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Biomedical subjects

A Gaur

Publications and source records attributed to A Gaur.

At least 37 records · Page 2Linked to original sources
PubMed1997

Immunosuppressive phenotype of corticotropin-releasing factor transgenic mice is reversed by adrenalectomy.

Stress elicits a wide range of physiological changes involving the nervous, endocrine, and immune systems. Corticotropin-releasing factor (CRF) plays a key role in orchestrating this response, activating both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, resulting in release of corticosteroids. The present study examines the immunological phenotype and responsiveness of CRF-transgenic (CRF-Tg) mice. The immune system of the CRF-Tg animals has profound changes compared to littermate controls, including a marked reduction in both cell number and immune responsiveness. There were also phenotypic changes in the lymphocytic composition of the various lymphoid organs, most notably in the spleen, where CRF-Tg mice had a greater percentage of T lymphocytes compared to littermate controls. Adrenalectomy of CRF-Tg reversed the immunological phenotype observed and restored immune responsiveness. These results demonstrate that CRF overexpression leads to profound impairment on lymphocyte development and function mediated via corticosteroids.

Adrenalectomy↗
PubMed1997

Amelioration of relapsing experimental autoimmune encephalomyelitis with altered myelin basic protein peptides involves different cellular mechanisms.

T-cells specific for a region of human myelin basic protein, amino acids 87-99 (hMBP87-99), have been implicated in the development of multiple sclerosis (MS) a demyelinating disease of the central nervous system. Administration of soluble altered peptide ligand (APL), made by substituting native residues with alanine at either positions 91(91K > A or A91) or 97 (97R > A or A97) in the hMBP87-99 peptide, blocked the development of chronic relapsing experimental autoimmune encephalomyelitis (R-EAE), in the SJL mouse. The non-encephalitogenic APL A91, appears to induce cytokine shifts from Th1 to Th2 in the target T-cells, whereas the encephalitogenic superagonist APL A97 causes deletion of the MBP87-99 responsive cells. Thus, single amino acid changes at different positions in the same peptide epitope can lead to APL capable of controlling auto-immune disease by different mechanisms.

Animals↗
PubMed1997

Accidental subdural injection of local anaesthetic: diagnosis by pressure measurement and response to aspiration of injectate.

A healthy 22-year-old man received an initial injection of 12 mL of lignocaine/bupivacaine solutions (2 mL test, then 10 mL) into an epidural catheter. This produced a satisfactory regional blockade that seemed to be epidural but, when a supplementary 6 mL injection was given 1 h later, the patient developed impaired motor function as far as the upper cranial nerves, with loss of pinprick sensation to the shoulder. The emergence of fluid dribbling freely from the catheter prompted measurement of the pressure, which was 36 mmHg. The fluid was proved not to be cerebrospinal fluid (CSF) by the absence of glucose (on dextrostix), by the appearance of turbidity with added thiopentone, and later by microscopy. Slow aspiration of 7 mL of the presumed injectate reduced the pressure in the catheter to 8 mmHg, which promptly reversed the additional excessive blockade, allowing surgery to proceed uneventfully. The retrieval of injectate argues strongly that the catheter tip had found its way subdurally, and the promptness of the reversal with aspiration argues for a mechanical rather than a pharmacological cause for the extensive neurological dysfunction after the second injection. Pressure measurement and aspiration may be helpful in other similar cases.

Adult↗
PubMed1997

Effect of antihypertensives on plasma potassium in end stage renal disease: a retrospective study.

The antihypertensive drug therapy and the peri-operative plasma potassium trend in end stage renal disease (ESRD) patients undergoing renal transplant were analysed. Out of consecutive 107 live related donor renal transplant, complete data available for 74 patients between June 1991 and March 1993, were entered in proforma and analysed. On the basis of antihypertensive or no antihypertensive drugs prescribed, patients were grouped in 6 categories. Group I patients taking no antihypertensives were taken as control. All patients were comparable for their age, sex, weight, immunosuppressive therapy, anaesthetic and fluid management during surgery. At the time of induction of anaesthesia, patients taking atenolol (plasma K+ levels being 5.34 +/- 0.75 mmol/l in group II and 5.44 +/- 0.63 mmol/l in group III) or captopril (serum K+ level being 5.05 +/- 0.94 mmol/l in group V) in combination with nifedipine and with or without clonidine had significant hyperkalaemia than the patient without antihypertensives (serum K+ level being 4.49 +/- 0.71 mmol/l). Patients, on these two antihypertensives, frequently needed active treatment of alarming hyperkalaemia (blood K+ more than 5 mmol/l and tall 'T' wave in lead II) and cardiac arrhythmias. In conclusion, ESRD patients taking atenolol or captopril are needed to be frequently monitored for blood potassium levels and it would be advisable to avoid these drugs to control hypertension in ESRD patients, especially, when scheduled for renal transplantation.

Adolescent↗
PubMed1996

Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.

Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.

