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Biomedical subjects

Ajay Kumar

Publications and source records attributed to Ajay Kumar.

At least 55 records · Page 3Linked to original sources

Determination of chlorpyrifos 20% EC (Dursban 20 EC) in scented rose and its products.

The method for determination of chlorpyrifos is validated and dissipation behaviour of residue in scented rose and percent transfer in different products is described. GC-electron-capture detection with a HP-1, 30 m x 0.53 mm, 3.0 microm capillary column and nitrogen at 1 ml/min was used in the study. Plant matrices studied were: leaves, flowers, soil, rose water, absolute and concrete. Detector response linearity and sensitivity, limit of detection and determination, percent recovery were determined based on area response (mm2) of the standard. Analytical field and laboratory samples (rose water by hydro-distillation of the flowers, concrete and absolute by hexane extraction and condensation) were analysed for evaluation of the method. Samples were extracted with acetone, partitioned with water, saturated sodium chloride solution and dichloromethane. The organic layer was rotary-evaporated to 2 ml for cleanup with silica-carbon column. The column was eluted with dichloromethane-toluene-acetone (10:2:2, v/v/v) and the derived solution was rotary-evaporated to 5 ml for end analysis. Matrix enhancement effect was observed for leaf and soil samples for which corrective approach was followed to compensate for overestimation of the residue. Limit of detection for chlorpyrifos standard was 0.05 mg/l with good linearity of detector response (R2 = 0.99). Percent recovery ranged from 78 to 117% in different plant matrices (fortification level 1, 4 and 8 mg/l). Dissipation behaviour showed that chlorpyrifos was below detection limit by the 12th day of application on the scented rose with half life of 3.40 days on leaves and 3.10 days on flowers at 0.1% dosage. Percent transfer studies showed that 5.71, 46.91 and 38.80% of the residue from flowers was transferred to rose water, concrete and absolute, respectively.

Calibration↗

KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation.

The vascular endothelium is a critical regulator of vascular function. Diverse stimuli such as proinflammatory cytokines and hemodynamic forces modulate endothelial phenotype and thereby impact on the development of vascular disease states. Therefore, identification of the regulatory factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Transcriptional profiling studies identified the Kruppel-like factor (KLF)2 as being inhibited by the inflammatory cytokine interleukin-1beta and induced by laminar shear stress in cultured human umbilical vein endothelial cells. Overexpression of KLF2 in umbilical vein endothelial cells robustly induced endothelial nitric oxide synthase expression and total enzymatic activity. In addition, KLF2 overexpression potently inhibited the induction of vascular cell adhesion molecule-1 and endothelial adhesion molecule E-selectin in response to various proinflammatory cytokines. Consistent with these observations, in vitro flow assays demonstrate that T cell attachment and rolling are markedly attenuated in endothelial monolayers transduced with KLF2. Finally, our studies implicate recruitment by KLF2 of the transcriptional coactivator cyclic AMP response element-binding protein (CBP/p300) as a unifying mechanism for these various effects. These data implicate KLF2 as a novel regulator of endothelial activation in response to proinflammatory stimuli.

Base Sequence↗

Substernal epicardial echocardiography: a recommended examination sequence and clinical evaluation in patients undergoing cardiac surgery.

BACKGROUND: Substernal epicardial echocardiography is a novel echocardiography window, utilizing a modified mediastinal drain incorporating a sleeve for the insertion of a transesophageal echocardiography probe. METHODS: Forty-six patients undergoing cardiac surgery from two institutions were evaluated, and an examination sequence was developed. RESULTS: An 11-view examination is presented as a consensus between the two institutions. In clinical usage, there were no major complications attributable to use of the device. Minor air leaks occurred in 6 patients, and 2 cases of sternal wound infection occurring in a cluster of infections are reported, but causation was not attributed to use of the device. There were no significant differences in measurements of the aortic valve area, pulmonary artery diameter, left ventricular outflow tract dimension, or the sinotubular junction between substernal and transesophageal examinations. All 16 wall-motion segments were well visualized in most patients with substernal epicardial echocardiography. CONCLUSIONS: Substernal epicardial echocardiography is a safe device for use in the postoperative environment.

Cardiac Surgical Procedures↗

Biocompatibility of sorbitol-containing polyesters. Part I: Synthesis, surface analysis and cell response in vitro.

