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Biomedical subjects

A Pradhan

Publications and source records attributed to A Pradhan.

At least 19 recordsLinked to original sources
PubMed2006

Can novice drivers be trained to scan for information that will reduce their likelihood of a crash?

Sixteen year old drivers are involved in 10.3 fatal crashes per 100 million vehicle miles, a rate almost double that of 18 year olds and almost eight times that of 45-64 year olds, who are the safest group of drivers. Crash rates are particularly higher during the first month of licensure and decline rapidly for about six months and 1000 miles and then much more slowly for at least two years, consistent with a typical learning curve. Research indicates that drivers who have their learner's permit or are just newly licensed have particular difficulties identifying areas of a scenario from which hidden risks could emerge. Standard driver education programs do not appear to address these difficulties adequately. This suggests that some alternative form of driver training could reduce the crashes, either in the classroom or on the road. A PC based program designed to teach drivers to recognize risks early on is shown to improve their awareness of hazards, both on an advanced driving simulator and on the road.

Accidents, Traffic↗
PubMed2006

Does the method of treatment affect the outcome in soft-tissue sarcomas of the adductor compartment?

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.

Adolescent↗
PubMed2005

Synthesis and antibacterial properties of silver nanoparticles.

Nanometer sized silver particles were synthesized by inert gas condensation and co-condensation techniques. Both techniques are based on the evaporation of a metal into an inert atmosphere with the subsequent cooling for the nucleation and growth of the nanoparticles. The antibacterial efficiency of the nanoparticles was investigated by introducing the particles into a media containing Escherichia coli. The antibacterial investigations were performed in solution and on petri dishes. The silver nanoparticles were found to exhibit antibacterial effects at low concentrations. The antibacterial properties were related to the total surface area of the nanoparticles. Smaller particles with a larger surface to volume ratio provided a more efficient means for antibacterial activity. The nanoparticles were found to be completely cytotoxic to E. coli for surface concentrations as low as 8 microg of Ag/cm2.

Anti-Bacterial Agents↗
PubMed2004

Differentially expressed genes in adult familial myelodysplastic syndromes.

The precise genetic events leading to myelodysplastic syndromes (MDSs) and leukemic transformation remain poorly defined. Even less is known about adult familial MDS. We report an adult MDS family in whom enriched tissue-specific transcripts were derived by subtractive hybridization of cDNA from the mononuclear and CD34+ cells of affected and unaffected family members. These expression libraries were then hybridized to Genome Discovery arrays containing 18 404 genes and expressed sequence tags, and several clusters of differentially expressed genes were identified. A group of 21 genes was underexpressed (>5-fold) in affected vs unaffected family members, and among these were transcription factors and genes involved in myeloid differentiation, such as ZNF140 and myeloid nuclear differentiation antigen (MNDA). Another group of 36 genes was overexpressed (>5-fold), and these encoded proteins belonging to signaling pathways, such as Ras- and Fos-related genes. The top two genes downregulated in this MDS family, ZNF140 and MNDA, were similarly altered in another MDS family, and in some cases of sporadic MDS. Our data suggest that we have identified genes differentially expressed in adult familial MDS, and that alteration of some of these genes may also be important for the evolution of different stages or severity of sporadic MDS.

Adolescent↗
PubMed2004

Value of routine transvaginal ultrasound scan in women requesting early termination of pregnancy.

This was a retrospective study of 140 women attending a termination clinic from 1 April 2002 to 31 March 2003. All women had a transvaginal ultrasound scan. Of 140 women, 56 women benefited from the scan; 26.7% had non-viable pregnancy, 35.71% did not remember their LMP, 12.5% had discrepancy between the scan and LMP. Incidental findings were noted in 24.6% of which two had a twin gestation, nine had ovarian cysts, one had an ectopic pregnancy, one had a hydatidiform mole, one conceived with an IUCD and one had a bicornuate uterus with pregnancy in one horn. Two of the nine women with ovarian cysts needed a laparotomy. This study concludes that routine transvaginal scan (TVS) scan is an essential investigation for proper assessment of all women requesting termination of pregnancy. TVS is a safe and effective procedure which provides useful information regarding gestational age, viability of pregnancy and uncertain dates. In cases of the ectopic pregnancy and the hydatidiform mole transvaginal ultrasound helped us in appropriate management from the outset and minimised complications.

Abortion, Induced↗
PubMed2002

High-dose cyclophosphamide without stem-cell rescue for refractory CIDP.

Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.

Adult↗
PubMed2002

High-dose cyclophosphamide for severe systemic lupus erythematosus.

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.

Adult↗
PubMed2000

Extinction transition in bacterial colonies under forced convection.

We report the spatiotemporal response of Bacillus subtilis growing on a nutrient-rich layer of agar to ultraviolet (UV) radiation. Below a crossover temperature, the bacteria are confined to regions that are shielded from UV radiation. A forced convection of the population is effected by rotating a UV radiation shield relative to the Petri dish. The extinction speed at which the bacterial colony lags behind the shield is found to be qualitatively similar to the front velocity of the colony growing in the absence of a hostile environment as predicted by the model of Dahmen, Nelson, and Shnerb. A quantitative comparison is not possible without considering the slow dynamics and time-dependent interaction of the population with the hostile environment.

Bacillus subtilis↗
PubMed1999

Synthesis and dopamine receptor modulating activity of unsubstituted and substituted triproline analogues of L-prolyl-L-leucyl-glycinamide (PLG).

