Biomedical subjects

Pradeep Kumar

Publications and source records attributed to Pradeep Kumar.

42 records · Page 3Linked to original sources

PubMed2003

Complexes of the uracil-DNA glycosylase inhibitor protein, Ugi, with Mycobacterium smegmatis and Mycobacterium tuberculosis uracil-DNA glycosylases.

Uracil, a promutagenic base, appears in DNA either by deamination of cytosine or by incorporation of dUMP by DNA polymerases. This unconventional base in DNA is removed by uracil-DNA glycosylase (UDG). Interestingly, a bacteriophage-encoded short polypeptide, UDG inhibitor (Ugi), specifically inhibits UDGs by forming a tight complex. Three-dimensional structures of the complexes of Ugi with UDGs from Escherichia coli, human and herpes simplex virus have shown that two of the structural elements in Ugi, the hydrophobic pocket and the beta1-edge, establish key interactions with UDGs. In this report the characterization of complexes of Ugi with UDGs from Mycobacterium tuberculosis, a pathogenic bacterium, and Mycobacterium smegmatis, a widely used model organism for the former, is described. Unlike the E. coli (Eco) UDG-Ugi complex, which is stable to treatment with 8 M urea, the mycobacterial UDG-Ugi complexes dissociate in 5-6 M urea. Furthermore, the Ugi from the complexes of mycobacterial UDGs can be exchanged by the DNA substrate. Interestingly, while EcoUDG sequestered Ugi into the EcoUDG-Ugi complex when incubated with mycobacterial UDG-Ugi complexes, even a large excess of mycobacterial UDGs failed to sequester Ugi from the EcoUDG-Ugi complex. However, the M. tuberculosis (Mtu) UDG-Ugi complex was seen when MtuUDG was incubated with M. smegmatis (Msm) UDG-Ugi or EcoUDG(L191G)-Ugi complexes. The reversible nature of the complexes of Ugi with mycobacterial UDGs (which naturally lack some of the structural elements important for interaction with the beta1-edge of Ugi) and with mutants of EcoUDG (which are deficient in interaction with the hydrophobic pocket of Ugi) highlights the significance of both classes of interaction in formation of UDG-Ugi complexes. Furthermore, it is shown that even though mycobacterial UDG-Ugi complexes dissociate in 5-6 M urea, Ugi is still a potent inhibitor of UDG activity in mycobacteria.

Amino Acid Sequence↗

PubMed2002

Analysis of the initiator tRNA genes from a slow- and a fast-growing Mycobacterium.

Initiation of protein synthesis is a major post-transcriptional regulatory step in gene expression. The initiator tRNA gene from Mycobacterium smegmatis, a fast-growing mycobacterium, was characterized and compared with its counterpart from Mycobacterium tuberculosis, a slow-growing mycobacterium. In both mycobacteria, the functional initiator tRNA genes were found in a single copy. Unlike the M. tuberculosis initiator tRNA, the CCA end of the M. smegmatis initiator is not encoded in the gene, and it is most likely added post-transcriptionally. Transcription start site mapping allowed accurate assignment of the hexameric -10 and -35 promoter elements for both genes. These elements of the M. smegmatis initiator tRNA gene contain single nucleotide changes compared to their respective counterparts in the M. tuberculosis gene. Chloramphenicol acetyl transferase reporter assays suggested that the promoter of the initiator tRNA gene from M. smegmatis is twice as strong as that of M. tuberculosis, irrespective of whether the assays were performed in the fast-growing homologous host (M. smegmatis) or the slow-growing heterologous host (M. tuberculosis). Characterization of the M. smegmatis metU promoter, in this study, provides a valuable tool for the expression of genes in mycobacteria.

Base Sequence↗

PubMed2002

Impact assessment of mass measles vaccination.

