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Goodpasture syndrome, a rare human autoimmune disorder, is characterized by the presence of pathogenic autoantibodies that react with the components of the glomerular basement membrane. The clinical condition of the Goodpasture syndrome is characterized by an acute necrotizing glomerulonephritis, often with accompanying pulmonary hemorrhage. Notably, the Goodpasture antigen has been localized to the noncollagenous domain of the alpha3 chain of type IV collagen. Additionally, human leukocyte antigen-DR2, and to a lesser extent human leukocyte antigen-DR4, have been identified as important restriction elements. The role of T cells in Goodpasture syndrome is indicated by the highly restricted specificity of the antibody response and the strong major histocompatibility complex class II association. In this review article, we briefly describe the latest views on the molecular and cellular themes of Goodpasture syndrome. [ABSTRACT FROM AUTHOR]

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-β, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-β, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

Unexpected antibodies, also called irregular antibodies, are not known to exist in a person's serum before testing. This research aims to assess the prevalence of unexpected antibodies and their correlation with several clinical conditions. This cross-sectional prospective study, undertaken from June 2019 to June 2020, included ABO, Rh grouping, cross-matching, and antibody screening. Antibody identification was performed only on patients who tested positive in the screening test. From a total of 9764 participants who were screened for unexpected antibodies, 107 (1.1%) tested positive. The Rh blood group system antibodies were the most frequent, particularly anti-D. There was also a significant correlation between the unexpected antibodies and history of transfusion, pregnancy, and autoimmune diseases as P ≤ 0.05. The most prominent unexpected antibodies in the study belong to the Rh system (Anti-D). Moreover, as a result of the strong correlation between the unexpected antibodies as well as the history of transfusion, pregnancy, and autoimmune diseases, the highest safety criteria must be followed during the transfusion of blood to patients with these clinical conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1β, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1β, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alosaimi, Mubarak, Hamed, Almutairi, Alrashed, AlJuryyan, Enani, Alenzi and Alturaiki.)

Introduction: Beta-thalassemias are a group of inherited blood disorders caused by reduced or absent synthesis of beta chain of hemoglobin resulting in variable phenotypes ranging from clinically asymptomatic individuals to severe anemia symptoms. The objective of this study is to screen for the whole beta gene globulin and the LCR region and its clinical relevance in β-Thalassemia patients., Methods: In this study, we collected 140 blood patients' samples with beta-thalassemia from different areas of Saudi Arabia. DNA was then extracted then the molecular scanning for the whole β-globin gene and the Locus control region (β-LCR) for patients' samples, was run using PCR., Results: Sixty one mutations found in this study, including 22 new mutations not recorded in the database before. These deletions including: (*C-1960-1961 ca/-- del in hbb5) and (*c-519C A het in hbb9). Interestingly, the highest percentage in gene deletion occurred in exon 03A by ∼33% of the samples, while the highest percentage in gene addition of the gene occurred in exon 03B by ∼25%., Conclusion: This study was unique to show several new mutations that would help in diagnosis and treatment. These results should be taken further to set up better management strategies to improve outcomes., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Sickle cell anemia (SCA) is a common hematological disease affecting humans. Detection of a single base pair mutation in β-globin gene is an important diagnostic tool for SCA. The aim was to study the molecular survey of locus control regions (LCR) in Saudi patients with sickle cell anemia, and to identify the genetic variables and their clinical manifestations., Methodology: Blood samples from 69 unrelated sickle cell disease patients were obtained from the KKUH, Riyadh between 2017-2019. In this study, the DNA was extracted and PCR was performed. Additional PCR amplifications reactions covering the LCR were performed by using another different set of primers. Seven specific primer pairs were used to amplify seven regions in the locus control region (LCR) of β globin family. The generated fragments were sequenced to identify the possible alterations in this region., Results: The results gained from sequencing experiments revealed a wide range of genomic alterations. A total of 69 gene alterations have been recognized in the locus control region;- The first fragment LCR-HS1 shows 20 alterations; The second fragment LCR-HS2 revealed six changes; The third fragment LCR-HS3 shows many changes; The fifth LCR-HS5 region revealed four changes; The sixth fragment LCR-HS6 revealed eight changes; The seventh LCR-HS7 fragment demonstrates ten changes., Conclusion: It clear that this study has successfully identified LCR mutations for random Saudi patients with SCD. The above results should be taken further to set up management strategies to improve outcomes., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Sickle cell anemia (SCA) is one of the most common hematologic diseases affecting humans. Detection of a single base pair mutation at 6th codon of β-globin gene is important for the diagnosis of SCA. The aim was to study the nucleotide sequences and the molecular survey of β-globin gene in Saudi patients. Blood samples from 77 unrelated SC patients were obtained from the KKUH, between 2015 and 2017. In this study, DNA was extracted then PCR was performed. Twelve overlapping fragments covering β-globin gene, have been generated by PCR. A total of 47 alterations have been recognized in β-globin gene. These alterations composed of: deletions, insertion or substitutions as follows:- one mutation identified on the 1st segment; three alterations on 2nd fragment; two alterations on 3rd segment; seven alterations on 4th segment; three substitution on 5th fragment; two changes on 6th fragment; five alterations on 7th fragment; seven substitution changes on 8th fragment; two heterozygous substitution changes on 9th fragment; three changes on 10th fragment and eight substitution changes on 11th fragment, and four changes on 12th fragment. SCA had profound negative effects on many organs, causing many complications. The results should be taken further to set up management strategies to improve outcomes., (© 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.)

