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Biomedical subjects

S Tyagi

Publications and source records attributed to S Tyagi.

At least 91 records · Page 5Linked to original sources

Quantitative assays based on the use of replicatable hybridization probes.

Amplifiable hybridization probes--molecules with a probe sequence embedded within the sequence of a replicatable RNA--will promote the development of sensitive clinical assays. To demonstrate their utility, we prepared a recombinant RNA that contained a 30-nucleotide-long probe complementary to a conserved region of the pol gene in human immunodeficiency virus type 1 (HIV-1) mRNA. Test samples were prepared, each containing a different number of HIV-1 transcripts that served as simulated HIV-1 mRNA targets. Hybridizations were carried out in a solution containing the chaotropic salt, guanidine thiocyanate. Probe-target hybrids were isolated by reversible target capture on paramagnetic particles. The probes were then released from their targets and amplified by incubation with the RNA-directed RNA polymerase, Q beta replicase (EC 2.7.7.48). The replicase copied the probes in an exponential manner: after each round of copying, the number of RNA molecules doubled. The amount of RNA synthesized in each reaction (approximately 50 ng) was sufficient to measure without using radioisotopes. Kinetic analysis of the reactions demonstrated that the number of HIV-1 targets originally present in each sample could be determined by measuring the time it took to synthesize a particular amount of RNA (the longer the synthesis took, the fewer the number of targets originally present). The results suggest that clinical assays involving replicatable hybridization probes will be simple, accurate, sensitive, and automatable.

Autoanalysis↗

Percutaneous transluminal balloon angioplasty of the aorta in patients with aortitis.

Four patients with aortitis and stenotic lesions of the aorta were successfully treated by percutaneous transluminal balloon angioplasty. The peak systolic gradient across the constrictions decreased from 82.5 +/- 35.7 to 37.5 +/- 18.5 mm Hg immediately after dilatation. Repeat angiography in the first three patients performed 2 months later showed a further decrease in the gradient to 13.8 +/- 9.5 mm Hg. There were no complications during or after the procedure, and all the patients have shown remarkable symptomatic relief during the follow-up.

Adolescent↗

Toxic effects of chromium in a freshwater teleost fish, Channa punctatus.

The effect of in vivo exposure to a sublethal concentration of hexavalent chromium for 30 days on blood glucose, blood liver and muscle lactic acid; haemoglobin, liver and muscle glycogen; and activities of lactate dehydrogenase (LDH), pyruvate dehydrogenase (PHD) and succinate dehydrogenase (SDH) in liver, muscle, kidney, gills and brain has been studied. Blood glucose and lactic acid levels were elevated. Liver glycogen was depleted but muscle glycogen content increase. The activities of LDH and SDH in liver were elevate. Elevation was also observed in muscle LDH and PDH activities, showing that the rate of glycolysis is increased. No change was noted in haemoglobin content of blood or in the activities of the three dehydrogenases in kidney and gills.

Animals↗

Effect of exogenous fatty acids on growth, membrane fluidity, and phospholipid fatty acid composition in yeast.

The growth response of a double-mutant fatty acid auxotroph of yeast Saccharomyces cerevisiae to exogenous saturated fatty acids of a homologous series from 12:0 to 16:0, each supplied with oleate, linoleate, linolenate, or cis-delta 11-eicosenoate, cannot be explained in terms of the efficiency of incorporation of the fatty acids into phospholipids or alteration of membrane fluidity. There is, however, a negative correlation between growth and levels of 12:0 plus 13:0 in phospholipids, as well as a positive correlation between growth and levels of 14:0, 15:0, and 16:0. We, therefore, conclude that the predominant factor in these phospholipid fatty acyl chain modifications is maintenance of an optimal concentration of C14:0 through C16:0 in phospholipids of this organism.

Electron Spin Resonance Spectroscopy↗

Origins of translation: the hypothesis of permanently attached adaptors.

