Search PubMed⌕ Search

Biomedical subjects

G Srinivasan

Publications and source records attributed to G Srinivasan.

At least 19 recordsLinked to original sources
PubMed2005

Two-generation marker-aided backcrossing for rapid conversion of normal maize lines to quality protein maize (QPM).

The low nutritive value of maize endosperm protein is genetically corrected in quality protein maize (QPM), which contains the opaque 2 gene along with numerous modifiers for kernel hardness. We report here a two generation marker-based backcross breeding program for incorporation of the opaque 2 gene along with phenotypic selection for kernel modification in the background of an early maturing normal maize inbred line, V25. Using the flanking marker distances from opaque 2 gene in the cross V 25 xCML 176, optimum population size for the BC(2) generation was computed in such a way that at least one double recombinant could be obtained. Whole genome background selection in the BC(2) generation identified three plants with 93 to 96% recurrent parent genome content. The three BC(2)F(2) families derived from marker identified BC(2) individuals were subjected to foreground selection and phenotypic selection for kernel modification. The tryptophan concentration in endosperm protein was significantly enhanced in all the three classes of kernel modification viz., less than 25%, 25--50% and more than 50% opaqueness. BC(2)F(3) lines developed from the hard endosperm kernels were evaluated for desirable agronomic and biochemical traits in replicated trials and the best line was chosen to represent the QPM version of V25, with tryptophan concentration of 0.85% in protein. The integrated breeding strategy reported here can be applied to reduce genetic drag as well as the time involved in a conventional line conversion program, and would prove valuable in rapid development of specialty corn germ plasm.

Crosses, Genetic↗
PubMed2005

Utility values among glaucoma patients: an impact on the quality of life.

AIM: To ascertain utility values and associated quality of life with different severity and duration of glaucoma among Indian patients. METHODS: Utility values of 105 consecutive patients with primary glaucoma of at least 12 months' duration were evaluated in a cross sectional study. Utility values were ascertained in five groups using both the time-trade off and standard gamble methods: group 1 (best corrected visual acuity in the better eye of 6/9 or better), group 2 (best corrected visual acuity in the better eye of 6/18 to 6/12), group 3 (best corrected visual acuity in the better eye of 6/36 to6/24), group 4 (best corrected visual acuity in the better eye of 3/60 to 6/60), and group 5 (best corrected visual acuity in the better eye of 3/60 or worse). RESULTS: The mean utility value for the glaucoma group as a whole was 0.64 (SD 0.69; 95% confidence interval (CI), 0.58 to 0.70) with the time-trade off method and 0.86 (SD 1.00; 95% CI, 0.81 to 0.90) with the standard gamble method for a gamble of death and 0.97 (SD 1.00; 95% CI, 0.94 to 0.99) for a gamble of blindness. The mean utility results by the time-trade off method were as follows: group 1 = 0.66, group 2 = 0.66, group 3 = 0.62, group 4 = 0.55, and group 5 = 0.61. The utility value was much lower (0.46) in those with no formal education or only primary education compared to those with postgraduate education (0.75) (p = 0.038). Those patients with glaucoma of less than 5 years' duration had a utility score of 0.62 while those with glaucoma for more than 10 years had a score of 0.74 (p = 0.40). CONCLUSIONS: Visual acuity loss occurring secondary to glaucoma is associated with a substantial decrease in patient utility value (and quality of life) in a developing country like India. The utility value is directly dependent on the degree of visual acuity loss associated with the disease and educational status and not on the duration of disease, the number of medications, or the visual field indices.

Adult↗
PubMed2004

Functional glutamatergic and glycinergic inputs to several superior olivary nuclei of the rat revealed by optical imaging.

