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Biomedical subjects

A Mahadevan

Publications and source records attributed to A Mahadevan.

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

Tissue/dose compensation to reduce toxicity from combined radiation and chemotherapy for advanced head and neck cancers.

This study was undertaken to quantify the reduction in normal tissue complications resulting from the aggressive management of advanced head and neck cancers (AHNCs) utilizing tissue/dose compensation (TDC). Thirty-nine patients with AHNC were treated on an intensive chemotherapy + radiation regimen. Eighteen of 39 patients were treated using TDC; the remaining 21 patients were radiated without TDC (NTDC). Acute and chronic toxicities, swallowing, speech function, and quality of life were assessed. The TDC group had a smaller radiation dose gradient across the entire treatment volume. Unscheduled treatment breaks were required in 11% of TDC patients as compared with 43% of the NTDC group (P = 0.04). The TDC group had fewer Grade 3 or 4 acute and chronic toxicities and lower SOMA scores. At 3 months posttreatment, patients in the TDC group had better oral intake, lower pharyngeal residue, and better oropharyngeal swallowing efficiency and were able to swallow more bolus types. Patients in the TDC group also had better articulation. Use of TDC resulted in reduced treatment-related interruptions, decreased acute and chronic toxicities, and better speech and swallowing functions. Techniques to improve radiation dose conformality around the target tissues while decreasing the radiation dose to the normal tissues should be an integral part of aggressive combined modality therapy.

Adult↗
PubMed2001

Functional analysis of a chromosomal arsenic resistance operon in Pseudomonas fluorescens strain MSP3.

We reported earlier about the detection of a chromosomally located arsenic operon (arsRBC) in a gram-negative bacterium Pseudomonas fluorescens strain MSP3, which showed resistance to elevated levels of sodium arsenate and sodium arsenite. The genes for arsenic resistance were cloned into the HindIII site of pBluescript vector producing three clones MSA1, MSA2 and MSI3 conferring resistance to sodium arsenate and arsenite salts. They were further sub-cloned to delineate the insert size and the sub-clones were designated as MSA11, MSA12 and MSI13. The sub-clone pMSA12 (2.6 kb) fragment was further packaged into EcoRI-PstI site of M13mp19 and sequenced. Nucleotide sequencing revealed the presence of three open reading frames homologous to the arsR, arsB and arsC genes of arsenic resistance. Three cistrons of the ars operon encoded polypeptides ArsR, ArsB and ArsC with molecular weights ranging approximately 12, 37and 24 kDa, respectively. These polypeptides were visualized on SDS-PAGE stained with Coomassie blue and measured in a densitometer. The arsenic resistance operon (arsRBC) of strain MSP3 plasmid pMSA12 consists of 3 genes namely, arsR--encoding a repressor regulatory protein, arsB--the determinant of the membrane efflux protein that confers resistance by pumping arsenic from the cells and arsC--a small cytoplasmic polypeptide required for arsenate resistance only, not for arsenite resistance. ArsB protein is believed to use the cell membrane potential to drive the efflux of intracellular arsenite ions. ArsC encodes for the enzyme arsenate reductase which reduces intracellular As(V) (arsenate) to more toxic As(III) (arsenite) and is subsequently extruded from the cell. The arsenate reductase activity was present in the soluble cytoplasmic fraction in E. coli clones. In the context of specified function of the arsenic operon encoded proteins, uptake and efflux mechanisms were studied in the wild strain and the arsenate/arsenite clones. The cell free filtrates of the arsenate clones (MSA11 and MSA12) obtained from P. fluorescens containing the arsC gene showed that arsenate reduction requires glutathione reductase, glutathione (GSH), glutaredoxin and ArsC protein. The protein was purified in an active form and a spectrophotometric assay was developed in which the oxidation of NADPH was coupled to reduction of arsenate. The molecular weights and the location of the polypeptides were obtained from Coomassie stained SDS-PAGE of extracellular and intracellular fractions of the cells.

Arsenates↗
PubMed2001

RCPH modulation of a multi-oscillator network: effects on the pyloric network of the spiny lobster.

The neuropeptide red pigment concentrating hormone (RPCH), which we have previously shown to activate the cardiac sac motor pattern and lead to a conjoint gastric mill-cardiac sac pattern in the spiny lobster Panulirus, also activates and modulates the pyloric pattern. Like the activity of gastric mill neurons in RPCH, the pattern of activity in the pyloric neurons is considerably more complex than that seen in control saline. This reflects the influence of the cardiac sac motor pattern, and particularly the upstream inferior ventricular (IV) neurons, on many of the pyloric neurons. RPCH intensifies this interaction by increasing the strength of the synaptic connections between the IV neurons and their targets in the stomatogastric ganglion. At the same time, RPCH enhances postinhibitory rebound in the lateral pyloric (LP) neuron. Taken together, these factors largely explain the complex pyloric pattern recorded in RPCH in Panulirus.

