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A Aggarwal

Publications and source records attributed to A Aggarwal.

At least 37 records · Page 2Linked to original sources

Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors.

Investigation of the large POU domain family of developmental regulators has revealed a molecular mechanism by which highly related transcription factors sharing common DNA-binding motifs act to functionally discriminate their cognate DNA sequences. Studies of two classes of neuron-specific POU domain factors (III and IV) indicate that functional specificity on their native response elements is achieved by accommodating different nucleotide spacing between variably oriented bipartite core DNA-binding motifs. The preferred orientation of the POU-specific domain of the neuronal factors on their native response elements appears to be opposite that of Pit-1 and Oct-1. Members of POU-III (Brn-2) class exhibit remarkable flexibility in DNA site recognition (tolerating core motifs spaced by 0, 2, or 3 nucleotides), whereas POU-IV (Brn-3) class is highly constrained (tolerating core motifs with a spacing of 3 nucleotides). The molecular determinant of the constraint in DNA site selection appears to be imparted by 3 amino acid residues in the amino-terminal basic region in concert, with helix 2 of the POU homeo domain which together are involved in minor groove and possibly phosphate backbone contacts. Similar mechanisms may underlie differential flexibility in spacing and orientation for diverse families of transcription factors.

Amino Acid Sequence

Does the ileocolonic junction differentiate between solids and liquids?

Previous observations from our laboratory have suggested that colonic filling from the ileum is characterised by a series of bolus movements. The present experiments were designed to test the hypothesis that bolus transit of ileal contents into the colon would not distinguish between solids and liquids. After a manometric infusion assembly was positioned by mouth into the ileum of 13 healthy volunteers, a mixture of nutrients (75 kcal), incorporating a solid phase radiolabel (111In labeled resin pellets) and a liquid phase marker (99mTc-DTPA), was infused into the ileum. Transit of both labels from the ileum to colon was quantified scintigraphically and ileal motility was also recorded. When markers were infused into the proximal ileum, 100 cm proximal to the ileocolonic junction (six), there were clear cut examples of discriminant transit, when liquids moved more rapidly from the small to the large bowel than did solids. When isotopes were instilled into the distal ileum, less than 50 cm from the ileocolonic junction, no separate transit of the solid and liquid phases was observed. No specific motor pattern of the ileum was regularly associated with bolus filling of the colon. These results support the hypothesis that the distal ileum can discriminate between solids and liquids but that the ileocecal junction cannot.

Adult

The trainee's view.

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Attitude of Health Personnel

Differential effects of halothane, enflurane, and isoflurane on Ca2+ transients and papillary muscle tension in guinea pigs.

These studies were designed to examine the effects of inhalational anesthetics on rapid changes in myocardial intracellular Ca2+ and Ca2+ sensitivity of the contractile apparatus. The effects of halothane, enflurane, and isoflurane on rapid changes in intracellular Ca2+ (Ca2+ transients as measured with bioluminescent protein aequorin) and contractile characteristics were compared in guinea pig right ventricular papillary muscles. In addition to examination of their potencies at equianesthetic concentrations, the effects of these agents on alterations in Ca2+ sensitivity at myofilaments were also investigated. The negative inotropic effects of halothane (0.65 and 1.15%) and enflurane (1.0 and 2.2%) were dose-dependent and closely related to a decrease in Ca2+ transients. In the presence of isoflurane (0.77 and 1.6%), the contractile force decreased in a dose-dependent manner, but the decrease was significantly less as compared to that with equianesthetic concentrations of halothane and enflurane. An additional feature observed in the presence of isoflurane was a dissociation between intracellular Ca2+ availability and contractile force. Although the magnitude of the Ca2+ transients did not change when the percentage of isoflurane was increased from 0.77 to 1.6, the contractile force decreased. Because of these findings, the effects of halothane (1.2%), enflurane (2.2%), and isoflurane (1.6%) on the relationship between intracellular Ca2+ and tension developed in the papillary muscle were examined in order to assess myofibrillar responsiveness to Ca2+. The results indicate that only isoflurane slightly but significantly shifted the Ca2+/isometric tension curve toward higher intracellular Ca2+ concentrations; no differences were observed in the absence and presence of equianesthetic concentrations of halothane and enflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Extrathoracic Castleman's disease.

