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Biomedical subjects

B Das

Publications and source records attributed to B Das.

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

Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.

Metamorphosis of anuran tadpoles is controlled by thyroid hormone (TH). Here we demonstrate that transgenic Xenopus laevis tadpoles expressing a dominant negative form of TH receptor-alpha are resistant to a wide variety of the metamorphic changes induced by TH. This result confirms that TH receptors mediate both early and late developmental programs of metamorphosis as diverse as growth in the brain, limb buds, nose and Meckel's cartilage, remodeling of the intestine, and death and resorption of the gills and tail.

Animals↗
PubMed2001

Optimization of solvation models for predicting the structure of surface loops in proteins.

A novel procedure for optimizing the atomic solvation parameters (ASPs) sigma(i) developed recently for cyclic peptides is extended to surface loops in proteins. The loop is free to move, whereas the protein template is held fixed in its X-ray structure. The energy is E(tot) = E(FF)(epsilon = nr) + summation operator sigma(i)A(i), where E(FF)(epsilon = nr) is the force-field energy of the loop-loop and loop-template interactions, epsilon = nr is a distance-dependent dielectric constant, and n is an additional parameter to be optimized. A(i) is the solvent-accessible surface area of atom i. The optimal sigma(i) and n are those for which the loop structure with the global minimum of E(tot)(n, sigma(i)) becomes the experimental X-ray structure. Thus, the ASPs depend on the force field and are optimized in the protein environment, unlike commonly used ASPs such as those of Wesson and Eisenberg (Protein Sci 1992;1:227-235). The latter are based on the free energy of transfer of small molecules from the gas phase to water and have been traditionally combined with various force fields without further calibration. We found that for loops the all-atom AMBER force field performed better than OPLS and CHARMM22. Two sets of ASPs [based on AMBER (n = 2)], optimized independently for loops 64-71 and 89-97 of ribonuclease A, were similar and thus enabled the definition of a best-fit set. All these ASPs were negative (hydrophilic), including those for carbon. Very good (i.e., small) root-mean-square-deviation values from the X-ray loop structure were obtained with the three sets of ASPs, suggesting that the best-fit set would be transferable to loops in other proteins as well. The structure of loop 13-24 is relatively stretched and was insensitive to the effect of the ASPs.

Hydrogen↗
PubMed2001

Effects of administration of nicorandil or bimakalim prior to and during ischemia or reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and infarct size in anesthetized rabbits.

We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (KATP) openers (nicorandil and bimakalim), and a specific mitochondrial KATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. The thorax was opened in the left fourth intercostal space and after pericardiotomy the heart was exposed. In Part I, occlusion of the left main coronary artery and hence, myocardial ischemia-induced arrhythmias were achieved by tightening a previously placed loose silk ligature for 30 min. In Part II, arrhythmias were induced by reperfusion following a 20-min ligation of the left main coronary artery. In Part I, early intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just prior to and during ischemia increased survival rate (75% and 67% vs. 60% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. In Part II also, early intervention by intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late intravenous administration of nicorandil or bimakalim at the onset and during reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects of both nicorandil and bimakalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus), a selective mitochondrial KATP channel blocker. In conclusion, intervention by intravenous administration of nicorandil and bimakalim (through the activation of mitochondrial KATP channels), increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion.

Animals↗
PubMed2001

Killing of cutaneous microbial species by photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) utilizes photosensitizers and light. Whereas PDT use in cancer treatment has been widely accepted, antimicrobial PDT (APDT) is still in its early stages of development. OBJECTIVES: To study microbial killing in vitro using APDT. METHODS: We used a combination of methylene blue and visible light, and a range of microbial species representative of those encountered on the skin in health and disease. Using standard light intensity conditions (slide projector, 25 cm distance from target, 42 mW cm(-2)) and methylene blue dye at 100 microg mL(-1), kill rates and subsequent D-values were determined against Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes, Corynebacterium minutissimum, Propionibacterium acnes and Candida albicans. RESULTS: D-values for these species were 72, 66, 48, 120, 30 and 660 s, respectively. The effects of light intensity on the killing of S. epidermidis showed the kill rate to be proportional to the light intensity. A high rate of cell kill was also obtained using natural sunlight. CONCLUSIONS: Overall, these results indicate that APDT of the skin may represent a useful alternative to conventional antimicrobial treatment.