Superior olivary complex (SOC) neurons receive excitatory and inhibitory inputs from both ears. We determined the nature of such inputs to the main SOC nuclei with an optical imaging system. To do so, brainstem slices of postnatal (P) rats (P3-13) were treated with the fast voltage-sensitive dye RH795, and ipsilateral and contralateral SOC inputs were activated electrically. Optical signals, equivalent to membrane potential changes, were detected by a 464-photodiode array. The signals consisted mostly of two components which were identified as pre- and postsynaptic potentials in experiments with Ca2+-free solutions. They correlated with morphological structures, i.e. the presynaptic components were prominent in neuropil regions whereas the postsynaptic components dominated in somata regions. Postsynaptic components were distinguished pharmacologically with the glycine receptor blocker strychnine and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Concerning the lateral superior olive, we confirmed the known glutamatergic inputs from the ipsilateral side and the glycinergic inputs from the ipsilateral and contralateral sides. Furthermore, we identified a CNQX-sensitive input from the contralateral side. In the medial superior olive, we corroborated the glutamatergic and glycinergic inputs from the ipsilateral and contralateral sides. Both ipsi- and contralaterally, the glutamatergic input was more pronounced than the glycinergic input. In the superior paraolivary nucleus, we also identified ipsilateral and contralateral inputs. Besides the known glycinergic input from the contralateral side, we found a novel glycinergic input from the ipsilateral side and identified CNQX-sensitive inputs from the contralateral and ipsilateral sides. The latter was very weak and appeared only in 30% of the experiments. The data show the feasibility of identifying functional inputs to the SOC with voltage-sensitive dye recordings.

Animals↗
PubMed2000

Methods to improve the hatchability of checked chicken eggs.

1. The hatchability of checked Leghorn and broiler parent hatching eggs was significantly improved by shell treatment: smearing with synthetic adhesive resin (Fevicol), or pasting cellophane tape or insulation tape over the checked portion of the shell. 2. Shell damage reduced hatchability by increasing evaporative loss, leading to embryonic dehydration. 3. Relative chick weight, expressed as a percentage of egg weight was lower in untreated checked eggs but comparable between intact and shell-treated hatching eggs. 4. The cost of chick production can be reduced by shell treatment of checked hatching eggs, especially in broiler parent eggs.

Animals↗
PubMed1999

Characterization of zinc-alpha(2)-glycoprotein as a cell adhesion molecule that inhibits the proliferation of an oral tumor cell line.

Zn-alpha(2)-glycoprotein (Znalpha(2)gp) is a soluble protein widely distributed in body fluids and glandular epithelia. We have found it to be expressed in stratified epithelia as well. Znalpha(2)gp is clinically correlated with differentiation in various epithelial tumors, including oral and epidermal tumors. We have cloned epidermal Znalpha(2)gp and report the preparation of the recombinant protein in a Baculovirus expression system. Like the native molecule, recombinant Znalpha(2)gp has RNase activity. Znalpha(2)gp functions as a matrix protein for the Tu-138 oral squamous cell carcinoma cell line. Cell attachment to Znalpha(2)gp is comparable to that for fibronectin and is inhibited by the synthetic RGD peptides RGD, RGDV, and RGDS. Attachment is also inhibited by the antibody to integrin alpha(5)beta(1) (the fibronectin receptor), but not by antibodies to integrins alpha(v)beta(3), alpha(3)beta(1), and alpha(2)beta(1). We find that the proliferation of Tu-138 cells is inhibited on a Znalpha(2)gp matrix, as compared with other matrix proteins (fibronectin, vitronectin, laminin, and collagens I and IV) on which growth resembles that on the BSA control. We believe that the role of Znalpha(2)gp in differentiation and its RNase activity are two likely suspects as agents of the inhibition of proliferation.

Antibodies↗
PubMed1999

Interdomain signaling in a two-domain fragment of the human glucocorticoid receptor.

Studies of individual domains or subdomains of the proteins making up the nuclear receptor family have stressed their modular nature. Nevertheless, these receptors function as complete proteins. Studies of specific mutations suggest that in the holoreceptors, intramolecular domain-domain interactions are important for complete function, but there is little knowledge concerning these interactions. The important transcriptional transactivation function in the N-terminal part of the glucocorticoid receptor (GR) appears to have little inherent structure. To study its interactions with the DNA binding domain (DBD) of the GR, we have expressed the complete sequence from the N-terminal through the DBD of the human GR. Circular dichroism analyses of this highly purified, multidomain protein show that it has a considerable helical content. We hypothesized that binding of its DBD to the cognate glucocorticoid response element would confer additional structure upon the N-terminal domain. Circular dichroism and fluorescence emission studies suggest that additional helicity as well as tertiary structure occur in the two-domain protein upon DNA binding. In sum, our data suggest that interdomain interactions consequent to DNA binding imparts structure to the portion of the GR that contains a major transactivation domain.