A mechanism for prebiotic translation is proposed in which primeval transfer-RNA (adaptors) are assumed to be permanently associated with messenger nucleic acid molecules. Residual 'fossil' evidences are found to be present within the base sequences of contemporary tRNAs, suggesting the existence of inter-primal-tRNA interactions necessary for the mechanism. The structure of proposed primal-tRNA is such that it can not only choose its own amino acid in the absence of aminoacyl synthetase, but can also associate nonspecifically with adjacent primal-tRNA molecules attached to the neighbouring codons. Such associations can give rise, through cooperative binding between message and adaptors to the 'static template surfaces' which can direct translation of nucleotide sequences into those of amino acids. The origins of ribosomes and contemporary genetic code are suggested by this hypothesis. Proposed structures and processes are thermodynamically compatible. The approximate date of occurrence of the proposed system is calculated, which is consistent with the period of occurrence of the earliest organism with ribosomes.

Amino Acids↗

A novel form of vitamin B-12 and its derivatives.

A new isomeric form of cobalamins is reported. The conversion of cobalamin to cobalamin (the new form) is achieved by substituting the benzimidazole base by a less bulky group like H2O or CN- and modest thermal treatment. The back conversion of adenosylcobalamin to the corresponding regular form occurs in the "base-off" form at room temperature. It seems that the corrin ring becomes quite flexible in the "base-off" form and the freer axial movement of the cobalt atom flips the corrin ring into a different conformation. The change in conformation is borne out by subtle changes in the proton magnetic resonances on the corrin ring and the base, and very marked variation in the emission Mössbauer spectra. The latter is indicative of appreciable changes in the spatial conformation in the immediate vicinity of the central metal atom. The ultraviolet-visible and infrared spectra of cobalamin are indistinguishable from those of its corresponding regular form. The new conformational isomeric species is present as an impurity in all commercially available cobalamins (including pharmaceutical preparations). It raises the question whether the cobalamins' constitute the real biologically active anti-anemic factor in humans.

Anemia↗

Emission Mössbauer studies of some organocobalamins.

Subtle changes in the Mössbauer parameters are observed while going from methyl- to ethyl- to adenosylcobalamin, and also when the "base" is detached from the cobalt. The observation of these changes demonstrates that the Co-C bond, among others, remains intact after the Auger event, accompanying the electron-capture decay of the cobalt-57. The differences between ethylcobalamin and the other two organocobalamins in the magnitude of the quadrupole splittings have been interpreted on the basis of the sigma-donating tendency of the organic moiety and the Co-C bond length. The latter is presumably determined by the steric hindrance offered to the group in approaching the cobalt atom. The ethyl- and adenosylcobalamins in their "base-off" form exhibit a larger quadrupole splitting than the corresponding "base-on" form. In the "bas-off" form, the cobalt atom is perhaps raised above the mean plane of the four equatorial nitrogen atoms of the corrin ring, which may result in the diminution of the delocalization of the 3dpi electron density. The higher population of dpi orbitals and the enhanced metallic character of the dz2, resulting from shrinkage of the Co-C bond length, enhances the magnitude of the quadrupole splitting.

Chemical Phenomena↗

Emission Mössbauer study of the stereochemical trigger that initiates cooperative interaction of hemoglobin subunits.

An important feature of Perutz's trigger mechanism for cooperativity in the reversible oxygenation of hemoglobin (Hb) is the tension along the histidine--metal linkage in deoxyHb and deoxycobaltohemoglobin (deoxy CoHb), supposedly due to the pull exerted by the globin on the metal atom. We have attempted to verify the existence of this pull by studying the emission Mössbauer spectra of deoxy 57CoHb and oxy 57 CoHb at different temperatures. The emission Mössbauer spectrum for none of the cobalt Hbs agrees with the absorption spectrum of the corresponding iron analog and, moreover, the spectrum of deoxy 57CoHb is characteristic of the intermediate-spin iron. These observations indicate that the daughter 57Fe atom is "frozen" almost in the same spatial situation as that of the parent 57Co. The protein is apparently holding the cobalt atom in position rather rigidly and, after the electron-capture decay of the 57Co atom, the protein does not permit the daughter 57Fe to move to a position characteristic of the iron atom.

Cobalt Radioisotopes↗

Stenting of the aorta for recurrent, long stenosis due to Takayasu's arteritis in a child.

