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Biomedical subjects

S Naqvi

Publications and source records attributed to S Naqvi.

At least 19 recordsLinked to original sources
PubMed2005

Security architecture for health grid using ambient intelligence.

OBJECTIVES: To propose a novel approach of incorporating ambient intelligence in the health grid security architecture. METHODS: Security concerns are severely impeding the grid community effort in spreading its wings in health applications. In this paper, we have proposed a high level approach to incorporate ambient intelligence for health grid security architecture and have argued that this will significantly improve the current state of the grid security paradigm with an enhanced user-friendly environment. We believe that the time is right to shift the onus of traditional security mechanisms onto the new technologies. The incorporation of ambient intelligence in the security architecture of a grid will not only render a security paradigm robust but also provide an attractive vision for the future of computing by bringing the two worlds together. RESULTS: In this article we propose an evolutionary approach of utilizing smart devices for grid security architecture. We argue that such an infrastructure will impart unique features to the existing grid security paradigms by offering fortified and relentless monitoring. This new security architecture will be comprehensive in nature but will not be cumbersome for the users due to its typical characteristics of not prying into their lives and adapting to their needs. CONCLUSIONS: We have identified a new paradigm of the security architecture for a health grid that will not only render a security mechanism robust but will also provide the high levels of user-friendliness. As our approach is a first contribution to this problem, a number of other issues for future research remain open. However, the prospects are fascinating.

Access to Information↗
PubMed2003

Inverse planning for intensity-modulated arc therapy using direct aperture optimization.

Intensity-modulated arc therapy (IMAT) is a radiation therapy delivery technique that combines gantry rotation with dynamic multi-leaf collimation (MLC). With IMAT, the benefits of rotational IMRT can be realized using a conventional linear accelerator and a conventional MLC. Thus far, the advantages of IMAT have gone largely unrealized due to the lack of robust automated planning tools capable of producing efficient IMAT treatment plans. This work describes an inverse treatment planning algorithm, called 'direct aperture optimization' (DAO) that can be used to generate inverse treatment plans for IMAT. In contrast to traditional inverse planning techniques where the relative weights of a series of pencil beams are optimized, DAO optimizes the leaf positions and weights of the apertures in the plan. This technique allows any delivery constraints to be enforced during the optimization, eliminating the need for a leaf-sequencing step. It is this feature that enables DAO to easily create inverse plans for IMAT. To illustrate the feasibility of DAO applied to IMAT, several cases are presented, including a cylindrical phantom, a head and neck patient and a prostate patient.

Algorithms↗
PubMed2003

A toolbox for intensity modulated radiation therapy optimization.

We have designed a toolbox that provides an environment for testing radiotherapy optimization techniques, objective functions, and constraints. A set of three-dimensional (3D) pencil beam dose distributions have been computed for a cylindrical phantom. The 6 MV pencil beams were computed using a superposition-based dose engine commissioned for an Elekta SL20 linear accelerator. Due to the cylindrical symmetry of the phantom, the pencil beam dose distributions for any arbitrary beam angle can be determined by simply rotating the pencil beam data sets. Thus, the full accuracy is maintained without the need for additional dose calculations or large data storage requirements. In addition to the pencil beam data sets, tools are included for (1) rotating the pencil beams, (2) calculating the beam's eye view, (3) drawing structures, (4) writing the pencil beam dose data out to the optimizer, and (5) visualizing the optimized results. The pencil beam data sets and the corresponding tools are available for download at http://medschool.umaryland.edu/departments/radiationoncology/pencilbeam/. With this toolbox, researchers will have the ability to rapidly test new optimization techniques and formulations for intensity modulated radiation therapy and 3D conformal radiotherapy.

Algorithms↗
PubMed2002

Structure-affinity relationships in the gp41 ELDKWA epitope for the HIV-1 neutralizing monoclonal antibody 2F5: effects of side-chain and backbone modifications and conformational constraints.

