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Biomedical subjects

A Agarwal

Publications and source records attributed to A Agarwal.

At least 271 records · Page 15Linked to original sources
PubMed1997

Post-thyroidectomy haemorrhage: an analysis of critical factors in successful management.

Haemorrhage following thyroidectomy is a well known complication and early intervention is advocated to avoid fatality. Traditionally more emphasis has been given to the amount of drainage, increasing size of the swelling and obvious signs of respiratory obstruction as indications of re-exploration leading to delay, and subtle features of hypoxia like tachycardia, sweating, irritability and confusion resulting from upper airway oedema are usually ignored. The authors described their experience of post-thyroidectomy haemorrhage in 396 thyroidectomies performed during a 6-year period (1989-1995) for various thyroid disorders. All these patients were detected early in the postoperative course based on subtle signs of hypoxia and re-explored. There were 10 cases of post-thyroidectomy haemorrhage and they were successfully managed early in the postoperative period with excellent outcome. Close postoperative monitoring for features of hypoxia rather than external evidence of haemorrhage is the key factor in early detection and successful management of such a fatal complication.

Adolescent↗
PubMed1997

Status of ammonia, glutamate, lactate and pyruvate during Plasmodium yoelii infection and pyrimethamine treatment in mice.

Ammonia, lactate, glutamate and pyruvate levels in blood, liver, brain, spleen and kidney were determined during Plasmodium yoelii infection and pyrimethamine treatment in mice. Ammonia and lactate levels showed significant increase with rise in parasitaemia except in spleen where decrease in the lactate levels was observed. The glutamate level displayed a marked decrease in blood, liver and splenic tissues, whereas, significant increase in glutamate level in kidney was observed, although its level in cerebral tissue remained unaltered. The pyruvate level in blood and liver showed a noticeable decrease but brain, spleen and kidney registered an elevation of the same due to the parasitic infection. Pyrimethamine (oral) treatment (10 mg/kg body weight) to infected mice (5-10%) for four days brought back the altered levels of the above cellular constituents in different tissues to normal, a week after cessation of drug treatment.

Ammonia↗
PubMed1996

Oxy free radical system in heart failure and therapeutic role of oral vitamin E.

Twenty patients of heart failure and ten matched healthy controls were included in the trial. Out of these 20 patients of heart failure, 12 patients were also studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde were increased while the levels of superoxide dismutase, catalase and glutathione reductase were decreased in patients of heart failure as compared to control subjects. The alteration in oxidative stress and antioxidant system did not correlate with the age and sex of patients or the etiology of heart failure. With the increasing severity of heart failure the malonyldialdehyde and superoxide anion increased significantly and catalase, glutathione reductase and superoxide dismutase levels decreased. The group of heart failure patients with ejection fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde than those with an ejection fraction > 40% (n = 13). The superoxide anion and malonyldialdehyde levels were significantly higher in patients of heart failure in the pre-treatment state as compared to those in post-treatment state. Conversely catalase, glutathione reductase and superoxide dismutase were higher in the post-treatment period as compared to their values before treatment. The addition of vitamin E in doses of 400 mg once a day orally for 4 weeks significantly reduced the malonyldialdehyde and superoxide anion levels and produced an elevation of the antioxidant enzymes. Thus, there is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.

Administration, Oral↗
PubMed1996

B cell responses to a peptide epitope. I. The cellular basis for restricted recognition.

Primary humoral responses in BALB/c mice to a variety of peptide constructs containing a common 15-amino acid residue antigenic determinant (PS1) in conjunction with one or more Th cell epitopes were examined. In all cases, the mature IgG response was found to focus primarily on a tetrapeptide sequence, Asp-Pro-Ala-Phe. The dominance of this segment was independent of the position of the PS1 determinant in the peptide sequence and was also observed in constructs with a random secondary structure. In contrast to the mature IgG response, the early primary IgM response was constituted by multiple specificities that collectively spanned a major proportion of the PS1 sequence. However, subsequent progression of this response entailed a strict selection for only those Abs directed against the Asp-Pro-Ala-Phe segment and apparently occurred at or around the time of the IgM to IgG class switch. Studies of murine responses to peptide analogs containing single amino acid substitutions within the Asp-Pro-Ala-Phe sequence revealed that emergence of this segment as the dominant epitope was a consequence of active suppression of B cells directed against alternate determinants. Positive selection of this subset of Abs correlated with overall higher avidity for epitope binding and was the outcome of a competitive process enforced by the limiting amounts of Th cell help available in the early stages of the primary response.