Balloon angioplasty followed by stenting of the thoracic aorta is reported in a 5-year-old girl with Takayasu's arteritis, who presented with severe hypertension and congestive heart failure. Her aortogram showed severe long segment stenosis of the descending thoracic aorta, which was successfully treated by balloon angioplasty on two occasions, but developed recurrences after 6 and 7 months of angioplasty. Balloon dilatation of the stenosed aorta, followed by sequential implantation of three 30-mm long Palmaz stents in tandem, bridging the full segment of the angioplastied aorta were performed successfully without any complications. The aortic diameter increased from 3.3 mm to 7.7 mm and the peak systolic pressure gradient decreased from 75 mmHg to 3 mmHg. There was no recurrence on clinical follow-up of 13 months.

Angioplasty, Balloon↗

Percutaneous transluminal angioplasty for stenosis of the aorta due to aortic arteritis in children.

Percutaneous transluminal balloon angioplasty for stenosis of the aorta due to aortic arteritis was attempted on 45 lesions in 41 children (age range, 4-14 years; mean, 9.9+/-4.2 years) presenting with symptoms of hypertension, severe congestive heart failure, and lower limb claudication. Balloon dilatation was technically successful in 38 (92.7%) patients for 41 stenotic lesions (91.1%). The mean peak systolic pressure gradient (PSG) decreased from 71.7 +/- 23.9 mmHg to 23.2 +/- 17.5 mmHg (p < 0.001) and the diameter of the stenosed segment increased from 3.3 +/- 1.1 mm to 7.5 +/- 2.2 mm (p < 0.001) immediately after angioplasty. Patients with short-segment (<3 cm) stenosis had a lower residual gradient (17.9 +/- 11.1 mmHg vs 30.5 +/- 22.6 mmHg; p < 0.05) and a wider diameter of the aorta (8.8 +/- 1.1 mm vs 7.5 +/- 2.2 mm; p < 0.02) compared to patients with long-segment (>/=3 cm) stenosis. Four patients required stent implantation; 2 for flow-limiting dissection, 1 for failure to reduce PSG by >50%, and 1 for recurrent restenosis. There was marked hemodynamic and angiographic improvement in these 4 patients. Hemodynamic and angiographic restudy in 21 of the 41 patients at mean follow-up period of 6.2 +/- 4.2 months (range, 3-24 months) showed restenosis in 4 (19%) patients. Restenosis was more common in patients with long-segment stenosis than those with short-segment stenosis (30% vs 9.1%). Late restudy in 8 patients, done at 3-7 years after first restudy, showed no recurrence of aortic narrowing. On clinical follow-up of 38 patients for a mean of 58.8 +/- 36.0 months (range, 8-146 months) there was marked improvement in symptoms. Hypertension was cured in 11 (29%), improved in 24 (63%), and persisted in 3 (8%). Six patients with associated severe renal artery stenosis showed further improvement in hypertension after successful renal angioplasty. Severe congestive heart failure improved in 21 (95.4%) of 22 patients. Mean left ventricular ejection fraction improved from 0.32 +/- 0.08 to 0. 48 +/- 0.10 (p < 0.001) at a mean follow-up of 28.7 +/- 8.4 months in these patients. Hemodynamic restudy in 10 of these patients showed improvements in left ventricular end-diastolic pressure from a mean 37 +/- 9 mmHg (range, 25-55 mmHg) to 16.4 +/- 6.2 mmHg (range, 6-25 mmHg) (p < 0.001). Lower limb claudication improved in all 4 patients. Our results suggest that percutaneous transluminal balloon angioplasty in children is safe and highly effective in relieving stenosis of the aorta due to aortic arteritis, with marked clinical improvement, and should be the treatment of choice particularly for discrete stenosis.

Adolescent↗

Early and long-term results of subclavian angioplasty in aortoarteritis (Takayasu disease): comparison with atherosclerosis.