The human monoclonal antibody, mAb 2F5, has broad HIV-1 neutralizing activity and binds a conserved linear epitope within the envelope glycoprotein gp41 having a core recognition sequence ELDKWA. In this study, the structural requirements of this epitope for high-affinity binding to mAb 2F5 were explored using peptide synthesis and competitive enzyme-linked immunosorbant assay (ELISA). Expansion of the minimal epitope to an end-capped, linear nonapeptide, Ac-LELDKWASL-amide, was sufficient to attain maximal affinity within the set of native gp41-sequence peptides assayed. Scanning single-residue alanine and d-residue substitutions then confirmed the essential recognition requirements of 2F5 for the central DKW sequence, and also established the importance of the terminal leucine residues in determining high-affinity binding of the linear nonapeptide. Further studies of side-chain and backbone-modified analogs revealed a high degree of structural specificity for the DK sequence in particular, and delineated the steric requirements of the Leu(3) and Trp(6) residues. The nine-residue 2F5 epitope, flanked by pairs of serine residues, retained a high affinity for 2F5 when it was conformationally constrained as a 15-residue, disulfide-bridged loop. However, analogs with smaller or larger loop sizes resulted in lower 2F5 affinities. The conformational effects of the gp41 C-peptide helix immediately adjacent to the N-terminal end of the ELDKWA epitope were examined through the synthesis of helix-initiated analogs. Circular dichroism (CD) studies indicated that the alpha-helical conformation was propagated efficiently into the LELDKWASL epitope, but without any significant effect on its affinity for 2F5. This study should guide the design of a second generation of conformationally constrained ELDKWA analogs that might elicit an immune response that mimics the HIV-neutralizing actions of 2F5.

Amino Acid Sequence↗
PubMed2002

Direct aperture optimization: a turnkey solution for step-and-shoot IMRT.

IMRT treatment plans for step-and-shoot delivery have traditionally been produced through the optimization of intensity distributions (or maps) for each beam angle. The optimization step is followed by the application of a leaf-sequencing algorithm that translates each intensity map into a set of deliverable aperture shapes. In this article, we introduce an automated planning system in which we bypass the traditional intensity optimization, and instead directly optimize the shapes and the weights of the apertures. We call this approach "direct aperture optimization." This technique allows the user to specify the maximum number of apertures per beam direction, and hence provides significant control over the complexity of the treatment delivery. This is possible because the machine dependent delivery constraints imposed by the MLC are enforced within the aperture optimization algorithm rather than in a separate leaf-sequencing step. The leaf settings and the aperture intensities are optimized simultaneously using a simulated annealing algorithm. We have tested direct aperture optimization on a variety of patient cases using the EGS4/BEAM Monte Carlo package for our dose calculation engine. The results demonstrate that direct aperture optimization can produce highly conformal step-and-shoot treatment plans using only three to five apertures per beam direction. As compared with traditional optimization strategies, our studies demonstrate that direct aperture optimization can result in a significant reduction in both the number of beam segments and the number of monitor units. Direct aperture optimization therefore produces highly efficient treatment deliveries that maintain the full dosimetric benefits of IMRT.

Algorithms↗
PubMed2001

Monte Carlo dose verification for intensity-modulated arc therapy.

Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan. Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-Ill computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

Dose-Response Relationship, Radiation↗
PubMed2001

Conformal photon-beam therapy with transverse magnetic fields: a Monte Carlo study.

