14 results on '"M. Shareef"'
Search Results
2. IDF2022-0513 Presentation and outcomes of diabetic heel ulcers; a single-center study from a resource constrained country, Pakistan
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R. Nawaz, M. Riaz, Z. Miyan, A.B. Zafar, M.S. Ulhaque, M. Shareef, M.Y. Ahmednai, and A. Basit
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine - Published
- 2023
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3. Fission fragment mass distribution studies inSi30+Hf180reaction
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G. Mohanto, C. Yadav, S. Nath, R. G. Thomas, Akhil Jhingan, B. R. S. Babu, K. M. Varier, A. Shamlath, P. Sugathan, S. Appannababu, M. Shareef, Ish Mukul, Avazbek Nasirov, A. M. Vinodkumar, S. Kailas, Devendra Singh, and E.V. Prasad
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Physics ,Nuclear and High Energy Physics ,Range (particle radiation) ,Mass distribution ,010308 nuclear & particles physics ,Fragment (computer graphics) ,Fission ,Mass ratio ,01 natural sciences ,medicine.anatomical_structure ,Saddle point ,0103 physical sciences ,medicine ,Atomic physics ,Nuclear Experiment ,010306 general physics ,Nucleus ,Bond cleavage - Abstract
Fission fragment mass–angle and mass ratio distributions have been measured for the 30Si + 180Hf reaction in the beam energy range 128–148 MeV. Quasifission signature is observed in this reaction, forming the compound system 210Rn. The results are compared with a very asymmetric reaction 16O + 194Pt, forming the same compound nucleus. Calculations assuming saddle point, scission point and DNS models have been performed to interpret the experimental results. The results strongly suggest the entrance channel dependence of quasifission in heavy ion collisions.
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- 2016
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4. Multiple sulfur sources for the volcanic hosted massive sulfides in Betul Belt, Central India: Evidence from the sulfide ore chemistry and sulfur isotope geochemistry
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Venkata Sri Surya Apla Naidu Badireddi, Sushanta Kumar Saha, Smitha Ramachandran Sarala Bai, M. Shareef, Manish M. John, Parwez Akhter, M. L. Dora, Mohammad Atif Raza, Shraddha Kumari, Tushar Meshram, Subhra Suchi Sarkar, Lalit Mohan Singh Maura, Srinivasa Rao Baswani, Hemraj Suryavanshi, Biswabara Panda, and Raghuram
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Mineralization (geology) ,Chemistry ,Chalcopyrite ,Volcanogenic massive sulfide ore deposit ,Geochemistry ,engineering.material ,010502 geochemistry & geophysics ,01 natural sciences ,Geophysics ,Sphalerite ,Ore genesis ,δ34S ,Geochemistry and Petrology ,Galena ,Isotope geochemistry ,visual_art ,engineering ,visual_art.visual_art_medium ,0105 earth and related environmental sciences - Abstract
This work provides an overview of the geological, petrological, and geochemical data available on the three volcanic-hosted massive sulfides (VHMS) deposits (Ghisi, Biskhan, and Jangaldehri) in Betul Belt, Central Indian Tectonic Zone. Sulfur isotope geochemistry was used for the first time from the Betul Belt to constrain the source of sulfur for a better understanding of the ore genesis process. Mineralization is hosted in a felsic dominant bimodal volcano-sedimentary sequence associated with syn-genetic hydrothermal alteration, i.e., intense Mg–Ca alteration (actinolite-tremolite-anthophyllite) and Al–Fe alteration zone (gahnite-garnet-biotite-staurolite) followed by regional metamorphism. Field observations, drill core logging, and petrography studies reveal different modes of mineralization, i.e., dissemination, stringers, and semi-massive sulfides vein, comprises of chalcopyrite, sphalerite, pyrite, galena with lesser pyrrhotite, are paragenetically distinct in three deposits. The petrography, SEM-EPMA studies show the presence of chalcopyrite disease in Fe-rich sphalerite at Biskhan and Jangaldehri in the east and absence of the same texture at Ghisi in the west. This difference reveals the variable physio-chemical nature of the hydrothermal fluid and partial melting of sulfides during subsequent metamorphism. Cu–Fe mineralization was deposited from high-temperature hydrothermal fluids with less sulfur activity at Biskhan-Jangaldehri. Later Zn–Cu–Pb mineralization was formed from lower temperature hydrothermal fluids with higher sulfur activity. The δ34S values of sulfides (sphalerite, chalcopyrite, and pyrite) from three deposits show a wide range of sulfur values (δ34S) from −12.87 to + 19.31‰ (n = 27), consistent with heterogeneous sourcing of S, probably combining magmatic source along with the reduction of seawater sulfate. Variation in the sulfur isotopic compositions of sulfide was the result of dilution and cooling of the metalliferous fluid at different stages after interaction with meteoric, seawater and hydrothermal fluids, which caused the deposition of base metal sulfides. Sulfides