Background and objective: On the basis that the inflammatory effects of TNF (tumour necrosis factor) are predominantly mediated through interaction with the TNF receptor-1 (TNFRSF1A), the current study was designed to establish the prevalence of the mutations, R92Q and P46L TNFRSF1A polymorphisms both in the general healthy Saudi population, and in Saudi patients carrying inflammatory diseases such as atherosclerosis or rheumatoid arthritis. We felt it important to report the frequency of the mutations, R92Q and P46L TNFRSF1A polymorphisms in healthy Saudi individuals, and those with inflammatory conditions, as well as to describe the pattern of immunological factors in individuals expressing R92Q or P46L TNFRSF1A. Patients and methods: We collected in PAX gene blood RNA tubes (for RT-PCR and sequencing) 500 blood samples from normal healthy individuals from the West and Center of Saudi Arabia, as well as 100 from patients with atherosclerosis, and 100 patients diagnosed with rheumatoid arthritis. All were screened for the levels of soluble TNF, C-reactive protein (CRP), interleukin6 (IL-6) and sTNFR1. In addition, they were screened for R92Q and P46L TNFRSF1A by RT-PCR. Moreover, phenotype and expression of peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry (FACS). Results: Across 500 normal individuals, 8 (1.6%) expressed both R92Q and P46L mutations. By contrast, of the 100 patients in our study with atherosclerosis, 34% expressed both the R92Q and P46L mutations, whilst 42% of patients with rheumatoid arthritis expressed both mutations R92Q and P46L. No significant differences were observed between cell markers of normal individuals (CD3, 4, 8, 16, 56, 19, 25, ICAM-1, VLA-4 & l-selectin) and patients with atherosclerosis. There were significantly high values of cell markers in patients with rheumatoid arthritis compared with normal individuals both in terms of percentage and absolute counts ( p  < 0.05). Soluble IL-6 and sTNFR1 showed significant decreases in atherosclerosis and rheumatoid arthritis when compared with controls ( p  < 0.05). In addition, CRP and sTNF showed significant increases in the atherosclerosis and rheumatoid arthritis groups when compared to controls ( p  < 0.05). Conclusion: Our findings reasonably anticipate the presence of TRAPS disease (low penetrance mutations) amongst the Saudi population although further studies are needed to confirm these results.

Aim: The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy., Methods: The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis., Results: Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04)., Conclusion: Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

Background: It has been documented that remote limb ischemic preconditioning (rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized that osteopontin (OPN), transforming growth factor beta (TGF-β), apoptotic proteins (survivin and caspase-3) and oxidative stress play role in the renoprotective effects of rIPC., Materials and Methods: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: sham group, I/R group (left renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind limb ischemia just before renal ischemia). Each group was subdivided into 24, 48 and 72 h groups according to the time of sacrifice. We measured serum creatinine and blood urea nitrogen (BUN) at the baseline and end points. Also, left kidney was harvested at study end points for assessment of the expression of OPN, TGF-β, apoptotic proteins (survivin and caspase-3) and oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) in kidney tissues and histopathological examination., Results: Serum creatinine and BUN levels and histopathological damage score were significantly lower in rIPC group than I/R group (p < 0.005). Also, compared to I/R group, the levels of MDA and the expression of OPN, TGF-β and caspase-3 in kidney tissues were significantly lower in rIPC group, while the levels of SOD and GSH and the expression of survivin in kidney tissues were significantly higher in rIPC group at all time points (p ≤ 0.05)., Conclusions: rIPC exhibited protective effects against renal I/R injury which might be due to inhibition of OPN expression, inflammatory cytokine TGF-β and caspase-3 and activation of anti-apoptotic protein survivin as well as improvement of oxidative stress in kidney tissues., (© 2016 S. Karger AG, Basel.)

Objective: Fungal urinary tract infections due to Candida have increased significantly in recent years. Our research objective was to study Candida species in urine samples of patients with urinary tract infections (UTIs) associated with obstructive uropathy and to investigate the virulence factors of the isolated Candida., Methods: Patients were divided into two groups: Group I (cases): 50 patients with UTIs and obstructive uropathy. Group II (control): 50 patients with UTIs but with no functional or anatomical obstruction of their urinary tract. Clinical histories and physical examinations, together with laboratory investigations of urine samples were carried out in all patients in this study. Mid stream urine samples were examined microscopically and by fungal cell culture. The isolated Candida species were identified by analytical profile index (API). Candida Virulence factors were determined for the isolated Candida. The susceptibility to fluconazole was evaluated., Results: This study revealed an overall isolation rate of 27% of Candida species among all patient groups. The rate was 36% in cases, and 18% in controls, a difference found to be statistically significant (P<0.05). By API, C.albicans was detected in 44% of Candida species in cases, and in 33% in controls. While C.glabrata was detected in 28% of Candida species in cases, and in 22% in controls. C.tropicalis was detected in 17% of Candida species in cases, and in 22% in controls. Both C.krusei and C.kyfr were detected in 5.5% of Candida species in cases, and in 11% in controls. In terms of virulence factors the study showed that 11 out of 27 (40.5%) of Candida isolates were biofilm positive by tube adherence. Phospholipase activity was demonstrated in 12 out of 27 (44.5%) of Candida isolates. Secretory aspartic proteinase activity was demonstrated in 13 out of 27 (48%) of the Candida isolates., Conclusion: Candida is an important cause of UTIs and obstructive uropathy is a major predisposing factor.

