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Biomedical subjects

R Hegde

Publications and source records attributed to R Hegde.

At least 19 recordsLinked to original sources
PubMed2006

The Jehovah's Witness and dementia: who or what defines 'best interests'?

An elderly woman with dementia presented for repeat surgical management of fractured neck of femur. Although no advance directive had ever been generated, the patient was declared to be a strict Jehovah's Witness by her daughter, who vetoed the transfusion of any blood products. The fracture was managed conservatively but the patient suffered repeated chest infections, from which she died 4 months after admission. This case raised several clinical, ethical and legal issues and generated a spectrum of opinion as to the appropriateness of operative intervention, transfusion and provision of intensive care. We suggest that professional guidelines and the new Mental Capacity Act 2005 do not provide explicit and comprehensive guidance for practitioners. Further deliberation is required to bring about convergence between the law, ethical principles and professional guidelines.

Aged, 80 and over↗
PubMed2004

A classical live attenuated vaccine for sheep pox.

A classical live attenuated sheep pox vaccine was prepared using the Ranipet strain of sheep pox virus (SPV) at the 50th passage in a secondary lamb testicular cell system. The TCID50 and RD50 were 10(9.63)/ml and 10(9.51)/ml. respectively. The SID50 of SPV challenge virus was 10(5)/ml. The vaccine was found to have no adverse effects in laboratory animals, and was safe and effective in SPV seronegative lambs. In the field, 660 sheep were vaccinated with an immunizing dose containing 1 x 10(2) TCID50. Randomly selected vaccinated sheep mounted good cell-mediated immunity and humoral responses as measured by glucose utilization test and serum neutralization test, respectively, for the study period of 6 months.

Animals↗
PubMed2002

Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC.

Death effector domain-containing proteins are involved in important cellular processes such as death-receptor induced apoptosis, NF-kappaB activation and ERK activation. Here we report the identification of a novel nuclear DED-containing protein, FLAME-3. FLAME-3 shares significant sequence (46.6% identical) and structural homology to another DED-containing protein, DEDD. FLAME-3 interacts with DEDD and c-FLIP (FLAME-1) but not with the other DED-containing proteins FADD, caspase-8 or caspase-10. FLAME-3 translocates to, and sequesters c-FLIP in the nucleus upon overexpression in human cell lines. Using the yeast two-hybrid system to identify DEDD-interacting proteins, the TFIIIC102 subunit of human transcription factor TFIIIC was identified as a DEDD- and FLAME-3-specific interacting protein. Co-expression of either DEDD or FLAME-3 with hTFIIIC102 in MCF-7 cells induces the translocation from the cytoplasm and sequestration of hTFIIIC102 in the nucleus, indicating that DEDD and FLAME-3 form strong heterocomplexes with hTFIIIC102 and might be important regulators of the activity of the hTFIIIC transcriptional complex. Consistent with this, overexpression of DEDD or FLAME-3 in 293 cells inhibited the expression of a luciferase-reporter gene under the control of the NF-kappaB promoter. Our data provide the first direct evidence for the involvement of DED-containing proteins in the regulation of components of the general transcription machinery in the nucleus.

Amino Acid Sequence↗
PubMed2002

Papillon-Lefevre syndrome: a report of two cases.

Papillon-Lefevre Syndrome (PLS) is an inherited autosomal recessive disorder presenting with Palmar plantar Keratoderma and Juvenile Periodontitis leading to early loss of both the dentitions. Two cases of PLS in a family with a history of consanguineous descent are presented.

Adolescent↗
PubMed2001

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.

X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.

Amino Acid Motifs↗
PubMed2001

Red cell distribution width in the diagnosis of iron deficiency anemia.

OBJECTIVE: 1. To compare peripheral smear (PS) and Red cell distribution width (RDW) in diagnosis of Iron deficiency anemia (IDA) in various grades. 2. To study the changes in RDW and PS after therapy. METHODS: Children in the age group of six months to five years with microcytic (MCV<80fl) anemia (Hemoglobin <11 g%) were evaluated. Those who had received blood transfusion and /or were already on iron therapy were excluded. Evaluation included clinical examination, complete blood count (CBC), RDW estimation microscopic examination of peripheral smear, measurement of serum iron and transferrin saturation. Children with IDA were treated with oral iron for 8 weeks and PS, CBC including RDW were repeated. RESULT: Of the 100 children evaluated, 89 had IDA. 48% had mild, 42% had moderate and 10% had severe anemia. Transferrin saturation correlated with severity of anemia. Peripheral smear showed microcytosis and hypochromia in all cases with severe anemia, 61.5% and 22.5% of those with moderate and mild anemia respectively. RDW was suggestive of iron deficiency in 100%, 82.05% and 100% of patient with mild, moderate and severe anemia respectively. CONCLUSION: In the diagnosis of mild and moderate iron deficiency anemia, RDW had a higher sensitivity than PS. Red cell morphology, Hb, PCV and RDW showed significant improvement after iron-therapy.

