Sarcoidosis and idiopathic thrombocytopenic purpura. First report of coexistence.
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Acute Disease↗
Biomedical subjects
D Dasgupta
Publications and source records attributed to D Dasgupta.
Structural basis of DNA recognition by anticancer antibiotics, chromomycin A(3), and mithramycin: roles of minor groove width and ligand flexibility.
Anticancer antibiotics, chromomycin A(3) (CHR) and mithramycin (MTR), inhibit cellular processes like transcription and replication, by binding reversibly to double-stranded DNA via minor groove, in the presence of bivalent metal ions like Mg(2+) with GC base specificity. Here, we have attempted to assess the roles of two parameters-namely DNA groove dimension and flexibility of the ligand-in the structural recognition between the ligands, (drug)(2)Mg(2+) and DNA. For the purpose we have employed three synthetic oligonucleotides with minor groove width lying between B- and A-type structures as model DNA sequences: d(GCGCGCGC)(2) in B-form, d(CCGGCGCCGG)(2) in B-form with unusual wide minor groove, and (GGGGCCCC)(2) in A-form. Association of the (drug)(2)Mg(2+) with the oligomers have been probed using spectroscopic techniques like absorbance, fluorescence, and CD. The binding and thermodynamic parameters for the different association processes have also been characterized. Major conclusions from the above studies are as follows. Groove size of the oligomers influences the conformation of the bound ligand. A saccharide dependent variation in structural rigidity of the ligands, (MTR)(2)Mg(2+) and (CHR)(2)Mg(2+), has been observed that leads to differences in the energetics of recognition of the same DNA sequence by the two ligands. In contrast to (CHR)(2)Mg(2+), higher flexibility in (MTR)(2)Mg(2+) makes its conformation in the DNA bound form less sensitive to the groove dimension of DNA.
Antibiotics, Antineoplastic↗
Evaluation of muscle relaxants in tetanus.
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Chlorpromazine↗
Reactivity of 3-HBA-6-hydroxylase with diethylpyrocarbonate and N-bromosuccinimide: effect of chemical modifications on kinetic and spectral properties of the enzyme.
The rapid inactivation of 3-HBA-6-hydroxylase by 100 microM diethylpyrocarbonate or 40 microM N-bromosuccinimide and protection offered by the substrate, 3-hydroxybenzoate, against these chemical modifications implicate the involvement of histidine and tryptophan in the catalytic activity of the enzyme. Inactivation of the enzyme by diethylpyrocarbonate followed pseudo-first-order kinetics, and an "n" value of 1.3 was obtained. Inactivation of the enzyme by N-bromosuccinimide was instantaneous and failed to follow pseudo-first-order kinetics. Distinct and incremental changes in the UV absorption, emission fluorescence, and near UV-CD spectra of the enzyme upon its titration with increasing concentrations of diethylpyrocarbonate or N-bromosuccinimide may be ascribed to modification and/or changes in the microenvironment of aromatic amino acid residue(s) such as tryptophan in the enzyme.
Bromosuccinimide↗
Interaction of 3-hydroxybenzoate with 3-hydroxybenzoate-6-hydroxylase.
The gradual quenching of the emission fluorescence of 3-HBA in the visible region upon titration with 3-HBA-6-hydroxylase and distinct changes in the near-UV circular dichroic spectrum of the enzyme in the presence of substrate suggest the formation of a stable enzyme-substrate complex. The binding of aromatic substrate 3-hydroxybenzoate to 3-hydroxybenzoate-6-hydroxylase occurs without gross changes in the backbone structure of the enzyme. The binding strength of the ES complex is partially reduced upon chemical modification of arginine, histidine, or tryptophan residues of enzyme, probably implicating their concerted action in the binding of substrate to enzyme. Partial inactivation of enzyme and diminished stability of the ES complex in response to treatment with 1 M urea could be ascribed to localized effects of the denaturant.
Amino Acids↗
Effect of myo-inositol(1,4,5)trisphosphate on the hydrolysis of phytic acid by phytase.
Phytase is a monomeric enzyme of molecular mass 160 kDa which catalyzes the hydrolysis of phytic acid (D-myo inositol hexakisphosphate, InsP6) in a stepwise manner to myo-inositol. The enzyme-InsPn (n = 1-6) interaction at the catalytic site has a dissociation constant in the micro molar range. There also exists in the enzyme, a non-catalytic site specific for InsP3 with dissociation constant in the nano molar range. We have probed the effect of the high affinity InsP3 binding on the dissociation constant (Kd) of the phytase-InsP6 interaction and the kinetics of hydrolysis. These studies demonstrate the effect exerted by the high affinity InsP3 binding on the catalytic site of the enzyme.
6-Phytase↗
Interactions of chromomycin A3 and mithramycin with the sequence d(TAGCTAGCTA)2.