Triprolines Pro-Pro-Pro-NH2 (4), Pro-Pro-D-Pro-NH2 (5), Pro-Pro(trans-3-Me)-D-Pro-NH2 (6), and Pro-Pro(cis-3-Me)-D-Pro-NH2 (7) were made as conformationally constrained analogues of Pro-Leu-Gly-NH2. Triprolines 4-6 produced significant increases in the high- and low-affinity state ratio (RH/RL) of the dopamine receptor, but only 4 was found to increase apomorphine induced rotations in 6-hydroxydopamine-lesioned rats.

Animals↗
PubMed1999

Synthesis and dopamine receptor modulating activity of substituted bicyclic thiazolidine lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide.

6-Substituted bicyclic thiazolidine lactam peptidomimetics of Pro-Leu-Gly-NH(2) (1) were synthesized to test the hypothesis that incorporation of a hydrophobic side chain into the bicyclic thiazolidine lactam scaffold would further enhance the dopamine receptor modulating activity of such peptidomimetics. The substituents employed were the isobutyl, butyl, and benzyl groups to give peptidomimetics 3-5, respectively. These peptidomimetics were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism and were compared with the unsubstituted bicyclic thiazolidine lactam Pro-Leu-Gly-NH(2) peptidomimetic 2. Peptidomimetics 3-5 each affected rotational behavior in a bell-shaped dose-response relationship producing maximal increases of 44% (1 microgram/kg,ip), 56% (0.1 microgram/kg,ip), and 30% (1 microgram/kg, ip), respectively. In comparison, unsubstituted peptidomimetic 2 increased rotational behavior by only 23% at a dose of 0.1 microgram/kg, ip.

Animals↗
PubMed1999

Synthesis and dopamine receptor modulating activity of novel peptidomimetics of L-prolyl-L-leucyl-glycinamide featuring alpha,alpha-disubstituted amino acids.

In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by the use of X-ray crystallography and circular dichroism. The effects of Pro-Leu-Gly-NH2 analogues 3a-3d and 4a-4d on enhancing rotational behavior induced by apomorphine in the 6-hydroxydopamine-lesioned animal models of Parkinson's disease were studied. The ability of these peptidomimetics to increase the binding of agonist N-propylnorapomorphine (NPA) to the dopamine D2 receptor was also examined. Extended analogue Pro-Leu-Deg-NH2 was the most active compound of this series. It was 10 times more potent and almost 2 times more effective than 1 in increasing apomorphine-induced rotations (56 +/- 15% at 1.0 mg/kg ip) and in enhancing [3H]NPA specific binding (40%).

Animals↗
PubMed1999

Design, synthesis, and dopamine receptor modulating activity of spiro bicyclic peptidomimetics of L-prolyl-L-leucyl-glycinamide.

In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [3H]spiroperidol/N-propylnorapomorphine (NPA) dopamine D2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 microM. Peptidomimetics 3 and 4 also increased the percentage of D2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the RH/RL ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).

Animals↗
PubMed1999

Size segregation of granular matter in silo discharges.

We present an experimental study of segregation of granular matter in a quasi-two-dimensional silo emptying out of an orifice. Size separation is observed when multisized particles are used with the larger particles found in the center of the silo in the region of fastest flow. We use imaging to study the flow inside the silo and quantitatively measure the concentration profiles of bidisperse beads as a function of position and time. The angle of the surface is given by the angle of repose of the particles, and the flow occurs in a few layers only near the top of this inclined surface. The flowing region becomes deeper near the center of the silo and is confined to a parabolic region centered at the orifice which is approximately described by the kinematic model. The experimental evidence suggests that the segregation occurs on the surface and not in the flow deep inside the silo where velocity gradients also are present. We report the time development of the concentrations of the bidisperse particles as a function of size ratios, flow rate, and the ratio of initial mixture. The qualitative aspects of the observed phenomena may be explained by a void filling model of segregation.

Journal Article↗
PubMed1997

Design, synthesis, and dopamine receptor modulating activity of diketopiperazine peptidomimetics of L-prolyl-L-leucylglycinamide.

The diketopiperazine "C5" conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG, 1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal "C5" conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [3H]spiroperidol/N-propylnorapomorphine (NPA) D2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal "C5" conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg i.p. and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

Animals↗
PubMed1995

Steady state and time-resolved fluorescence properties of metastatic and non-metastatic malignant cells from different species.

Steady state and time-resolved fluorescence spectroscopy were employed to study the fluorescence from non-metastatic, metastatic and non-tumorigenic cell lines from different species. Excitations at 310 nm and 350 nm were used to monitor tryptophan and reduced nicotinamide adenine dinucleotide (NADH) fluorescence respectively. Subtle and consistent differences were observed between different categories of cell lines. It was found that the tryptophan to NADH fluorescence intensity ratio is higher in metastatic cell lines than in non-metastatic and normal cell lines. The fluorescence decay of the tryptophan residue in different cell lines was best described by triple exponential kinetics, whereas the NADH fluorescence decay was best described by mainly double and, in some cases, triple exponential kinetics. The average fluorescence lifetimes for tryptophan were in the range 2.5-3.7 ns. The average lifetime of NADH was lower (by a factor of approximately three) in metastatic cells than in non-metastatic cells and this finding is consistent for cell lines from different origins (rat or human). Correcting the fluorescence intensity for the average fluorescence lifetime of each species and for the volume of each cell line, it was shown that the concentrations of tryptophan and NADH are consistently higher in malignant metastatic cancer cells than in non-metastatic cells.

Animals↗