Animals↗
PubMed2001

Novel pyrazole cannabinoids: insights into CB(1) receptor recognition and activation.

Synthesis of an antagonist, SR141716A, that selectively binds to brain cannabinoid (CB(1)) receptors without producing cannabimimetic activity in vivo, suggests that recognition and activation of cannabinoid receptors are separable events. In the present study, a series of SR141716A analogs were synthesized and were tested for CB(1) binding affinity and in a battery of in vivo tests, including hypomobility, antinociception, and hypothermia in mice. These analogs retained the central pyrazole structure of SR141716A with replacement of the 1-, 3-, 4-, and/or 5-substituents by alkyl side chains or other substituents known to impart potent agonist activity in traditional tricyclic cannabinoid compounds. Although none of the analogs alone produced the profile of cannabimimetic effects seen with full agonists, several of the 3-substituent analogs with higher binding affinities showed partial agonism for one or more measures. Cannabimimetic activity was most noted when the 3-substituent of SR141716A was replaced with an alkyl amide or ketone group. None of the 3-substituted analogs produced antagonist effects when tested in combination with 3 mg/kg Delta(9)-tetrahydrocannabinol (Delta(9)-THC). In contrast, antagonism of Delta(9)-THC's effects without accompanying agonist or partial agonist effects was observed with substitutions at positions 1, 4, and 5. These results suggest that the structural properties of 1- and 5-substituents are primarily responsible for the antagonist activity of SR141716A.

Analgesics, Non-Narcotic↗
PubMed2001

Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis.

A retrospective analysis of clinicopathological data of 10 patients with clinically unsuspected cerebral metastatic choriocarcinoma was carried out. All patients were young adult females. History of preceding pregnancy/abortion was forthcoming in 5 cases but none had a prior history of abnormal gestation. Features of raised intracranial tension followed by hemiparesis were the commonest presenting symptoms. A clinicoradiologic diagnosis of intracerebral haemorrhagic mass, either primary or secondary to tumour bleed, cortico-venous thrombosis or arteriovenous malformation, was entertained in 8 out of 10 cases. In other two cases, ring enhancing lesions prompted the diagnosis of granulomatous masses. Eight patients were operated upon, of whom two died after short hospital stay, and were autopsied. All had haemorrhagic masses noted at surgery/autopsy. Accurate diagnosis of metastatic choriocarcinoma was established only by histologic examination of these haemorrhages. This report emphasizes the importance of considering metastatic choriocarcinoma as an important differential diagnosis of haemorrhagic intracerebral lesions in women of child bearing age group. Measurement of serum/CSF level of HCG in suspected cases helps to implement early therapy. The diagnostic value of histopathologic examination of surgically resected blood clots in determining aetiology of intracerebral haemorrhagic masses is highlighted.

Adolescent↗
PubMed2001

Vasculitic neuropathy in HIV infection: a clinicopathological study.

Vasculitis causing peripheral neuropathy may be the first sign of HIV infection. We report four such cases in whom the onset of peripheral neuropathy led to the detection of HIV infection. Two patients presented with features of mononeuritis multiplex, while the other two had a lumbosacral polyradiculopathy. A prior history of blood transfusion was forthcoming in one of the patients. Sural nerve biopsies in all the four cases and the muscle biopsy in two, histologically showed evidence of vasculitis. Immunohistochemically, the viral antigen was not demonstrable in any of the biopsies, but on electron microscope, virus-like particles were identifiable in the Schwann cell cytoplasm and the perivascular macrophages in one case. To the best of our knowledge, this is the only report that has documented the virus in the Schwann cells as well as the perivascular macrophages lending credence to the fact that these viruses are neurotropic as well as lymphotropic. Immunoglobulin deposits were not demonstrable in any of the cases, suggesting that direct viral invasion may have a role in the pathogenesis of peripheral nerve vasculitis.

Adult↗
PubMed2001

Effect of phenol on protein and amino acid content of Xanthomonas oryzae pv. oryzae.