Amino Acid Sequence↗
PubMed1996

Cloning of Murine T Cells

T-cell clones have been extremely useful in studying the cellular arm of the mammalian immune response. A method for generating homogeneous long-term, antigen-specific cultures of murine T cells is discussed, with emphasis on obtaining CD4(+) T-cell clones. Some procedures and assays that will be helpful in characterizing the T-cell clones are also included.

Journal Article↗
PubMed1996

Expression of myosin heavy chain transcripts in normal and cardiac mutant Mexican axolotls.

In this study, we have cloned a 1.0 kb myosin heavy chain (MHC) cDNA by screening an axolotl heart cDNA library with the monoclonal antibody MF20 against a light meromyosin (LMM) region of MHC. The nucleotide sequence analysis shows 85-86% homology at the amino acid and 78-81% homology at the nucleic acid level with MHC from other vertebrates. Phylogenetic analyses suggest that axolotl beta-MHC forms a cluster with the myosin II group of vertebrate striated muscles. Within the myosin II cluster, axolotl beta-MHC forms a distinct subclade from avian MHC and is instead closer to mammalian MHC. RT-PCR analyses show that transcripts of beta-MHC are present at stage 2 and the onset of the MHC gene expression is at stage 8-10 (gastrulation). Expression increases with embryonic development and reaches a maximum at stage 20. Beyond stage 35, the heart-beat initiation stage, the expression level of beta-MHC is higher in cardiac muscle than in skeletal muscle. We could not detect significant differences in the levels of expression of MHC transcripts in normal and cardiac lethal mutant (c/c) axolotls (Ambystoma mexicanum).

Ambystoma mexicanum↗
PubMed1995

Identification and expression of a homologue of the murine HoxA5 gene in the Mexican axolotl (Ambystoma mexicanum).

An excellent model for studying heart development in vertebrates is the cardiac non-function lethal mutant (gene c) Mexican axolotl, Ambystoma mexicanum. In order to facilitate our analyses of the mutant system, we have undertaken a search for stage-specific molecular markers during embryonic development of the axolotl. We have concentrated on homeobox genes as suitable candidates for monitoring molecular changes during development. A 270-bp probe encoding a portion of the axolotl homeobox gene Ahox-1 was generated by PCR from a stage-18 axolotl embryonic cDNA library. 32P-labelled PCR-amplified Ahox-1 DNA was used as the probe for screening a lambda AM18 cDNA library using moderately stringent conditions. We isolated six clones and determined their partial nucleotide (nt) sequences. One of the clones, which has very high homology to human, mouse and rat Hox A5 (83 and 99% at the nt and amino-acid levels, respectively, in the homeodomain region), was analyzed further. RT-PCR analyses show that the level of expression of HoxA5 is very low at stage 11 of embryonic development (gastrula). The level of expression reaches maximum at stage 25 (tailbud) and then plateaus at stages 30 and 35 (heartbeat onset). Although the expression of Ahox-1 was also found to start at stage 11, it reaches a maximum level at stage 25 and declines at stage 35. We have also studied, using RT-PCR, the tissue-specific expression of HoxA5 and Ahox-1 in juvenile axolotl.

Ambystoma↗
PubMed1994

Lipid components of mustard seeds (Brassica juncea L.) as influenced by cadmium levels.

In a pot experiment the soil application of different levels of Cd2+ (0, 10, 20, 30, 40 and 60 micrograms g-1 soil) affected the lipid components of mustard seeds (Brassica juncea L. Cv. RH-30) markedly. Total lipids declined with the Cd2+ levels regularly while phospho and glycolipids increased only at higher levels. Fatty acids profile of total, neutral and polar lipid fractions were affected considerably. Erucic acid in total and neutral lipids was observed to increase while it decreased in polar lipids with Cd2+ as compared to control. On the other hand palmitic, oleic and linoleic acids had reverse trend. Cadmium concentration increased consistently with increasing levels of Cd2+. Plant dry weight was also decreased significantly with Cd2+ levels.

Cadmium↗
PubMed1993

Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen.

The role of infection in the pathogenesis of clinical relapses that occur in most autoimmune diseases, including multiple sclerosis, remains to be established. Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis, with episodes of relapsing paralysis. In certain strains of mice, T-lymphocytes expressing the V beta 8 T-cell receptor (TCR) engage the amino-terminal epitope Ac1-11 of myelin basic protein, leading to EAE. The bacterial superantigen staphylococcal enterotoxin B (SEB) activates V beta 8-expressing T cells. Here we show that after immunization with Ac1-11, or after transfer of encephalitogenic T-cell lines or clones reactive to Ac1-11, SEB induces exacerbation or relapses of paralytic disease in mice that are in clinical remission following an initial episode of paralysis, and triggers paralysis in mice with subclinical disease. Tumour necrosis factor has a critical role in the mechanism underlying SEB-induced exacerbation of disease, because anti-tumour necrosis factor antibody given in vivo delays the onset of paralysis triggered by SEB. On reactivation of autoaggressive cells through their T-cell receptor, superantigens may induce clinical relapses of autoimmune disease.