Circular Dichroism↗
PubMed1999

26Al in eucrite piplia kalan: plausible heat source and formation chronology

Aluminum-magnesium isotopic analysis of plagioclase in the eucrite Piplia Kalan, with 27Al/24Mg ratio between 2000 to 7000, reveals the presence of excess magnesium-26 resulting from in situ decay of the short-lived nuclide aluminum-26. This observation confirms aluminum-26 as a plausible heat source for melting and differentiation of the eucrite parent body in particular and for planetesimals in general. The inferred initial abundance of 26Al/27Al of (7.5 +/- 0.9) x 10(-7) indicates that melting, differentiation, and crust formation in the parent body of Piplia Kalan was complete within 5 million years of the formation of the solar system.

Journal Article↗
PubMed1999

Trimethylamine N-oxide-induced cooperative folding of an intrinsically unfolded transcription-activating fragment of human glucocorticoid receptor.

A number of biologically important proteins or protein domains identified recently are fully or partially unstructured (unfolded). Methods that allow studies of the propensity of such proteins to fold naturally are valuable. The traditional biophysical approaches using alcohols to drive alpha-helix formation raise serious questions of the relevance of alcohol-induced structure to the biologically important conformations. Recently we illustrated the extraordinary capability of the naturally occurring solute, trimethylamine N-oxide (TMAO), to force two unfolded proteins to fold to native-like species with significant functional activity. In the present work we apply this technique to recombinant human glucocorticoid receptor fragments consisting of residues 1-500 and residues 77-262. CD and fluorescence spectroscopy showed that both were largely disordered in aqueous solution. TMAO induced a condensed structure in the large fragment, indicated by the substantial enhancement in intrinsic fluorescence and blue shift of fluorescent maxima. CD spectroscopy demonstrated that the TMAO-induced structure is different from the alpha-helix-rich conformation driven by trifluoroethanol (TFE). In contrast to TFE, the conformational transition of the 1-500 fragment induced by TMAO is cooperative, a condition characteristic of proteins with unique structures.

Circular Dichroism↗
PubMed1999

Activation of human O6-methylguanine-DNA methyltransferase gene by glucocorticoid hormone.

O6-methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein, removes the mutagenic DNA adduct O6-alkylguanine, which is synthesized both endogenously and after exposure to alkylnitrosamines and alkylating antitumor drugs such as 2-chloroethyl-N-nitrosourea (CNU). The MGMT gene is highly regulated in mammalian cells and its overexpression, observed in many types of tumor cells, is often associated with cellular resistance to CNU. Dexamethasone, a synthetic glucocorticoid hormone, was found to increase MGMT expression in HeLa S3 cells, concomitant with their increased resistance to CNU. Two putative glucocorticoid responsive elements (GREs) were identified in the human MGMT (hMGMT) promoter. Transient expression of the luciferase reporter gene driven by an hMGMT promoter fragment containing these GREs was activated by dexamethasone. DNase I footprinting assays demonstrated the binding of glucocorticoid receptor to these sequences. In vitro transcription experiment showed that these DNA sequences are functional in glucocorticoid receptor signal-mediated activation of transcription. These results suggest glucocorticoid-mediated induction of the MGMT gene contributes to high level expression of MGMT.

DNA Footprinting↗
PubMed1999

13N-ammonia myocardial blood flow and uptake: relation to functional outcome of asynergic regions after revascularization.