from Ghisi in the west display both +ve and −ve values (−12.88 to + 0.38‰; n = 10), suggest sulfur predominantly derived by thermochemical reduction of seawater sulfate with minor input of magmatic sulfur reduction lead to polymetallic Zn–Cu–Pb mineralization. The gradual increasing in the δ34S values (more + ve values +18.65 to +19.31‰; n = 8) from west to east at Biskhan and Jangaldehri (+ 5.01 to + 8.3‰, n = 9) may be due to involvement of both the leaching of igneous basement rocks and chemical process of seawater sulfates by thermochemical reduction (TSR) from deep water levels lead to Zn–Cu mineralization. This δ 34S variation occurs in three deposits of the Betul Belt due to modifications of the primary mineralization during subsequent stages of ore formation and metamorphism, indicating a complex fluid evolution history for VHMS deposits in Betul Belt, Central India, where S derived from a heterogeneous source by multiple geological processes. This situation is more akin to many established VHMS deposits of ancient and modern submarine hydrothermal systems.
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- 2020
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5. Trace element geochemistry of magnetite and pyrite and sulfur isotope geochemistry of pyrite and barite from the Thanewasna Cu-(Au) deposit, western Bastar Craton, central India: Implication for ore genesis
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Sameer Ranjan, Srinivasa Rao Baswani, Dewashish Upadhyay, M. L. Dora, M. Shareef, and Kirtikumar Randive
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Chalcopyrite ,020209 energy ,Geochemistry ,Geology ,Skarn ,02 engineering and technology ,engineering.material ,010502 geochemistry & geophysics ,Iron oxide copper gold ore deposits ,01 natural sciences ,Porphyry copper deposit ,Ore genesis ,Geochemistry and Petrology ,visual_art ,0202 electrical engineering, electronic engineering, information engineering ,engineering ,visual_art.visual_art_medium ,Economic Geology ,Argillic alteration ,Pyrite ,Ilmenite ,0105 earth and related environmental sciences - Abstract
The Thanewasna copper belt in Bastar Craton of central India is well-known for Cu ± Au mineralization. In this study, we use major and trace element chemistry of magnetite, hematite, and pyrite, as well as the sulfur isotope composition of chalcopyrite, pyrite and barite from the deposit to characterize the mineralization and to constrain its petrogenesis. The mineralization is hosted in quartz-chlorite veins associated with 2.5 Ga and 1.6 Ga granitoids. The mineralization is focused along the NW-SE trending Thanewasna brittle-ductile shear zone and comprises disseminated and vein-hosted Cu-sulfides, mainly chalcopyrite and pyrite intergrown with minor magnetite, hematite, and sulfide-free barite. The associated hydrothermal alteration is characterized by pervasive potassic-sodic alteration and chloritization. Calcite and sulfide-bearing barite veins postdate the Fe-oxide and Cu-sulfide ores. At least two generations of magnetite, hematite, and pyrite were identified based on their textural and trace element characteristics. Texturally early magnetite (Mag-I) displays oxy-exsolution of ilmenite and is of magmatic origin, representing the pre-mineralization igneous assemblage of the host rocks. Texturally later magnetite (Mag-II) is of hydrothermal origin and replaces Mag-I. It has high Co and Mg concentrations and shows dissolution and re-precipitation texture as well as evidence for high-temperature annealing. Martitisation of Mag-I and II associated with chloritization and Cu-Au mineralization produced hematite. The δ34SVCDT of syn-mineralization pyrite and chalcopyrite (−0.77‰ to −4.28‰) is suggestive of magmatic sources for the sulfur. Post-mineralization barite veins have δ34SVCDT between +10.31‰ and +17.55‰ which indicate that the sulfur was derived from seawater sulfate without going through an intermediate stage of reduction. Variation in the sulfur isotopic compositions of sulfide and sulfate was the result of dilution and cooling of the metalliferous fluid after interaction with meteoric fluids, which triggered the deposition of Cu ± Au along structural weak planes. The widespread presence of iron-rich breccias, association with crustal-scale shear zone, pervasive K-Na alteration, chloritic and advanced argillic alteration, the involvement of magmatic and non-magmatic fluid and Cu-Fe-Au-Ag-Ba-REE metal association are all suggestive of IOCG-style mineralization at Thanewasna. This supported by the Ti, Al + Mn, Ti + V concentrations and Ti/V, Ni/Cr, Ni/(Cr + Mn) ratios of Mag-II and hematite. The Co/Ni ratios of pyrite further supports a hydrothermal origin of the deposit, unrelated to skarns or copper porphyry, having similarity with known IOCG deposits. The identification of IOCG-type deposits in the Thanewasna region gives a boost to deeper sub-surface exploration in this belt as well as in similar geological setting elsewhere.