This work studies the idea of using strong transverse magnetic (B) fields with high-energy photon beams to enhance dose distributions for conformal radiotherapy. EGS4 Monte Carlo code is modified to incorporate charged particle transport in B fields and is used to calculate effects of B fields on dose distributions for a variety of high-energy photon beams. Two types of hypothetical B fields, curl-free linear fields and dipole fields, are used to demonstrate the idea. The major results from the calculation for the linear B fields are: (1) strong transverse B fields (> 1 T) with high longitudinal gradients (G) (> 0.5 T/cm) can produce dramatic dose enhancement as well as dose reduction in localized regions for high-energy photon beams; (2) the magnitude of the enhancement (reduction) and the geometric extension and the location of this enhancement (reduction) depend on the strength and gradient of the B field, and photon-beam energy; (3) for a given B field, the dose enhancement generally increases with photon-beam energy; (4) for a 5 T B field with infinite longitudinal gradient (solenoidal field), up to 200% of dose enhancement and 40% of dose reduction were obtained along the central axis of a 15 MV photon beam; and (5) a 60% of dose enhancement was observed over a 2 cm depth region for the 15 MV beam when B = 5 T and G = 2.5 T/cm. These results are also observed, qualitatively, in the calculation with the dipole B fields. Calculations for a variety of B fields and beam configurations show that, by employing a well-designed B field in photon-beam radiotherapy, it is possible to achieve a significant dose enhancement within the target, while obtaining a substantial dose reduction over critical structures.

Biophysical Phenomena↗
PubMed2000

Cole-Hughes macrocephaly syndrome and associated autistic manifestations.

Based on cases that had been excluded from a previous clinical study of Sotos syndrome, Cole and Hughes [1991: Am J Med Genet 41:115-124] reported a new syndrome associated with marked obesity, occasional delayed bone age, distinctive facial anomalies, mental retardation, and progressive postnatal macrocephaly in the context of autosomal dominant familial macrocephaly. Subsequently, Stevenson et al. [1997: Lancet 349:1744-1745] emphasized the association of progressive postnatal macrocephaly with autism, and they suggested that this might comprise a recognizable autism syndrome. We report two additional patients with Cole-Hughes syndrome and associated autistic characteristics with attention deficit hyperactivity disorder. These patients seem to manifest a distinctive behavioral phenotype associated with Cole-Hughes syndrome and they manifest a distinct subgroup of persons with autism that may ultimately shed light on the pathogenesis of this disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Differential anti-inflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production.

OBJECTIVE AND DESIGN: Cyclosporin, FK-506 and rapamycin have similar but distinct modes of interaction with cyclophilins, calcineurins and transcription factors. These immunosuppressive drugs have also been shown to inhibit cytotoxic and inflammatory responses in macrophage. Therefore, we evaluated the mechanism of action of these drugs on iNOS and COX-2 expression by macrophages, the products of which (NO and PGE2) have cytotoxic and proinflammatory activities. MATERIALS AND METHODS: The murine macrophage cell line RAW 264.7 was grown as monolayer cultures. The effects of pharmacologically relevant concentrations of cyclosporin, rapamycin and FK-506 were evaluated in the presence and absence of lipopolysaccharide (LPS) which is a known inducer of iNOS and COX-2. Subsequently the expression of iNOS and COX-2 were analyzed by Western and Northern analysis. The production of NO and PGE2 were assayed by Greiss and RIA respectively. RESULTS: Cyclosporin (1-5 microg/ml) and rapamycin (1.0-10 nM) but not FK-506 (5-10 nM) inhibited both iNOS and COX-2 expression at mRNA level which led to significant inhibition of NO and PGE2 production. CONCLUSION: These studies characterize differential mechanistic capacity of the immunophilin-binding immunosuppressive drugs (comparable to hydrocortisone) to inhibit both iNOS and COX-2 expression. Inhibition of iNOS and COX-2 mRNA accumulation by cyclosporin and rapamycin seem to be distinct. These studies also highlight potential anti-inflammatory properties of these drugs in addition to their known immunosuppressive activity.

Animals↗
PubMed2000

Control of photon beam dose profiles by localized transverse magnetic fields.

Unlike electron beams, scant attention has been paid in the literature to possible magnetic field effects on therapeutic photon beams. Generally, dose profiles are considered to be fully determined by beam shape, photon spectrum and the substances in the beam path. Here we show that small superconducting magnets can exercise potentially useful control over photon dose profiles. The magnet produces a locally strong transverse field with large gradients and is applied to the tissue surface below which the photon beam is passing. For one practical magnet design, our simulations, which use the EGS-4 Monte Carlo code modified to include magnetic field effects, show significant intensification and shielding effects. In water phantoms, the effects extend to 3-4 cm or more beyond the warm face of the cryostat and greater distances are achieved in phantoms simulating lung (density approximately 0.3). Advances in applying the concept and in superconducting materials and magnet design hold promise for extending these ranges.

