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D Gopal

Publications and source records attributed to D Gopal.

13 recordsLinked to original sources
PubMed2002

Clinical and biochemical profiles of young diabetics in North-Eastern India.

OBJECTIVE: We compared the clinical and biochemical profiles of young diabetics in North Eastern India. METHODS: Seventy diabetics who were detected at less than 30 years of age were studied. Patients with ketoacidosis or ketonuria on insulin withdrawal were grouped as insulin dependent diabetes mellitus (IDDM), patients with history of chronic abdominal pain with or without exocrine pancreatic dysfunction who either on ultrasonography (USG) or endoscopic retrograde cholangiopancreaticoduodenography (ERCP) revealed pancreatic calcification and/or ductal dilatation were grouped as fibrocalculous pancreatic diabetes (FCPD), those having BMI < 19 kg/m2 with history or stigmata of childhood malnutrition and who were ketosis resistant were taken to be protein deficient diabetes mellitus (PDDM)/malnutrition modulated diabetes mellitus (MMDM) and those who neither had ketonuria nor history of chronic abdominal pain, malabsorption or stigmata of malnutrition were grouped as NIDDM of young (NIDDY). RESULTS: Amongst the young diabetics studied FCPD constituted 32.9%, IDDM 28.6%, MMDM 21.4% and NIDDY 17.11%. USG abnormalities were observed in 21 of the 23 patients of FCPD. Seven out of these showed pancreatic head calcification on X-ray while 14 showed pancreatic duct dilatation and calcification or calculi on USG. In the two remaining patients, ERCP revealed tortuousity of main pancreatic duct and calcification which were not detected on USG. Majority of FCPD and MMDM patients revealed insulin resistance on insulin tolerance test (ITT). HDL was significantly lower in NIDDY, while VLDL and triglycerides were significantly higher in FCPD and MMDM as compared to controls. Microvascular complications of diabetes were seen in all these groups, with peripheral neuropathy being more common in FCPD (43.5%) and background diabetic retinopathy in NIDDY (41%). CONCLUSIONS: We conclude that FCPD and MMDM together form majority (54.29%) of young diabetics at our center and a sizeable proportion of them may have microvascular complications, even at the time of diagnosis.

Adolescent↗
PubMed2001

Novel 2,5-hexanedione analogues. Substituent-induced control of the protein cross-linking potential and oxidation susceptibility of the resulting primary amine-derived pyrroles.

The neurotoxic gamma-diketone, 2,5-hexanedione (2,5-HD), induces neurofilamentous swellings at prenodal sites in proximal axons as a consequence of pyrrolation of lysine epsilon-amino groups on neurofilament proteins. However, there is disagreement as to whether pyrrole formation and the associated alteration of noncovalent interactions is sufficient to cause neurofilament accumulation, or whether pyrrole autoxidation and subsequent protein-protein cross-linking is an obligatory event. To investigate gamma-diketones that might form pyrroles inert to autoxidative-induced cross-linking, we synthesized 1,1,1-trifluoro-2,5-hexanedione, 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD), and two 3-(dialkylaminocarbonyl)-2,5-diketones and assessed their rates of pyrrole formation with amines, the oxidation susceptibility of the resulting pyrroles, and the protein cross-linking potential in vitro, relative to those of 3-methyl-2,5-hexanedione. 1,1,1-Trifluoro-2,5-hexanedione does not form pyrroles, but the three 2,5-HD analogues with an electron-withdrawing 3-substituent all rapidly formed pyrroles that were inert to autoxidation. Although 3-TMFHD nonetheless still induced cross-linking of ribonuclease A, by a nonoxidative mechanism independent of the pyrrole, the two 3-(dialkylaminocarbonyl)-2,5-diketones did not exhibit any protein cross-linking. As these two gamma-diketones possess aqueous-organic partitioning properties similar to those of 2,5-HD, they should serve as useful mechanistic probes in further studies.

Axons↗
PubMed1999

Echocardiography in patients with cerebral infarction.

Fifty consecutive patients of cerebral infarction underwent a detailed evaluation for the presence of cardiac disease, by means of a standard questionnaire, clinical examination, a 12 lead electrocardiogram, and a 2-D echo and colour Doppler examination. Only 9 patients had a normal echocardiogram, while as many as 27 (54%) demonstrated potential cardio-embolic abnormalities. Clinical and ECG evidence of pre-existent cardiac disease had been demonstrable in only 13 (26%) patients.

Adult↗
PubMed1997

Structural determination of a dimeric side-product accompanying dihydropyrazine preparation.