Oral cancer awareness among future dental practitioners may have an impact on the early detection and prevention of oral cancer. A cross-sectional survey was undertaken to assess the current knowledge of future Saudi dentists on oral cancer and their opinions on oral cancer prevention. A pretested questionnaire was sent to 550 undergraduate dental students in the fourth, fifth, and sixth year of the Al-Farabi College for Dentistry and Nursing, Riyadh, Saudi Arabia. Questions relating to knowledge of oral cancer, risk factors, and opinions on oral cancer prevention and practices were posed. Four hundred seventy-nine students returned the questionnaire (87.1 %). Eighty-one percent of respondents correctly answered questions relating to oral cancer awareness. Eighty-seven percent of respondents felt confident in performing a systematic oral examination to detect changes consistent with oral malignancy. Interestingly, 57 % of respondents had seen the use of oral cancer diagnostics aids. Thirty-seven percent of respondents felt inadequately trained to provide tobacco and alcohol cessation advice. There is a need to reinforce the undergraduate dental curriculum with regards to oral cancer education; particularly in its prevention and early detection. Incorporating the use of oral cancer diagnostic aids should be made mandatory.

Objective: This study was aimed at characterizing alterations in the immunohistochemical expression of p16 in carcinoma ex-pleomorphic adenomas., Study Design: A selected series of 27 cases of carcinoma ex-pleomorphic adenomas were examined., Results: The results showed that p16 expression in non tumour duct cells was strongly positive nuclear staining in 23 (85%) cases out of 27 cases, that 3 (11.1%) had moderate staining, and that 1 (3.7%) had weak staining. p16 expression in carcinoma ex-pleomorphic adenomas was indicated as a negative nuclear staining in 22 (81.4%) cases out of 27cases, and 5 (18.5%) cases expressed moderate staining., Conclusion: This study suggests that alteration of p16 expression is detected in carcinoma ex-pleomorphic adenomas. p16 has a role in development of carcinoma ex-pleomorphic adenomas.

Oral cancer is the sixth most common malignancy worldwide with more than 263,000 patients diagnosed in 2008. Nonspecialists' negative attitudes and poor working knowledge of oral cancer significantly contribute to suboptimal detection of early-stage disease which leads to delays in diagnosis. We aimed to assess the working knowledge and views associated with oral cancer prevention among medical students in Saudi Arabia. A cross-sectional questionnaire-based survey of 4th, 5th, and 6th year undergraduate medical students was undertaken. Questions included knowledge of oral cancer, risk factors, and opinions on oral cancer prevention. The overall response rate was 82 % (137/167). Mean score of cancer knowledge was 57.8 % which was below the expected standard of 70 %. Only 53 % correctly answered all questions related to oral cancer. This result had no association with either the academic year (p = 0.23) or gender (p = 0.37). Interestingly, 72 % of the respondents did not feel confident in performing an oral examination. Sixty-three percent of the medical students believed it to be beyond their role to aid patients in smoking cessation measures or to take part in other disease preventative strategies. This study demonstrates a dearth of knowledge relating to the diagnosis and management of oral cancer among clinical students within an established Saudi medical school. An immediate refinement of current medical curricula to address these deficiencies is warranted.

Background: The importance of specific animal allergy in immunopathology of asthma and atopic diseases remained to be defined., Methods: We measured total and specific IgE. Western blotting of some allergens was also characterised., Result: There was a significant elevation of IgE in 3 persons among 15 samples collected. Western blotting showed common husbandry allergens from 3 sources that have common allergenicity., Conclusion: Exposure to animal products exacerbates allergic asthma in adults, suggesting that preventive measures should be taken to reduce their sensitivity.

Background: Wheat allergy has been suggested to represent an important allergic disease. This study collates clinical and laboratory aspects in patients with wheat allergy in Al-Kharj city, Saudi Arabia., Methods: Total and specific IgE were measured in 15 suspected cases of wheat allergy. Protein allergenicity was assessed with Western blotting., Results: Significant elevation of total and specific IgE was found in 4 cases. Basophlia was also demonstrated on blood film. Western blotting results showed 2 bands (83 and 40 kDa)., Conclusion: Wheat allergy must also be considered when planning treatment of asthma and eczema of adult patients.

Background: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphia chromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate., Methods: All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively., Results: Of the 12 cases, 9 (75%) were males and 3 (25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presented mainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%) was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7 years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecular response (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells., Conclusion: Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.

Continuous monitoring of specimen acceptability, collection and transport can result in the prompt identification and correction of problems, leading to improved patient care and a reduction in unnecessary redraws and delays in reporting results. This study aims to identify unacceptable blood specimens and to calculate the specimen rejection rate (SRR) before and after the implementation of automated checks of serum indices. This study was conducted between January 2009 and December 2010. The number of rejected specimens, location and reason for rejection were recorded. The Architect c8000 analyser (Abbott, Illinois, USA) was used to assess serum indices based on characteristic spectral patterns and mathematical manipulations of absorbance values measured at several wavelengths. The SRR was calculated, and the target cut-off value for the SRR was < 0.5%, as established by the College of American Pathologists (CAP). The SRR values were 0.13% and 0.21% for the years 2009 and 2010, respectively. Haemolysis was the most significant reason for sample rejection, with cumulative rejection rates (CRR) of 49.3% and 61.4% for 2009 and 2010, respectively. Adult intensive care units (ICUs) had the most sample rejections (23.5%), followed by neonatal ICUs (13.8%), cardiac ICUs (13%), paediatric ICUs (10.8%) and long-term wards (10.5%), of which 60%, 79%, 84.9%, 36.6% and 75%, respectively, of the rejected samples were haemolysed. The increase in rejected samples may be due to an improvement in staff awareness of sample rejection, aided by automatic sample integrity grading by automated chemistry analysis systems.