Amino Acid Sequence↗
PubMed1996

Factors influencing redox thermodynamics and electron self-exchange for the [Fe4S4] cluster in Chromatium vinosum high potential iron protein: the role of core aromatic residues in defining cluster redox chemistry.

The roles of aromatic core residues in regulating the reduction potential, the enthalpy and entropy of reduction, and the self-exchange rate constants for electron-transfer reactions for the prosthetic [Fe4S4]3+/2+ cluster of Chromatium vinosum high potential iron protein (HiPIP) have been addressed by a combination of site-directed mutagenesis, high field NMR (EXSY) experiments, and variable temperature spectrochemical redox titration measurements. Minimal changes are observed following nonconservative mutation of residues Tyr19, Phe48, and Phe66. Apparently these hydrophobic residues play only a minor role in defining the electronic properties of the cluster. These data support a model, first defined from results obtained on Tyr19 mutant HiPIP's [Agarwal, A., Li, D., & Cowan, J.A. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 9440-9444], in which the aromatic core restricts solvent accessibility and thereby stabilizes the oxidized [Fe4S4]3+ cluster.

Bacterial Proteins↗
PubMed1996

Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes.

Transforming growth factor-beta (TGF-beta) plays a major role in regulating connective tissue deposition by controlling both extracellular matrix production and degradation. In this study, we show that TGF-beta transcriptionally represses both basal and tumor necrosis factor-alpha-induced collagenase (matrix metalloprotease-1) gene expression in dermal fibroblasts in culture, whereas it activates its expression in epidermal keratinocytes. We demonstrate that this differential effect of TGF-beta on collagenase gene expression is due to a cell type-specific induction of distinct oncogenes of the Jun family, which participate in the formation of AP-1 complexes with different trans-activating properties. Specifically, our data indicate that the inhibitory effect of TGF-beta in fibroblasts is likely to be mediated by jun-B, based on the following observations: (a) TGF-beta induces high levels of jun-B expression and (b) over-expression of jun-B mimics TGF-beta effect in inhibiting basal collagenase promoter activity and preventing tumor necrosis factor-alpha-induced trans-activation of the collagenase promoter. In contrast, TGF-beta induction of collagenase gene expression in keratinocytes is preceded by transient elevation of c-jun proto-oncogene expression. Over-expression of c-jun leads to trans-activation of the collagenase promoter in both cell types, suggesting that c-jun is a ubiquitous inducer of collagenase gene expression. Transfection of keratinocytes with an antisense c-jun construct together with a collagenase promoter/reporter gene construct inhibits basal and TGF-beta-induced up-regulation of the collagenase promoter activity, implying that c-jun mediates TGF-beta effect in this cell type. Collectively, our data suggest differential signaling pathways for TGF-beta in dermal fibroblasts and epidermal keratinocytes, leading to cell type-specific induction of two AP-1 components with opposite transcriptional activities.

3T3 Cells↗
PubMed1996

An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta.

Previous studies have shown that transforming growth factor-beta (TGF-be ta) and tumor necrosis factor-alpha (TNF-alpha) modulate type I collagen gene expression in fibroblasts. To fine-map the corresponding response elements in the human alpha2(I) collagen (COL1A2) promoter, we have generated a series of 5' deletion promoter/chloramphenicol acetyltransferase (CAT) reporter gene constructs. Transient cell transfection assays using human dermal fibroblasts and stable transfection experiments using NIH 3T3 fibroblasts identified the region located between residues -265 and -241, as critical for TGF-beta response. Specifically, we demonstrate that this 25-base pair region mediates the up-regulatory effect of TGF-beta on COL1A2 promoter activity and allows antagonistic activity of TNF-alpha on the TGF-beta effect. Gel mobility shift assays indicate that nuclear factor binding to this 25-base pair region of COL1A2 promoter is competed by AP-1, but not NF-1 or NF-kappaB, oligonucleotides. Transient cell transfection experiments with plasmid constructs in which the potential AP-1-binding site located within this short region of promoter was modified by site-directed mutagenesis indicated that this element plays a significant role in the basal activity of the promoter. Furthermore, this sequence is essential for TGF-beta response and does not require the presence of the three Sp-1-binding sites located further upstream, between nucleotides -273 and -304. In addition, overexpression of c-jun in co-transfection experiments with COL1A2 promoter/CAT constructs blocks the TGF- beta response, further implicating AP-1 in the regulation of COL1A2 gene expression. Our results clarify the molecular mechanisms involved in the regulation of type I collagen gene expression and further emphasize the importance of AP-1 in mediating some of the TGF-beta effects on gene transcription.