OBJECTIVE: The mass measles vaccination campaign was conducted in the slums of Surat City, in Gujarat State, as a part of urban measles control initiative in India. One dose each of the vaccine was administered to children in the age range of 9-59 months residing in these slums, regardless of their previous vaccination status. METHODS: One year later, (October 2000), the present study was carried out in order to assess the impact of the mass vaccination campaign on the vaccination coverage and on the incidence of measles by comparing the findings with those of the baseline survey carried out in May 98. This was a retrospective study with a recall period of the preceding year. 3,147 children under five were studied in thirty slum clusters selected by the cluster sampling method. The parents/caretakers of these children were interviewed for information on any episode of fever with rash conforming to the case definition. RESULT: The incidence rate for measles declined from 7.7 percent reported in the baseline (May 1998) to 3.5 percent in the impact assessment study. The incidence was 8 times higher in unvaccinated children. The mean and median age at contracting the illness increased from 26 +/- 14.2 months and 26 months in the baseline to 30.9 +/- 14.7 months and 30 months respectively in the impact assessment. The vaccination coverage had improved from 48.3 percent to 73.7 percent following the campaign. CONCLUSION: The compaign increased vaccination coverage decreased disease incidence and caused a shift towards higher age-groups in vaccinated children.

Chi-Square Distribution↗

PubMed2002

Formation of Bowman-Birk inhibitors during the germination of horsegram (Dolichos biflorus).

Three Bowman-Birk type inhibitors (HGGI-I, II and III), which appear in the cotyledons of 120 h germinated horsegram (Dolichos biflorus) seeds have been purified to homogeneity by size-exclusion chromatography and ion-exchange chromatography. HGGI-I, HGGI-II and HGGI-III differ from each other and from the dormant seed inhibitors in amino acid composition, molecular size and charge. The amino-terminal sequence analyses indicate that these inhibitors are derived from the isoinhibitors of the dormant seed by a limited proteolysis and not by de novo synthesis. These inhibitors differ from each other at their amino-terminus. HGGI-II identical to HGGI-I except for the loss of a single amino-terminal aspartyl residue, where as HGGI-III shows the loss of a pentapeptide. All the three inhibitors are potent competitive inhibitors of trypsin and chymotrypsin. The dissociation constants (K(i)s) for trypsin inhibition indicate that amino-terminal tail of the inhibitors play a role in trypsin binding probably through electrostatic interaction.

Amino Acid Sequence↗

PubMed2002

Left atrial myxoma presenting with acute pulmonary oedema in an elderly woman.

A previously healthy 76-year-old woman presented with an acute onset of shortness of breath due to acute pulmonary oedema. A transthoracic echocardiogram showed a large mobile mass attached to the inter-atrial septum occupying the whole of the left atrium. She was totally asymptomatic prior to this presentation. She was transferred to a tertiary cardiothoracic unit and had it surgically removed. Histology confirmed a benign atrial myxoma. Her symptoms resolved spontaneously without the need for further medication. This highlights the importance of echocardiography for patients of any age who present to hospital with a first episode of pulmonary oedema. This report also emphasises the fact that all patients, including the elderly, should be immediately referred for surgery because of its good prognosis.

Journal Article↗

PubMed2002

Effect of trichloroethylene (TCE) inhalation on biotransformation enzymes of rat lung and liver.

Trichloroethylene (TCE) is widely used as an industrial solvent and cleaning fluid. In the present study the toxic effects of TCE inhalation on pulmonary and hepatic biotransformation enzymes in rats have been investigated by assay of aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), benzo-a-pyrene hydroxylase (BH) and glutathione-s-transferase (GST) activities and glutathione (GSH) contents in liver as well as lungs of exposed animals. In both organs phase I and phase II drug metabolizing enzymes have been found to be increased along with decrease in GSH contents following TCE inhalation. Pulmonary as well as hepatic MFO's seem to be activated by inhaled TCE probably in an attempt for its rapid detoxification and reduced glutathione is used during its biotransformation.

Administration, Inhalation↗