Bacteria↗
PubMed2001

Virus transmission through compromised synthetic barriers: part I--effect of unsteady driving pressures.

Although synthetic membranes such as gloves, condoms, and instrument sheaths are used in environments with highly time-varying stresses, their effectiveness as barriers to virus transmission is almost always tested under static conditions. In this paper it is shown how a previously developed mathematical model can be used to transform information from static barrier tests into predictions for more realistic use conditions. Using a rate constant measured for herpes adsorption to latex in saline, and an oscillatory trans-membrane pressure representative of coitus, the amount of virus transmitted through a hole (2 microm diameter) in a condom is computed. Just beyond the exit orifice of the pore, transport is dominated by the rapidly dissipating viscous jet of virus suspension, which results in an accumulation of viruses roughly 20 pore radii from the barrier surface during each cycle. Due to virus adsorption to the barrier surfaces, the simulations reveal a gradual decrease in virus flow with increasing number of cycles, and thus a slow divergence from predictions based upon steady-state conditions. Still, over the 500 cycles simulated, steady-state predictions approximate the net number of viruses transmitted to within 25 percent error.

Biomechanical Phenomena↗
PubMed2001

Virus transmission through compromised synthetic barriers: part II--influence of pore geometry.

When stressed during normal use, synthetic barriers such as gloves and condoms can develop tears that are undetectable by the user. It is of considerable public-health importance to estimate the quantity of virus transmitted through the tear, in the event of viral contamination of the fluid medium. A mathematical model that accounts for virus adsorption to the barrier material was used to compute the quantity of virus transmitted through defects of various geometries. Slits were modeled as cylinders of elliptic cross section, and upper and lower bounds for the transmission rate of HIV and Hepatitis B virus (HBV) were calculated for barrier-use scenarios such as coitus and gripping of surgical instruments. For a 1-microm high slit, HIV transmission was found to be negligible for all likely use scenarios. HIV transmission became potentially significant for a 5-microm slit. Due to its high titer, HBV transmitted at potentially important levels even through the 1-microm slit. The dependence of the transmission rate upon pore aspect ratio was determined and found to be very strong for high-adsorption situations and near-circular pores. Numerical predictions of virus transport through a laser-drilled hole in a condom matched experimental measurements well, even when the tapered nature of the geometry is ignored.

Biomechanical Phenomena↗
PubMed2001

Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.

The aim was to study the effects of nicorandil (an ATP-sensitive K+ channel opener) and tolbutamide (an ATP-sensitive K+ channel blocker) on reperfusion-induced arrhythmias in pentobarbitone and ketamine anesthetized rabbits. Arrhythmias were induced by reperfusion for 20 min following a 15-min ligation of the left main coronary artery with a silk ligature. Rabbits were pretreated with nicorandil (0.47, 0.93 or 1.86 mg/kg i.v.) or tolbutamide (180 mg/kg i.p.) or vehicle (dimethylsulfoxide/saline) before the coronary artery occlusion. In the control group (n = 10), only 60% of the animals survived during reperfusion. Intravenous pretreatment with 0.47, 0.93 or 1.86 mg/kg of nicorandil increased the survival rate to 86% (n = 7), 75% (n = 8) and 86% (n = 7), respectively. Nicorandil pretreatment significantly decreased the incidence and duration of reperfusion-induced life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. Tolbutamide pretreatment was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias. Pretreatment with nicorandil may result in protection against reperfusion-induced arrhythmias and increased survival in anesthetized rabbits.

Anesthesia↗
PubMed2001

Nosocomial infections due to Acinetobacter baumannii in a neurosurgery ICU.

Invasive infections caused by Acinetobacter baumannii in a post-operative neurosurgery ICU were studied. Sixty one patients admitted during a span of 11 months were culture positive for acinetobacter species from blood and/or CSF samples. They were followed up prospectively for evidence of infection and clinical outcome. 40 cases had clinical evidence of infection due to acinetobacter species while in 21 patients, the isolation of the organism was considered a contaminant. Acinetobacter baumannii was the most common organism associated with invasive infections. Respiratory tract was found to be the most common primary source of infection in patients with bacteraemia or meningitis. The age, sex and pre-operative hospital stay were not significantly different in the two groups (p>0.05), while post-operative hospital stay and mortality was significantly higher in patients with invasive infection (p<0.05). Acinetobacter baumannii was isolated from multiple sites (p<0.05) and repeatedly from the same site (p<0.001) in a significantly higher number of patients with invasive infections. Mortality was high in the patients infected with Acinetobacter baumannii. Even amongst the infected group, the patient shaving meningitis showed a higher mortality as compared to the patients having bacteraemia.