Amino Acid Sequence↗
PubMed1993

SEB induced anergy: modulation of immune response to T cell determinants of myoglobin and myelin basic protein.

Superantigens have the ability to stimulate a subset of T cells based upon their expressed TCR beta-chain. It has been demonstrated that the administration of staphylococcal enterotoxin B (SEB) in mice leads to unresponsiveness in V beta 8+ T cells in vivo which are the same T cells that could be stimulated in vitro by this enterotoxin. We present here data on the effect of SEB administration in DBA/2 and (PL/J x SJL)F1 mice on their T cell response to two different T cell determinants, the responses against which are dominated by the use of V beta 8+ T cells. Treatment of mice with SEB not only diminished their primary T cell proliferative response to these determinants, but also was able to effectively reduce the memory T cell response. SEB treatment, however, showed only a modest effect in preventing Ac 1-11-induced experimental autoimmune encephalomyelitis in H-2u mice.

Amino Acid Sequence↗
PubMed1993

B cell tolerance induction by cross-linking of membrane IgM, but not IgD, and synergy by cross-linking of both isotypes.

Previous studies in our laboratory demonstrated that overnight exposure of adult splenic B cells to anti-Ig resulted in an unresponsive state characterized by decreased antibody synthesis but normal mitogen-driven proliferation (i.e., energy). Because both anti-F(ab')2 and anti-mu were equally effective at inducing tolerance, it was important to determine whether cross-linking of IgD together with or separately from IgM influenced the induction of unresponsiveness. Although anti-mu induced significant unresponsiveness, treatment of adult splenic B cells with anti-delta alone generally failed to reduce the subsequent response to either LPS or fluoresceinated Brucella abortus. Interestingly, anti-delta synergized with suboptimal concentrations of anti-mu to induce tolerance. Synergy could be observed in this system when anti-delta was added either simultaneously with or before (but not after) anti-mu; moreover, anti-delta was effective in a pretreatment (wash-out) protocol. To investigate the role of protein tyrosine kinase (PTK) activity in tolerance induction, splenic B cells were treated with tyrphostin before treatment with either anti-mu or anti-delta. We found that pretreatment with tyrphostin for 2 h before the addition of anti-mu prevented the induction of unresponsiveness with this antibody, whereas this PTK inhibitor facilitated tolerance when used with anti-delta treatment only. We propose that cross-linking of surface IgM directly or indirectly invokes a tyrphostin-sensitive, PTK-dependent pathway leading to the early events in tolerance induction, which can be augmented under limiting conditions by anti-IgD. Because cross-linking of either receptor initiates several common pathways, simultaneous cross-linking can lead to synergy and a dominance of the IgM signal. In contrast, IgD alone may fail to elicit tolerance because this isotype may also be associated with different PTK that cause positive signaling.

Animals↗
PubMed1993

Requirement for CD8+ cells in T cell receptor peptide-induced clonal unresponsiveness.

T cell receptor (TCR) vaccination in rats prevents the development of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. The mechanism of this potential immunotherapy was examined by vaccinating mice with an immunogenic peptide fragment of the variable region of the TCR V beta 8.2 gene. Another immunogen that usually induces an immune response mediated by V beta 8.2+ T cells was subsequently inhibited because specific clonal unresponsiveness (anergy) had been induced. Depletion of CD8+ cells before TCR peptide vaccination blocked such inhibition. Thus, the clonal anergy was dependent on CD8+ T cells, and such immunoregulatory T cells may participate in the normal course of EAE.

Animals↗
PubMed1993

Rectal nifedipine for the management of intraoperative hypertension.

The effect of rectal administration of nifedipine for the management of intraoperative hypertension was studied in 12 adult neurosurgical patients, physical status II and III. A rise in mean arterial pressure (MAP) of > 20 mm Hg over the preoperative value was taken as the point at which rectal nifedipine (150 micrograms kg-1) was administered. Onset of action of nifedipine was observed in 4.5 +/- 1.5 min (mean +/- SD) with a peak effect at 30.8 +/- 10.7 min. MAP decreased from 124 +/- 4.5 mm Hg to 97 +/- 2.4 mm Hg. Heart rate and central venous pressure were unchanged. Endoscopic examination of the rectal mucosa 48 h after administration of nifedipine did not show any abnormality. Rectal nifedipine was found to be effective and safe for the management of intraoperative increases in arterial blood pressure as well as being convenient to administer to patients undergoing neurosurgical procedures.

Administration, Rectal↗
PubMed1993

Bancroftian filarial pleural effusion.

This paper describes a case of filarial pleural effusion, the fifth such to be reported. Microfilariae of Wuchereria bancrofti were detected in the pleural fluid on cytological examination. There was a prompt and complete response to treatment with diethylcarbamazine. There were, however, no symptoms and signs of tropical pulmonary eosinophilia nor any peripheral eosinophilia.

Adolescent↗