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71.
The cardiovascular, uterine stimulant and gastrointestinal effects of prostaglandins E2, F2α and 15 (S) 15 methyl PGE2 methyl ester in the East African Baboon (P. Anubis) have been studied. In these three parameters the baboon responds both qualitatively and quantitatively in a similar manner to man. The lethal doses of the prostaglandins given by bolus intravenous injelctions have been determined and the human lethal doses estimated. 相似文献
72.
S. M. M. Karim D. C. Carter D. Bhana P. Adaikan Ganesan 《BMJ (Clinical research ed.)》1973,1(5846):143-146
The effect of orally administered prostaglandin E2 and its synthetic 15-methyl analogues on gastric secretion in man was studied. The parent E2 compound did not inhibit basal secretion, whereas both the 15 (S) 15-methyl-E2 methyl ester and its isomer, 15 (R) 15-methyl-E2 methyl ester inhibited basal acid secretion. This action is likely to be a direct one on the parietal cell, and it could prove of value in the treatment of peptic ulcer. 相似文献
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E. K. Ganesan 《Journal of phycology》1974,10(4):415-418
Details of structure and reproduction, particularly pre- and postfertilization development, are given for the first time in Pseudogloiophloea halliae. In general, the author's observations agree with what is known for most species of the genus. Some remarks on the identity of 3 species of Pseudogloiophloea in the tropical and subtropical American Atlantic shores are also included. 相似文献
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Venkateswaran Ganesan Goutam Ulgekar Anandhi Ramalingam Souvik Sen Sharma Nirmalya Ganguli Subeer S. Majumdar 《Cell biochemistry and function》2024,42(2):e3982
Bone Morphogenetic Protein 2 (BMP2), a member of the Transforming Growth Factor-β (TGF-β) super family of proteins and is instrumental in the repair of fractures. The synthesis of BMP2 involves extensive post-translational processing and several studies have demonstrated the abysmally low production of rhBMP2 in eukaryotic systems, which may be due to the short half-life of the bioactive protein. Consequently, production costs of rhBMP2 are quite high, limiting its availability to the general populace. Therefore, there is an urgent need to identify better in-vitro systems for large scale production of rhBMP2. In the present study, we have carried out a comparative analysis of rhBMP2 production by the conventionally used Chinese Hamster ovarian cells (CHO) and goat mammary epithelial cells (GMEC), upon transfection with appropriate construct. Udder gland cells are highly secretory, and we reasoned that such cells may serve as a better in-vitro model for large scale production of rhBMP2. Our results indicated that the synthesis and secretion of bioactive rhBMP2 by goat mammary epithelial cells was significantly higher as compared to that by CHO-K1 cells. Our results provide strong evidence that GMECs may serve as a better alternative to other mammalian cells used for therapeutic protein production. 相似文献
78.
Maria Teresa Borrello Benjamin Schinor Katharina Bartels Hanae Benelkebir Sara Pereira Wafa T. Al-Jamal Leon Douglas Patrick J. Duriez Graham Packham Günter Haufe A. Ganesan 《Bioorganic & medicinal chemistry letters》2017,27(10):2099-2101
We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p-substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement. 相似文献
79.
Rajkumar Ganesan Ernest L. Raymond Detlev Mennerich Joseph R. Woska Jr. Gary Caviness Christine Grimaldi 《MABS-AUSTIN》2017,9(7):1143-1154
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP). We report the discovery and characterization of MAB92, a potent, high affinity anti-human IL-36 receptor antagonistic antibody that blocks human IL-36 ligand (α, β and γ)-mediated signaling. In vitro treatment with MAB92 directly inhibits human IL-36R-mediated signaling and inflammatory cytokine production in primary human keratinocytes and dermal fibroblasts. MAB92 shows exquisite species specificity toward human IL-36R and does not cross react to murine IL-36R. To enable in vivo pharmacology studies, we developed a mouse cross-reactive antibody, MAB04, which exhibits overlapping binding and pharmacological activity as MAB92. Epitope mapping indicates that MAB92 and MAB04 bind primarily to domain-2 of the human and mouse IL-36R proteins, respectively. Treatment with MAB04 abrogates imiquimod and IL-36-mediated skin inflammation in the mouse, further supporting an important role for IL-36R signaling in epithelial cell-mediated inflammation. 相似文献
80.
The impact of natural products upon modern drug discovery 总被引:1,自引:0,他引:1
Ganesan A 《Current opinion in chemical biology》2008,12(3):306-317
In the period 1970-2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the 'Lipinski universe' and complies with the Rule of Five. The second is a 'parallel universe' that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of logP and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug. 相似文献