Acinetobacter↗
PubMed2001

Trigeminal neuralgia: current concepts and management.

Trigeminal neuralgia is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. It presents with stabbing pain often in the distribution of the mandibular and maxillary divisions of the trigeminal nerve. An accurate history of pain is important in the diagnosis of trigeminal neuralgia. A patient with tic douloureux and no neurological abnormality on clinical examination does not need diagnostic tests. The available options for management of trigeminal neuralgia are: Pharmacotherapy, destructive procedures and non-destructive procedures. The pharmacotherapy includes (i) monotherapy with one anticonvulsant, (ii) combined therapy with more than one anticonvulsant, (iii) add-on therapy with newer drugs and (iv) polytherapy with anticonvulsant + add-on drugs + antidepressants/anxiolytics. Destructive procedures include (i) non-surgical methods--injections along trigeminal pathways, percutaneous trigeminal radiofrequency thermocoagulation and (ii) surgical methods--trigeminal branch avulsion or peripheral neurectomy, avulsion of trigeminal nerve, trigeminal tractotomy, radiosurgery. Though various modalities of treatment are available for the management of trigeminal neuralgia, pharmacotherapy with carbamazepine still remains the first line of treatment. The alternative approach followed at most centres is percuatenous Gasserian rhizolysis (chemical/radiofrequency thermal) or microvascular decompression.

Analgesics, Non-Narcotic↗
PubMed2001

Uropathogenic Escherichia coli causing urinary tract infections.

BACKGROUND & OBJECTIVES: The information on the characteristics of Escherichia coli causing urinary tract infections is limited. We have characterised the urovirulence factors of Esch. coli isolated from symptomatic patients of urinary tract infections (UTI) in order to determine their pathogenic potential and the antibiotic sensitivity profile. METHODS: Semi-quantitative urine culture was done on 370 symptomatic patients suffering from urinary tract infections. Phenotypic characterization of the urovirulence factors of Esch. coli was undertaken and the antibiotic susceptibility was determined. RESULTS: Esch. coli was responsible for 45.5 per cent of infections. Resistance to amoxycillin, cotrimoxazole, nalidixic acid, norfloxacin and ciprofloxacin among Esch. coli isolates ranged from 70-95 per cent. Serotype O101 was found to be the commonest serotype (7/26). The virulence factors associated with uropathogenic Esch. coli were haemolysin production (5/30), presence of mannose resistant P-fimbriae (5/30), presence of mannose sensitive type 1 fimbriae (6/30) and the presence of mannose resistant F-fimbriae (2/30). Siderophores production was seen in all the isolates causing UTI. INTERPRETATION & CONCLUSION: Esch. coli was found to be the commonest cause of UTI in our study population. Antibiotic resistance was high among the strains circulating which emphasises the need for judicious use of antibiotics. Certain virulence factors like haemolysin production and presence of fimbriae in the Esch. coli may be associated with the urovirulence.

Anti-Bacterial Agents↗
PubMed2000

Multicopy molecular dynamics simulations suggest how to reconcile crystallographic and product formation data for camphor enantiomers bound to cytochrome P-450cam.

Multiple ligand binding modes are possible in many enzyme active sites; their presence in cytochrome P450cam (P450cam) is evident from crystallographic studies of the binding of thiocamphor and phenylimidazoles. Here, we use multicopy molecular dynamics simulations to compare the binding modes of (1R)- and (1S)-camphor in the active site of P450cam. Simulations with (1R)-camphor, the natural substrate, serve to calibrate our protocol: 19 out of 20 copies of (1R)-camphor converged to coordinates very close to those observed for (1R)-camphor in its crystallographic complex with P450cam during the simulations. Simulations with the (1S)-camphor enantiomer showed greater mobility of the substrate, consistent with spectroscopic data, and resulted in 3 major binding modes. One of these is similar to the major conformation (of the two conformations assigned) in a recently determined crystal structure, but this conformation is not correctly oriented for regiospecific hydroxylation at C-5. The simulations, however, provide evidence for reorientation of (1S)-camphor upon formation of the reactive Fe-O intermediate to an orientation suitable for hydroxylation. The simulations thus permit rationalisation of the apparent inconsistency between the crystal structure and the reaction products.

