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Biomedical subjects

K Krishnamurthy

Publications and source records attributed to K Krishnamurthy.

At least 19 recordsLinked to original sources

A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells.

The elevated expression of prostate apoptosis response-4 (PAR-4) induces apoptosis in differentiating mouse embryonic stem (ES) cells. In embryoid body (EB) cells and the E15.5 stage of embryonic mouse brain, PAR-4 is expressed as two isoforms (38 and 33 kDa). Using mouse EB-derived RNA as a template we have cloned and characterized a novel isoform of PAR-4 (PAR-4/p33) that lacks exon 3 and shows a bona fide splice junction of exons 2 and 4. The molecular mass for PAR-4/p33 is estimated to be 33 kDa, corresponding to the short form found in the EB cells and E15.5 mouse brain. The fluorescent fusion protein of PAR-4/p33 is mainly found in the cytosol and is co-distributed with F-actin filaments, while that of the 38 kDa full length PAR-4/p38 is predominantly translocated to the nucleus. In contrast to the full length PAR-4 (PAR-4/p38), ectopic expression of PAR-4/p33 does not result in the activation of caspase 3 and the induction of apoptosis. PAR-4/p33 forms a complex with PAR-4/p38, which inhibits its nuclear translocation and the induction of apoptosis. PAR-4/p33 is suggested to be a dominant negative isoform of PAR-4/p38 and may regulate PAR-4-dependent apoptosis.

Actins↗

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.

AIM: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease. PATIENTS AND METHODS: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored. RESULTS: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars. CONCLUSION: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.

Adult↗

Granulocyte macrophage colony stimulating factor augmented hepatitis B vaccine protocol for rapid seroprotection in voluntary kidney donors.

BACKGROUND & OBJECTIVES: Conventional hepatitis B vaccine protocols do not provide rapid seroprotection against hepatitis B. This randomized controlled trial was carried out to investigate the efficacy of granulocyte macrophage-colony stimulating factor (GM-CSF) augmented double-dose vaccine protocol in voluntary kidney donors prior to donor nephrectomy. METHODS: A total of 54 kidney donors, who had no history of hepatitis B infection, hepatitis B vaccination and tested negative for anti-HBs and anti-HBc antibodies were randomly allocated to the control or test groups. GM-CSF (300 microg) was administered subcutaneously on day 0, followed by 40 microg of recombinant hepatitis B vaccine intramuscularly on the same deltoid on day 1. The control group received only 40 microg of intramuscular hepatitis B vaccine. Anti-HBs titres were measured at the end of 4 wk. RESULTS: Of the 54 donors studied, there was a significant (P<0.003) seroconversion in the GM-CSF group (82%) compared to the control group (37%), after a single immunization with double-dose recombinant hepatitis B vaccine by 4 wk. Minor side effects such as fever in four patients and myalgia in three were noticed. INTERPRETATION & CONCLUSION: GM-CSF augmented double-dose hepatitis B vaccine could be used in unvaccinated patients when a rapid response is desired.

Adjuvants, Immunologic↗

Hadamard excitation sculpting.

An approach to Hadamard phase encoding and editing in an excitation sculpting experiment is presented. When band- and/or frequency-selective experiments are performed at more than one site using excitation sculpting, use of Hadamard excitation sculpting (HEX sculpting) will reduce the total measuring time to achieve a target S/N. The application of HEX sculpting is demonstrated using selective 1D and NOESY1D experiments.

Journal Article↗

Improved resolution using symmetrically shifted pulses.

An approach to Hadamard phase encode the two halves of the F(1) dimension of a gHSQC experiment is presented. The phase encoding is achieved by excitation sculpting of the F(1) dimension using symmetrically shifted pulses. This approach (IMPRESS-improved resolution using symmetrically shifted pulses) increases the resolution of the F(1) dimension by exploiting spectral folding, but the folding is coded in the fashion of a Hadamard H(2) matrix. Editing of the IMPRESS spectra during processing sorts out spectral crowding which is a typical consequence of F(1) spectral folding. It is shown that for the same total experiment time, the IMPRESS-gHSQC experiment provides narrower peaks along the F(1) dimension compared to the normal gHSQC experiment. As a consequence of decreased linewidth, the peak height (sensitivity) is also increased.

Journal Article↗

Expression of wheat puroindoline genes in transgenic rice enhances grain softness.

The puroindoline genes (pinA and pinB) are believed to play critical roles in wheat (Triticum aestivum L.) grain texture. Mutations in either gene are associated with hard wheat. No direct evidence exists for the ability of puroindolines to modify cereal grain texture. Interestingly, puroindolines appear to be absent in cereal species outside of the tribe Triticeae, in which the dominant form of grain texture is hard. To assess the ability of the puroindolines to modify cereal grain texture, the puroindolines were introduced into rice (Oryzae sativa L.) under the control of the maize ubiquitin promoter. Textural analysis of transgenic rice seeds indicated that expression of PINA and/or PINB reduced rice grain hardness. After milling, flour prepared from these softer seeds had reduced starch damage and an increased percentage of fine flour particles. Our data support the hypothesis that puroindolines play important roles in controlling wheat grain texture and may be useful in modifying grain texture of other cereals.