Humans↗
PubMed2000

Interactions between the prohormone convertase 2 promoter and the thyroid hormone receptor.

The majority of prohormones are cleaved at paired basic residues to generate bioactive hormones by prohormone convertases (PCs). As PC1 and PC2, two neuroendocrine-specific PCs, appear to be the key enzymes capable of processing a variety of prohormones, alterations of PC2 and/or PC1 levels will probably have a profound effect on hormonal homeostasis. We investigated the regulation of PC2 messenger RNA (mRNA) by thyroid hormone using GH3 cells to demonstrate that T3 negatively regulated PC2 mRNA levels in a dose- and time-dependent fashion. Functional analysis of progressive 5'-deletions of the human (h) PC2 promoter luciferase constructs in GH3 cells demonstrated that the regulation probably occurs at the transcriptional level, and that putative negative thyroid hormone response elements were located within the region from -44 to + 137 bp relative to the transcriptional start site. Transient transfections in JEG-3 cells and COS-1 cells showed that the suppressive effect of T3 was equally mediated by the thyroid hormone receptor (TR) isoforms TRalpha1 and TRbeta1. Electrophoretic mobility shift assays using purified TRal and retinoid X receptor-beta protein as well as GH3 nuclear extracts showed that regions from +51 to +71 bp and from +118 to +137 bp of the hPC2 promoter bind to TRalpha1 as both a monomer and a homodimer and with TRalpha1/retinoid X receptor-beta as a heterodimer. Finally, the in vivo regulation of pituitary PC2 mRNA by thyroid status was demonstrated in rats. These results demonstrate that T3 negatively regulates PC2 expression at the transcriptional level and that functional negative thyroid hormone response elements exist in the hPC2 promoter. We postulate that the alterations of PC2 activity may mediate some of the pathophysiological consequences of hypo- or hyperthyroidism.

Animals↗
PubMed1997

Effects of blood pH and blood lactate on growth hormone, prolactin, and gonadotropin release after acute exercise in male volunteers.

It has recently been found that prevention of the acidosis of anaerobic exercise blocks beta-endorphin release. Because heavy exercise affects secretion of other anterior pituitary hormones, we studied the results of alkali infusion and ingestion upon blood levels of four hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Eight male subjects were studied after either 2 mEq/kg placebo (NaCl) or alkali (NaHCO3) administered before and during exercise to exhaustion. Blood samples were obtained before exercise and then 15, 30, 60, 90, 120, and 180 min postexercise. GH and PRL but not FSH or LH increased significantly postexercise, with a peak at 60 min, and subsequently declined back to baseline by 180 min. Base treatment reduced GH at baseline and postexercise (except at 60 min) and increased PRL significantly, particularly at 60 min. While the precise mechanisms on how acid/base changes affect hormone release remain to be defined, there are possible consequences on gonadal function and substrate availability during exercise.

Acidosis↗
PubMed1996

Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is complicated by restenosis within 6 months in > 40% of patients. Theoretical, animal experimental, and human epidemiological and clinical trial findings have suggested that fish oils (n-3) might reduce restenosis. Low-molecular-weight heparin (LMWH) has reduced cellular proliferation and restenosis in several experimental systems. METHODS AND RESULTS: We randomized 814 patients to fish oils (5.4 g n-3 fatty acids) or placebo a median of 6 days before PTCA and continued for 18 weeks. At the time of sheath removal, 653 patients with at least one successfully dilated lesion were randomized to LMWH (30 mg SC BID) or control for 6 weeks in a 2 x 2 factorial design. Follow-up with quantitative coronary angiography (QCA; target, 18 weeks) was interpretable on 96% of these patients. Restenosis rates per patient were for n-3, 46.5%; placebo, 44.7%; LMWH, 45.8%; and control, 45.4%. Restenosis rates per lesion were for n-3, 39.7%; placebo, 38.7%; LMWH, 38%; and control, 40.4%. At follow-up QCA, mean minimal lumen diameters were (mm) for n-3, 1.12; placebo, 1.10; LMWH, 1.12; and control, 1.10. Fifteen percent of patients permanently discontinued n-3/placebo before study completion, and 21% of patients discontinued LMWH early. There were no significant differences in the occurrences of ischemic events. Bleeding was more common with LMWH, usually was mild, and led to early discontinuation of study medication in only 0.9% of patients. Gastrointestinal side effects were more common in patients receiving n-3 than placebo. CONCLUSIONS: There is no evidence for a clinically important reduction of PTCA restenosis in this trial by either n-3 or LMWH. Evaluation of the results for n-3 in the context of previously published data on the reduction of PTCA restenosis indicates that n-3 is not efficacious and that further trials are unwarranted.