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- 2020
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6. Defect induced enhancement of exchange bias by swift heavy ion irradiation in zinc ferrite–FeNiMoB alloy based bilayer films
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P. Geetha, A. Shamlath, P.B. Aravind, Raju V. Ramanujan, Sunil Ojha, R. Lisha, T. Hysen, M. R. Anantharaman, and M. Shareef
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Nuclear and High Energy Physics ,Materials science ,Condensed matter physics ,Physics::Instrumentation and Detectors ,Bilayer ,Physics::Medical Physics ,Coercivity ,Condensed Matter::Materials Science ,Zinc ferrite ,Swift heavy ion ,Exchange bias ,Nuclear magnetic resonance ,Sputtering ,Irradiation ,Thin film ,Instrumentation - Abstract
Exchange biased systems consisting of ferromagnetic (FM)–antiferromagnetic (AFM) interfaces are increasingly being investigated because of their application potential in spin valves and tunnel junctions. In bilayer systems, ion irradiation is capable of modifying the interface and thereby offers unique opportunities to tailor exchange field. In the present study, irradiation with 100 MeV Ag 8+ ions is utilized to alter the exchange bias field in zinc ferrite–FeNiMoB bilayer system. The thin films which were deposited by RF sputtering technique and annealed at 600 °C were irradiated at various fluences. Structural and magnetic studies were carried out by using Glancing X Ray Diffractometer (GXRD) and Superconducting Quantum Interference Device Vibrating Sample Magnetometer (SQUID VSM) respectively. It was observed that the as deposited films exhibited exchange bias and on ion irradiation, bias field could be enhanced at certain fluences. The enhancement in bias field is attributed to defects created in the antiferromagnet as a result of ion irradiation. The experimental result is fitted in accordance with the diluted antiferromagnet model. Coercivity was also found to vary with ion fluence. Ion fluence was thus effectively used to enhance bias field as well as coercivity in the bilayer consisting of zinc ferrite–FeNiMoB.
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- 2015
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7. Grey water characteristics and treatment options for rural areas in Jordan
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W. Suleiman, M. Shareef, Marwa M. Sayed, M. Mansour, M. Safi, S. Dalahmeh, and Maha Halalsheh
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Crops, Agricultural ,Engineering ,Environmental Engineering ,media_common.quotation_subject ,Sand filter ,Bioengineering ,Wetland ,Septic tank ,Rural Health ,Reuse ,Water Supply ,Hybrid reactor ,Waste Management and Disposal ,Effluent ,media_common ,geography ,Jordan ,geography.geographical_feature_category ,Waste management ,Renewable Energy, Sustainability and the Environment ,business.industry ,Environmental engineering ,General Medicine ,Reclaimed water ,Oxygen ,Volume (thermodynamics) ,Wetlands ,business - Abstract
Low water consumption in rural areas in Jordan had resulted in the production of concentrated grey water. Average COD, BOD and TSS values were 2568 mg/l, 1056 mg/l and 845 mg/l, respectively. The average grey water generation was measured to be 14 L/c.d. Three different treatment options were selected based on certain criterions, and discussed in this article. The examined treatment systems are septic tank followed by intermittent sand filter; septic tank followed by wetlands; and UASB-hybrid reactor. Advantages and disadvantages of each system are presented. It was concluded that UASB-hybrid reactor would be the most suitable treatment option in terms of compactness and simplicity in operation. The volume of UASB-hybrid reactor was calculated to be 0.268 m 3 with a surface area of 0.138 m 2 for each house having 10 inhabitants on average. Produced effluent is expected to meet Jordanian standards set for reclaimed water reuse in irrigating fruit trees.