The identity of a major side-product of attempted 2,3-dihydropyrazine dehydrogenation has been elucidated using a geminal dimethyl analog [2,2,5,6-tetramethyl-2,3-dihydropyrazine (1)] which cannot aromatize. 1H, 13C NMR and GC-MS analyses were consistent with the formulation of the product as a symmetrical dimer of 1, but did not allow unambiguous distinction between two possible isomers, each of which could exist as either syn or anti diastereoisomers. X-Ray diffraction studies identified the product as the anti isomer of 3,3,5a,8,8,10a-hexamethyl-1,2,3,5,5a,6,7,8,10,10a-decahydropyra zino [2,3-g] quinoxaline (2). Compound 2 crystallizes in the tetragonal space group I41/a (No. 88) with a = 12.090(1), c = 22.007 (3) A, V = 3216.8(7) A3 and Z = 8. The solid-state structure also displays extensive hydrogen bonding between molecules of 2. A likely mechanism for the formation of 2 is presented.

Chemical Phenomena↗
PubMed1996

Chemomechanical transduction in the actomyosin molecular motor by 2',3'-dideoxydidehydro-ATP and characterization of its interaction with myosin subfragment 1 in the presence and absence of actin.

The effect of torsional freedom about the N-glycoside bond of ATP in the ability of the nucleoside triphosphate to support chemomechanical transduction (Takenaka et al., 1978) has been investigated by examining the ability of the nucleotide analogue 2',3'-dideoxy-2',3'-didehydro-ATP (1b, enf-ATP) to act as a substrate for myosin subfragment 1 in the presence and absence of actin and to support actin sliding in the standard in vitro motility assay. By converting the ribosyl ring of the natural substrate to the rigid and almost planar enofuranosyl ring, effects on torsional freedom about the N-glycoside bond due to changes in ribosyl ring pucker and/or by steric interferences of the protons attached to the 2' and 3' carbons are eliminated allowing for increased torsional freedom about the N-glycoside bond. The data indicate that this enofuranosyl analogue is an excellent substrate for subfragment 1 and actosubfragment 1 and produces actin sliding velocities which are twice as fast as those observed with ATP in the standard in vitro motility assay. The analogue diphosphate is trapped in S1 by the common P(i) analogues, but the rate of formation of the ternary complex formed with Vi is very slow compared to that observed with MgADP. Similar conformations of S1 are formed with Mg.enf-ATP and MgATP under steady-state conditions, but S1 with bound Mg.enf-ADP differs significantly from that observed with MgADP.

Actins↗
PubMed1996

Myosin subfragment 1 hydrophobicity changes associated with different nucleotide-induced conformations.

Myosin subfragment 1 hydrophobicity was found to be sensitive to the occupancy and nature of bound nucleotide at its active site, as shown by changes in elution behavior of unmodified and chemically modified S1 during phenyl hydrophobic chromatography. The elution properties of S1 were unaltered by alkylation of SH1 (Cys-707) with N-ethylmaleimide or by covalent bridging between SH1 and SH2 (Cys-697) with p-phenylenedimaleimide with trapping of MgADP. Although addition of MgADP or MgATP to the elution buffers had minimal effect on the elution properties of these modified S1 species, the presence of these nucleotides was found to produce differential effects with unmodified S1. With MgADP, where S1 is in the S1** MgADP state, the elution times were decreased slightly, whereas with MgATP, where S1 is primarily in the S1** MgADP.Pi state, the elution times were significantly lowered, indicating reduced accessibility for the immobilized phenyl ligand. Stable S1 ternary complexes, formed with MgADP and various Pi analogues, showed elution times similar to that for S1 in the buffers containing MgATP. Thus, two main classes of nucleotide-induced S1 conformations can be defined according to their interaction with immobilized phenyl. These nucleotide-induced changes in S1 hydrophobicity correlate well with reported changes in radius of gyration of S1 associated with different states of the bound nucleotide [Wakabayashi, K., Tokunga, M., Kohno, I., Sugimoto, Y.; Hamanaka, T., Takezawa, Y., Wakabayashi, T., & Amemiya, Y. (1992) Science 258, 443-447], suggesting that the observed hydrophobicity interaction may be measuring accessibility of the immobilized phenyl ligand into a hydrophobic crevice, and that this crevice is closed or tightened when S1 is in the S1** MgADP.Pi state.

Adenosine Diphosphate↗
PubMed1995

Structural basis for actomyosin chemomechanical transduction by non-nucleoside triphosphate analogues.

Methylation of 2-[(2,4-dinitrophenyl)amino]ethyl triphosphate (dNOTP) was found to abolish its ability to support actin sliding in the in vitro motility assay. A comparative study of the interaction of myosin subfragment 1 (S1) and actoS1 with methylated (MdNOTP) and non-methylated dNOTP was undertaken. Both analogues were shown to be substrates for S1 NTPase in the presence of K+/EDTA, Ca2+, or Mg2+, although their rates of hydrolysis in the presence of the divalent cations were significantly greater than that occurring for ATP. However, actin had only a marginal effect on the rate of hydrolysis of MdNOTP, in sharp contrast to its effect on the hydrolysis of dNOTP and ATP which were quite similar. Moreover, while dNODP is able to form stable ternary S1 complexes with orthovanadate (Vi) or berylium fluoride (BeFx), whose formation results in increased thermal stability of S1, the methylated diphosphate analogue was unable to do so. These differences can be related to methylation-induced changes in the conformation of dNOTP indicated by molecular-modeling approaches. These studies suggest that methylation prevents the specific interaction of the aryl ring of dNOTP with S1 in the adenine binding region necessary for the formation of the force-producing intermediate (M. D. P*) during the S1 Mg(2+)-NTPase cycle.