Rationale: Adoptive T cell therapy depends on the harvesting of the cells from the host, their activation in vitro, and their infusion back to the same host. The way of activating the T cells in vitro is a critical factor for their homing, survival and function in vivo. Sustaining T cell homing molecules, particularly CD62L, is benefic for the trafficking of the adoptive transferred cells., Objective: The aim of the present study is to test whether insulin-like growth factor-1 (IGF-1), thymosin- α1 (T-α1) as well as all-trans retinoid acid (ATRA) alone or in combination with IL-2, IL-12, IL-15 can enhance the activation and survival phenotypes of antigen-activated T cells in vitro., Methods & Results: To this end, OT-1 transgenic T cells were used as a model. These CD8+ T cells recognize OVA peptide presented by MHC class-I. The results showed that antigen stimulation of OT1 cells resulted in their activation as evidenced by the decrease in surface expression of CD62L, analyzed for 3 days after antigen stimulation and was more pronounced on day 5. The addition of IL-12 or IGF-1 alone but not of IL-2, IL-15 augmented OT-1 cell activation measured on day 5. Interestingly, the combination of IL-12 with IGF-1 sustained the expression of CD62L on OT1 cells. Although the addition of ATRA alone or in combination with IL-12 resulted in decreases in CD62L expression on day 3, they showed a dose-dependent effect on the restoration of CD62L expression on day 5. The analysis of the activation-induced cell death (apoptosis) of OT1 cells showed an increased rate of death on day 5 than on day 3-post antigen stimulation. The addition of only IL-12 or IGF-1 alone, but not of IL-2, IL-15 or T- α1, decreased OT1 cell apoptosis on day 3. These anti-apoptotic effects of IL-12 and IGF- 1, however, were recovered on day 5-post stimulation., Discussion: In conclusion, these results indicate that the activation phenotype and the survival of antigen-specific T cells can be differently modulated by immunomodulatory factors, where, interleukin-12 and IGF-1 induced the favorable effect. These results have a significant implication for T cell adoptive immunotherapy in different settings.

Recent preclinical and clinical studies provide evidence that adoptive transfer of in vitro activated T cells can results in significant antitumour responses in vivo upon acquisition of certain survival and homing properties during in vitro activation. Based on recent studies showing in vivo antioxidant effects of thymoquinone (TQ), the active ingredient of Nigella sativa seeds, this study aims to determine whether or not TQ can increase survival and sustain the expression of the homing receptor CD62L in antigen-specific T cells in vitro. The results showed that stimulation of OT-1 (transgenic CD+) T cells with OVA antigen resulted in activation, as shown by a decrease in the surface expression of CD62L which coincided with significant apoptosis measured three and five days after antigen stimulation. Addition of low concentrations of TQ during CD85+ T-cell activation resulted in enhanced survival of the activated T cells and sustained expression of CD62L. These effects coincided with enhancement in the capability of CD8+ T cells to produce the effector cytokine interferon-gamma (IFNgamma). These results suggest that TQ has a beneficial effect in conditioning T cells in vitro for adoptive T-cell therapy against cancer and infectious disease.

Apoptosis stimulating proteins of p53 (ASPP-l and ASPP-2) are a novel family of proteins that have been found to co-stimulate p53 activation of Bax (Bcl-2 associated protein X) inducing caspase-mediated apoptosis. Therefore, these proteins may play an important role in regulating apoptosis in normal and neoplastic cells. However, their cellular and tissue distribution has not been documented. The aim of this study was to determine the localization pattern of ASPP-2 in a variety of normal and malignant human tissues, including liver, lung, prostate, small intestine, kidney, ovary, bladder, cervix, breast, stomach, bowel, gallbladder, endometrium, pancreas, spleen and thyroid.The distribution and expression of ASPP-2 was assessed by immunohistochemistry in a range of formalin-fixed, paraffin embedded, benign and malignant human tissues, using a mouse monoclonal antibody against ASPP-2.The results showed a variable pattern of positivity of ASPP-2 within the tissues studied. ASPP-2 expression was localized in the cytoplasmic paranuclear granules in the epithelial cells of most of the organs we studied. The pattern of staining intensity of ASPP-2 correlated to the maturation state in benign tissue and to the differentiation state in the context of bladder cancer.This study indicates that ASPP-2 has a specific distribution pattern within tissues and cells in a way that appears to be related to differentiation. However, the patterns are neither simplistic nor straightforward and will require further investigation in order to appreciate fully their physiological/pathological significance.

Both stem cell and gene therapy research are currently the focus of intense research in institutions and companies around the world. Both approaches hold great promise by offering radical new and successful ways of treating debilitating and incurable diseases effectively. Gene therapy is an approach to treat, cure, or ultimately prevent disease by changing the pattern of gene expression. It is mostly experimental, but a number of clinical human trials have already been conducted. Gene therapy can be targeted to somatic or germ cells; the most common vectors are viruses. Scientists manipulate the viral genome and thus introduce therapeutic genes to the target organ. Viruses, in this context, can cause adverse events such as toxicity, immune and inflammatory responses, as well as gene control and targeting issues. Alternative modalities being considered are complexes of DNA with lipids and proteins. Stem cells are primitive cells that have the capacity to self renew as well as to differentiate into 1 or more mature cell types. Pluripotent embryonic stem cells derived from the inner cell mass can develop into more than 200 different cells and differentiate into cells of the 3 germ cell layers. Because of their capacity of unlimited expansion and pluripotency, they are useful in regenerative medicine. Tissue or adult stem cells produce cells specific to the tissue in which they are found. They are relatively unspecialized and predetermined to give rise to specific cell types when they differentiate. The current review provides a summary of our current knowledge of stem cells and gene therapy as well as their clinical implications and related therapeutic options.