Castleman's disease is an uncommon clinical entity. We report two cases of this disease with a brief review of literature. Both of them had extrathoracic disease which is relatively infrequent. One of them presented with localized hyaline vascular type of the disease and the other with the multicentric plasmacytic variety. The patient with the latter form of Castleman's disease had sclerodactyly, which has not been reported earlier in association with this disease.

Adolescent

Central venous air embolism without a catheter.

Venous air embolism is a well-recognized complication of central venous catheterization. Although previous reports have documented venous air embolism occurring in a number of ways, including during initial catheterization, when catheters crack or are disconnected, and after catheter removal, no reports mention the possibility of air embolism occurring when a guide wire without a catheter was in place. A patient is presented who displayed signs and symptoms of venous air embolism (tachypnoea, chest pain, and arterial hypoxaemia) during central venous catheter manipulation while a guide wire alone was in place. Pulse oximetry was used to detect hypoxaemia and suggest an aetiology for the patient's clinical symptoms. It is postulated that a previously described gasp reflex or some sort of sustained negative pressure manoeuvre caused venous air embolism around the guide wire and accounted for the patient's signs and symptoms. During central venous catheter placement, a high index of suspicion for venous air embolism should be maintained, pulse oximetry should be used, the skin entrance site should be kept covered by an occlusive dressing, and the patient should be positioned head-down.

Adult

Carboxy-terminal sequence conservation among variant-specific surface proteins of Giardia lamblia.

Antigenic variation in the parasitic protozoan Giardia lamblia was studied by characterizing the expression and genomic organization of a variant-specific surface protein (VSP) gene. Transcripts from this gene, vsp1267, were abundant in the cloned variant WB/1267, but undetectable in the parental clone from which WB/1267 was derived or in variant progeny of WB/1267. Two identical copies of vsp1267 exist in the WB/1267 genome, separated by 3 kb and arranged as convergent transcription units. Primer extension sequencing and S1 nuclease protection analysis suggested that the 5' untranslated region (UTR) of VSP1267 mRNA consists of a single nucleotide (nt). Primer extension sequencing mapped the site of VSP1267 transcript polyadenylation 25 nt beyond the termination codon. vsp1267 contained no introns and predicted a cysteine-rich polypeptide with features common to other VSPs. Comparison of vsp1267 with another VSP gene sequence revealed striking conservation, both at the nucleotide and amino acid levels, and the 3' ends of the genes. An oligonucleotide derived from this region detected size-variant VSP transcripts in 4 of 5 G. lamblia clones analyzed, suggesting the general utility of this probe in studying VSP genes and their expression.

Amino Acid Sequence

Occurrence of systemic autoimmune disorders & autoantibodies in house-hold contacts of patients with systemic lupus erythematosus.

Household contacts of 22 randomly selected patients with systemic lupus erythematosus (SLE) were screened for autoimmune diseases and autoantibodies. Thirty nine consanguineous and 17 nonconsanguineous household contacts were studied. In the first group symptomatic SLE was seen in 5 per cent, rheumatoid arthritis in 2.5 per cent, antinuclear antibody (ANA) in 10 per cent and rheumatoid factor (RF) in 5 per cent while anti-dsDNA, anti-nRNP and anti-Sm antibodies were not detected in any individual. The second group showed total absence of any marker of autoimmunity. In normal controls only RF was detected in 3 per cent. The occurrence of markers of autoimmunity only in consanguineous household contacts of patients with SLE further confirms the recognised role of genetic factors in the etiology of SLE.

Aged

Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells.

Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.

Animals

Pulmonary artery occlusion pressure is not accurate immediately after cardiopulmonary bypass.