A series of sorbitol-containing polyesters were synthesized via a one-pot lipase-catalyzed condensation polymerization. Thin films were prepared by spin coating on silicon wafers and surfaces were analyzed by tapping mode atomic force microscopy and contact angle measurements. Surface morphologies and surface energies across the series of polyester films, including a poly(epsilon-caprolactone) (PCL) control were nearly indistinguishable. Biocompatibility of the sorbitol-containing polyester series was evaluated against a PCL control by measuring cell spreading and proliferation of a mouse fibroblast 3T3 cell line in vitro. Results confirmed that the sorbitol-containing polyester surfaces elicited cell behavior similar to the PCL control. These results establish the sorbitol-containing polyester series as a promising material for tissue engineering research and development.

3T3 Cells↗

Environmental radon studies using solid state nuclear track detectors.

The results of radon activity recorded in 70 dwellings of Nurpur area, Kangra district, Himachal Pradesh, India are reported. LR-115 Type 2 films in the bare mode were exposed for four seasons of three months each covering a period of one year for the measurement of indoor radon levels. The calibration constant of 0.020 tracks cm(-2) d(-1) per Bq m(-3) has been used to express radon activity in Bq m(-3). The annual average indoor radon concentrations in 17 different villages of the area are found to vary from 168+/-46 to 429+/-71. Most of the indoor radon values lie in the range of action levels (200-600 Bq m(-3)) recommended by International Commission on Radiological Protection.

Air Pollution, Indoor↗

Is chest x-ray or high-resolution computed tomography scan of the chest sufficient investigation to detect pulmonary metastasis in pediatric differentiated thyroid cancer?

We reviewed the clinical characteristics, pattern of disease at presentation, histopathologic subtype, treatment, course, and outcome of differentiated thyroid cancer (DTT) in children and adolescents presenting with pulmonary metastasis and tried to assess the effectiveness of routine chest x-ray and high-resolution computed tomography (CT) scan of the chest vis-à-vis 131I whole-body scan (WBS) in revealing pulmonary metastasis. In our series of 1754 patients, 122 (7%) were 20 years of age or younger, of whom 28 (23%) had pulmonary metastasis. Mean age was 13.9 +/- 4.4 years (F:M ratio = 12:16). All but 2 patients had undergone near-total thyroidectomy with some form of neck dissection. Histopathologic examination was papillary in 89% and follicular in 11% cases, with confirmed nodal metastasis in all. Twenty-one (75%) patients had normal chest x-ray. However, WBS revealed pulmonary metastasis in all cases. In 15 (54%) children pulmonary metastasis was detected by first postsurgery 2-3 mCi 131I WBS and in 4 (14%) patients by postablation 131I WBS. Seven cases (25%) and 2 cases were detected by first and second posttherapy 131I WBS, respectively. No statistically significant difference was observed in any of the demographic or clinical parameters in patients in whom pulmonary metastasis was detected by first postsurgical low-dose WBS versus those in whom metastasis was discovered at a later stage. When chest x-ray-positive children were compared to x-ray-negative children, a statistically significant difference was observed only for mean first dose, cumulative dose, and total number of doses of 131I, which were significantly higher in x-ray-positive children. Eighteen of 21 children who had normal chest x-ray also underwent CT scan of the chest. CT could detect micronodular pulmonary shadows in 5 (28%) children only. Complete radioiodine treatment and outcome information was available in 20 patients. Mean first dose and cumulative doses of administered 131I were 75.4 +/- 39.5 mCi and 352 +/- 263 mCi, respectively. After an average number of 3.3 doses of (131)I and mean duration of 33.2 +/- 28.5 months, pulmonary lesions disappeared in 14 (70%) patients and thyroglobulin (Tg) becoming undetectable. In 4 children, however, there was no radiologic or scintigraphical evidence of pulmonary metastasis, Tg was high and in 2 patients, disease was persisting clinically. To conclude, a large majority of pediatric patients with DTC have x-ray- and even high-resolution-negative pulmonary metastasis. However, these metastases are 131I avid, and thus are amenable to detection and treatment with radioiodine. Therefore, postsurgical evaluation with 131I is recommended in all children and adolescents.

Adolescent↗

Technetium-99m-L,L-ethylenedicysteine renal scan as a single-modality investigation for the evaluation of renal morphology and function: a comparative study with technetium-99m-dimercaptosuccinic acid.