Anemia, Iron-Deficiency↗
PubMed2001

Menetrier's disease.

An 8-year-old girl presented with persistent vomiting, pain abdomen and generalized edema. Barium studies and gastroscopy suggested hypertrophic gastropathy. Histopathological examination pointed the diagnosis towards Menetrier's Disease. There was spontaneous remission and the child required only supportive therapy.

Barium Sulfate↗
PubMed1998

Identification and characterization of murine caspase-14, a new member of the caspase family.

We report here the identification and characterization of a new member of the mouse caspase family, named caspase-14. Northern blot analysis of mRNA from various tissues with caspase-14-specific probe showed a major transcript size of approximately 2.4 kb and variant transcripts of 2.0 kb and 1.5 kb. The major transcript is detected mainly in the liver and to a lesser extent in the brain and kidney. Caspase-14 cDNA encodes a 257-amino acid-long protein that has significant homology to other members of the caspase family. Like other caspases, caspase-14 has a conserved active site, pentapeptide QACRG. However, it lacks an NH2-terminal prodomain or a caspase recruitment domain, suggesting that it could be a downstream caspase that depends on other initiator caspases for activation. Consistent with this, procaspase-14 can be processed in vitro by the death receptor-associated caspase-8 and caspase-10 but not other caspases, and in vivo after stimulation of cells with anti-Fas agonist antibody or Tumor Necrosis Factor-Related Apoptosis Inducing Ligand. Furthermore, procaspase-14 can be cleaved by granzyme B. These observations suggest that caspase-14 may play a role in death receptor and granzyme B-induced apoptosis.

Amino Acid Sequence↗
PubMed1998

Evolution of tetrameric lectin Ricinus communis agglutinin from two variant groups of ricin toxin dimers.

Seeds of Ricinus communis contain two types of lectins; the toxin ricin (approximately 60 kDa) and R. communis agglutinin (approximately 120 kDa). The toxin is a heterodimer composed of a toxic A subunit and a lectin B subunit, while R. communis agglutinin is a tetramer, constituted of two ricin-like dimers held together by non-covalent forces. The lactamyl Sepharose affinity-purified ricin consists of two major groups of variants designated ricin II and III [Hegde, R. & Podder, S. K. (1992) Eur. J. Biochem. 204, 155-164]. The purified A subunits of all the variants of ricins and R. communis agglutinin show heterogeneity in the molecular mass as shown for ricin before [Fulton, J. R., Blakey, C. D., Knowles, P. P., Uhr, J. W., Thorpe, P. E. & Vitetta, E. S. (1986) J. Biol. Chem. 261, 5314-5319]. Since the isoelectric points of the R. communis agglutinin variants fall between the isoelectric points of ricin II and III, we investigated the possibility that this lectin is made up of ricin II and III. The isoelectric points of the purified B subunits of R. communis agglutinin matched well with those of ricin II and III on urea-polyacrylamide isoelectric focussing gel. Further, two-dimensional electrophoretic analysis of the ricin constituants of R. communis agglutinin in the presence of 9 M urea, showed two protein bands, differing by nearly pH 2 in their isoelectric points, the more alkaline one corresponding to that of ricin III analyzed under the same conditions, while the other, although a higher molecular mass variant, corresponding well with ricin II in its isoelectric point. Based on these results and those obtained from adenine binding to A chains of both ricin and R. communis agglutinin, we provide a plausible evolutionary relationship between R. communis agglutinin and two groups of ricin variants; ricin II and III. The model predicts that one half of R. communis agglutinin is derived from ricin I and II, and the other half from ricin III. The results presented, contrary to the existing notion, unequivocally show that the two halves of R. communis agglutinin are not identical protein units, but differ both in surface charge and molecular mass.

Ricinus communis↗
PubMed1998

Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.

We identified and cloned a novel murine member of the pro-apoptotic Bcl-2 family. This protein, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane. Blk contains a conserved BH3 domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL. Ectopic expression of Blk in mammalian cells induces apoptosis, which can be inhibited by mutations in the BH3 domain and by overexpression of Bcl-2 or Bcl-xL but not by CrmA. The apoptotic activity of Blk is also inhibited by a dominant negative caspase-9, suggesting that Blk induces apoptosis through activation of the cytochrome c-Apaf-1-caspase-9 pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The 24-kDa subunit of the bovine mitochondrial NADH:ubiquinone oxidoreductase is a G protein.