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- 2008
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8. Inhibition of Transforming Growth Factor-β Signaling in Normal Lung Epithelial Cells Confers Resistance to Ionizing Radiation
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Marianna Zagurovskaya, Mohammed M. Shareef, Mohammed Mohiuddin, Anna E. Reeves, Seema Gupta, and Mansoor M. Ahmed
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Cancer Research ,Reporter gene ,Radiation ,TUNEL assay ,biology ,business.industry ,Transforming growth factor beta ,Molecular biology ,Oncology ,Terminal deoxynucleotidyl transferase ,Cell culture ,Immunology ,biology.protein ,Medicine ,Radiology, Nuclear Medicine and imaging ,Signal transduction ,Clonogenic assay ,business ,Transforming growth factor - Abstract
Purpose: To address the functional role of radiation-induced transforming growth factor-β (TGF-β) signaling in a normal epithelial background, we selected a spontaneously immortalized lung epithelial cell line derived from the normal lung tissue of a dominant-negative mutant of the TGF-β RII (ΔRII) transgenic mouse that conditionally expressed ΔRII under the control of the metallothionein promoter (MT-1), and assessed this cell line’s response to radiation. Methods and Materials: A spontaneously immortalized lung epithelial cell culture (SILECC) was established and all analyses were performed within 50 passages. Colony-forming and terminal transferase dUPT nick end labeling (TUNEL) assays were used to assess clonogenic inhibition and apoptosis, respectively. Western-blot analysis was performed to assess the kinetics of p21, bax, and RII proteins. Transforming growth factor-β-responsive promoter activity was measured using dual-luciferase reporter assay. Results: Exposure to ZnSO 4 inhibited TGF-β signaling induced either by recombinant TGF-β1 or ionizing radiation. The SILECC, treated with either ZnSO 4 or neutralizing antibody against TGF-β, showed a significant increase in radio-resistance compared to untreated cells. Furthermore, the expression of ΔRII inhibited the radiation-induced up-regulation of the TGF-β effector gene p21 waf1/cip1 . Conclusions: Our findings imply that inhibition of radiation-induced TGF-β signaling via abrogation of the RII function enhances the radio-resistance of normal lung epithelial cells, and this can be directly attributed to the loss of TGF-β signaling function.
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- 2007
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9. Nuclear localization of Munc18-1 (p67) in the adult rat brain and PC12 cells
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Rita Christopher, Taranath K. Shetty, Y. Ramamohan, Pavankumar A. Shetty, Momin M. Shareef, Savitha Kalidas, Vandana M. Sharma, Harish C. Pant, and Kiran Bhaskar
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Male ,Cytoplasm ,Vesicle docking ,Immunoelectron microscopy ,Nuclear Localization Signals ,Active Transport, Cell Nucleus ,Vesicular Transport Proteins ,Fluorescent Antibody Technique ,Nerve Tissue Proteins ,Biology ,PC12 Cells ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Munc18 Proteins ,Microscopy, Electron, Transmission ,medicine ,Animals ,Cytoskeleton ,Gene knockout ,Cell Nucleus ,Neurons ,Brain ,Cyclin-Dependent Kinase 5 ,DNA ,Cell Biology ,DNA-binding domain ,Immunohistochemistry ,Molecular biology ,Cyclin-Dependent Kinases ,Cell Compartmentation ,Protein Structure, Tertiary ,Rats ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Neuron ,Nuclear transport ,Nuclear localization sequence - Abstract
Munc18-1, also referred to as p67, co-purifies with Cdk5 and has an important role in neurotransmitter release. The role of Munc18-1 for functional connectivity of the nervous system was demonstrated by gene knockout experiments in mice, wherein accumulation of neurotransmitter and silencing of synaptic activity was observed. Our earlier studies have shown that both Munc18-1 and Cdk5 co-purify and co-localize with cytoskeletal components, implying that apart from having a regulatory role in vesicle docking and fusion, Munc18-1 could also affect the dynamics of neuronal cytoskeleton. In the present study we have shown the presence of Munc18-1 in nuclear rich fraction from rat brain and confirmed the nuclear localization of this protein in PC12 cells and adult rat brain neurons by immunofluorescence and immunoelectron microscopy. We also demonstrate the binding of Munc18-1 to double stranded (ds) DNA. The ability of Munc18-1 to bind dsDNA, albeit the lack of DNA binding domains, suggests that the binding may be mediated through protein-protein interaction through some other DNA-binding proteins. The presence of both nuclear import and export signals in Munc18-1 primary structure corroborates its nuclear localization and makes it a putative shuttle protein between nuclear and cytoplasmic compartments, the precise physiological relevance of which needs to be elucidated.
