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Latest Paper:
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603, USA. singh@afrri.usuhs.mil
PURPOSE: The purpose of this study was to further elucidate the role of granulocyte-colony stimulating factor (G-CSF)-induced in response to alpha-tocopherol succinate (TS) administration in protecting mice from total body irradiation (TBI). MATERIAL AND METHODS: The dose, route, and schedule of TS administration for optimal G-CSF induction were determined by giving TS through subcutaneous (sc) and oral routes to male CD2F1 mice. The level of cytokine in serum was determined by multiplex Luminex. The role of G-CSF on survival after TBI was determined by first treating mice with a protective dose (400 mg/kg) of TS 24 h before exposure to a lethal dose (9.2 Gy, 0.6 Gy/min) of cobalt-60 gamma-irradiation. The treated mice were then given neutralising antibody to G-CSF 16 h before TBI to abrogate the radioprotective efficacy of TS. The efficacy of whole blood samples obtained from TS-treated mice was evaluated to protect naïve lethally irradiated mice. The hematopoietic stem cells in blood from TS-treated mice were analysed by fluorescence-activated cell sorting (FACS). RESULTS: Maximal levels of G-CSF were observed in peripheral blood 24 h after sc administration of TS. When TS-treated mice were given neutralising antibody to G-CSF, TS failed to protect against TBI. After being challenged with an LD90/30 (lethal dose causing 90% mortality over 30 days) dose of gamma-radiation, mice infused with whole blood from TS- and AMD3100 (1,1'-{1,4-phenylenebis(methylene)}bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride)-treated mice exhibited significantly higher survival compared with those infused with whole blood from vehicle-injected mice. FACS data revealed that hematopoietic stem cells were mobilised into the peripheral blood. CONCLUSIONS: The results indicate that G-CSF-induced by the administration of TS, mobilises hematopoietic stem cells and is responsible for the protection from ionising radiation.
To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group (n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased in workers. The results indicated significant decrease in the mean value of hemoglobin, hematocrit and platelets count; however, significantly higher count of leukocytes was also observed in the exposed group (sprayers) compared to that observed in the control group (P < 0.05). Monitoring of PBChE in pesticide sprayers could be useful to predict and prevent health hazards of OPs.
Royal Hallamshire Hospital, Sheffield, South Yorkshire, United Kingdom. we.publish@googlemail.com
BACKGROUND/OBJECTIVE: Glioblastoma multiforme (GBM) is the most common glial cell tumor of the adult brain. However, primary GBM of the spinal cord is a rare condition. METHODS: Case report. RESULTS: A young man presented with acute onset quadriparesis after a whiplash injury. A magnetic resonance scan showed the typical appearance of a high-grade intramedullary tumor with fusiform expansion of the entire cervical cord. Subtotal decompression and biopsy was done by posterior laminectomy, followed by external beam radiotherapy. Signs and symptoms improved after the completion of radiotherapy but did not resolve completely. Death caused by respiratory failure occurred 3 months later. CONCLUSIONS: This presentation of GBM of the cervical cord is rare; an intramedullary tumor should be considered when minor cervical trauma results in disproportionate neurologic deficit. To the best of our knowledge, this is the first reported case of spinal GBM with extensive pan-cervical involvement.
Department of Zoology, D.D.U. Gorakhpur University, Gorakhpur 273009, U.P., India Tel.:+91 0551 220 2187 (Office);+91 941 585 5488 (Mobile) E-mail: vksinghgpu@yahoo.co.in.
Lymnaea acuminata breeds round the year. The effect of pH, temperature, dissolved oxygen, carbon dioxide, light/dark period and clean/polluted water on the fecundity, hatchability and survival of young snails of L. acuminata were studied. It was observed that these environmental variant abiotic factors caused a significant variation in fecundity, hatchability and survival of young snails. Maximum reproduction of this snail was observed in the months of March to May. A significant positive correlation (p<0.05) between D.O.(3.1-7.7 ppm)/pH (7.01-8.96) of water with fecundity (6.0-196.33/20 snails), hatchability (54.69-96.91%) and survival (61.3-95.86%) of young snails was observed for each month and each interval of 24-72 h. In contrast, a significant negative correlation between dissolved CO(2)(4.6-16.6 ppm)/temperature (16-37 degrees C) of water was noted with fecundity, hatchability and survival of snails. Percent hatchability in the eggs in different regimens of water was between 96.91-54.69%. The hatching period was prolonged (2-14 days) in snail exposed to different groups of water compared to the control group (2-9 d). This study conclusively shows that variant abiotic factors in different months of the year can significantly alter the reproductive ability and development process in the snail Lymnaea acuminata.
Department of Chemistry, Indian Institute of Technology, Kanpur, India 208 016, and Indian Institute of Science Education and Research, ITI Campus (Gas Rahat) Building, Govindpura, Bhopal, India 460 023.
A highly enantioselective Friedel-Crafts alkylation of pyrroles with 2-enoylpyridine N-oxides catalyzed by chiral PYBOX-DIPH-Zn(II) complexes has been developed. The catalyst offers substantial substrate scope and furnished alkylated pyrroles in excellent yields (up to 99%) and enantioselectivities (up to >99% ee).
Department of Biotechnology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, India.