Anti-cancer antibiotics, chromomycin A3 (CHR) and mithramycin (MTR) inhibit DNA directed RNA synthesis in vivo by binding reversibly to template DNA in the minor groove with GC base specificity, in the presence of divalent cations like Mg2+. Under physiological conditions, (drug)2Mg2+ complexes formed by the antibiotics are the potential DNA binding ligands. Structures of CHR and MTR differ in their saccharide residues. Scrutiny of the DNA binding properties reveal significant differences in their sequence selectivity, orientation and stoichiometry of binding. Here, we have analyzed binding and thermodynamic parameters for the interaction of the antibiotics with a model oligonucleotide sequence, d(TAGCTAGCTA)2 to understand the role of sugars. The oligomer contains two potential binding sites (GpC) for the ligands. The study illustrates that the drugs bind differently to the sequence. (MTR)2Mg2+ binds to both sites whereas (CHR)2Mg2+ binds to a single site. UV melting profiles for the decanucleotide saturated with the ligands show that MTR bound oligomer is highly stabilized and melts symmetrically. In contrast, with CHR, loss of symmetry in the oligomer following its association with a single (CHR)2Mg2+ complex molecule leads to a biphasic melting curve. Results have been interpreted in the light of saccharide dependent differences in ligand flexibility between the two antibiotics.
Binding Sites↗
Interaction of mithramycin with chromatin.
Mithramycin (MTR) is an anti-cancer antibiotic that blocks the macromolecular biosynthesis via reversible interaction with DNA template in the presence of bivalent metal ion such as Mg2+. In absence of DNA, mithramycin forms two types of complexes with Mg2+, complex I (with 1:1 stoichiometry in terms of MTR: Mg2+) and complex II (with 1:2 stoichiometry in terms of MTR: Mg2+). In an eukaryotic system, the drug would interact with chromatin, a protein-DNA complex. We have employed the spectroscopic techniques such as absorption and fluorescence to study the interaction of MTR: Mg2+ complexes with rat liver chromatin. In this report, we have shown that the two types of ligands have different binding potentials with the same chromatin. This supports our proposition that complexes I and II, are different molecular species. We have also shown that the histone protein(s) reduce the binding potential and the number of available sites for both ligands.
Animals↗
Probing the nucleotide binding sites in T7 RNA polymerase using cibacron blue.
T7 RNA polymerase (T7 RNAP) is an enzyme that utilizes ribonucleotides to synthesize the nascent RNA chain in a template-dependent manner. In this work we have studied the interaction of T7 RNAP with cibacron blue, an anthraquinone monochlorotriazine dye, and its effect on the function of the enzyme. T7 RNAP binds to the dye in a bi-phasic manner. The first phase of the binding is characterized by a high affinity (Kd in the nanomolar range) and reversible inactivation of the enzyme. The second binding site is the common substrate binding site. The association of the dye with T7 RNAP is a good model to understand the physiological significance of a high affinity binding of the initiating nucleotide, GTP, earlier reported from our laboratory. The results will be discussed to understand the role of the high affinity GTP binding.
Binding Sites↗
Cardiomediastinal tamponade and shock following three-stage transthoracic oesophagectomy.
Massive gastric tube dilatation causing cardiomediastinal tamponade is an unusual cause of obstructive shock after transthoracic oesophagectomy. A 55-year-old female was operated for total transthoracic oesophagectomy. Twelve hours after the surgery, she developed hypotension and raised central venous pressure unresponsive to fluid infusion and ionotropes. X-ray chest showed a massively dilated stomach, which was causing intrathoracic tamponade. Suction applied to the nasogastric tube led to aspiration of 150-200 ml of fluid and a large volume of air, which led to resolution of the haemodynamic instability. A simple manoeuvre like nasogastric suction in postoperative case of oesophagectomy can serve as a diagnostic as well as therapeutic tool. It must be performed before resorting to invasive and expensive examination or intervention.
Blood Pressure↗
Awareness of post-exposure prophylaxis guidelines against occupational exposure to HIV in a Mumbai hospital.
BACKGROUND: Exposure to the human immunodeficiency virus (HIV) is a matter of concern for healthcare workers. We conducted a survey to determine the level of awareness amongst operating room personnel regarding post-exposure prophylaxis in case of needlestick injuries from confirmed or suspected cases of HIV. METHODS: A structured questionnaire was presented to 39 anaesthetists and 31 surgical residents. Questions were related to identification of high risk fluids, risk of transmission, drugs, costs and procedure to be adopted for post-exposure prophylaxis. RESULTS: Fourteen respondents (20%) were aware of the true risk of transmission. About one-third identified all high risk fluids correctly. Fifty-five respondents (78%) correctly stated that washing the site with soap and water was the initial measure, but less than a third knew whom to contact immediately after a needlestick injury. Though 45 respondents (64%) correctly stated that prophylaxis should be initiated within 1 hour of injury, none knew exactly which drugs were to be used. Thirty respondents (42%) were aware of the use of zidovudine but none were aware of the second or third drugs used for post-exposure prophylaxis. Only 4 respondents (6%) knew the correct duration of post-exposure prophylaxis. Five respondents (7%) knew that the drugs were available in medical stores and 7 knew the approximate cost of therapy. CONCLUSION: There is surprisingly poor knowledge of post-exposure prophylaxis against HIV. Ongoing awareness and training programmes are necessary to improve the same.
Anti-HIV Agents↗