Background: There is a dire need in the Arab world and Middle Eastern countries to reform the higher education, research policy and planning for improving the quality to meet the needs of modern society. The impact factor (IF) was developed in the 1960s by Eugene Garfield of the Institute for Scientific Information (ISI) in the USA. It has been extensively used for more than 40 years. The SCImago Journal Rank (SJR) indicator belongs to this new family of indicators based on eigenvector centrality was introduced since 2007. The SJR indicator is a size-independent metric aimed at measuring the current 'average prest (se text) per paper' of journals for use in research evaluation processes., Methods: We present the status o the biomedical scientific research in the Middle Eastern countries through the newly developed SJR indicator showing some of the proposed ways that clearly can be applied for enhancing and development of that field in the Middle Eastern countries., Results: During the period from 1996 to 2008, Northern America, Western Europe and Asiatic region are the major contributors of the scientific research Worldwide. In the Middle East, the prominent two main Arab countries are Egypt and Saudi Arabia, nevertheless, they need more planned strategies for optimal contribution to their Middle East, Arab region and the World, despite the tangible achievements of the Arab states in the higher education and scientific research during the last decade., Conclusion: The SJR is seemingly satisfactory for ranking the countries for their scientific contribution and impact.

Objective: Monoclonal gammopathies reflect conditions of plasma B-cell disorders. Our objective was to identify the prevalence and types of these gammopathies in our population., Methods: A 10year retrospective study was conducted. Serum and/or urine protein electrophoresis were performed on 6624 samples. Positive bands were further tested by immunofixation (IFE)., Results: Homogenous bands were detected in 7% of the patients. IFE method confirmed 6.3% in which 59% were males and 41% were females. The mean age was 64.7 for females and 66.5 for males. The sensitivity and specificity were 91% and 99% respectively. The most common protein was IgG kappa 41%, followed by IgG lambda 19%. Sixty-eight percent of these patients had monoclonal gammopathy of undetermined significance and 14.6% had multiple myeloma., Conclusion: The majority of the studied population had MGUS. This observation is in concord with other western populations. The sensitivity and specificity of protein electrophoresis is diagnostically and reasonably acceptable., (2010. Published by Elsevier Inc.)

There is worldwide concern on the spreading pandemic wave of the new swine influenza virus (S-OIV). The WHO has placed the pandemic threat alert to level 6. World leaders and scientists importantly stress that regulations and pandemic preparedness may lower the morbidity and mortality. This review describes the background, origin, epidemiology, signs and symptoms, methods of detecting H1N1, the risk of H1N1 pandemic control plans, immunity to H1N1, vaccination against H1N1, hospital management, patient management, and treatment of symptoms. It also describes in considerable detail the responsibilities of health professionals in navigating the complex areas of laboratory diagnosis, patient isolation procedures, and how to minimize and manage any accompanying staff infections, all of which are vital processes to help mitigate and minimize the seriousness of local and national de-novo outbreaks of emerging H1N1 infection.

Background and Objective: Bcl-2 family members can be functionally divided into anti-apoptotic and proapoptotic groups. The balance between these two groups may determine the fate of tumor cells. In hepatocellular carcinoma (HCC), this balance is often tilted towards the anti-apoptotic members in tumor cells, leading to resistance to cell death and rapid proliferation., Material and Methods: In the current study, we investigated Bcl-2 and proliferating cell nuclear antigen (PCNA) immunohistochemically, using specific monoclonal antibodies in liver tissues obtained from two patient groups. The first group included fifty patients infected with hepatitis C virus (HCV) without hepatocellular carcinoma, the other group included twenty five HCVinfected patients but with confirmed HCC. Serum Bcl-2 was assayed using enzyme immunoassay., Results: Results showed serum Bcl-2 was elevated in 82% versus 100% in HCC-free and HCC patients, respectively. Moreover, cytoplasmic staining of Bcl-2 was found in only 16% of chronic HCV patients without HCC, versus 8% in HCC patients. On the other hand, nuclear staining of PCNA was detected in 100% of HCC patients, but in none of the HCV patients without HCC., Conclusion: The results collectively suggest that in HCV-infected patients with and without HCC, apoptosis is dysregulated and proliferation activity perturbed. There may be prognostic and/or diagnostic potential in estimating Bcl-2 and PCNA proteins in these patient groups., Key Words: Bcl-2 - PCNA - Apoptosis - HCC - HCV.

Caspases are key intracellular molecules in the control of apoptosis, but little is known concerning their relative contribution to the cascade of events leading to eosinophil apoptosis. We examined caspase-3, -8, and -9 activities in receptor ligation dependent apoptosis induction in the cultured eosinophils (CE). CE cultured alone for 48 hours exhibited constitutive apoptosis (12% ± 1.2). Significant (P < 0.05) enhancement of eosinophil apoptosis was observed following monoclonal antibody (Mab) treatment with CD45 (40% ± 0.7), CD95 (36% ± 1.6), or CD69 (34% ± 0.2). Caspase activity was analysed using the novel CaspaTagTM technique and flow cytometry. CE ligated with CD45 (Bra55), CD95 (Fas) and CD69 Mab resulted in caspase-3 and -9 activation after 16 hours post-ligation. This trend in caspase-3 and -9 activation continued to increase significantly through to the 20 and 24 hours time points when compared to isotype control. Activated up-stream caspase-8 was detected 16 and 20 hours after treatment with CD45, CD95 and CD69 Mab followed by a trend toward basal levels at 24 hours. Ligation of CD95 was followed by mitochondrial permeabilization, as demonstrated by marked increase in mitochondrial transmembrane potential ([Formula: see text]) at all time points. However, ligation with CD45 and CD69 failed to induce a change in [Formula: see text] at 16 hours post-treatment compared to isotype control even though there was an alteration in mitochondrial downstream-caspase activity following ligation with these Mab(s) at this time point. At 20 and 24 hours post-ligation, CD45 or CD69 induce significantly altered levels of [Formula: see text]. Thus, the intrinsic and extrinsic caspase pathways are involved in controlling receptor ligation-mediated apoptosis induction in human eosinophils, findings that may aid the development of a more targeted, anti inflammatory therapy for asthma.