Base Sequence↗
PubMed1996

Gas-generating systems in acute renal allograft rejection in the rat. Co-induction of heme oxygenase and nitric oxide synthase.

Gases are now viewed as biologic messengers, and in this regard, carbon monoxide and nitric oxide are incriminated in signaling processes in neural tissue. Carbon monoxide is generated by heme oxygenase (HO), an enzyme inducible by heme, cytokines, and oxidative stress and considered an antioxidant response; nitric oxide is generated by nitric oxide synthase, an enzyme also inducible by cytokines. Since mononuclear cells infiltrate the acutely rejecting kidney, and foster within the kidney oxidative stress and a cytokine-enriched milieu, we examined the expression of these enzymes in acute renal allograft rejection (AR) (Brown Norway kidney to a Lewis rat; n = 17) and in control isografts (Lewis kidney to a Lewis rat; n = 17). No immunosuppressives were used. We found marked induction of HO mRNA and protein in renal allografts at day 5 after transplantation. Prominent expression of HO protein, as detected by immunofluorescence, was observed in the mononuclear cells infiltrating the renal allograft. More than 80% of these cells were macrophages, as identified by positive staining with ED1 antibody. ED1+ cells were rare in isografts and did not stain for HO. We also found co-expression of mRNA and protein for the inducible isoform of nitric oxide synthase (iNOS) in AR at day 5 after transplantation. Induction of HO and iNOS may reflect the cellular effect of diverse cytokines elaborated in the rejecting kidney. HO may enable the macrophage to degrade heme-containing proteins released from erythrocytes and other damaged cells; alternatively, induction of HO may defend the macrophage against oxidant injury. Increased nitric oxide, as a result of iNOS activity, may antagonize the vasoconstrictive effects of a number of mediators (i.e., thromboxane and endothelin) present in acute rejection; conversely, nitric oxide may prove cytotoxic through a number of recognized effects. Our studies provide the first demonstration of the induction of HO in the rejecting renal allograft as well as the first demonstration in vivo for the induction of HO in macrophages at the site of an inflammatory response. Such expression, linked as it is to the expression of iNOS, indicates that the macrophage mimics the behavior of neural cells by generating these gaseous messengers; thus, neural cells are not alone in deploying these mediators. Through a number of effects, these products of HO and iNOS may influence the nature and severity of tissue injury in AR.

Animals↗
PubMed1996

Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22.

CD22 is a B lymphocyte-specific membrane protein that functions as an adhesion molecule via its interactions with a subset of alpha 2-6-linked sialic acid-containing glycoproteins. Engagement of CD22 with a monoclonal antibody (HB22.23) that blocks the binding of CD22 to its ligands results in rapid CD22 tyrosine phosphorylation and in increased association of CD22 with p53/56lyn kinase, p85 phosphatidyl inositol-3 kinase, and p72syk kinase. Synthetic peptides that span various regions of the intracellular portion of CD22 were used to map potential kinase binding sites. All three kinases associated with a tyrosine-phosphorylated peptide that spans tyrosine amino acid residues 822 and 842, implicating this as an important region in mediating CD22 signal transduction. In addition, purified p56lyn directly bound to the same peptide. Engagement of CD22 with HB22.23 was sufficient to stimulate normal B cell proliferation. This study further substantiates the importance of CD22 as a B lymphocyte signaling molecule and begins to unravel the mechanisms by which CD22 cross-linking can alter B cell function.

Amino Acid Sequence↗
PubMed1996

Role of reactive oxygen species in male infertility.

Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly H2O2 and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of anti-oxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.

