Biomedical subjects
A Agrawal
Publications and source records attributed to A Agrawal.
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system.
Immunoglobulin and T-cell-receptor genes are assembled from component gene segments in developing lymphocytes by a site-specific recombination reaction, V(D)J recombination. The proteins encoded by the recombination-activating genes, RAG1 and RAG2, are essential in this reaction, mediating sequence-specific DNA recognition of well-defined recombination signals and DNA cleavage next to these signals. Here we show that RAG1 and RAG2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule. The products formed contain a short duplication of target DNA immediately flanking the transposed fragment, a structure like that created by retroviral integration and all known transposition reactions. The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.
Screening for simultaneous esophageal primary tumors: esophagoscopy vs esophagography.
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In Situ High-Temperature Transmission Electron Microscopy Observations of the Formation of Nanocrystalline TiC from Nanocrystalline Anatase (TiO2).
: In this work, the high-temperature behavior of nanocrystalline TiO2 is studied using in situ transmission electron microscopy (TEM). These nanoparticles are made using wet chemical techniques that generate the anatase phase of TiO2 with average grain sizes of 6 nm. X-ray diffraction studies of nanophase TiO2 indicate the material undergoes a solid-solid phase transformation to the stable rutile phase between 600 degrees and 900 degreesC. This phase transition is not observed in the TEM samples, which remain anatase up to temperatures as high as 1000 degreesC. Above 1000 degreesC, nanoparticles become mobile on the amorphous carbon grid and by 1300 degreesC, all anatase diffraction is lost and larger (50 nm) single crystals of a new phase are present. This new phase is identified as TiC both from high-resolution electron microscopy after heat treatment and electron diffraction collected during in situ heating experiments. Video images of the particle motion in situ show the nanoparticles diffusing and interacting with the underlying grid material as the reaction from TiO2 to TiC proceeds.
Gossypiboma revisited: a case report and review of the literature.
Gossypiboma (retained surgical sponge) is a rare but preventable occurrence. In this case it presented as a chronic abdominal mass which simulated a primary small bowel tumour. The findings on pelvic ultrasonography were typical for this condition and the role of plain abdominal radiology in the gynaecological patient are highlighted.
RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination.
During V(D)J recombination, RAG1 and RAG2 cleave DNA adjacent to highly conserved recombination signals, but nothing is known about the protein-DNA complexes that exist after cleavage. Using a properly regulated in vitro V(D)J cleavage system, together with nuclease sensitivity, mobility shift, and immunoprecipitation experiments, we provide evidence that a stable complex is formed postcleavage between synapsed recombination signals. This complex includes the proteins RAG1, RAG2, HMG-1 or the closely related HMG-2 protein, and the components of the DNA-dependent protein kinase. The existence of such a stable complex explains a number of in vivo observations and suggests that remodeling of postcleavage synaptic complexes is an important step in the resolution of signal ends in V(D)J recombination.
Site-directed mutagenesis of the phosphocholine-binding site of human C-reactive protein: role of Thr76 and Trp67.
We have reported previously that residues Lys57, Arg58, and Trp67 of human C-reactive protein (CRP) contribute to the structure of the phosphocholine (PCh)-binding site. In this study, based on the three-dimensional structures of human CRP and serum amyloid P, we constructed an additional mutant, T76Y, to probe the structural determinants of the PCh-binding site of CRP. Binding properties of four mutant CRPs, K57Q/R58G, W67K, K57Q/R58G/W67K, and T76Y were compared. Wild-type (wt) and all mutant CRPs were purified by affinity chromatography on PCh-, pneumococcal C-polysaccharide (PnC)-, or phosphoethanolamine-conjugated agarose columns. Purified mutant CRPs, K57Q/R58G/W67K and T76Y failed to bind to solid phase, PCh-substituted BSA. They did, however, bind to immobilized PnC, although with substantially decreased avidity compared with wt CRP. W67K, K57Q/R58G/W67K, and T76Y CRP required a 10-fold higher Ca2+ concentration than wt CRP to bind PnC and exhibited decreased avidity for mAb EA4.1, which recognizes a Ca2+-dependent epitope. We conclude that Thr76 is a determinant of the PCh-binding site, probably interacting with the choline group. This conclusion is supported by recent crystallographic data indicating that this residue participates in the formation of a hydrophobic pocket that constitutes the binding site for choline. Trp67, Lys57, and Arg58 do not directly contact PCh, but appear to be required for the proper conformation of the binding site.