Constituents of the Nigella sativa seed are reported to possess potent antioxidant effects. Treatment with anticancer drugs such as cyclophosphamide (CTX) is associated with significant toxicity due to over-production of reactive oxygen species, resulting in increased levels of oxidative stress. The aim of this study is to test whether or not N. sativa L oil (NSO) or its active ingredient, thymoquinone (TQ), can reduce CTX-induced toxicity. Male albino rats were treated with intraperitoneal administration of phosphate buffered saline (PBS) or 200 mg/Kg CTX followed by intragastric administration of NSO or TQ on alternate days for 12 days. Administration of NSO and TQ was initiated 6 h before or after CTX injection. Twenty-four hours after the last NSO and TQ treatment, blood and liver were harvested to analyse toxicity-related parameters. Treatment with CTX induced significant toxicity as shown by decrease in haemoglobin concentration and increases in blood sugar levels, activities of liver enzymes, bilirubin, urea, creatinine, lipids (triglyceride, cholesterol and low-density lipoprotein (LDL)-cholesterol) and lipid peroxidation in the liver. Treatment with NSO or TQ induced significant reduction in overall toxicity. The antitoxic effects of NSO and TQ were associated with induction of antioxidant mechanisms. These results suggest that administration of NSO or TQ can lower CTX-induced toxicity as shown by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimise the toxic effects of treatment with anticancer drugs.

Apoptosis represents a crucial process in modulating organ development in the embryo, in organ homeostasis in the adult, and in fostering appropriate immunological function. Caspases represent two central classes of molecules that are either involved with the stimulation of the apoptotic cascade (initiator caspases), or the various sequential biological pathways required for its execution (effector caspases). With an eye towards therapeutic opportunities, this review discusses in detail the lineage of initiator and effector caspases, how they are each activated, their substrates, their regulation, and maps out how they interact throughout the process from initiation of the first apoptotic signal to the final consequential breakdown of cellular integrity.

Objective: To investigate the performance of hepatitis B virus polymerase chain reaction (HBV PCR) using one of the commercial methods used around the world to screen for HBV in some blood donors where other conventional serological assays have limitations to detect the virus., Methods: This study was designed to use Amplicor AmpliScreen for HBV testing to detect the presence of the HBV DNA in the specimens tested by COBAS AmpliPrep system using a modified manufacture protocol COBAS AmpliPrep of total nucleic acid isolation (TNAI) kit. All serological tests were carried out on the donors' samples to detect the hepatitis B surface antigen (HBsAg), Australian antibody anti-HBs (AUSAB) and hepatitis B core antigen (HBcAg) in the 2 periods of the study. The first period was started in February 2005 and the second period was started in April 2007. Both periods were continued for 2 months after beginning in the molecular pathology laboratory, Al-Hada Armed Forces Hospital, Taif, Kingdom of Saudi Arabia. The 600 donors' data were then studied and analyzed., Results: Five nucleic acid amplification test (NAT-HBV) positives were found out of 600. There were 3 positive for HBcAb and negative for HBsAg, 2 had reading with <100 mIU/mL anti-HBs (AUSAB), and one had >100 mIU/mL AUSAB readings., Conclusion: Our results show that there is a possibility to have occult HBV infection in some donors that cannot be detected by the HBsAg routine serological assays. Moreover, the study can be useful to formulate a new deferral policy based on the implementation of NAT-HBV for blood screening.

Helicobacter pylori (H. pylori) is the etiologic agent of a variety of gastrointestinal disorders. The rationale of the current study is to evaluate six enzyme immunoassays for detection of anti-H. pylori immunoglobulin G (IgG) and IgA in Jordanian patients. Biopsy specimens and blood samples were obtained from patients underwent the endoscopy unit at Al-Bashir hospital in Jordan. The serum samples were investigated for the presence of anti-H. pylori IgG and IgA antibodies in patients with positive H. pylori biopsy samples. The results showed that IgG utilizing kits are more sensitive than of IgA kits and the IgA kits are more specific than of that IgG kits. Moreover, the biopsy is seemingly the gold standard for diagnosis of H. pylori is followed by H. pylori culture on brucella agar medium. An imperfect relation between the presence of H. pylori infection and the antibody response was existed that could be explained either because of the unsatisfactory sensitivities and specificities of the commercial kits used or because of weak immunological response in our patients to H. pylori antigens. Collectively, the H. pylori diagnosis that depends on the detection of anti-H. pylori antibodies in the hospital setting and in the screening programs should consider another test for confirmation the initial diagnosis.

The aim of this descriptive study was to determine the prevalence of Klebsiella pneumoniae from different clinical specimens, their antibiotic susceptibility pattern and the extended-spectrum beta-lactamase (ESBL) production among such isolates at Armed Forces Hospital, Al-Kharaj, Saudi Arabia, from November, 2004 to October, 2007. A total of 328 isolates of K. pneumoniae recovered from 8152 different specimens were studied for ESBL production and antimicrobial susceptibility. The prevalence of K. pneumoniae was 4% (328/8152). We observed a high percentage of K. pneumoniae resistant to ampicillin (100%) and tetracycline (92%). The prevalence of ESBL-producing K. pneumoniae was found to be 10.4% (34/328). The ESBL-producing strains were mostly from aspirates (25%) followed by sputum (20%) and blood (18.2%). These ESBLproducing isolates were highly resistant to gentamicin and ciprofloxacin. All isolates were susceptible to imipenem. Our findings demonstrate a high percentage of ESBL-producers among clinical isolates of K. pneumoniae and a high rate of multidrug resistance. Continued infection control measures and prudent use of antimicrobial agents are essential in reducing the spread of multi-resistant ESBL-producing K. pneumoniae.

