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Biomedical subjects

A Arora

Publications and source records attributed to A Arora.

At least 37 records · Page 2Linked to original sources
PubMed2001

Biophysical approaches to membrane protein structure determination.

Recently, there have been several technical advances in the use of solution and solid-state NMR spectroscopy to determine the structures of membrane proteins. The structures of several isolated transmembrane (TM) helices and pairs of TM helices have been solved by solution NMR methods. Similarly, the complete folds of two TM beta-barrel proteins with molecular weights of 16 and 19 kDa have been determined by solution NMR in detergent micelles. Solution NMR has also provided a first glimpse at the dynamics of an integral membrane protein. Structures of individual TM helices have also been determined by solid-state NMR. A combination of NMR with site-directed spin-label electron paramagnetic resonance or Fourier transform IR spectroscopy allows one to assemble quite detailed protein structures in the membrane.

Biophysics↗
PubMed2001

Axonal Guillain-Barré syndrome: a critical review.

Axonal Guillain-Barré Syndrome (GBS) was first described by Feasby et al. in 1986, challenging the existent notion of GBS being a primarily demyelinating disease. The severe course and slow recovery commonly seen in these patients was ascribed to axonal degeneration. Other authors challenged this claim on several grounds. Amidst these controversies, epidemics of a similar illness were reported from China, which were given the acronym AMAN, having exclusive motor involvement in contrast to the cases already described in which both motor and sensory involvement were present (AMSAN). Pathologically, Wallerian degeneration, minimal lymphocytic response, absent demyelination or inflammation and periaxonal macrophages are prominent features. Ultrastructural studies have revealed node of Ranvier to be the prime target of immune attack. A frequent occurrence of antecedent Campylobacter jejuni infection and a strong association between elevated titres of IgG GM1 and axonal GBS on a background of preceding C. jejunii infection has been observed and molecular mimicry between lipopolysaccharides of C. jejuni and neural epitopes has been proposed as a mechanism of injury. Clinically axonal variant is similar to AIDP, but a more severe course, with frequent respiratory involvement, ventilator dependence and significant residue may be seen. Diagnosis is essentially electrophysiological. Treatment is similar to AIDP, preferential benefit of either IVIG or plasmapheresis needs to be further evaluated. A critical review of existing literature in axonal GBS is presented.

Axons↗
PubMed2001

Structure of outer membrane protein A transmembrane domain by NMR spectroscopy.

We have determined the three-dimensional fold of the 19 kDa (177 residues) transmembrane domain of the outer membrane protein A of Escherichia coli in dodecylphosphocholine (DPC) micelles in solution using heteronuclear NMR. The structure consists of an eight-stranded beta-barrel connected by tight turns on the periplasmic side and larger mobile loops on the extracellular side. The solution structure of the barrel in DPC micelles is similar to that in n-octyltetraoxyethylene (C(8)E(4)) micelles determined by X-ray diffraction. Moreover, data from NMR dynamic experiments reveal a gradient of conformational flexibility in the structure that may contribute to the membrane channel function of this protein.

Bacterial Outer Membrane Proteins↗
PubMed2001

Interactions of beta-carotene and cigarette smoke in human bronchial epithelial cells.

Results from recent intervention trials indicated that supplemental beta-carotene enhances lung cancer incidence and mortality among smokers. It was hypothesized that beta-carotene was exerting its deleterious effects through a prooxidant effect in the smoke-exposed lung. To test this hypothesis we examined the interactions of beta-carotene and cigarette smoke in transformed human bronchial epithelial cells. We studied the effects of beta-carotene supplementation on rates of gas phase smoke-induced lipid peroxidation, membrane damage and depletion of endogenous antioxidants in BEAS-2B cells. Gas phase cigarette smoke caused cellular beta-carotene levels to decrease over time. The oxidation of beta-carotene by smoke generated various oxidation products, including 4-nitro-beta-carotene, beta-apo-carotenals and beta-carotene epoxides. Peroxidation of membrane lipids by gas phase smoke progressed at a slower rate than did oxidation of beta-carotene and incorporation of beta-carotene into the cells did not enhance the overall rate of lipid peroxidation. Additionally, lactate dehydrogenase release during smoke exposure was also unaffected by the presence or absence of beta-carotene in cells. beta-Carotene incorporation in cells was not found to accelerate the rates of alpha-tocopherol and glutathione depletion by cigarette smoke. Our results indicate that beta-carotene is more sensitive than lipids to cigarette smoke oxidation, but that this preferential oxidation of beta-carotene does not lead to a prooxidant effect in human bronchial epithelial cells.