OBJECTIVES: In this study we determined whether 13N-ammonia uptake measured late after injection provides additional insight into myocardial viability beyond its value as a myocardial blood flow tracer. BACKGROUND: Myocardial accumulation of 13N-ammonia is dependent on both regional blood flow and metabolic trapping. METHODS: Twenty-six patients with chronic coronary artery disease and left ventricular dysfunction underwent prerevascularization 13N-ammonia and 18F-deoxyglucose (FDG) positron emission tomography, and thallium single-photon emission computed tomography. Pre- and postrevascularization wall-motion abnormalities were assessed using gated cardiac magnetic resonance imaging or gated radionuclide angiography. RESULTS: Wall motion improved in 61 of 107 (57%) initially asynergic regions and remained abnormal in 46 after revascularization. Mean absolute myocardial blood flow was significantly higher in regions that improved compared to regions that did not improve after revascularization (0.63+/-0.27 vs. 0.52+/-0.25 ml/min/g, p < 0.04). Similarly, the magnitude of late 13N-ammonia uptake and FDG uptake was significantly higher in regions that improved (90+/-20% and 94+/-25%, respectively) compared to regions that did not improve after revascularization (67+/-24% and 71+/-25%, p < 0.001 for both, respectively). However, late 13N-ammonia uptake was a significantly better predictor of functional improvement after revascularization (area under the receiver operating characteristic [ROC] curve = 0.79) when compared to absolute blood flow (area under the ROC curve = 0.63, p < 0.05). In addition, there was a linear relationship between late 13N-ammonia uptake and FDG uptake (r = 0.68, p < 0.001) as well as thallium uptake (r = 0.76, p < 0.001) in all asynergic regions. CONCLUSIONS: These data suggest that beyond its value as a perfusion tracer, late 13N-ammonia uptake provides useful information regarding functional recovery after revascularization. The parallel relationship among 13N-ammonia, FDG, and thallium uptake supports the concept that uptake of 13N-ammonia as measured from the late images may provide important insight regarding cell membrane integrity and myocardial viability.

Adult↗
PubMed1998

Stress-induced reversible and mild-to-moderate irreversible thallium defects: are they equally accurate for predicting recovery of regional left ventricular function after revascularization?

BACKGROUND: In patients with coronary artery disease, stress-redistribution-reinjection thallium scintigraphy provides important information regarding myocardial ischemia and viability. Although both reversible and mild-to-moderate irreversible thallium defects retain metabolically active, viable myocardium, we hypothesized that stress-induced reversible thallium defects may better differentiate reversible from irreversible regional left ventricular dysfunction after revascularization. METHODS AND RESULTS: Twenty-four patients with chronic coronary artery disease underwent prerevascularization and postrevascularization exercise-redistribution-reinjection thallium single photon emission CT, gated MRI, and radionuclide angiography. After revascularization, mean left ventricular ejection fraction increased from 30+/-9% to 37+/-13% at rest (P<0.001). Before revascularization, abnormal contraction at rest was observed in 56 of 110 reversible and 20 of 37 mild-to-moderate irreversible thallium defects (51% and 54%, respectively). After revascularization, regional contraction improved in 44 of 56 reversible compared with 6 of 20 mild-to-moderate irreversible thallium defects (79% and 30%, respectively; P<0.001). The final thallium content (maximum tracer uptake on redistribution-reinjection images) was significantly higher in regions with reversible defects that improved than in those that did not improve after revascularization (86+/-16% versus 66+/-9%, P<0.001). In contrast, final thallium content was similar in regions with mild-to-moderate irreversible defects that improved and in those that did not improve after revascularization (69+/-9% versus 65+/-10%, P=NS). Furthermore, when asynergic regions were grouped according to the final thallium content, at 60% threshold value, functional recovery was observed in 83% of regions with reversible defects compared with 33% of regions with mild-to-moderate irreversible defects (P<0.001). CONCLUSIONS: These findings suggest that although both reversible and mild-to-moderate irreversible thallium defects after stress retain viable myocardium, the identification of reversible thallium defect on stress in an asynergic region more accurately predicts recovery of function after revascularization. Even at a similar mass of viable myocardial tissue (as reflected by the final thallium content), the presence of inducible ischemia is associated with an increased likelihood of functional recovery.