AIM: To evaluate whether cortical scars can be detected using the summed images of technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC) renal dynamic scan, and to compare the results with technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) scan. To evaluate the inter-observer variability for 99mTc-L,L-EC and 99mTc-DMSA scan reporting. METHODS: One hundred and three patients were initially included in the study; 21 were excluded, five due to a single functioning kidney and 16 due to impaired renal function (serum creatinine>2.5 mg.dl(-1)). Eighty-two patients (39 females, 43 males), including 31 children, with a mean age of 33.4+/-11.3 years (range, 4 months to 74 years), underwent both 99mTc-DMSA and 99mTc-L,L-EC scintigraphy within a period of 14 days. 99mTc-L,L-EC images were regrouped into 2 min image sets, and the initial 2 min summed image (cortical phase) was used for the evaluation of scars. Three independent observers analysed both images separately on different days without being aware of the identity and clinical details of the patients. Their 99mTc-L,L-EC findings were compared with the consensus 99mTc-DMSA scan findings taken as reference. RESULTS: The overall sensitivity of 99mTc-L,L-EC scans was 93% and the specificity was 96%. The inter-observer variability was 0.91 for 99mTc-L,L-EC and 0.94 for 99mTc-DMSA scan reporting, using the weighted kappa analysis at P<0.05. CONCLUSIONS: 99mTc-L,L-EC is an excellent single-modality comprehensive investigational agent for renal morphology, function and outflow tract evaluation with the added advantages of lower cost, convenience and low radiation exposure to the patient.

Adolescent↗

Prominent ears in children younger than 4 years of age: what is the appropriate timing for otoplasty?

The present study was conducted to determine whether otoplasty performed in children younger than 4 years of age has an acceptable long-term outcome. This two-part study consisted of (1) a questionnaire mailed to 481 members of the American Association of Plastic Surgeons to ask their opinion on the timing of otoplasty, and (2) a consecutive series of 12 patients who had otoplasty performed before the age of 4 years. The survey demonstrated that the majority (57 percent) of the respondents perform otoplasty on patients who are aged 5 years or older. The prospective series consisted of 12 patients ranging in age from 9 months to 3 years at the time of the procedure. Otoplasty was bilateral in nine patients and unilateral in three patients. Length of follow-up ranged from 21 months to 7(1/2) years, with a median follow-up of 41 months. Growth following otoplasty was evaluated in three patients who underwent unilateral otoplasty by measuring the length of both ears at the time of final follow-up. No difference in ear length was noted between the sides that were and were not operated on during a follow-up period of 46 to 63 months. Noticeable recurrence was noted in only one (8 percent) of 12 patients. In response to a follow-up questionnaire to the patients' families, all respondents (n = 10) stated that if again asked to choose the timing of otoplasty in their children, they would opt to have it performed at the same age of younger than 4 years. Otoplasty can be safely performed at ages younger than previously thought without interfering with growth of the operated ear.

Age Factors↗

Radioiodine dose for remnant ablation in differentiated thyroid carcinoma: a randomized clinical trial in 509 patients.

Remnant ablation can be achieved by either administering an empiric fixed dose or using dosimetry-guided techniques. Because of the technical and logistic difficulties, most centers have adapted the fixed-dose or standard-dose technique for remnant ablation using (131)I. In the late 1970s, low-dose (131)I remnant ablation was introduced, and subsequently many centers confirmed the effectiveness of such therapy. However, the optimal dose (administered activity) of (131)I for remnant ablation is not yet settled. In a randomized clinical trial to find out the smallest possible effective dose for remnant ablation in cases of differentiated thyroid carcinoma, between July 1995 and January 2002, 565 patients were randomized into eight groups according to (131)I administered activity, starting at 15 mCi and increasing activity in increments of 5 mCi until 50 mCi. In the postrandomization phase, 56 patients were excluded from the study for various reasons, and final analysis was done with 509 patients. The mean age of the patients was 37.5 +/- 12.7 yr with a female to male ratio of 2.6. The surgical procedure was total/near-total thyroidectomy in 72% and subtotal or hemithyroidectomy in the rest. Histology was papillary thyroid carcinoma in 80.6% of patients and follicular thyroid carcinoma in the rest. With one dose of (131)I, remnant ablation was achieved in 59.6, 63.6, 81.4, 83.6, 79.4, 78.3, 84.4, and 81.8% of patients in the 15- to 50-mCi groups, respectively (overall ablation rate, 77.6%). The successful ablation rate was statistically different in patients receiving less than 25 mCi of (131)I compared with those receiving at least 25 mCi [63 of 102 (61.8%) vs. 332 of 407 (81.6%); P = 0.006]. However, there was no significant intergroup difference in outcome among patients receiving 25-50 mCi of (131)I. Patients with small tumor size (</=5 cm), adequate surgery (total/near-total thyroidectomy), and radioiodine neck uptake of less than or equal to 10% had odds ratios of 2.4 [confidence interval (CI), 1.3-3.98], 2.6 (CI, 1.6-4.2), and 2.2 (CI, 1.4-3.5), respectively, for successful remnant ablation. Patients receiving at least 25 mCi of (131)I had a three times better chance of getting remnant ablation than patients receiving lesser activity of (131)I. Any activity of (131)I between 25 and 50 mCi appears to be adequate for remnant ablation.