Bronchi↗
PubMed2001

Isolated dislocation of the second metacarpal at both ends.

A dislocation of the second metacarpal at both ends is reported herein for the first time. Six weeks after injuring her right hand in a fall while climbing stairs, a 34-year-old woman visited our clinic with pain, swelling, and deformity of her hand. The radiographs showed a volar dislocation of the head and a dorsal dislocation of the base of the second metacarpal. The probable mechanism of injury was the hyperextension at the metacarpophalangeal joint; this force dislocated the metacarpal head toward the volar plate. Force then further continued along the second metacarpal shaft in the hyperflexed wrist, thus dislocating the base dorsally. We performed an open reduction and K-wire fixation of the second metacarpophalangeal joint and an arthrodesis of the second carpometacarpal joint. At the six-month follow-up, the patient had restricted flexion (0 to 50 degrees) at the second metacarpophalangeal joint, but full range of motion at the interphalangeal joints. The grip strength on the right side was 70% of that measured in the uninvolved hand. Key Words: Dislocation, Second metacarpal.

Accidental Falls↗
PubMed2001

Albendazole therapy for solitary persistent cysticercus granuloma.

Use of Albendazole therapy for the treatment of patients having persisting intracranial solitary cysticercus granuloma is controversial. Most of the times these patients are treated empirically with variety of drugs for variable period. Some authors advocate biopsy before definitive treatment. 25 patients having radiologicaly persistent solitary cysticercus granuloma (>6 months) were given 15 days course of oral albendazole (15 mg/kg body wt). Cranial CT scan was repeated one month after the completion of albendazole therapy. It was evaluated for complete resolution, partial response (> 50% decrease in size of lesion) or no change as compared to previous scan. 12 patients (48%) showed complete resolution, 4 patients (16%) showed a partial response, while 9 patients (36%) did not show any change on follow up. Albendazole therapy may be useful for patients having persistent cysticercus granuloma.

Adolescent↗
PubMed2001

Transplacental carcinogenic potential of the carbamate fungicide mancozeb.

We evaluated the effects of mancozeb (Dithane M4-5), a protective carbamate fungicide, on transplacental carcinogenesis in Swiss albino mice. Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, is reported to possess carcinogenic and cocarcinogenic activity in various tumor models. In the present study, pregnant Swiss albino mice were administered mancozeb intraperitoneally on the 14th day of gestation. The first filial generation (F1 progeny) was promoted with a well-known tumor promoter 12-o-tetradecanoyl phorbol-13-acetate (TPA). The results revealed a significantly high tumor incidence (72%) in the F1 progeny of the animals initiated with mancozeb or a well known carcinogen 7,12-dimethyl benzanthracene (DMBA) and promoted with TPA in comparison to animals that were either from mothers given only the vehicle (DMSO) and promoted with TPA in F1 progeny or not promoted with TPA in F1 progeny. No significantly higher tumor incidence was observed in any other experimental groups. These results suggest that mancozeb or its metabolites are capable of crossing the placental barrier and can exert DNA damage and tumor initiating consequences in the fetal cells that, after promotion with TPA, get converted into neoplastic cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Management of community acquired respiratory infections.