Binding Sites↗
PubMed2000

Cytochrome c methyltransferase, Ctm1p, of yeast.

Cytochromes c from plants and fungi, but not higher animals, contain methylated lysine residues at specific positions, including for example, the trimethylated lysine at position 72 in iso-1-cytochrome c of the yeast Saccharomyces cerevisiae. Testing of 6,144 strains of S. cerevisiae, each overproducing a different open reading frame fused to glutathione S-transferase, previously revealed that YHR109w was associated with an activity that methylated horse cytochrome c. We show here that this open reading frame, denoted Ctm1p, is specifically responsible for trimethylating lysine 72 of iso-1-cytochrome c. Unmethylated forms of cytochrome c but not other proteins or nucleic acids are methylated in vitro by Ctm1p produced in S. cerevisiae or Escherichia coli. Iso-1-cytochrome c purified from a ctm1-Delta strain is not trimethylated in vivo, whereas the K72R mutant form, or the trimethylated Lys-72 form of iso-1-cytochrome c, are not significantly methylated by Ctm1p in vitro. Like apocytochrome c, but in contrast to holocytochrome c, Ctm lp is located in the cytosol, consistent with the view that the natural substrate is apocytochrome c. The ctm1-Delta strain lacking the methyltransferase did not exhibit any growth defect on a variety of media and growth conditions, and the unmethylated iso-1-cytochrome c was produced at the normal level and exhibited the normal activity in vivo. Ctm1p and cytochrome c were coordinately regulated during anaerobic to aerobic transition, a finding consistent with the view that this methyltransferase evolved to act on cytochrome c.

Amino Acid Sequence↗
PubMed2000

Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding.

Vav and Sos1 are Dbl family guanine nucleotide exchange factors, which activate Rho family GTPases in response to phosphatidylinositol 3-kinase products. A pleckstrin homology domain adjacent to the catalytic Dbl homology domain via an unknown mechanism mediates the effects of phosphoinositides on guanine nucleotide exchange activity. Here we tested the possibility that phosphatidylinositol 3-kinase substrates and products control an interaction between the pleckstrin homology domain and the Dbl homology domain, thereby explaining the inhibitory effects of phosphatidylinositol 3-kinase substrates and stimulatory effects of the products. Binding studies using isolated fragments of Vav and Sos indicate phosphatidylinositol 3-kinase substrate promotes the binding of the pleckstrin homology domain to the Dbl homology domain and blocks Rac binding to the DH domain, whereas phosphatidylinositol 3-kinase products disrupt the Dbl homology/pleckstrin homology interactions and permit Rac binding. Additionally, Lck phosphorylation of Vav, a known activating event, reduces the affinities between the Vav Dbl homology and pleckstrin homology domains and permits Rac binding. We also show Vav activation in cells, as monitored by phosphorylation of Vav, Vav association with phosphatidylinositol 3,4,5-trisphosphate, and Vav guanine nucleotide exchange activity, is blocked by the phosphatidylinositol 3-kinase inhibitor wortmannin. These results suggest the molecular mechanisms for activation of Vav and Sos1 require disruption of inhibitory intramolecular interactions involving the pleckstrin homology and Dbl homology domains.

3T3 Cells↗
PubMed2000

Maximum reach envelope for the seated and standing male and female for industrial workstation design.

Maximum reach envelopes for the 5th, 50th and 95th percentile reach lengths of males and females in seated and standing work positions were determined. The use of a computerized potentiometric measurement system permitted functional reach measurement in 15 min for each subject. The measurement system captured reach endpoints in a dynamic mode while the subjects were describing their maximum reach envelopes. An unbiased estimate of the true reach distances was made through a systematic computerized data averaging process. The maximum reach envelope for the standing position was significantly (p<0.05) larger than the corresponding measure in the seated position for both the males and females. The average reach length of the female was 13.5% smaller than that for the corresponding male. Potential applications of this research include designs of industrial workstations, equipment, tools and products.

Adult↗