Adenocarcinoma, Follicular↗

Effect of partial exchange transfusion in asymptomatic polycythemic LBW babies.

This randomized controlled trial was conducted to determine the effect of partial exchange transfusion in polycythemic babies. Forty five asymptomatic polycythemic babies with birth weight < or = 2000 g were included and randomly assigned to undergo either partial exchange transfusion using isotonic saline within 4 hours of screening or routine medical management. Outcome measures were neonatal morbidity (especially hypoglycemia and neurological alterations) and mortality; developmental delays using DDST-II, neurological deficits, tone and DTR abnormalities over 18 months follow up period. The overall neonatal morbidity in this study was low and comparable in the two groups. Some of the polycythemic babies in the non-exchanged group found initially at 3 months age with "suspected development" grew out of their developmental delay at 18 months of age or later while those who underwent exchange transfusion and with retarded development at 3 months of age remained so even at 18 months of age.

Developmental Disabilities↗

Anterior lens capsule vascularity in evaluating gestation in small for gestation neonates.

This study evaluated the role of anterior lens capsule vascularity in assessing gestation in small for gestational age (SGA) neonates in a prospective manner. Neonates with birth weight less than 2000 g were recruited. Those with gross congenital malformations, including corneal opacity or cataract and evidence of TORCH infection were excluded from the study. A total of 139 subjects were enrolled into the study (60-appropriate for gestational age (AGA) and 79 small for gestational age (SGA) neonates). Clinical gestational age assessment and ophthalmoscopic examination for anterior lens capsule vascularity grading were done within 24 hours of birth by independent blinded observers. The correlation of lens capsule grading with clinical gestation in AGA neonates (r2 = 0.75) was stronger compared to SGA neonates (r2 = 0.50). Gestational age assessment by lens capsule grading had a better agreement with clinical gestation in AGA subjects (Kappa Index - 0.56 in AGA vs. 0.26 in SGA). The lens capsule grading under-estimated the gestation of SGA subjects by an average of three weeks compared to AGA neonates.

Female↗

Synthesis, characterization and in vitro anti-invasive activity screening of polyphenolic and heterocyclic compounds.

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

Antineoplastic Agents↗

Differentiated thyroid cancer.

OBJECTIVE: The retrospective analysis of the case files of children with differentiated thyroid carcinoma (DTC) was performed to define the disease by its presentation, clinical course and outcome of radioiodine therapy. METHODS: Between 1967 to October 2002, 1754 patients with thyroid cancer were treated in the Dept of Neuclear Medicine, AIIMS, out of which 122 (7%) were < or = 20 years of age (71 girls and 51 boys). The mean age was 15.8 +/- 3.6 years and the mean duration of follow-up was 90 +/- 59.3 months. Mean tumor size was 4.4 cm. Histologically, 85% of the patients had papillary and rest follicular carcinoma. Cervical lymph node involvement was seen in 64%, and distant metastases, mainly pulmonary, in 23% of the patients. The presentation of the disease was very aggressive in the first decade of life with male preponderance. All but one patient in this age group had nodal and/or distant metastases; in 83.3% the disease had spread to the lymph nodes and 67% had metastases to the lungs. The post-surgery 48-hour mean radioiodine neck uptake was 10.5 +/- 7.6%. RESULTS: 94% of the residual thyroid, 88% of nodal metastases and 71% of pulmonary metastases were ablated requiring mean cumulative doses of 2.8 +/- 2.7 GBq, 4.5 +/- 2.7 GBq and 10.4 +/- 7.9 GBq of 131I, respectively. Average number of doses required for remnant, nodal and pulmonary metastases ablation were 1.3, 2.2 and 3.3, respectively. 80% of the patients with only remnant thyroid tissue and 50% with cervical lymph node metastases got ablated with a single dose of 131I. Overall, 87% patients were currently free of disease. While, nine patients had nodal recurrence between surgery and radioiodine treatment, no recurrence was observed thereafter and 3 disease related deaths producing overall mortality of 2.5% (all in children < or =10 years of age) were seen in the mean follow-up of 7.5 years. CONCLUSION: Differentiated thyroid cancer in children and adolescents is rare but aggressive. The biological behavior differs from that in adults and is related to the age. Younger the age (< or =10 years), more aggressive and widespread is the disease with male preponderance and high mortality. The post-surgical radioiodine ablation/therapy is an important and effective adjuvant in the management of DTC in children and adolescents and even though they present with advance disease, long-term survival and overall prognosis is good.