Respiratory tract infections (RTIs) are the most common diagnosis in children visiting outpatient departments in both developing and developed countries. The impact of these infections is enormous in terms of total morbidity and mortality. Management of these infections requires a meticulous evaluation and a comprehensive but rational use of supportive, symptomatic and specific therapy. Antibiotics are widely prescribed for the treatment of community acquired respiratory infections to compensate uncertainties of diagnosis and prognosis; unnecessary anti-microbial drug therapy is expensive and resistance by respiratory pathogens is increasing at an exponential rate at a time when new anti-viral as well as anti-bacterial agents are being introduced into the therapeutic armamentarium. Major dilemmas persist regarding symptomatic therapy and the indications of antimicrobial agents. A comprehensive but brief review along with latest protocols and advancements is the management of community acquired respiratory infections in children in cited.

Adolescent↗
PubMed2001

Reversible posterior leukoencephalopathy syndrome: a report of 2 cases.

Reversible posterior leukoencephalopathy syndrome (RPLE) is an increasingly recognised disorder, most commonly associated with malignant hypertension, toxaemia of pregnancy or the use of immunosuppressive agents. Two cases of RPLE syndrome occurring in the setting of accelerated hypertension and eclampsia are described. Both patients had seizures, altered sensorium and typical findings on neuroimaging. They had complete clinical and radiological recovery. The clinical course, pathophysiology and neuroimaging features of RPLE syndrome are discussed.

Adolescent↗
PubMed2001

Immunization with HIV-1 subtype B gp160-DNA induces specific as well as cross reactive immune responses in mice.

BACKGROUND & OBJECTIVES: HIV-1 gp160 is an important structural protein for the virus cell interaction and virus entry. Therefore, it is regarded as the most important target for HIV-1 vaccine development. In this study we investigated the use of HIV-1 gp160-DNA construct in eliciting specific and cross reactive cell mediated immune response in mice. METHODS: DNA segment encoding env, tat and rev genes of HIV-1 subtype B (strain BRU-2) was amplified and cloned into mammalian expression vector pCI to generate plasmid pCIBRU-TRE. Mice were injected intramuscularly four times at biweekly intervals with 100 micrograms/dose of pCIBRU-TRE in normal saline, and subsequently analysed for anti HIV-envelope (env) immune responses. RESULTS: A low antibody level was detected as determined by ELISA after 4 doses. Subsequent inoculations failed to increase the antibody titres significantly. Spleen cells from the immunized mice were used for the detection of cellular immune response by lymphocyte proliferation assays (LPA), in vitro production of cytokines and cytotoxic T lymphocyte (CTL) assays. T cell response which was seen from the second week onwards, persisted even at the end of 24 wk following the last dose. Similar levels of T cell proliferation were observed on stimulation with either homologous or heterologous peptides. Cytokine studies showed a Th1 type of response. A cross clade MHC class I restricted CTL response was observed against target cells stimulated with either homologous or heterologous HIV antigens. INTERPRETATION & CONCLUSION: This study demonstrated that DNA encoding full length HIV-1 env glycoprotein gp160 induces specific as well as cross reactive cell mediated immune responses in mice. However, the induction of antibody response was poor.

AIDS Vaccines↗
PubMed2000

Refolded outer membrane protein A of Escherichia coli forms ion channels with two conductance states in planar lipid bilayers.

Outer membrane protein A (OmpA), a major structural protein of the outer membrane of Escherichia coli, consists of an N-terminal 8-stranded beta-barrel transmembrane domain and a C-terminal periplasmic domain. OmpA has served as an excellent model for studying the mechanism of insertion, folding, and assembly of constitutive integral membrane proteins in vivo and in vitro. The function of OmpA is currently not well understood. Particularly, the question whether or not OmpA forms an ion channel and/or nonspecific pore for uncharged larger solutes, as some other porins do, has been controversial. We have incorporated detergent-purified OmpA into planar lipid bilayers and studied its permeability to ions by single channel conductance measurements. In 1 M KCl, OmpA formed small (50-80 pS) and large (260-320 pS) channels. These two conductance states were interconvertible, presumably corresponding to two different conformations of OmpA in the membrane. The smaller channels are associated with the N-terminal transmembrane domain, whereas both domains are required to form the larger channels. The two channel activities provide a new functional assay for the refolding in vitro of the two respective domains of OmpA. Wild-type and five single tryptophan mutants of urea-denatured OmpA are shown to refold into functional channels in lipid bilayers.