Based on the results obtained from GTP overlay assay, immunoprecipitation, two dimensional electrophoresis and radiolabeled GTP binding, we provide evidence that the bona fide subunit of Complex I, the long known 24 kDa protein is a G protein. Bacterially expressed 24 kDa protein with additional N-terminal methionine and alanine residues or naturally expressed truncated isoform fail to bind GTP suggesting that secondary modification/ processed N-terminal end is necessary for GTP binding. Competitive inhibition of binding of radiolabeled GTP to electroblotted 24 kDa protein with unlabelled nucleotides showed that the protein binds GTP and GDP with high affinity in presence of Mg2+, and has decreased to very low affinity for ITP, CTP, GMP and UTP. A comparative binding of [gamma-35S]-GTP to Complex I and 24 kDa protein (electroblotted) suggests that the GTP binding in the native Complex is solely due to 24 kDa protein. Further, four fold difference in the binding affinities between native Complex I and 24 kDa protein (electroblotted) as seen by Scatchard analysis of the binding data indicates that protein undergoes structural rearrangement in Complex I bound form, that presumably triggers divalent cation dependent GTPase activity in native complex. We were unable to detect the effect of GTP/ GDP on the ubiquinone/ferricyanide reductase activity. Since the subunit is found missing in tissues affected by mitochondrial respiratory chain diseases, we presume that the subunit has regulatory role in the Complex I function in the electron transport chain.

Animals↗
PubMed1997

A- and B-subunit variant distribution in the holoprotein variants of protein toxin abrin: variants of abrins I and III have constant toxic A subunits and variant lectin B subunits.

The cytotoxic lectin abrin shows more than 30 variant forms (R. Hegde, T. K. Maiti, and S. K. Podder, 1991, Anal. Biochem. 194, 101-109). The lectin B subunit as cause for variance in abrins I and III was detected by a combination of one- and two-dimensional electrophoresis and Western blotting. Intriguingly, in abrin I but not in abrin III, association of a single A subunit with the variant B subunits shifts the holoprotein pI toward the alkaline side indicating that the subunit association involves neutralization of few negative charges. The B-subunit variants of abrins I and III overlap in their pI, and the A-subunit association gives the holoproteins a distinctness on isoelectric focusing gel. The results were also confirmed by analyzing the pH titration curves. These differences in the subunit association pattern between abrins I and III are in corroboration with the previously observed differences in the kinetics of protein synthesis inactivation and accessibility of the disulfide bridge to reducing agents in the presence or absence of putative receptor (R. Hegde, A. Karande, and S. K. Podder, 1993 Eur. J. Biochem. 215, 411-419). Further, the genetic origin of variance was confirmed by peptide mapping of the individual subunit variants. Considering a theoretical value of 0.1 to 0.2 pI/charge, a 15-17 charge difference could be predicted between the variants of two extreme pIs. The fact that the A subunits are not shared between the groups was taken to interpret that the protein synthesized as prepro form is processed posttranslationally and the processing takes place only after the disulfide bond formation between A and B subunits. The N-terminal 16 amino acids of A subunits of abrins I and III showed 26% dissimilarity. The A subunits of abrins I and III did not react with concanavalin A, indicating that the heterogeneity in the molecular weight is because of differential processing but not because of glycosylation.

Abrin↗
PubMed1996

Pseudocyst of the auricle: a new method of treatment.

Pseudocyst of the auricle is a condition where spontaneous serous fluid collection is seen on the lateral surface of the pinna. The aetiology of this condition is not known. Several methods of treatment have been advocated in the past. We report 10 cases of unilateral pseudocyst who were treated with aspiration and pressure dressing by a plaster of Paris cast over the pinna for two weeks.

Casts, Surgical↗
PubMed1994

The crystal structure of the bacterial chaperonin GroEL at 2.8 A.

The crystal structure of Escherichia coli GroEL shows a porous cylinder of 14 subunits made of two nearly 7-fold rotationally symmetrical rings stacked back-to-back with dyad symmetry. The subunits consist of three domains: a large equatorial domain that forms the foundation of the assembly at its waist and holds the rings together; a large loosely structured apical domain that forms the ends of the cylinder; and a small slender intermediate domain that connects the two, creating side windows. The three-dimensional structure places most of the mutationally defined functional sites on the channel walls and its outward invaginations, and at the ends of the cylinder.

Amino Acid Sequence↗