Adult↗
PubMed1994

Primary structure of hemoglobin from cobra Naja naja naja.

Cobra snake Naja naja naja hemoglobin shows four bands on Triton electrophoresis. We present the primary structure of one alpha and one beta chain. The separation of polypeptide chains was achieved by ion exchange chromatography on carboxymethyl cellulose column. The amino acid sequence was established by automatic Edman degradation of the native chains and tryptic and hydrolytic peptides in a gas-phase sequencer. The structural data are compared with those of human and other reptile hemoglobins and reveal not only large variations from human but within reptiles. The amino acid exchanges involve several subunit contacts and heme binding sites. This is the first study on the hemoglobin of a land snake. There are only two amino acid sequences of sea snake hemoglobin (Microcephalophis gracilis gracilis and Liophis miliaris) reported in the literature.

Amino Acid Sequence↗
PubMed1993

Thyroid hormones in diabetic ketoacidosis before and after therapy.

Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM % on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH response to TRH was blunted due to suppression of hypothalamic pituitary thyroid axis which takes more than a week for complete recovery.

Adolescent↗
PubMed1992

Glucoregulatory hormones in hepatic cirrhosis.

In the present study hormonal responses to 75 gm oral glucose were studied in 34 biopsy proven cases of hepatic cirrhosis and 15 normal subjects. Though fasting blood glucose was similar in both controls and cirrhotics the latter showed higher glucose values throughout the study. The peak of glucose level in cirrhotics was delayed to 60 minutes. Two of 34 (5.8%) cirrhotics showed marginal fasting hyperglycaemia and 44% had (impaired glucose tolerance (IGT). There was no significant difference (P > 0.05) in blood glucose levels in patients with and without varices. The fasting serum insulin was significantly raised in cirrhotics (24.9 +/- 2.2 vs 8.4 +/- 1.2 mu/ml, p > 0.05). Hyperinsulinaemia was significantly marked in cirrhotics with abnormal Oral glucose tolerance test (OGTT) as compared to those who had normal OGTT. The mean fasting serum insulin concentration in patients with and without varices was similar showing thereby that portasystemic shunt in cirrhotics is not the cause for peripheral hyper-insulinaemia. Basal cortisol was similar in cirrhotics and controls though expected fall in cirrhotics like control was absent. Twelve percent cirrhotics had basal human growth hormone (hGH) more than 10 ng/ml. Forty four percent showed paradoxical rise of hGH. hGH has significantly high (p < 0.01) in cirrhotics with abnormal OGTT as compared to those with normal OGTT.

Adult↗
PubMed1987

Partial sequence of hemoglobin from cobra (Naja naja naja).

Hemoglobin from the cobra snake, Naja naja naja, was isolated and its chains separated on a CM-cellulose column. The separation profile revealed an alpha and two beta chains having the molar proportions of [alpha]2[beta 1]1[beta 2]1. The N-terminal amino acid sequence of the intact chains and of the CNBr peptides were carried out. The beta 2 chain was found to be heterogeneous comprising a minor component amounting to 11%. This later showed changes at two positions 9 and 14 in the first 30 residues sequenced.

Amino Acid Sequence↗