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S Sarma

Publications and source records attributed to S Sarma.

27 records · Page 2Linked to original sources
PubMed1996

1H, 13C and 15N NMR assignments and secondary structure of the paramagnetic form of rat cytochrome b5.

Modern multidimensional double- and triple-resonance NMR methods have been applied to assign the backbone and side-chain 13C resonances for both equilibrium conformers of the paramagnetic form of rat liver microsomal cytochrome b5. The assignment of backbone 13C resonances was used to confirm previous 1H and 15N resonance assignments [Guiles, R.D. et al. (1993) Biochemistry, 32, 8329-8340]. On the basis of short- and medium-range NOEs and backbone 13C chemical shifts, the solution secondary structure of rat cytochrome b5 has been determined. The striking similarity of backbone 13C resonances for both equilibrium forms strongly suggests that the secondary structures of the two isomers are virtually identical. It has been found that the 13C chemical shifts of both backbone and side-chain atoms are relatively insensitive to paramagnetic effects. The reliability of such methods in anisotropic paramagnetic systems, where large pseudocontact shifts can be observed, is evaluated through calculations of the magnitude of such shifts.

Amino Acid Sequence↗
PubMed1996

Pseudocontact shifts used in the restraint of the solution structures of electron transfer complexes.

The geometry of the ferricytochrome b5-ferricytochrome c complex has been analysed using long-range interprotein paramagnetic dipolar shifts. Heteronuclear filtered NMR spectra of samples containing 15N-labelled cytochrome b5 in complex with unlabelled cytochrome c allowed unambiguous assessment of pseudocontact shifts relative to diamagnetic reference states. Because pseudocontact shifts can be observed for protons as much as 20 A from the paramagnetic centre, this approach allows study of electron transfer proteins in fast exchange. Our findings provide the first physical evidence confirming hypotheses presented in previous theoretical studies. This absence of certain predicted shifts that are expected based on the best fit to a static model of the complex suggests that cytochrome b5 is more dynamic in solution than in the crystal, in agreement with molecular dynamics simulations.

Animals↗
PubMed1995

Multiple lineages of tumors express a common tumor antigen, P1A, but they are not cross-protected.

Whether tumors of different lineages share common Ags is a critical issue for understanding anti-tumor immune responses and for designing Ag-specific tumor immunotherapy. Because of lack of cross-protection among individually derived tumors, it has been proposed that tumor Ags are specific for individual tumors. Here we show that lack of cross-protection is not due to lack of a shared tumor Ag. Thus, a plasmocytoma J558 transfected with the costimulatory molecule B7 activates a cross-reactive CTL response in vivo. The major Ag recognized by the cross-reactive CTL is P1A, which is expressed in mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Surprisingly, no significant cross-protection can be detected among P1A-expressing tumors after immunization with either P1A-expressing or B7-transfected P815 cells. Our results demonstrate that multiple lineages of tumors are not cross-protected even though they share a tumor Ag that can be recognized by CTL. These results have important implications for tumor immunotherapy.

Amino Acid Sequence↗
PubMed1995

Low vision aids training in the home.

BACKGROUND: In a continuing effort to better serve the low vision community, The Center for the Partially Sighted has developed an in-home low vision aids training (LVAT) program. Of interest to anyone working in the field of low vision is a description of our training materials and methodology, and a discussion of the efficacy of this program. METHODS: The previous literature on low vision was evaluated and organized into an orderly program geared toward the visual rehabilitation of low vision patients. RESULTS: Implementation of LVAT in the home began as a pilot project directed toward patients with macular degeneration who have begun reading as a primary goal of rehabilitation. CONCLUSIONS: Successful vision rehabilitation with low vision devices can be accomplished with proper training. Typically the exam does not allow ample opportunity to ensure that a patient is proficient in the use of a device. Follow-up training in the home environment may provide the necessary intervention to maximize patients' comfort and efficiency with low vision devices and their ability to accomplish near point tasks.