Antioxidants↗
PubMed1996

Sperm kinematics of cryopreserved normozoospermic specimens after artificial stimulation.

OBJECTIVES: Cryopreservation of semen is associated with reduced motility after thawing, resulting in a decreased pregnancy rate. Artificial stimulation of motility has been used in fresh semen samples. This study measured the effect of motility stimulants on various motion characteristics and other sperm functions using cryopreserved semen. METHODS: Frozen semen samples from healthy donors were thawed, and motility stimulants were added in vitro and incubated for 60 minutes. The percentages of motile spermatozoa in each specimen and other motion characteristics were measured. In addition, spermatozoon's viability, membrane integrity, and ability to penetrate bovine cervical mucus were studied after addition of stimulants. RESULTS: Percentage motility and all other motion characteristics improved after stimulation with pentoxifylline, caffeine, or 2-deoxyadenosine. Linearity did not significantly differ in the control samples after adding any of the stimulants. Viability, membrane integrity, and penetration ability did not improve significantly and were comparable with control values. CONCLUSIONS: Pentoxifylline, caffeine, and 2-deoxyadenosine can stimulate sperm motility and other motion characteristics. This may be beneficial in the cryopreservation of sperm from normal donors and oligozoospermic patients for use in assisted reproduction.

Caffeine↗
PubMed1996

Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native and transplant kidneys.

Previous studies suggest that there is an association between hepatitis C (HCV) infection and glomerular diseases in native and transplanted kidneys. However, the data are controversial. To reexamine this issue, we determined the prevalence of serum anti-HCV antibodies in patients with glomerulopathies of native kidneys (n = 105) and in patients with acute and chronic transplant glomerulopathy (TxGN) (n = 62). Compared with a control group of patients with diabetic nephropathy (n = 37, 0% HCV+), the prevalence of HCV antibodies was significantly higher in patients with focal glomerulosclerosis (FGS) (4 of 32, 13%, P = 0.04 by chi-square), but not in patients with membranous nephropathy (MGN) (1 of 19, 5%) or in patients with membranoproliferative glomerulonephritis (MPGN) (2 of 17, 12%). All of the patients with positive HCV serology had histories of intravenous (IV) drug use. Thus, HCV serology was negative in all of the patients with native glomerulopathies without histories of IV drug use. Compared with a group of 105 transplant patients without TxGN (1.8% HCV+), the prevalence of HCV antibodies was significantly higher in patients with acute (A)TxGN (12 or 41: 29%. P = 0.0004) and in patients with chronic (C)TxGN (9 of 27: 33%. P = 0.0004). Compared with controls, patients with ATxGN also had a significantly higher prevalence of serum immunoglobulin (Ig) M antibodies to cytomegalovirus (CMV) (3% and 26% of patients, respectively, P = 0.0004). However, there were no statistical associations between HCV and CMV serologies. These results do not support the postulate that HCV infection is associated with idiopathic native glomerulopathies; instead, the data suggest that the presence of HCV positivity in these patients can be explained by the inclusion of patients with a history of IV drug use. In contrast, these studies demonstrate for the first time an association between HCV infection and transplant glomerulopathies.

Case-Control Studies↗
PubMed1996

Completion total thyroidectomy in the management of differentiated thyroid carcinoma.

BACKGROUND: Completion thyroidectomy is the removal of any thyroid tissue that remains after a less than total thyroidectomy. This procedure has been commonly performed when the final histopathology of the excised ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Complete thyroidectomy carries little morbidity if performed by experienced surgeons using a lateral approach. The purpose of this study is to reinforce the usefulness of a lateral approach. METHODS: A retrospective analysis over a 5 year period at the Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) yielded 19 patients who underwent completion thyroidectomy. This group represents 23% of 82 patients who underwent total thyroidectomy for differentiated thyroid cancer (DTC) during that period. The residual thyroid tissue was excised through a lateral approach and could be resected safely, preserving the recurrent laryngeal nerve (RLN) and the parathyroid glands. RESULTS: A lateral approach dissection could be performed with ease in a virgin area. Excision of residual thyroid tissue could be performed safely even in cases with prior partial lobectomy or bilateral subtotal resection. Tumour was found in 52% of the re-operative specimens: in three out of four of those after a previous partial lobectomy, in six out of 12 of those after a total lobectomy, and in one out of three of those after a prior bilateral (although incomplete) thyroid resection. Postoperative complications included transient RLN palsy (n = 2) and transient hypoparathyroidism (n = 4). CONCLUSIONS: Completion thyroidectomy using a lateral approach is safe in re-operative thyroid surgery.