Bacterial Outer Membrane Proteins↗
PubMed2000

Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids.

The polyphenolic structures of flavonoids and isoflavonoids confer them with the ability to scavenge free radicals and to chelate transition metals, a basis for their potent antioxidant abilities. Another possible contributory mechanism toward their antioxidant activities is their ability to stabilize membranes by decreasing membrane fluidity. In this study, the effects of representative flavonoids, isoflavonoids, and their metabolites on membrane fluidity and their preferential localization in the membrane were investigated using large unilamellar vesicles (LUVs) as the membrane models. These results were compared with those of cholesterol and alpha-tocopherol. Changes in fluorescence anisotropy values for a series of n-(9-anthroyloxy) fatty acid probes (n = 6, 12, 16) upon addition of the test compounds were used to monitor alterations in membrane fluidity at graded depths in lipid bilayer. The results of the study suggest that the flavonoids and isoflavonoids, similar to cholesterol and alpha-tocopherol, partition into the hydrophobic core of the membrane and cause a dramatic decrease in lipid fluidity in this region of the membrane. Localization of flavonoids and isoflavonoids into the membrane interiors and their resulting restrictions on fluidity of membrane components could sterically hinder diffusion of free radicals and thereby decrease the kinetics of free radical reactions.

Chromans↗
PubMed2000

Cubitus varus: problem and solution.

A lateral closing wedge osteotomy was performed in 39 children with cubitus varus deformity resulting from a supracondylar fracture. All had a deformity of 15 degrees or more, with 5 having more than 30 degrees of varus. The osteotomy was fixed by three different methods. In 8 cases the osteotomy was fixed with 2 parallel Kirschner wies (group K). A modified French technique (group TBW) was used in 25 cases and held with a figure-of-8 wire loop tightened over the screw heads. In the last 6 cases the osteotomy was fixed with an external fixator (group EF). The only poor result (i.e. loss of carrying angle of more than 10 degrees and loss of flexion and extension of 20 degrees or more) was in group K due to pin tract infection and loosening of the K-wires. In the TBW group 5 patients lost some degree of correction, and none became infected. In the EF group no patient suffered pin tract infection or loss of correction. Based on our experience and results, we feel that the best age at which to correct cubitus varus deformity was 6-11 years and that the external fixator is a safe, effective and reliable method to fix the osteotomy. We propose this method of fixation as a good alternative method to the modified French technique, especially in cases of severe cubitus varus deformity, where removal of a large wedge can produce a big step at the osteotomy site, increasing the possibility of disengagement of the stainless steel wire from the screw head. In addition, minor postoperative modifications of correction, if required, can also be performed. It also avoids a second operation for implant removal.

Adolescent↗
PubMed2000

Reactions of Genistein with alkylperoxyl radicals.

Antioxidant actions of the soy isoflavone genistein are believed to contribute to its overall chemopreventive activity. However, the mechanisms of its antioxidant reactions remain unknown. The objective of this study was to characterize the reaction products of genistein (5,7,4'-trihydroxyisoflavone) with peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). Genistein oxidations with AMVN-derived peroxyl radicals yielded orobol (5,7,3',4'-tetrahydroxyisoflavone), a hydroxylated derivative of genistein, and several stable adducts of 4'-oxogenistein with AMVN-derived radicals. Some of these adducts include novel structures resulting from secondary oxidations of the AMVN-derived moiety. For all the observed oxidation products, the modifications occurred on the B-ring of the molecule. Genistein oxidation product structures provide potentially useful markers of genistein antioxidant chemistry.

Acetonitriles↗