Acid Anhydride Hydrolases↗
PubMed1995

Formation of stable inhibitory complexes of myosin subfragment 1 using fluoroscandium anions.

Evidence is presented that MgADP can be noncovalently trapped in myosin subfragment 1 in the presence of ScFx resulting in the concomitant loss of ATPase function. The rate of inactivation in the presence of MgCl2 at 25 degrees C is 8.7 M-1 s-1 which is too slow for a simple collisional mechanism and suggests that a subsequent slow isomerization step is responsible for formation of a stable tenary complex, S1.MgADP.ScFx in a manner analogous to that proposed for the Vi stabilized complex by Goodno (Goodno, C. C. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 2620-2624). It is also found that ADP can be trapped in subfragment 1 in the absence of MgCl2 indicating the formation of an S1.ADP.ScFx complex. The stability of these complexes at 4 degrees C was studied by following the loss of trapped [14C]ADP with a chase with ADP. The rate of nucleotide loss at 4 degrees C was biphasic for both complexes suggesting that the inhibitory complexes exist in two distinct states as previously proposed for the ternary complex stabilized by Vi (Mihashi, K., Ooi, A., and Hiratsuka, T. (1990) J. Biochem. (Tokyo) 107, 464-469). Formation of these complexes resulted in a marked enhancement of the intrinsic tryptophyl fluorescence suggesting that conformationally they may resemble the steady-state intermediate formed with MgATP. The failure to observe photolysis in the presence of excess Vi at sites associated with the ATP consensus sequence suggests that in these complexes ScFx occupies the site responsible for these cleavage reactions and that it is not displaced by the added Vi.

Actins↗
PubMed1992

Synthesis and evaluation of analogues of (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene as potential cytotoxic and antimitotic agents.

A series of stilbenes has been prepared and tested for cytotoxicity in the five human cancer cell lines A-549 non-small cell lung, MCF-7 breast, HT-29 colon, SKMEL-5 melanoma, and MLM melanoma. The cis stilbenes 6a-f proved to be cytotoxic in all five cell lines, with potencies comparable to that of combretastatin A-4. These cytotoxic compounds were all potent inhibitors of tubulin polymerization. The corresponding trans stilbenes 7b-f were inactive as tubulin polymerization inhibitors and were significantly less cytotoxic in the five cancer cell lines. In the dihydro series, 8b, 8c, and 8f were inactive as tubulin polymerization inhibitors, while 8a, 8d, and 8e were less active than the corresponding cis compounds 6a, 6d, and 6e. The lack of tubulin polymerization inhibitory activity and cytotoxicity displayed by the phenanthrene 23b, which was synthesized as a conformationally rigid analogue of the lead compound 1, indicates that the activity of the stilbenes is not due to a totally planar conformation. Similarly, inactivity of the conformationally restricted analogue 26 suggests that the biologically active conformation of 1a resembles that of the cis alkene 1. Additional inactive compounds prepared include the benzylisoquinoline series 28-32 as well as the protoberberines 38 and 39. Shortening the two-carbon bridge of 1a to a one-carbon bridge in the diphenylmethane 20 resulted in a decrease in cytotoxicity and tubulin polymerization inhibitory activity. Although the corresponding benzophenone 18 was as active as 1a as a tubulin polymerization inhibitor, it was less cytotoxic than 1a, and the benzhydrol 19 was essentially inactive. With the exception of the amide 15c, which displayed low antitubulin activity, all of the phenylcinnamic acid derivatives 14a-c and 15a-f were inactive in the tubulin polymerization inhibition assay. The acid 14b and the ester 15a were cytotoxic in several of the cancer cell cultures in spite of their inactivity as tubulin polymerization inhibitors.

Antineoplastic Agents↗
PubMed1991

Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization.

An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a greater than 8a greater than 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a greater than 8a greater than 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed.

Antineoplastic Agents↗
PubMed1988

Cytochrome c: ion binding and redox properties. Studies on ferri and ferro forms of horse, bovine, and tuna cytochrome c.

The ion binding properties of horse, bovine, and tuna cytochrome c (both oxidized and reduced) have been measured using a combination of ultrafiltration, neutron activation, and ion chromatography. The ions investigated were chloride, phosphate, and Tris-cacodylate. Ion chromatography and neutron activation analysis techniques were employed to determine the concentration of free anions. Binding constants are obtained from modified Scatchard plots (in the range of 10-2000 M-1). The redox potentials for cytochrome c at different ionic strengths, pH 7.0, have been determined. In this paper we report the ionic strength and ion binding effects on the redox properties of horse, bovine, and tuna cytochrome c. Potential versus ionic strength dependence for horse, bovine, and tuna cytochrome c from the experimental data were compared with a theoretical model.

Animals↗