Adult↗
PubMed1998

[18F]fluorodeoxyglucose single photon emission computed tomography: can it replace PET and thallium SPECT for the assessment of myocardial viability?

BACKGROUND: New high-energy collimators for single photon emission computed tomography (SPECT) cameras have made imaging of positron-emitting tracers, such as [18F]fluorodeoxyglucose (18FDG), possible. We examined differences between SPECT and PET technologies and between 18FDG and thallium tracers to determine whether 18FDG SPECT could be adopted for assessment of myocardial viability. METHODS AND RESULTS: Twenty-eight patients with chronic coronary artery disease (mean left ventricular ejection fraction [LVEF]=33+/-15% at rest) underwent 18FDG SPECT, 18FDG PET, and thallium SPECT studies. Receiver operating characteristic curves showed overall good concordance between SPECT and PET technologies and thallium and 18FDG tracers for assessing viability regardless of the level of 18FDG PET cutoff used (40% to 60%). However, in the subgroup of patients with LVEF< or =25%, at 60% 18FDG PET threshold value, thallium tended to underestimate myocardial viability. In a subgroup of regions with severe asynergy, there were considerably more thallium/18FDG discordances in the inferior wall than elsewhere (73% versus 27%, P<.001), supporting attenuation of thallium as a potential explanation for the discordant observations. When uptake of 18FDG by SPECT and PET was compared in 137 segments exhibiting severely irreversible thallium defects (scarred by thallium), 59 (43%) were viable by 18FDG PET, of which 52 (88%) were also viable by 18FDG SPECT. However, of the 78 segments confirmed to be nonviable by 18FDG PET, 57 (73%) were nonviable by 18FDG SPECT (P<.001). CONCLUSIONS: Although 18FDG SPECT significantly increases the sensitivity for detection of viable myocardium in tissue declared nonviable by thallium (to 88% of the sensitivity achievable by PET), it will occasionally (27% of the time) result in falsely identifying as viable tissue that has been identified as nonviable by both PET and thallium.

Adult↗
PubMed1998

Specific interaction of wild-type and truncated mouse N-methylpurine-DNA glycosylase with ethenoadenine-containing DNA.

N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, is responsible for the removal of a wide variety of alkylated base lesions in DNA, e.g., N-alkylpurines and cyclic ethenoadducts of adenine, guanine, and cytosine. These lesions, some of which are mutagenic and toxic, are generated endogenously or by genotoxic agents such as N-alkylnitrosamines and vinyl chloride. Wild-type mouse MPG, expressed from recombinant baculovirus, was purified to near homogeneity for studying its specific interaction with substrate, 1,N6-ethenoadenine- (epsilonA-) containing DNA. Electrophoretic mobility shift assays (EMSA) indicated that MPG formed a specific complex with a 50-mer epsilonA-containing duplex oligonucleotide. This complex was shown to be a transient reaction intermediate, because it could be formed only with the unreacted substrate and contained active enzyme molecules. DNA footprinting studies confirmed the specific binding of the protein to the epsilonA-containing duplex oligonucleotide; eight nucleotides on the epsilonA-containing strand and 16-17 nucleotides in the complementary strand spanning the base adduct were protected from DNase I digestion. A systematic deletion analysis of MPG was carried out in order to determine the minimally sized polypeptide capable of forming a stable substrate complex that is also suitable for characterization by NMR spectroscopy and X-ray crystallography. A truncated polypeptide (NDelta100CDelta18) lacking 100 and 18 amino acid residues from the amino and carboxyl termini, respectively, was found to be the minimal size that retained activity. The truncated and wild-type enzymes have similar kinetic properties. Moreover, both EMSA and DNase I footprinting studies indicated identical pattern of specific binding by the truncated and full-length polypeptides. Removal of five and nine additional residues from the amino- and carboxyl-termini of this polypeptide, respectively, resulted in a complete loss of activity. These results suggest that minimal structural change occured as a result of truncation in the NDelta100CDelta18 mutant, which may thus be suitable for elucidating the structure and mechanism of MPG.

Adenine↗