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- 2005
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10. Novel Drosophila Heterochromatin Protein 1 (HP1)/Origin Recognition Complex-associated Protein (HOAP) Repeat Motif in HP1/HOAP Interactions and Chromocenter Associations
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Mohammed M. Shareef, Rebecca Kellum, and RamaKrishna Badugu
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Male ,animal structures ,Multiprotein complex ,Chromosomal Proteins, Non-Histone ,Heterochromatin ,government.form_of_government ,Amino Acid Motifs ,Immunoblotting ,Molecular Sequence Data ,Origin Recognition Complex ,Biology ,Biochemistry ,Chromosomes ,Centromere ,Animals ,Drosophila Proteins ,Amino Acid Sequence ,Molecular Biology ,Crosses, Genetic ,Genetics ,Polytene chromosome ,Cell Biology ,Telomere ,Precipitin Tests ,Chromatin ,Recombinant Proteins ,Protein Structure, Tertiary ,DNA-Binding Proteins ,Microscopy, Fluorescence ,embryonic structures ,Chromatography, Gel ,government ,Origin recognition complex ,Drosophila ,Female ,Heterochromatin protein 1 ,Peptides ,Protein Binding ,Centric heterochromatin - Abstract
Association of the highly conserved heterochromatin protein, HP1, with the specialized chromatin of centromeres and telomeres requires binding to a specific histone H3 modification of methylation on lysine 9. This modification is catalyzed by the Drosophila Su(var)3-9 gene product and its homologues. Specific DNA binding activities are also likely to be required for targeting this activity along with HP1 to specific chromosomal regions. The Drosophila HOAP protein is a DNA-binding protein that was identified as a component of a multiprotein complex of HP1 containing Drosophila origin recognition complex (ORC) subunits in the early Drosophila embryo. Here we show direct physical interactions between the HOAP protein and HP1 and specific ORC subunits. Two additional HP1-like proteins (HP1b and HP1c) were recently identified in Drosophila, and the unique chromosomal distribution of each isoform is determined by two independently acting HP1 domains (hinge and chromoshadow domain) (47). We find heterochromatin protein 1/origin recognition complex-associated protein (HOAP) to interact specifically with the originally described predominantly heterochromatic HP1a protein. Both the hinge and chromoshadow domains of HP1a are required for its interaction with HOAP, and a novel peptide repeat located in the carboxyl terminus of the HOAP protein is required for the interaction with the HP1 hinge domain. Peptides that interfere with HP1a/HOAP interactions in co-precipitation experiments also displace HP1 from the heterochromatic chromocenter of polytene chromosomes in larval salivary glands. A mutant for the HOAP protein also suppresses centric heterochromatin-induced silencing, supporting a role for HOAP in centric heterochromatin.
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- 2003
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11. Ameliorative effects of sodium bentonite on phagocytosis and Newcastle disease antibody formation in broiler chickens during aflatoxicosis
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I.K Ibrahim, A. M. Shareef, and K.M.T Al-Joubory
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Male ,Aflatoxin ,Newcastle Disease ,Phagocytosis ,Newcastle disease ,chemistry.chemical_compound ,Immune system ,Animal science ,Aflatoxins ,Animals ,Mycotoxin ,Poultry Diseases ,Sodium Bentonite ,General Veterinary ,biology ,Vaccination ,Broiler ,Mycotoxicosis ,Hemagglutination Inhibition Tests ,biology.organism_classification ,chemistry ,Bentonite ,Immunology ,Chickens - Abstract
The ameliorative effect of graded levels of dietary sodium bentonite (0.2, 0.4 and 0.6 per cent wt/wt of feed) on in vitro-impaired phagocytosis and suppressed immune response to Newcastle disease vaccine during aflatoxicosis (AF) in broiler chicks was investigated. Both percentage and mean of phagocytic activities were decreased significantly (P0.05) in chicks fed 2.5 mg aflatoxin per kg feed. The addition of sodium bentonite was significantly effective in ameliorating the negative effect of AF on the percentage and mean of phagocytosis. The presence of AF alone in the diet depressed the immune response of chicks as measured by haemagglutination inhibition (HI) test. Sodium bentonite was also effective in ameliorating the suppressive effect of AF on the HI -titre in chicks vaccinated against Newcastle disease. The best results obtained when sodium bentonite was added at the rate of 0.4 per cent wt/wt of feed to the AF-containing diets.
