Abdul Hameed

Background Multiple myeloma is a plasma cell disorder characterised by bone marrow infiltration with clonal plasma cells that secrete monoclonal immunoglobulin which is detected in serum or urine samples. Bone disease is a well-known devastating complication. It has a significant impact to the quality of life and morbidity in multiple myeloma. The uncoupling effect of osteoblast and osteoclast activity is the major element in development of myeloma bone disease (MBD). Imaging techniques are used as the current standard method for detection of bony lesions. They have limitations as they cannot provide a real-time assessment of bone turnover. Early detection of relapse disease is crucial to allow preventative therapeutic intervention as it could significantly impact on quality of life. Aims Bone biomarkers such as C-terminal telopeptide of type 1 collagen (CTX-1) and procollagen type 1 N-propeptide (P1NP) can be used as an early predictor marker for MBD relapses and a monitor for MBD at different stages of the disease. Methods CTX-1 and P1NP were measured by chemiluminescent immunoassay on fasting plasma samples from 111 patients including newly diagnosed multiple myeloma (n=28), remission (n=34), relapses (n=22) and control (n=27). These were measured at regular intervals over a 30 month study period. Relapse disease was identified by conventional biomarkers like paraprotein and serum free light chains, and confirmed by imaging and bone marrow biopsy. In a subset of patients with disease relapse, the Mann-Whitney test was used to compare bone markers pre-relapse and at relapse. Results CTX-1 levels were significantly higher in newly diagnosed multiple myeloma compared to remission and control groups (p < 0.0001). In relapse group, CTX-1 rose significantly at the time of pre-relapse to relapse state (p=0.0001). A rise of ≥ 2.0 fold rise in the level of CTX-1 from remission to relapse disease was noted. The median time between the pre-relapse sample and relapse disease was 3 months (range 1-14 months). Most of them had new bone lesions at relapse. This proves that it has potential as an early predictor of relapse or progressive bone disease. A case showed CTX-1 level was the only biochemical parameter to rise significantly prior to relapse as compared to the other conventional biomarkers (ie. paraprotein and serum free light chain). As for P1NP, the rise in P1NP from pre-relapse to relapse was not significant (p=0.0810). Conclusion Osteoclast biomarker serum CTX-1 correlates accurately with the disease burden in newly diagnosed multiple myeloma patients as compared to the rest of the groups. It is a more sensitive early predictor of relapse/progressive disease than established biomarkers. It is a more robust marker than P1NP. The rise in P1NP goes against the theory that there is an uncoupling of bone turnover in MBD and requires further study. CTX-1 is more cost effective and accessible than imaging and should be used routinely when monitoring bone disease activity in multiple myeloma patients, facilitating early intervention when relapse occurs. Disclosures: No relevant conflicts of interest to declare.

To map the disease locus of a two-generation, consanguineous Pakistani family with autosomal recessive cone-rod dystrophy (arCRD). All affected individuals had night blindness, deterioration of central vision, photophobia, epiphora in bright light, and problems with color distinction. Fundoscopy revealed marked macular degeneration and attenuation of retinal vessels. Mild pigmentary changes were present in the periphery. Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Alleles were assigned to individuals that allowed calculation of LOD scores using the Cyrillic (Cherwell Scientific, Oxford, UK) and MLINK (accessed from ftp://linkage. rockefeller.edu/softeware/linkage/) software programs. The cellular retinoic acid-binding protein 2 (CRABP2), cone transducin alpha-subunit (GNAT2), potassium inwardly rectifying channel, subfamily J, member 10 (KCNJ10), genes were analyzed by heteroduplex analysis and direct sequencing for mutations. A new locus for arCRD (CORD8) has been mapped to chromosome 1q12-q24. A maximum two-point LOD score of 4.22 was obtained with marker D1S2635 at recombination fraction of theta = 0.00. Two critical recombinations in the pedigree positioned this locus to a region flanked by markers D1S457 and D1S2681. A region of homozygosity was observed within the loci D1S442 and D1S2681, giving a probable critical disease interval of 21 cM. Mutation screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations. The findings therefore suggest that this phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 1q12-q24 chromosomal region.

A facile method for the modulation of 2-alkoxy side chain of 3-formylchromone enamines has been exploited for the synthesis of a series of 2-alkoxy-3-(sulfonylarylaminomethylene)-chroman-4-ones. This modulation was achieved by simply changing the alcoholic reaction media from methanol to ethanol, iso-propanol and n-butanol while reacting various 3-formylchromones with aminobenzenesulfonamides. Alcohols are sufficiently nucleophilic and add into the C2-C3 olefinic bond of 3-formylchromones without causing any ring cleavage. The resulting 2-alkoxy-3-(sulfonylarylaminomethylene)-chroman-4-ones were found to be potent and selective inhibitors of ecto-5'-nucleotidase and alkaline phosphatases (TNAP and IAP). Detailed enzyme kinetics studies revealed competitive inhibition against alkaline phosphatases and un-competitive inhibition against rat and human ecto-5'-nucleotidase. The most active TNAP inhibitor 23 (Ki = 0.078 ± 0.001 μM), exhibited 28 times more selectivity for TNAP over IAP (Ki = 2.18 ± 0.12 μM). Compound 9 was most active IAP inhibitor (Ki = 0.24 ± 0.01 μM), and was 300 times more selective towards IAP than TNAP (Ki = 72.9 ± 1.68 μM). Compound 40 was most active human ecto-5'-nucleotidase inhibitor exhibiting inhibition in low nanomolar range (Ki = 14 nM).