Elevated pulmonary vascular resistance (PVR), differential cardiac dynamics, and increased lung water following cardiopulmonary bypass (CPB) have been proposed as limitations to the accuracy of the pulmonary artery occlusion pressure (PAOP) in estimating left ventricular preload. A prospective study of 22 patients undergoing elective myocardial revascularization is described wherein PAOP was compared with directly measured left atrial pressure (LAP). The reliability of PAOP to estimate LAP in the hour immediately following CPB and at 1, 4, 8, and 12 hours post-CPB was examined with repeated measures analysis of variance. Relationships between the PAOP-LAP difference and PVR, core temperature, arterial CO2 tension, and right and left ventricular stroke work indices (RVSWI, LVSWI) were tested by linear regression analysis. There was greater variability in measurements at 15, 30, and 45 minutes immediately after CPB, demonstrated by a pooled correlation coefficient of 0.73 versus 0.90 in the postoperative period. The degree of discrepancy between PAOP and LAP lessened with time. There was no determinable relationship of the PAOP-LAP gradient to PVR, level of PCO2, temperature, RVSWI, or LVSWI. Potential sources of discrepancy include airway pressure effects, position of the measuring catheters, positive end-expiratory pressure, infusion of protamine sulfate, extremes of pulmonary artery pressures, and effects of an open pericardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Evaluation of vaccines designed to induce protective cellular immunity against the Plasmodium yoelii circumsporozoite protein: vaccinia, pseudorabies, and Salmonella transformed with circumsporozoite gene.

In an attempt to induce a protective cytotoxic T-cell mediated immunity against sporozoites of Plasmodium yoelii, the gene encoding the P. yoelii circumsporozoite (CS) protein was engineered into three live vectors: vaccinia, attenuated pseudorabies, and attenuated Salmonella typhimurium. Balb/c mice were immunized with 1-4 doses of 10(8) pfu of the vaccinia construct (IP), 3 doses of 10(5), 10(6) or 10(7) pfu of pseudorabies construct (IV), and 3 doses of 10(9) salmonella transformants (orally). In the case of vaccinia and pseudorabies constructs, an excellent immune response was obtained as measured by antibodies to sporozoites. No protection or delay in prepatent period was seen in any of the experimental animals when challenged with 200 (vaccinia, pseudorabies) or 100 (salmonella) sporozoites, although mice immunized with irradiation-attenuated sporozoites were consistently protected against challenge with greater than 10(4) sporozoites. Since other vaccinia, pseudorabies, and salmonella CS constructs have been shown to induce cytotoxic T lymphocytes (CTL) against the CS protein, it is likely that CTL against the CS protein were induced during these studies. It is currently unclear if the vaccines did not induce the appropriate CTL or inadequate numbers of CTL, or if CTL against the P. yoelii CS protein are inadequate to protect against sporozoite challenge.

Animals

Cysteine-rich variant surface proteins of Giardia lamblia.

Surface antigenic variation was previously demonstrated in vitro and in vivo using Giardia lamblia isolate WB. To determine whether other isolates undergo similar changes, isolates GS and N were cloned and exposed to cytotoxic anti-isolate sera or monoclonal antibodies (MAbs) specific to particular surface antigen. The surviving Giardia (progeny) and clones showed different surface antigens as judged by resistance to cytotoxicity, loss of antigens determined by surface radiolabeling, and failure of MAbs to recognize epitopes by immunoprecipitation. The major varying surface antigens incorporate large amounts of [35S]cysteine compared to [35S]methionine. Surface antigenic variation occurs commonly in Giardia isolates, and the major surface antigens appear to comprise a family of cysteine-rich proteins.

Animals

Inheritance and phenotypic expression of a t(7;9)(q36;q34)mat.

We describe a subtle familial chromosome rearrangement which involves 7q36 and 9q34. The clinical manifestations of 3 apparently balanced individuals with presumed identical translocation breakpoints are presented. In addition, the phenotypes of 2 cytogenetically unbalanced sibs in the same nuclear family are compared.

Adolescent