Adolescent↗

Fetal hydrocolpos leading to Pierre Robin sequence: an unreported effect of oligohydramnios sequence.

The presence of distal atretic vagina causing accumulation of fluid and mucus secretions in the proximal vaginal cavity resulted in fetal hydrocolpos. Obstructive uropathy developed gradually because of direct compression of hydrocolpos on bilateral lower ureters, resulting in oligohydramnios from decreased urine formation. Oligohydramnios inhibited normal mandibular development with resulting cleft palate and glossoptosis (Pierre Robin Sequence). The development of sequence of events in this case indicates Pierre Robin Sequence as another effect of Oligohydramnios Sequence arising out of deformational forces acting on cranio-facial structures.

Adult↗

The high-risk human papillomavirus type 16 E6 counters the GAP function of E6TP1 toward small Rap G proteins.

We have recently identified E6TP1 (E6-targeted protein 1) as a novel high-risk human papillomavirus type 16 (HPV16) E6-binding protein. Importantly, mutational analysis of E6 revealed a strong correlation between the transforming activity and its abilities to bind and target E6TP1 for ubiquitin-mediated degradation. As a region within E6TP1 has high homology with GAP domains of known and putative Rap GTPase-activating proteins (GAPs), these results raised the possibility that HPV E6 may alter the Rap small-G-protein signaling pathway. Using two different approaches, we now demonstrate that human E6TP1 exhibits GAP activity for Rap1 and Rap2, confirming recent findings that a closely related rat homologue exhibits Rap-specific GAP activity. Using mutational analysis, we localize the GAP activity to residues 240 to 945 of E6TP1. Significantly, we demonstrate that coexpression of HPV16 E6, by promoting the degradation of E6TP1, enhances the GTP loading of Rap. These results support a role of Rap small-G-protein pathway in E6-mediated oncogenesis.

Cell Line↗

Cloning, expression, activity and folding studies of serine hydroxymethyltransferase: a target enzyme for cancer chemotherapy.

All the members of pyridoxal-5'-phosphate-dependent enzymes are involved in the metabolism of amino acids. The sequence homology studies further divide this family into three distinct groups. A fine scrutiny of the reactions catalyzed by these enzymes shows their regio specificity; they have been considered as the largest group of enzymes having tendency to affect the valency of the same carbon atom that carries the amino group forming an amine linkage with the coenzyme. Thus, this group was named 'alpha-class of enzymes'. Serine hydroxymethyltransferase (SHMT) is a member of this alpha-class; it reversibly catalyses the conversion of serine into glycine while the hydroxymethyl group is transferred to 5,6,7,8-tetrahydrofolate. The resultant compound is the sole precursor of purine biosynthesis. Henceforth, this enzyme greatly affects nucleic acid biosynthesis in all the organisms. It is obvious that SHMT plays an indispensable role in nucleic acid biosynthesis; therefore, designing and developing a repressor/inhibitor of the SHMT gene/protein may resolve the problem of drug resistance to cancer chemotherapy. SHMT has been widely studied in many living systems (e.g. Escherichia coli, humans, sheep, rabbits, Trypanosoma, Arabidopsis, peas, tobacco) in terms of its structure, cloning, expression, purification and folding patterns. Such studies have enabled one to assess the pattern of overall kinetic and activity behaviour of the enzyme, which may further help in developing a suitable cancer therapeutic molecule.

Amino Acid Sequence↗

Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator.

The expression of human papillomavirus (HPV) E6 oncoprotein is causally linked to high-risk HPV-associated human cancers. We have recently isolated hADA3, the human homologue of yeast transcriptional co-activator yADA3, as a novel E6 target. Human ADA3 binds to the high-risk (cancer-associated) but not the low-risk HPV E6 proteins and to immortalization-competent but not to immortalization-defective HPV16 E6 mutants, suggesting a role for the perturbation of hADA3 function in E6-mediated oncogenesis. We demonstrate here that hADA3 directly binds to the retinoic X receptor (RXR)alpha in vitro and in vivo. Using chromatin immunoprecipitation, we show that hADA3 is part of activator complexes bound to the native RXR response elements within the promoter of the cyclin-dependent kinase inhibitor gene p21. We show that hADA3 enhances the RXR(alpha)-mediated sequence-specific transactivation of retinoid target genes, cellular retinoic acid-binding protein II and p21. Significantly, we demonstrate that E6 inhibits the RXR(alpha)-mediated transactivation of target genes, implying that perturbation of RXR-mediated transactivation by E6 could contribute to HPV oncogenesis.

Animals↗