1. Hum Genet. 2005 May;116(6):542. Gene symbol: AIPL1. Disease: LCA4. Khaliq S, Abid A, Hameed A, Anwar K, Mohyuddin A, Ismail M, Mehdi SQ. Dr. AQ Khan Research Laboratories, Biomedical and Genetic Engineering Division, Islamabad, Pakistan. skhaliq@comsats.net. ...

To find genetic association of sperm mitochondrial deoxyribonucleic acid cytochrome c oxidase III subunit 15bp deletion with male infertility in Pakistan. The case-control study was conducted from July 2011 to December 2013, and comprised semen samples that were divided into two main groups; the control group had normozoospermic patients while the other group had infertile subjects. The Infertile group was sub-divided into four groups on the basis of semen analysis. Deoxyribonucleic acid was extracted using modified organic extraction method, amplified by polymerase chain reaction with cytochrome c oxidase III-specific primers. The fragments were separated by agarose gel electrophoresis; 135bp wild fragment and 120bp deleted one. Data was analysed using SPSS 22. Of the 194 samples, 44(22.6%) were controls, and 150(77.3%) were infertile. The infertile group sub-division was oligozoospermic 20(13.3%), asthenozoospermic 36(24%), oligoasthenoteratozoospermic 88(58.6%) and necrozoospermi...

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 μg/l), and lowest in the remission grou...

The major problem encountered by the islanders in the Lakshadweep group of Islands, India, is the limited availability of fresh water for drinking and cooking purposes. Groundwater is the only source of fresh water. The demand for groundwater is increasing every year due to growing population and urbanization. A proper understanding of the groundwater condition is important in order to meet this increasing demand and to formulate future development and management strategies. It is in this context, principal hydrogeological units, water table fluctuation pattern, general groundwater potential, existing groundwater withdrawal structures and draft, water quality, etc., have been studied in the Minicoy Island of Union Territory of Lakshadweep, India, through field investigations and secondary data collection. To improve the availability of fresh water to meet the increasing drinking water demand various management strategies such as, roof-top rain water harvesting, artificial recharge of groundwater through already existing wells and ponds, public participation in water conservation and wise-use of groundwater, etc, have been attempted. The experience and success of these experimentations are briefly presented in this paper.

Background: Type IV PHA synthase is a key enzyme responsible for catalyzing the formation of non-toxic, biocompatible, and biodegradable short-chain-length polyhydroxyalkanoates (scl-PHA) under the growth-limiting conditions in the members of the genus Bacillus. Results: The comparative in vitro and in silico analysis of the phaC subunit of type IV PHA synthases among Bacillus cereus FA11, B. cereus FC11, and B. cereus FS1 was done in our study to determine its structural and functional properties. Conserved domain analysis demonstrated that phaC subunit belongs to the alpha/beta (α/β) hydrolase fold. The catalytic triad comprising of cysteine (Cys), histidine (His), and aspartate (Asp) was found to be present at the active site. A shorter inter-atomic distance was found between the carboxyl (-COO) group of Asp and amino (NH2) group of His. Furthermore, slightly long inter-atomic distances between sulfhydryl (SH) group of Cys and NH2 group of His may be pointing toward the broader substrate specificity of type IV PHA synthases. However, a shorter distance between the SH group of Cys and NH2 group of His in case of B. cereus FC11 leads to a higher enzymatic activity and maximum PHA yield (49.26%). Conclusion: The in silico study verifies that the close proximity between SH group of Cys and NH2 group of His in phaC subunit of type IV PHA synthases can be crucial for synthesis of scl-PHA. However, the catalytic activity of type IV PHA synthases declines as the distance between the sulfur (S) atom of the SH group of Cys and the nitrogen (N) atom of NH2 group of His increases.

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objecctive of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9μM compared to that of the standard drug, prednisolone <1.5μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between…

... 142 Extracellular Alkaline Protease by a Newly Isolated Halophilic Bacillus sp Shama Sehar and Abdul Hameed Microbiology Research Laboratory, Department of Microbiology, Quaid-i-Azam University, Islamabad 45320, Pakistan ... Acta, A. Sellami-Kamoun and M. Nasri, 2009. ...

... 1993. Focus on bacterial blight of rice. Plant Disease, 77: 5-12. Mew, TW and A. Majid. 1977. Bacterial Blight of rice in Pakistan. ... Deptt. Plant pathology Univ. of Georgia. pp. 28. Swings, J.,M. Van den Mooter, L. Vauterin, B. Hoste, M. Gillis, TW Mew and K. Kersters. 1990. ...