Insulin dependent diabetes mellitus (IDDM) results from irreversible loss of beta cells (beta-cells) of the pancreas. A Streptozotocin (STZ)-induced diabetes in animal model mimics, in some aspects, recent onset IDDM. This study was conducted to investigate the effect of nicotinamide on experimentally-induced IDDM. Thirty Spraque Dawley rats were divided into 3 groups; a control group, a diabetic group which received an intraperitoneal (i.p.) injection of 55 mg/kg STZ and a nicotinamide group (1g/kg/day) which were dosed orally for 3 days followed by (i.p.) STZ (55 mg/kg) with the nicotinamide treatment continuing for an additional 14 days. Rats receiving STZ became diabetic after 2 weeks. This diabetic group showed hyperglycemia, and a very low level of C-peptide. Furthermore, pancreatic islets exhibited increased nitric oxide (NO) production together with an increased apoptotic index (as detected by TUNEL and electron microscopy). Nicotinamide treatment prevented STZ-induced diabetes, it also antagonized an increase in NO, and inhibited beta-cell apoptosis. Fasting blood glucose, serum insulin and serum C-peptide were all within the normal range in the nicotinamide group. The nicotinamide protection of beta-cells may be facilitated via inhibition of apoptosis and nitric oxide generation. It is suggested that nicotinamide might be considered an effective agent for the prevention and treatment of IDDM in prediabetic, and early stages, of IDDM.

Self renewal and apoptosis of haemopoietic stem cells (HSC) represent major factors that determine the size of the haemopoietic cell mass. Changes in self renewal above or below the steady state value of 0.5 will result in either bone marrow expansion or aplasia, respectively. Despite the growing body of research that describes the potential role of HSC, there is still very little information on the mechanisms that govern HSC self renewal and apoptosis. Considerable insight into the role of HSC in many diseases has been gained in recent years. In light of their crucial importance, this article reviews recent developments in the understanding of the molecular, biological, and physiological characteristics of haemopoietic stem cells.

Lymphocytes and granulocytes from healthy donors and SLE patients were used to investigate the role of Fas/FasL system in the pathogenesis of systemic lupus erythematosus (SLE). Determination of lymphocyte subpopulations was carried out by flowcytometry. Fas and FasL expression in lymphocytes and granulocytes were measured by immunofluorescence. Apoptotic cells were measured by TUNEL assay. sFas in the plasma was measured by ELISA. Thirty five normal blood donors and 45 SLE patients were selected for this study. This study was carried out between 2005 and 2007. The number of peripheral leukocytes undergoing apoptosis in SLE patients was greater than those of healthy donors. The degree of DNA damage in lymphocytes and granulocytes of SLE patients was much higher than those of healthy donors (P < 0.05 & P < 0.5, respectively). Additionally, a positive relationship was seen between the level of apoptotic lymphocytes'and the dosage of prednisolone used for treatment of SLE (r = 0.6). The level of Fas and FasL expression on different lymphocyte subpopulations increased depending on the activity of the disease (P < 0.5 & P < 0.05, respectively). There was an inverse correlation between the sFas and the stage of disease. Finally, we have demonstrated a relationship between the titre of autoantibodies and the degree of DNA damage in lymphocytes and granulocytes (r = 0.7 & r = 0.6, respectively). In conclusion, Fas and FasL are likely to play an important role in the pathogenesis of SLE. The real value may be used as a predictor for the activity of disease as well.

More than 25 million lives have been claimed by AIDS and 33.2 million people are estimated to have HIV, the majority of which are living in the underdeveloped countries. Failed tests on vaccines, virucides and complete virus eradication have caused scientists to refocus on the basic questions of what makes an effective HIV immune response. The "gloom" over disappointing research results on vaccine development and virucides "threatens to overshadow more positive" HIV/AIDS-related news, such as findings that male circumcision might reduce the likelihood of HIV transmission and that giving antiretroviral drugs to "high-risk" HIV-negative people (pre-exposure prophylaxis) could help protect them from infection. Something like pre-exposure prophylaxis has a good chance of becoming available before we have a 100% efficacious vaccine. The future in the field of HIV/AIDS will be much brighter if global research is appropriately coordinated and sufficient funds are available.

Dendritic cells (DC) are professional antigen presenting cells expressing MHC class II, derived from a common marrow precursor. They are motile, diffused and have a spidery shape with many long cytoplasmic processes. The aim of this project was to test the hypothesis that cellular injury induces the activation and functional maturation of DC. To test the effects of injury on DC activation, immature DCs were used as substrate for DC activation assays. They were obtained from their precursor in peripheral blood mononuclear cells (PBMNCs) by culturing them GM-CSF and IL-4. Expression of surface B7 was measured by immunofluorescence and flowcytometry. beta- chemokines were used as potential injury mediators, including: RANTES, MIP-1alpha, MIP-1beta, MCP-1, -2, -3 and -4, as well as other inflammatory cytokines such as TNF-alpha and IL-1. They were screened on immature DCs to examine whether or not they modulate B7-1 and B7-2. A model of cellular injury was established to investigate whether the injured parenchymal cells deliver signals to initiate DC activation or upregulation of B7-1/B7-2 by release of soluble mediators. H2O2 was used as an injury mediator to injure renal tubular epithelial cells (RTECs). RANTES, MIP-1alpha and MIP-1beta upregulated B7-1. MCP-1, -2, -3 and -4 downregulated the expression of HLA-DR greatly. Furthermore, MCP-1, -2, -3 and -4 upregulated B7.2, while and -4 and MCP2 upregulated B7.1. We observed that immature DCs could not be readily stimulated with chemokines and pro-inflammatory cytokines IL-1 and TNF-alpha unless GM-CSF and IL4 were used continuously. The supernatant of injured renal epithelial cells had an effect on DC activation. These findings may explain the role of DCs as a link between the innate and the adaptive immune response, as well as being an active participant in determining the outcome of an antigen encounter.