Amino Acid Sequence↗

Wheat puroindolines enhance fungal disease resistance in transgenic rice.

Antimicrobial peptides play a role in the immune systems of animals and plants by limiting pathogen infection and growth. The puroindolines, endosperm-specific proteins involved in wheat seed hardness, are small proteins reported to have in vitro antimicrobial properties. Rice, the most widely used cereal crop worldwide, normally does not contain puroindolines. Transgenic rice plants that constitutively express the puroindoline genes pinA and/or pinB throughout the plants were produced. PIN extracts of leaves from the transgenic plants reduced in vitro growth of Magnaporthe grisea and Rhizoctonia solani, two major fungal pathogens of rice, by 35 to 50%. Transgenic rice expressing pinA and/or pinB showed significantly increased tolerance to M. grisea (rice blast), with a 29 to 54% reduction in symptoms, and R. solani (sheath blight), with an 11 to 22% reduction in symptoms. Puroindolines are effective in vivo in antifungal proteins and could be valuable new tools in the control of a wide range of fungal pathogens of crop plants.

Gene Expression Regulation, Plant↗

Epileptologist's assistant: a cost effective expert system.

Epileptologist's Assistant is an expert system designed to cost effectively handle routine care in an epilepsy follow up clinic. The system guides nurses in gathering patient histories and then generates progress notes and a patient information sheet. The progress note, organized in the SOAP format, is reviewed by the physician with the patient. For difficult cases the physician may modify the Assessment or Plan sections; the Subjective and Objective sections rarely need modifications. The assertion of cost-effectiveness is based on time/motion data. Without the system a physician in our epilepsy clinic spends about 21 minutes seeing a patient. With the system the nurse spends about 14 minutes with the patient and the physician spends about 7 minutes. Two nurses and a physician handle the work load of 3 physicians. Physician time is cut by about 66%. Using the average salaries for physicians and nurses at the Department of Veterans Affairs, the cost of a clinic visit is reduced 39% by using the expert system and nurses. In addition, the progress note is more legible, it contains more information, Q/A procedures are implemented at the point of patient contact, and the data is entered into a computer system in a data field format.

Ambulatory Care Facilities↗

A cost effective expert system to assist physicians: epileptologists' assistant.

While medical expert systems helped demonstrate that artificial intelligence was possible, few medical systems have been heralded as practical successes. We believe that expert systems will be practical successes if they cost effectively handle most of a physician's workload (i.e., routine care). To accomplish this goal, technology must appear invisible to the user; the system must be intuitive and anticipate users' needs. "Epileptologists' Assistant" is an example of our approach of combining a graphical user interface with an expert system and data base in a system to help in a routine specialty clinic. The goal is for two nurses and a physician to handle the workload of three physicians while increasing the quality of care. The current system reduces physician time by 66%. Our ultimate goal is to create a unified family of systems for medical specialties.

Costs and Cost Analysis↗

Enzymic basis of deranged foetal flavin-nucleotide metabolism consequent on immunoneutralization of maternal riboflavin carrier protein in the pregnant rat.

A comparison of the kinetic and other parameters of enzymes of flavin-nucleotide metabolism in the whole foetus vis-à-vis the maternal liver in the pregnant rat revealed relatively lower activities of foetal flavokinase and FAD pyrophosphorylase. Passive immunoneutralization of the maternal riboflavin carrier protein suppresses foetal FAD pyrophosphorylase rather selectively. Additionally, although the activities of foetal nucleotide pyrophosphatase and FMN phosphatase were unchanged owing to immunoneutralization, higher activities of these enzymes in the whole foetus as compared with the maternal liver may be responsible for the drastic depletion of FAD levels that precipitates foetal degeneration.

Animals↗

Mechanism of foetal wastage following immunoneutralization of riboflavin carrier protein in the pregnant rat: disturbances in flavin coenzyme levels.

Immunoneutralization of maternal RCP results in a greater than 90% decrease in the content and the incorporation of [2-14C]riboflavin into embryonic FAD as well as a percentage redistribution of both embryonic FMN and riboflavin. This is unaccompanied by any discernible changes in flavin distribution pattern in the maternal liver. Embryonic alpha-glycerophosphate dehydrogenase and NADPH-cytochrome c reductase register significant decreases in activities in the RCP antiserum-treated rats. These alterations readily explain the arrest of foetal growth culminating in pregnancy termination in the antiserum-treated animals.

Animals↗