ڈاکٹر نعیم احمد
افسوس ہے کہ گذشتہ ماہ پروفیسر ڈاکٹر نعیم احمد ، صدر شعبۂ اردو علی گڑھ مسلم یونیورسٹی انتقال کرگئے، وہ بڑے خلیق ، ملنسار اور مرنجاں مرنج شخص تھے۔ ابھی وسط نومبر میں انھوں نے اپنے شعبہ میں توسیعی خطبہ دینے کے لیے مجھے مدعو کیا تھا مگر میں نے اپنی مشغولیت کی بنا پر اس وقت معذرت کردی تھی۔ اﷲ تعالیٰ ان کی مغفرت فرمائے۔
(ضیاء الدین اصلاحی، فروری ۱۹۹۶ء)
The study was conducted to examine some of the important questions raised by both the religious scholars and the proponents of the Enlightenment movement. The purpose of the study was to interpret enlightenment in Western and Islamic context and to examine the impact of western enlightenment on contemporary Pakistani society in the light of Islamic teachings. The study was quantitative in nature. Survey was conducted to probe into the perceptions of the Pakistani people regarding impact of western enlightenment on various aspects of contemporary Pakistani society. The sample of the study was 1000 people from four provincial headquarters of Pakistan including male and female from urban and rural areas of the provincial capitals. Two research instruments were developed by the researcher based on review of the related literature. First was a questionnaire named WEBI, Western Enlightenment Beliefs Inventory; second was a checklist named WEKAPC, Western Enlightenment Knowledge, Attitude and Practices Checklist. Results showed that most of the respondents were of the view that western enlightenment exerted significant influences on their thinking, lifestyles, and education, culture, media and social practices. Majority of the respondents thought that western enlightenment emphasized on tolerance, cultural harmony, equality, social justice and independent thinking. Gender-wise comparisons indicated that male respondents were more positive towards western enlightenment than the female respondents. It was recommended that Pakistani society needs to be made aware of the philosophy of western enlightenment and Islamic values which are characteristics of western enlightenment movement. There is need to initiate interfaith dialogue to understand socio-cultural dynamics of a Muslim society and a western society.
Breast cancer is the most common type of cancer—related mortality among women world-wide. Physiological changes of the patients were noted. Comparative study of analytical assay of GzmH was carried out in two different methods using serum samples of normal subjects with breast cancer patients of same age, socio—economic background and environmental conditions. One method is by using the substrate PARP and isocoumarin inhibitor. Other one is electrophoresis. It is found that the electrophoretic technique as compared to using substrate can be used for the detection of granzyme H is simple, accurate, and quick and may give better results than enzyme substrate assay. Identification by electrophoresis shows GzmH having a mass of appearance 32 KDa. 3D structure of GzmH was constructed by Modeller 9.0 in order to find out the different sites of granzyme. It showed highest homology with GzmB. The predicted 3D homology models show a conserved two similar domain structure, i.e., an N—terminal domain and a C—terminal domain comprising predominantly of beta—sheet structure with a little alpha—helical content. The basic mechanism of the role of GzmH like other granzymes especially GzmB, showed that the Gzm having two cationic sites; cs1and cs2. These binding sites participate in the binding of Gzm to cell surface thereby Ipromoting its uptake and release from the cytotoxic lymphocytes to the cell cytoplasm of virus or tumor or cell undergo autolysis. In the cell it causes the cleavage of proteins at its specific site like tyrosine or phenylalanine shows chymotrypsin-like activity. This cleavage stimulate the process of proteolysis which may cause the mitochondrial disruption (caspase independent pathway), it is predicted that cystiene residues present near the catalytic residues Ser202 and Cys49 may help in triggering the cell death in a caspase dependent manner. Besides this pathway GzmH may stimulate the conversion of procaspase to caspase which acts on the nuclear protein like Poly-amino ribose polymerase and causes DNA fragmentation that leads to cell death (caspase dependent pathway). However, significant differences between GzmH and GzmB in the X- ray structure and the protein model lie at the important functional sites. In the crystal structure of GzmB the catalytic triad is His57, Ser195 and Asp102, while in GzmH the catalytic triad is His64, Ser202 and Asp108. An ideal peptide present as cs1 site of GzmH. The peptide may promote the conversion of pro-caspase to caspase which successively cause cell death. A segment of Gly214 to Asn220 is present near the catalytic triad of GzmH. This segment may provide a template for substrate binding bulges out of the active site. On the other hand, a hydrophobic patch of Trp238, Ileu239, Lys240 and Arg241 present in the helical form that provides a site for enzyme substrate interaction. IIEnzyme inhibitor study showed that the inhibitor CMK (MAI-Pro-DPN) act as competitive inhibitor for GzmH which totally inhibit the enzyme activity by forming number of H-bonds with catalytic triad. The enzyme inhibitor study may be useful to probe and discuss the disease state with which they are associated. Present study tried to mutate amino acids of granzyme H but only few showed significant effect of mutation e.g., mutation of Lys222→Ala222 & Pro225®Arg225 causes to change their distance with the cs2 which may affect on the stability of cs2. The mutation of Lys222 to Ala markedly decreased the surface accessibility. It is stated that this mutation in turn may affect the uptake of GzmH into target cells; cytoplasmic distribution with reduced accumulation in target cell; and slightly impaired cytotoxicity of GzmH. Arg55 forms number of H—bonds with other amino acids and thereby showed apoptotic promoting activity, present near the peptide of cationic site cs1. It is observed that the mutation of Arg55®Gly55 causes the loss of H- bonds between mutated Gly to Asp57. It is therefore possible that mutation of Arg may affect the cytotoxic activity of GzmH. Mutational effect of Arg116 to Glu also observed. Present study observed that mutation of Arg116 to Glu may lose its H—bonds and salt bridges with Glu115. This shows that the mutation of both Arg55 and Arg116 affects the cytotoxic activity of GzmH. Asp210 is near to the cs2 binding site of GzmH. This mutation from Asp210—Gly210 may affect the H—bonding pattern of cs2 which may reduce IIIbinding to heparin; slightly reduced uptake into target cells; cytoplasmic distribution with reduced accumulation in cell; and in turn may impaired cytotoxicity. It is therefore concluded that GzmH due to its important functional effects may have diagnostic importance and it may be used as a tumor marker in breast cancer.