Home Care Services↗
PubMed1993

Novel heteronuclear methods of assignment transfer from a diamagnetic to a paramagnetic protein: application to rat cytochrome b5.

15N and 1H resonance assignments for backbone and side-chain resonances of both equilibrium forms of rat ferricytochrome b5 have been obtained, using a combination of novel heteronuclear assignment transfer methods from the known assignments of the diamagnetic protein [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375] and computational methods which depend on an accurate determination of the orientation of the components of the susceptibility tensor. The transfer of amide proton resonance assignments takes advantage of the apparent insensitivity of amide 15N resonances to pseudocontact effects, evident in overlays of 15N-1H heteronuclear correlation spectra. Amide-proton resonance assignments tentatively transferred from the known diamagnetic assignments to the paramagnetic form of the protein were confirmed using conventional assignment strategies employing 600-MHz COSY, HOHAHA, and NOESY spectra of the oxidized protein. As was observed in rat ferrocytochrome b5, more than 40% of all residues exhibited NMR detectable heterogeneity due to the two different orientations of the heme. Complete assignment of both forms enabled accurate determination of the orientation of the susceptibility tensor for both conformations of the heme. The orientation of the z-component of the susceptibility tensors for the two forms are indistinguishable, while the in-plane components appear to differ by about 6 degrees. Differences in the orientation of the in-plane susceptibility components are undoubtedly due dominantly to the relative axial rotation of the heme of between 5 degrees and 10 degrees indicated by the NOESY contacts to the protein observed in the spectra of the ferrocytochrome [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375; Pochapsky, T. C., Sligar, S. G., McLachlan, S. J., & LaMar, G. N. (1990) J. Am. Chem. Soc. 112, 5258-5263].

Amino Acid Sequence↗
PubMed1990

Gemfibrozil cost-benefit study. Targeting subgroups for effective hyperlipidaemia drug therapy.

This cost-benefit analysis attempts to translate the clinical findings of the Helsinki Heart Study (HHS) and published results regarding additional cardiovascular conditions into economic terms meaningful to US managed care providers. The study has the following 3 key objectives: to define the cost effectiveness of gemfibrozil in the prevention of coronary heart disease (CHD); to assess the net impact of gemfibrozil on total treatment costs for CHD; and to identify those patient groups for whom gemfibrozil therapy is most cost effective. In order to reach these findings a cost-effectiveness model was constructed based on original clinical data provided by the HHS, published findings for CHD risk and cost of treatment in the US, expert opinion and extension of HHS to other cardiovascular conditions, and documented costs and treatment protocols of US Medicaid and privately managed health care programmes. The model was applied to the California Medicaid (Medi-Cal) programme to estimate costs of hyperlipidaemia therapy using gemfibrozil. In parallel, savings to Medi-Cal from averted coronary events were estimated. From these data, the net expected savings to Medi-Cal were calculated. The probability of experiencing CHD varies with cholesterol level, age, sex and risk factors such as smoking, hypertension and diabetes. Therefore, it is possible to use risk-factor profiles to define groups of individuals with low, moderate or high risk of experiencing acute myocardial infarction (AMI) or sudden cardiac death. The probability of a cardiac event within 5 years ranges from 1.1% in a 45-year-old low risk male to over 36% in a 55-year-old high risk male. The average total cost of CHD care was found to be US$22,271 within 5 years. Using the probability of a CHD event to calculate the expected 5-year cost of CHD care produces a range from US$242 in the 45-year-old low risk male to US$8084 in the 55-year-old high risk male. Treatment with gemfibrozil reduces the probability of AMI and sudden cardiac death events by 34%, as demonstrated in the HHS. Therefore, the corresponding probability ranges are reduced to 0.7% in the 45-year-old low risk male and 27.3% in the 55-year-old high risk male after treatment with gemfibrozil. The expected cost of a coronary event is reduced by US$82 and US$1997, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