PURPOSE: To compare the early and long-term outcomes of subclavian artery angioplasty in patients with aortoarteritis and atherosclerosis. METHODS: Sixty-one subclavian artery angioplasties were performed in 55 consecutive patients with aortoarteritis (n = 32) and atherosclerosis (n = 23) between 1986 and 1995. An arch aortogram followed by a selective subclavian artery angiogram was done to profile the site and extent of the lesion, its relation to the vertebral artery, and the distal circulation. Percutaneous transluminal angioplasty (PTA) was performed via the femoral route for 56 stenotic lesions and 5 total occlusions. RESULTS: PTA was successful in 52 (92.8%) stenotic lesions and 3 (60%) total occlusions. Three patients (5.4%) had complications, that could be effectively managed nonsurgically. Compared with atherosclerosis, patients with aortoarteritis were younger (27.4 +/- 9.3 years vs 54.5 +/- 10.5 years; p < 0.001), more often female (75% vs 17.4%; p < 0.001), gangrene was uncommon (0% vs 17.4%; p < 0.05), and diffuse involvement was seen more often (43.8% vs 4.4%; p < 0.001). The luminal diameter stenoses were similar before PTA (88.6 +/- 9.7% vs 89.0 +/- 9.1%; p = NS). Higher balloon inflation pressure was required to dilate the lesions of aortoarteritis (9.9 +/- 4.6 ATM vs 5.5 +/- 1.0 ATM; p < 0.001). This group had more residual stenosis (15.5 +/- 12.4% vs 8.3 +/- 9.4%; p < 0.05) after PTA. There were no neurological sequelae, even in PTA of prevertebral lesions. On 3-120 months (mean 43.3 +/- 28.9 months) follow-up of 40 patients, restenosis was more often observed in patients with aortoarteritis, particularly in those with diffuse arterial narrowing. These lesions could be effectively redilated. Clinical symptoms showed marked improvement after successful angioplasty. CONCLUSION: Subclavian PTA is safe and can be performed as effectively in aortoarteritis as in atherosclerosis, with good long-term results. Long-term follow-up shows that it provides good symptomatic relief.

Adult↗

Endovascular stenting for unsuccessful angioplasty of the aorta in aortoarteritis.

PURPOSE: The efficacy and safety of endovascular stent implantation to correct dissection or a suboptimal result after percutaneous transluminal angioplasty (PTA) was evaluated in patients suffering from aortic stenosis due to aortoarteritis. METHODS: Twelve children and young adults [aged (mean +/- SD) 18.2 +/- 8.7 years] underwent stent implantation after PTA of the aorta, seven for obstructive dissection, four for ineffective balloon dilatation, and one for recurrent restenosis. Nine patients underwent implantation of self-expandable stents and three received balloon-expandable Palmaz stents. RESULTS: Stent implantation could be successfully performed in all 12 patients. After stent implantation, the peak systolic pressure gradient decreased from 91 +/- 33.5 mmHg to 12.4 +/- 12.5 mmHg (p < 0.001). The diameter of the stenosed segment increased from 4.6 +/- 0.8 mm to 11.1 +/- 1.9 mm (p < 0.001). The dissection was completely covered in all seven patients with dissection. Except for epigastric pain with vomiting in one patient, there was no complication. On follow-up, over 12-57 months (mean 26.8 +/- 10.8 months), 11 patients (91.6%) had marked improvement in their blood pressure. Patients with congestive heart failure and claudication also showed improvement. Repeat catheterization in five patients, between 6-30 months (mean 16.8 +/- 9.1 months) after stent implantation, showed sustained improvement in four and a fusiform, long segment, intrastent restenosis after 30 months in one child. The stenosis was safely redilated. CONCLUSION: Endovascular aortic stent implantation is safe and provides good immediate relief in patients with unsatisfactory results after balloon angioplasty. Improvement is sustained in most patients on intermediate-term follow-up.

Adolescent↗

Aortoarteritis presenting with hypoparathyroidism.

Clinical manifestations of aortoarteritis (Takayasu's arteritis) are varied, depending on the involved segment of the aorta and its branches. A case of a young Indian woman with aortoarteritis presenting primarily with hypoparathyroidism is reported. Aortogram showed total occlusion of the arch arteries. To the best of our knowledge, the occurrence of hypoparathyroidism in aortoarteritis has not been reported. Possible mechanisms of such an involvement are discussed.

Adult↗