Leaf blight disease of rice (Oryza sativa) is caused by the bacterium Xanthomonas oryzae pv. oryzae. Phenol (1 to 4 mM) induced changes in protein profiles of X. o. pv. oryzae and a stress protein with a molecular mass of 69,000 appeared. HPLC analysis indicated occurrence of amino acids such as asparagine, alanine, methionine and cystine in phenol treated cells. Proton NMR analysis also revealed variation on the presence of amino acids in the cells treated with phenol.

Amino Acids↗
PubMed2001

Effect of phenol on lipid and fatty acid profile of Xanthomonas oryzae pv. oryzae.

Effect of phenol on total lipid and fatty acid composition of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight of rice (Oryzae sativa) was studied. Lipid level was low in phenol treated cells. Number of fatty acids detected from phenol treated cells was more than those found in untreated cells as revealed by Gas chromatography. Pentadecanoic acid (C15:0), linolenic acid (C18:3) and behenic acid (C22:0) were present only in the treated cells. Palmitic acid which is usually found in bacteria was not detected both in control and treated cells.

Electrophoresis, Polyacrylamide Gel↗
PubMed2000

Novel cannabinol probes for CB1 and CB2 cannabinoid receptors.

The observation that the phenolic hydroxyl of THCs was important for binding to the CB1 receptor but not as critical for binding to the CB2 receptor prompted us to extend this finding to the cannabinol (CBN) series. To study the SAR of CBN analogues, CBN derivatives with substitution at the C-1, C-3, and C-9 positions were chosen since these positions have played a key role in the SAR of THCs. CBN-3-(1',1'-dimethylheptyl) analogues were prepared by sulfur dehydrogenation of Delta(8)-THC-3-(1',1'-dimethylheptyl) analogues. 9-Substituted CBN analogues were prepared by the standard sulfur dehydrogenation of 9-substituted Delta(8)-THC analogues (Scheme 1), which in turn were prepared following our previous procedure using selenium dioxide oxidation of the corresponding Delta(8)-THCs followed by sodium chlorite oxidation to give the 9-carboxy-Delta(8)-THC derivatives. 11-Hydroxy-CBN analogues were prepared from the corresponding 9-carbomethoxy-CBN analogues by reduction with LiAlH(4). Deoxy-CBN analogue 14 was prepared from the corresponding Delta(8)-THC analogue 11 by conversion of the phenolic hydroxyl to the phosphate derivative 12, followed by lithium ammonia reduction to provide the deoxy-Delta(8)-THC analogue 13, which in turn was dehydrogenated with sulfur to provide the deoxy-CBN analogue 14 (Scheme 2). The various analogues were assayed for binding both to the brain and the peripheral cannabinoid receptors (CB1 and CB2). We have found that the binding profile differs widely between the CBN and the THC series. Specifically, in the CBN series the removal of the phenolic hydroxyl decreases binding affinity to both the CB1 and CB2 receptors, whereas in the THC series, CB1 affinity is selectively reduced. Thus, in the CBN series, the selectivity of binding observed with the removal of the hydroxy group is decreased severalfold as compared to what occurs in the THC series. Generally, high affinity for the CB2 receptor was found in analogues when the phenolic hydroxyl was present. The 3-(1', 1'-dimethylheptyl) derivatives were found to have much higher affinities than the CBN analogues, which is in complete agreement with previously reported work by Rhee et al.

Animals↗
PubMed2000

Cannabinoid properties of methylfluorophosphonate analogs.

Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize this class of compounds, methylfluorophosphonate compounds with saturated alkyl chains ranging from C8 to C20 along with C20 unsaturated derivatives were synthesized and evaluated for their ability to interact with the CB1 receptor, inhibit FAAH, and produce in vivo pharmacological effects. These analogs demonstrated widely varying affinities for the CB1 receptor. Of the saturated compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low affinity (900 nM), but the introduction of unsaturation into the C20 analogs restored receptor affinity. However, none of the analogs were capable of fully displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to completely inhibit FAAH enzyme activity, with the C20:0 analog being the least potent. The most potent FAAH inhibitor was the short-chained saturated C12:0, whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and C12:0 analogs were highly potent and fully efficacious in producing tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either inactive or acted as partial agonists. None was capable of attenuating the agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0) underscores the complexity of manipulating the endogenous cannabinoid system.

Analgesics, Opioid↗
PubMed2000

X-ray microanalysis of elements of VA mycorrhizal and non-mycorrhizal Pennisetum pedicellatum roots.