Carcinoma, Papillary↗
PubMed1996

Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL.

In protein-uric states, renal tubular epithelial cells are exposed to diverse macromolecules, including low-density lipoproteins (LDL), normally excluded from the urinary space. Oxidized LDL (LDLox) is incriminated in atherogenesis and glomerulosclerosis. Since urine is prooxidant, we considered whether LDLox injuries renal tubular epithelial cells (LLC-PK1). We demonstrate that the cytotoxicity of LDLox on LLC-PK1 cells resembles its toxicity to human umbilical vein endothelial cells (HUVEC) in that oxidized but not native LDL is injurious. Pretreatment of LLC-PK1 cells and HUVEC with antioxidants markedly reduced the cytotoxicity of LDLox. Pretreatment of LDL with antioxidants, prior to oxidation of LDL, vitiated its cytotoxicity. That LDLox is prooxidant was supported by expression of heme oxygenase, a redox-sensitive enzyme. LDLox induced heme oxygenase mRNA and enzyme activity. Pretreatment of LDL with antioxidants prior to oxidation attenuated heme oxygenase mRNA induction in LLC-PK1 and HUVEC. An iron chelator prevented cytotoxicity and heme oxygenase expression induced by LDLox. Based on these effects of LDLox, we draw an analogy between tubulointerstitial disease and atherogenesis and speculate that LDLox contributes to tubulointerstitial disease in proteinuric states.

Animals↗
PubMed1996

Nocturnal blood pressure in treated hypertensive African Americans Compared to treated hypertensive European Americans.

Previous studies have shown that African Americans (blacks) tend to have higher nocturnal blood pressure than European Americans (whites). The study presented here was undertaken to determine whether treatment of hypertension influences nocturnal blood pressure differently in blacks than in whites. To answer this question, this study measured nocturnal blood pressure by ambulatory blood pressure monitoring (ABPM) in treated hypertensive blacks and whites whose daytime blood pressures were comparable. Inclusion criteria for this study were: diagnosis of essential hypertension, absence of renal failure, and documentation of antihypertensive therapy, diabetic status, proteinuria status, and body weight. All of the black patients in our programs who underwent ABPM and met the above criteria were included in this study. White patients were included on the basis of having the same inclusion criteria as blacks and showing, by ABPM, daytime mean arterial pressure (MAP) in the same range as that of the blacks selected for this study. The results of nocturnal blood pressure were unknown to the investigators when the patients were selected for this study. In the blacks (N = 62) and whites (N = 72) selected for study, the mean daytime (0600 to 2200 h) MAP was 107 +/- 1 SE mm Hg for both the black and white cohorts. To assess nocturnal blood pressure, the period from 0100 to 0500 h was chosen because it likely encompassed an interval of sleep, which is associated with the nadir of nocturnal blood pressure. This interval was termed 0100 to 0500 h, "middle night." Mean middle night MAP was 97 +/- 12 mm Hg in blacks versus 90 +/- 14 mm Hg in whites (P < 0.006, unpaired t test). The greater middle night MAP in blacks compared with whites was a result of the higher diastolic pressure in blacks (80 +/- 11 mm Hg) versus whites (75 +/- 11 mm Hg) (P = 0.003). Mean middle night systolic blood pressure was numerically higher in blacks than whites (131 +/- 18 mm Hg versus 128 +/- 17 mm Hg), but this difference did not achieve statistical significance. The higher middle night blood pressure in blacks versus whites could not be explained by differences between the groups in daytime MAP, age, gender, body weight, serum creatinine level, proteinuria, diabetic status, or greater use of short-acting antihypertensive agents in blacks versus whites. It was concluded that when treated hypertensive blacks and whites are matched for the same daytime blood pressure, blacks tend to have significantly higher nocturnal blood pressure than whites. The magnitude of this difference suggests that it could contribute importantly to the greater target-organ damage that is seen in hypertensive blacks compared with hypertensive whites.

Antihypertensive Agents↗