C-reactive protein: structural biology, gene expression, and host defense function.
Over the past few years substantial insight was gained into the biology and biochemistry of human C-reactive protein (CRP). X-ray crystallography in conjunction with mutational analyses, generated the three-dimensional structure of the protein and indicated the topology and structure of ligand-binding sites. Using human CRP transgenic mice infected with Streptococcus pneumoniae, we obtained data that clearly established CRP as an important host defense molecule. Studies using the same mice revealed a previously unknown testosterone-dependence of constitutive expression of human CRP. In this article we provide a brief overview of these recent findings.
Amino acid transport in cerebral microvessels during Plasmodium yoelii infection in mice.
Plasmodium yoelii infected cerebral microvessels of mice had an enhanced time-dependent, temperature-sensitive, and saturable uptake of [14C]-amino acid. viz. leucine, valine and glycine. Metabolic inhibitors caused a noticeable inhibition of amino acid uptake in normal microvessels as compared to infected cerebral microvessels indicating that the uptake of [14C]-L-leucine, [14C]-L-valine and [14C]-glycine is an energy dependent process.
Postdural puncture headache and ACTH.
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Safety analysis: relative risks of ultraviolet exposure from fluorescence spectroscopy and colposcopy are comparable.
Fluorescence spectroscopy is a promising tool for use in the diagnosis of disease in human tissue. However, few published reports have evaluated the safety of this technique, despite the fact that many spectroscopic systems use UV illumination. This study determined the relative risk associated with light exposure from spectroscopic systems compared with the traditional light sources that are used to illuminate tissue and direct biopsies. We compared spectroscopic detection systems for the cervix to the colposcope, a low-power microscope routinely used to illuminate the cervix, which does not cause any known photochemical damage. We measured the average spectral irradiance (W/[cm2nm]) and the average tissue exposure time during a diagnostic colposcopy examination. To quantify the relative risks, we multiplied illumination spectra by several action spectra from the literature and compared the areas under the curves corresponding to each procedure. The risk associated with the average power colposcope served as our basis for comparison. We conclude that the risks of illumination using spectroscopic systems are lower than or comparable to those already encountered in routine diagnostic procedures such as colposcopy with an average power colposcope. Spectroscopic examination can be associated with a somewhat higher risk than a colposcopy with the lowest power colposcope or a shorter than average colposcopy. The analysis presented can be repeated to estimate the magnitude of risks associated with other spectroscopic diagnostic devices.
Impact of mode of delivery on maternal mortality in eclampsia.
Determinants of maternal mortality and causes of death pertaining to mode of delivery have been discussed. There were 23 deaths (case fatality rate of 7.2%) and maximum deaths occurred in intrapartum eclampsia (12 ie, 52.17%). Caesarean section was performed in 92 cases (28.7%) of which 4 women died (4.3%). Maternal mortality in cases who delivered vaginally was 7.1% (16 out of 225) and 3 cases died undelivered. Authors feel that at the referral centres early caesarean section in eclampsia may help in reducing maternal mortality.
Status of urea and related enzymes during Plasmodium yoelii infection and pyrimethamine treatment in mice.
Plasmodium yoelii infection alters the hepatic levels of key enzymes of urea cycle, viz.carbamoyl phosphates synthetase (EC 6.3.4.16) and ornithine transcarbamoylase (EC 2.1.3.3) and urea levels in mice. The urea level was found elevated in liver, brain and plasma during P. yoelii infection. However, carbamoyl phosphate synthetase and ornithine transcarbamoylase were noticeably decreased during P. yoelii infection. Pyrimethamine treatment (10 mg/kg body weight for 4 days) brought back the altered parameters to normal a week after cessation of drug treatment.