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- 2000
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12. Disseminated herpes simplex virus infection presenting as fever in newborn — A lethal outcome
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Aliya N. Husain, M.D. Raible, M. Shareef, Anne H. Rowley, R. Jain, and T.F. Myers
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Male ,Microbiology (medical) ,Coma ,business.industry ,medicine.drug_class ,Herpesvirus 2, Human ,viruses ,Antibiotics ,Infant, Newborn ,Herpes Simplex ,medicine.disease ,medicine.disease_cause ,Tachypnea ,Virus ,Herpesviridae ,Fatal Outcome ,Infectious Diseases ,Immunology ,Coagulopathy ,Humans ,Medicine ,Viral disease ,Differential diagnosis ,medicine.symptom ,business - Abstract
The clinical course of a neonate who presented with fever and tachypnea on day 6 of life is described. He developed disseminated intravascular coagulopathy, hepatic failure, coma and expired at 14 days of age. The post mortem viral cultures from liver, adrenal and lungs were positive for HSV type 2. The fatal outcome of this case of fever, due to HSV infection, emphasizes the need for early treatment of suspicious cases of HSV infection. HSV should be considered in the differential diagnosis of the newborn with persistent fever unresponsive to antibiotics.
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- 1996
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13. Truncated E2F1 Radiosensitizes Prostate Cancer Cells by Inhibiting The E3 Ubiquitin Ligase SKP2
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Alan Pollack, Mansoor M. Ahmed, Thirupandiyur S. Udayakumar, and Mohammed M. Shareef
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Cancer Research ,Radiation ,biology ,business.industry ,medicine.disease ,Ubiquitin ligase ,Prostate cancer ,Oncology ,SKP2 ,biology.protein ,Cancer research ,Medicine ,E2F1 ,Radiology, Nuclear Medicine and imaging ,business - Published
- 2010
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14. Skin and liver cancer induced by monomethylarsonous acid (MMAIII) in mice
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Michael R. Moore, Alan A. Seawright, Jack C. Ng, Mansoor M. Ahmed, David J. Carey, M. Krishnamohan, and Mohammed M. Shareef
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business.industry ,Metabolite ,chemistry.chemical_element ,General Medicine ,Toxicology ,medicine.disease ,medicine.disease_cause ,Excretion ,chemistry.chemical_compound ,chemistry ,Detoxification ,Immunology ,medicine ,Cancer research ,Skin cancer ,Liver cancer ,business ,Carcinogenesis ,Carcinogen ,Arsenic - Abstract
Although arsenic is toxic and a proven carcinogen, the mechanism underlying carcinogenesis is unknown. Until recently the metabolism of arsenic was thought to be a detoxification process. MMAIII is a toxic intermediate of arsenic metabolism. Recent studies show that MMAIII is more cytotoxic and genotoxic than AsIII or AsV. Our aim was to develop an animal model to study the role of MMAIII in arsenic carcinogenesis and in particular to study the development of skin cancer, the predominant presenting feature in humans.Female C57BL/6J mice were given drinking water containing 0 mg/L and 500 mg/L arsenic as MMAIII ad libitum for 2 years. Five animals from each group were sacrificed at various times up to 24 months for arsenic and biomarker measurements. HPLCnICPMS was used to assess excretion of As species. DMAV was the major metabolite which showed a significant dose-dependent increase over 2 years of exposure.An excess of tumors were observed in the MMAIII-treated animals around 18 months. MMAIII treatment resulted in firstly, dermatitis which progressed to trichoepithelioma. There was also an excess of liver cancer. Genome-wide expression profiling of the liver tumors induced by MMAIII by Affymetrix (Mouse genome 430 2.0Array) system for 45,000 probe sets, indicated the disruption of signaling pathways. The components mediating the outcome were different in treatment modalities with the same end result of increase in the expression of Bcl2 a prosurvival gene.Our results show MMAIII is carcinogenic in female C57BL/6J mice and supports the contention that methylation is a toxic process, not a detoxification pathway. MMAIII derived metabolically from inorganic arsenic is likely to be the proximal carcinogen.
- Published
- 2006
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