A total of 48 full-length protein sequences of pectin lyases from different source organisms available in NCBI were subjected to multiple sequence alignment, domain analysis, and phylogenetic tree construction. A phylogenetic tree constructed on the basis of the protein sequences revealed two distinct clusters representing pectin lyases from bacterial and fungal sources. Similarly, the multiple accessions of different source organisms representing bacterial and fungal pectin lyases also formed distinct clusters, showing sequence level homology. The sequence level similarities among different groups of pectinase enzymes, viz. pectin lyase, pectate lyase, polygalacturonase, and pectin esterase, were also analyzed by subjecting a single protein sequence from each group with common source organism to tree construction. Four distinct clusters representing different groups of pectinases with common source organisms were observed, indicating the existing sequence level similarity among them. Multiple sequence alignment of pectin lyase protein sequence of different source organisms along with pectinases with common source organisms revealed a conserved region, indicating homology at sequence level. A conserved domain Pec_Lyase_C was frequently observed in the protein sequences of pectin lyases and pectate lyases, while Glyco_hydro_28 domains and Pectate lyase-like beta-helix clan domain are frequently observed in polygalacturonases and pectin esterases, respectively. The signature amino acid sequence of 41 amino acids, i.e. TYDNAGVLPITVNSNKSLIGEGSKGVIKGKGLRIVSGAKNI, related with the Pec_Lyase_C is frequently observed in pectin lyase protein sequences and might be related with the structure and enzymatic function.
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India. vinodks@iitk.ac.in.
Organocatalysts have emerged as a third major way of catalyzing a wide variety of reactions, besides metal catalysts and biocatalysts. They have gained tremendous importance because of their green chemistry perspective. The criteria for green chemistry would be largely fulfilled if the major component of the reaction mixture, i.e. the solvent, is water which is a suitable solvent in various biosynthetic reactions. In this feature article we have described reactions promoted by organocatalysts in a large excess of water, without any organic solvent or excess of any reactant. We have also explained the structural features required for organocatalysts to work well in aqueous media.
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, MD, USA; Department of Radiation Biology, Bethesda, MD, USA.
OBJECTIVE: Victims of a terrorist attack presenting with the hematopoietic syndrome resulting from exposure to excessive levels of ionizing radiation will succumb to sepsis if not adequately treated. The probability of survival is increased substantially if the victim's immune system is allowed to recover before sepsis sets in. We report here preclinical development of a new bridging-therapy which will allow the victim's immune system to recover from damage caused by ionizing radiation. METHODS: The hematopoietic progenitor cells in blood from tocopherol succinate (TS)-injected mice were analyzed quantitatively by standard in vitro soft matrix colony procedures. CD2F1 mice were irradiated with lethal, whole-body doses (9.2Gy) of (60)Co gamma-rays and then transfused intravenously (iv, peri-orbital sinus, venous plexus behind the eye) with whole blood, peripheral blood mononuclear cells (PBMC) or plasma from TS-injected mice 2 and 24h post irradiation. Survival was monitored for 30 days after transfusion of whole blood, PBMC or plasma. RESULTS: Progenitor cell analyses revealed that hematopoietic progenitors were mobilized into the peripheral blood of TS-injected mice. Our results demonstrated that infusions of whole blood or PBMC from TS-injected mice greatly improved chances of extended survival of lethally irradiated mice. CONCLUSION: TS-stimulated granulocyte-colony stimulating factor (G-CSF) mobilizes high numbers of progenitors into the peripheral circulation; in turn, this blood- these progenitors- can be used upon subsequent transfusion to effectively mitigate and repair primary acute radiation injury. The transfused cells act secondarily as a bridging therapy for irradiated mice while their own immune system recovers from the radiation induced damage.
Spinal "stroke" is an uncommon cause of paraplegia. Spinal cord infarction from unruptured aortic aneurysm is rare. When encountered it poses diagnostic challenge to the clinician due to its rarity, which may lead to incorrect or delayed diagnosis. We report a case of 62-year-old man presenting to casualty as caudaequina syndrome due to spinal cord infarction secondary to emboli from an infra renal abdominal aortic aneurysm. To the authors knowledge this is first case of its kind and has not been reported in literature. Patient had improvement in proximal motor function following repair of the aneurysm, although he remained doubly incontinent in six months follow up.
Brain State International Research Center, Scottsdale, AZ 85260, USA. vj1000s@yahoo.com
BACKGROUND: Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism. METHODS: Autoimmune markers were analyzed in the sera of autistic and normal children, but the cerebrospinal fluid (CSF) of some autistic children was also analyzed. Laboratory procedures included enzyme-linked immunosorbent assay and protein immunoblotting assay. RESULTS: Autoimmunity was demonstrated by the presence of brain autoantibodies, abnormal viral serology, brain and viral antibodies in CSF, a positive correlation between brain autoantibodies and viral serology, elevated levels of proinflammatory cytokines and acute-phase reactants, and a positive response to immunotherapy. Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)--salient features that characterize autoimmune pathology in autism. Autistic children also showed elevated levels of acute-phase reactants--a marker of systemic inflammation. CONCLUSIONS: The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy. The author has advanced a speculative neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a key player. The latter should be targeted by immunotherapy to help children with autism.