Chemical composition of inter and intracellular hyphae was elucidated in Pennisetum pedicellatum roots colonized by Gigaspora margarita by employing energy dispersive X-ray microanalysis. Maximum amount of phosphate was estimated in polyphosphate granules present in the roots. Amount of phosphate was low in fungal hyphae, arbuscular trunks and degenerated arbuscules. Elements S, K and Ca were present in the hyphae, arbuscular trunk and degenerated arbuscules.

Electron Probe Microanalysis↗
PubMed2000

Comparison of protein profiles and enzymes in non-mycorrhizal and mycorrhizal roots of Pennisetum pedicellatum.

Pennisetum pedicellatum plants were inoculated with Glomus mosseae, G. aggregatum and Gigaspora margarita. There were both quantitative and qualitative changes in the protein pattern of inoculated plants. Gi. margarita induced increase in protein in the plants. Acid phosphatase, alkaline phosphatase, superoxide dismutase and chitinase activities were high at the beginning of infection, but declined as the infection advanced. Gi. margarita was an efficient fungus in enhancing enzyme activity and proteins in roots compared with G. mosseae and G. aggregatum. Protein profile revealed the presence of 12 peaks in mycorrhizal plants compared with 8 in nonmycorrhizal plants.

Fungi↗
PubMed1998

Laparoscopic cholecystectomy in multiple laparotomy Crohn's disease.

Patients with complicated Crohn's disease often require several surgical procedures resulting in multiple adhesions. They also have an increased incidence of gallstones. Laparoscopic cholecystectomy is associated with several advantages but is problematic for the inexperienced surgeon in the presence of multiple adhesions. Laparoscopic cholecystectomy was performed successfully in three patients with Crohn's disease who had previous extensive abdominal surgery. The average operative time was 75 min, with an average hospital stay of 2 days and minimal blood loss. There were no postoperative complications. Provided specific precautions are taken during establishment of the pneumoperitoneum, an adequate adhesiolysis can be performed, rendering laparoscopic cholecystectomy feasible and safe in such patients.

Cholecystectomy, Laparoscopic↗
PubMed1997

The role of radiotherapy in the surgical management of gastrointestinal cancer.

Surgery is the main mode of treatment in most gastrointestinal malignancies. Radiotherapy with or without chemotherapy is playing an increasing role as an adjunct to improve local control, survival and palliation. The principles of radiotherapy and the rationale for combination therapy are presented. The current role of radiation therapy in the GI tract is discussed by various sites. New and investigational radiotherapy techniques are outlined.

Anus Neoplasms↗
PubMed1997

Identification by replicon-typing of indigenous plasmids of Burkholderia (Pseudomonas) solanacearum.

Fifteen strains of Burkholderia (Pseudomonas) solanacearum were isolated, identified from different parts of India and screened for plasmid profile. They harboured 1-3 plasmids, but most of the isolates contained a single plasmid. Plasmids were classified on the basis of replicon typing by Southern hybridization using incompatible specific rep probes. Plasmids of 9 strains hybridized with repP probe, plasmids of 5 strains hybridized with repW probe and one plasmid hybridized with repQ probe. Fingerprint and cluster analyses of plasmids from 10 strains of B. solanacearum digested with Eco RI revealed that plasmids of race 3 strains clustered in one group and the plasmids of race 1 strains clustered in another group.

Burkholderia↗
PubMed1996

Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo.

BACKGROUND AND OBJECTIVE: A general multivariate statistical algorithm has been developed to analyze the diagnostic content of cervical tissue fluorescence spectra acquired in vivo. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess the data to reduce inter-patient and intra-patient variation of tissue spectra within a diagnostic category, without a priori information, (2) dimensionally reduce the preprocessed fluorescence emission spectrum with minimal information loss and use it to select the minimum number of the original emission variables of the fluorescence spectrum required to achieve classification with negligible decrease in predictive ability, and (3) assign a posterior probability to the diagnosis of each sample, so that samples with relative uncertain diagnosis can be reevaluated by a clinician. The algorithm was tested retrospectively and prospectively on cervical tissue spectra acquired from 476 sites from 92 patients at 337 nm excitation. RESULTS: The algorithm based on the entire fluorescence spectrum differentiates squamous intraepithelial lesions (SILs) from normal squamous epithelia and inflammation with an average sensitivity and specificity of 88% +/- 1.4 and 70% +/- 1, respectively. The average sensitivity and specificity of the identical algorithm based on intensity selected at only two emission wavelengths is 88% +/- 1.4 and 71% +/- 1.4, respectively. CONCLUSION: The multivariate statistical algorithm based on both types of spectral inputs at 337 nm excitation has a similar sensitivity and significantly improved specificity relative to colposcopy in expert hands.

Algorithms↗