To compare the clinical response to amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children and to see the cost effectiveness of each treatment. Randomized clinical control trial. Department of Pediatrics, Khyber teaching hospital, Peshawar, from October 2001 to February 2002. Patients between 3 to 72 months of age, admitted in the hospital with community acquired pneumonia, were randomly divided into three groups,1,2,3. They were started on amoxicillin, cefuroxime and clarithromycin respectively. The patients were assessed daily. If there was no clinical improvement at 48 hours the antibiotic was changed. ANOVA statistical test was applied to see the clinical response to the treatment in the three groups. Cost effectiveness of the treatment was compared. There was no statistical difference in the clinical response at 48 hours of initiating treatment and at discharge (p > 0.01 each). The mean hospital stay in group 1 and 2 was 3.3 d...

Polyhydroxyalkanoates (PHAs) are non-toxic, biocompatible, piezoelectric, and biodegradable thermoplastic. This study was designed to isolate the bacterial strains from trinitrotoluene (TNT)-contaminated soil capable of giving PHAs at high yields with tailor-made compositions. The isolated bacterial strain B. cereus FC11 gave PHA yield at 76.40 wt% using 500 mL Erlenmeyer flasks each containing 200 mL synthetic medium in the presence of glucose as a sole carbon source at pH value 7.0, 30 degrees C and 150 rpm after 48 h of incubation under submerged fermentation. Furthermore, tailor-made PHA compositions were synthesized by B. cereus FC11 by adding different co-substrates along with glucose in the medium. High performance liquid chromatography analysis revealed that the retention time of crotonic acid (by-product) obtained from digested PHA was approximately 24.97 min which was similar to the retention time of crotonic acid (by-product) obtained from the digestion of commercially av...

Problem Statement: CC Chemokine receptor type 5 (CCR5) is a cell surface protein which is a receptor for CC Chemokines. It has high effinity for chemically stimulated cytokines. Moreover, it also stimulates immune response and recruits immune cells to the site. Open reading frame of CCR5 gene contains a deletion of 32 bp (CCR5Δ32), leading to the synthesis of malformed receptor and consequently its weakened function. It has been implicated that CCR5Δ32 is associated with the development and dissemination of cancer. The aim of this study is to observe CCR5Δ32 mutation and detect its pivotal role in breast cancer metastasis. Methods: Total 500 blood samples were taken from breast cancer patients. The samples were compared with age and sex matched controls. Mutations of CCR5Δ32 were examined by polymerase chain reaction (PCR) and direct DNA sequencing. Data was analyzed by online available statistical and bioinformatics tools. Results: The two types of allelic mutations found in CCR5 g...

University of Sheffield, Sheffield, United Kingdom, University of Sheffield, sheffield, United Kingdom, University of Sheffield, Medical 1 ... School / LU123, L Floor, Sheffield, United Kingdom ... Corresponding author's email: a.hameed@sheffield.ac.uk ... Despite an improvement ...

Production of antimicrobial compounds seems to be a general phenomenon for most bacteria. The prevalence of antimicrobial resistance among key microbial pathogens is increasing at an alarming rate worldwide. Current solutions involve development of a more rationale approach to antibiotic use and discover of new antimicrobials. Bacillus species produce a large number of biological compounds active against bacteria, fungi, protozoa and viruses. The process of production usually involves screening of wide range of microorganisms, testing and modification. Production is carried out using fermentation. Thermophilic spore-forming, gram positive, motile rod bacterial strains were isolated from the Thar Desserts, Sindh Province, Pakistan. These strains were screened and checked for antibacterial activity. The best activity was observed by SAT4 against Micrococcus luteus, Staphylococcus aureus and Pseudomonas aeroginosa. The activity was only observed against gram positive bacteria and no activity was seen against Pseudomonas aeroginosa. Thermophilic Bacillus specie SAT4 was found to be active in the fermentation process to produce the antimicrobial agents. Further optimizations of different conditions (time of incubation, media, pH, glucose concentrations, nitrogen concentrations, and temperature) for antimicrobial production by the selected bacterial strain was performed. Agar diffusion assay was performed to evaluate the antibacterial activity. Optimum conditions for the production of antimicrobials by selected isolate were observed to be 48 hour, pH 5, temperature 55 degrees C, 2% glucose and 1.5% nitrogen concentration. This newly isolated bacterial strain has great potential for antimicrobial production at industrial scale.

An efficient resource allocation is a fundamental requirement in high performance computing (HPC) systems. Many projects are dedicated to large-scale distributed computing systems that have designed and developed resource allocation mechanisms with a variety of architectures and services. In our study, through analysis, a comprehensive survey for describing resource allocation in various HPCs is reported. The aim of the work is to aggregate under a joint framework, the existing solutions for HPC to provide a thorough analysis and characteristics of the resource management and allocation strategies. Resource allocation mechanisms and strategies play a vital role towards the performance improvement of all the HPCs classifications. Therefore, a comprehensive discussion of widely used resource allocation strategies deployed in HPC environment is required, which is one of the motivations of this survey. Moreover, we have classified the HPC systems into three broad categories, namely: (a)...