Objective: Proliferation, differentiation and apoptosis are essential processes in the normal functions of the mammary epithelium. The hypothesis examined in this study is that BCL-6 is critically important not only for regulating B cell growth and development, but also for influencing mammary epithelial apoptosis., Methodology: Full length BCL-6 cDNA was retrovirally transduced into EpH-4 cell line. We used flow cytometry of BrdUrd-stained cells to investigate the cell cycle duration of control and transduced cells. TUNEL was used as a marker of apoptosis to find out differences in the frequencies of apoptotic cells in control and transduced cells., Results: Restoration of human BCL-6 into EpH4 cells not only inhibits apoptosis, but also prolongs the cell cycle. The results also indicated that the cell cycle time of BCL-6-transduced EpH4 cells was prolonged by about 3 hours. We found differences in the frequencies of viable and apoptotic cells in cultures of the parent EpH4 cells, control transduced EpH4 cells and BCL-6-transduced EpH4 cells., Conclusion: The results suggest that BCL-6 may be involved in mammary growth or mammary gland cell kinetics, but not in mammary gland development.

Apoptosis, or program cell death, is a process of fundamental biological importance, and eosinophil apoptosis is believed to be the primary mechanism for removing eosinophils from the lung followed by their recognition and phagocytosis by macrophages or resident bronchial epithelial cells. There is, therefore, an increased interest in the fundamental role of the signals and intracellular signaling molecules that initiate and control apoptosis in human eosinophils though much remains to be established. This article reviews briefly the cross talks between apoptosis and eosinophils and summarizes the recent developments in this field.

Objective: To develop an assay for the measurement of this anti-human beta2-glycoprotein I (abeta2-GPI) METHODS: This study was conducted from September 2004 to December 2006. The patients attending the Rheumatology Clinic were chosen from several centers in the Eastern region of Saudi Arabia because they had complications. An enzyme-linked immunosorbent ELISA assay was optimized and developed to measure IgG abeta2-GPI antibody levels in humans. Fifty normal blood donors and 50 systemic lupus erythematosis SLE patients were selected for this experiment., Results: Raised IgG abeta2-GPI antibody levels were found in 80% of SLE patients. Interestingly, raised IgG a-beta2-GPI antibody levels were associated with the presence of venous thrombosis and thrombocytopenia., Conclusion: The real value of IgG abeta2-GPI as a predictor for the future clinical complications needs to be confirmed in prospective controlled studies investigating clinical complications in relationship to IgG abeta2-GPI and to other risk factors for thrombosis.

In chronic myeloid leukemia (CML) proliferation is increased and resistance to apoptosis has been proposed as a mechanism accounting for myeloid cell expansion. There is still controversy on whether apoptosis plays an important role in the regulation of myelopoiesis. This study aims to investigate whether apoptosis-related proteins play a role in the evolution of CML and to identify, the relationship between Fas, p53 and apoptosis protease activating factor (Apaf-1) in CML. We found increased p53 and Apaf-1 messenger ribonucleic acid (mRNA) in patients with CML. However, one patient, who had a p53 point mutation, showed a massive elevation of p53 mRNA during blast crisis yet, conversely, a considerable reduction in Apaf-1 mRNA and Fas mRNA. Our results show an in-vivo linkage between Fas, p53 and Apaf-1 transcription regulation. This suggests that key genes involved in apoptosis are also involved in CML disease progression.

Objective: To investigate the performance of the commercial Roche COBAS AmpliScreen assay, and demonstrate whether the COBAS AmpliScreen human immunodeficiency virus-1 (HIV-1) test, v1.5, and COBAS AmpliScreen hepatitis C virus (HCV) v 2.0 for screening for HIV-1 and HCV RNA in the donated blood units from which plasma mini pools were collected, by nucleic acid amplification technology (NAT), could detect the positive pools and reduce the risk of transmission of infections for those routinely tested by serological assays., Methods: The study was performed on 3288 plasma samples collected from blood donors in a period of 13 months, from August 2004 to August 2005, at Al-Hada Armed Forces Hospital, Molecular Pathology Laboratory, Taif, Kingdom of Saudi Arabia. The samples were tested by the reverse transcriptase polymerase chain reaction (RT-PCR) after RNA extraction (this represents the major method in NAT assays), in parallel with the routine serological testing to detect qualitatively for HIV-1 and HCV., Results: The NAT assays that include an automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays, and the routine serological screening assays for the detection of the HIV-1 and HCV RNA in the plasma samples from the blood donors have shown to be a reliable combination that would meet our requirements. The collected data further confirms the results from the serological assays and enables us to decrease the residual risk of transmission to a minimum with the finding of no seronegative window period donation. The results demonstrate that out of 3288 samples, the percentages of RT-PCR (NAT) negative blood donations that were also confirmed as seronegative were 99% for HCV, and 99.1% for HIV-1., Conclusion: The modified combined systems (automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays) for NAT screening assays has allowed the release of all blood donations supplied in the specified period of the study with no seronegative window period donations. This facilitates keeping the residual risk of transmission of HIV-1 and HCV to its minimum through blood transfusion.