Medical treatment for cysticercosis.
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Studies on ammonia-metabolizing enzymes during Plasmodium yoelii infection and pyrimethamine treatment in mice.
Blood ammonia content and enzymes involved in ammonia metabolism, namely glutamine synthetase (GS), glutamate dehydrogenase (GDH), monoamine oxidase (MAO), alanine amino-transferase (ALT) and aspartate aminotransferase (AST), were studied in Plasmodium yoelii-infected drug-treated mice tissues. The ammonia content in blood increased with the rise of parasitaemia. Hepatic GS, GDH and MAO showed a marked decrease in enzyme activity during parasitic infection. In contrast, cerebral GS and MAO showed a significant increase during infection. However, the parallel measurement of renal enzymes did not show any noticeable alterations except for ALT and AST. Oral pyrimethamine treatment (10 mg/kg for 4 days) in infected mice (5-10%) returned the altered levels of the above enzymes to almost normal 1 week after the cessation of drug treatment.
Permeability function related to cerebral microvessel enzymes during ageing in rats.
Cerebral microvessels from rats were prepared and characterized by their enrichment of specific markers, namely alkaline phosphatase (AP) and tau-glutamyl transpeptidase (tau-GT). Further, it was observed that AP and tau-GT registered marked increase in aged rats. On the contrary, lactate dehydrogenase (LDH) activity decreased with the increasing age. Monoamine oxidase A activity in the microvessels decreased with age whereas MAO-B moved in the reverse direction. No noticeable change was seen in acetyl-cholinesterase activity with increasing age of rats.
Body plethysmographic measurement of thoracic gas volume without panting against a shutter.
When a subject breathes through a pneumotachograph in a body box, the measured value of specific airway resistance (sRaw1) is equal to the product of thoracic gas volume (TGV) and the sum of the airway resistance (Raw) and the instrument resistance (Rins). If an additional resistance (Radd) is put in the breathing path, the measured specific, airway resistance (sRaw2) exceeds sRaw1 by the product of TGV and Radd and can be used for determining TGV. With the use of a device increasing Rins by a known amount (Radd) during normal breathing, sRaw1 and sRaw2 were measured in 3 normal subjects, 16 asthmatic patients, 2 patients with chronic obstructive pulmonary disease, and 1 patient with restrictive lung disease from the slopes of the x-y plots of airflow vs. box signals obtained before and after adding Radd. TGV was calculated by dividing (sRaw2-sRaw1) bu Radd. We also determined subjects' TGV by the panting method of A. B. DuBois, S. Y. Botelho, G. N. Bedell, and J. H. Comroe, Jr. (J. Clin. Invest. 35: 322-326, 1956) and functional residual capacity by the helium-dilution method. The results of the new method were quite reproducible (coefficient of variation = 5.6) and equivalent to those obtained by the other two methods.
Vitiligo: repigmentation with dermabrasion and thin split-thickness skin graft.
BACKGROUND: Vitiligo is a common benign condition of great concern. Though a large number of medical and surgical treatment methods are available, none of them is fully dependable in all the areas. OBJECTIVE: Split-thickness skin grafting (STSG) has been used for the treatment of vitiligo for over three decades, but it did not gain popularity. This presentation evaluates the degree of repigmentation achieved with this technique, its complications, and drawbacks. METHODS: A case series of 21 patients with 32 localized, stable, and refractory vitiligo patches treated institutionally by dermabrasion and thin STSG has been presented. The patients have been followed up for 1-6 years. Three patients lost to follow-up before 1 year have not been included. RESULTS: The graft take was 100% in 27 patches and 90-95% in the remaining five. One hundred percent repigmentation was achieved in 22 patches and 90-95% in 10. Time taken for satisfactory color match was 4-9 months (average, 6.3 months). The complications encountered were all minor and did not affect the results. CONCLUSION: This is a simple, outpatient procedure performed under local anesthesia resulting in an excellent color match on a long-term follow-up. This technique can be used over any part of the body, including the hair-bearing areas, without compromising the end results.