency website. Available at http:// www.ema.europa.eu/docs/en_GB/document_ library/EPAR_-_Product_Information/human/ 000074/WC500030873.pdf. Last accessed March 12, 2012). 6 Fiore M, Firah N, Pillois X, Nurden P, Heilig R, Nurden AT. Natural history of platelet antibody formation against aIIbb3 in a French cohort of Glanzmann thrombasthenia patients. Haemophilia 2012; 1–9. doi: 10.1111/j.1365-2516.2011.02744.x.
Introduction: Patients with end stage renal disease (ESRD) develop increased bleeding ten-dency... more Introduction: Patients with end stage renal disease (ESRD) develop increased bleeding ten-dency, which is characterized by defective interaction of platelets with damaged sub endothelium due to impaired platelet functions. This study was carried out to ...
JPMA. The Journal of the Pakistan Medical Association, 2017
TTo measure levels of platelet-derived microparticles and soluble P-selectin in patients of acute... more TTo measure levels of platelet-derived microparticles and soluble P-selectin in patients of acute myocardial infarction and their comparison with healthy controls. This case-control study was conducted in Department of Haematology, University of Health Sciences Lahore from April to September 2013, and comprised patients of acute myocardial infarction in group 1 and healthy controls in group 2. Platelet-derived microparticles and soluble P-selectin were measured by enzyme-linked immunosorbent assay. SPSS21 was used for data analysis. Of the 80 participants, 50(62.5%) were patients and 30(37.5%) were controls. The mean levels of platelet-derived microparticles and soluble P-selectin were significantly higher in group 1 compared to group 2 (45.70±10.30 vs 10.60±0.96, and 51.46±9.30 vs 9.16±1.04, respectively) (p<0.001). There was no significant difference in levels of platelet-derived microparticles and soluble P-selectin in three intervals after acute myocardial infarction (p>0....
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