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Biomedical subjects

T Naqvi

Publications and source records attributed to T Naqvi.

14 recordsLinked to original sources
PubMed2002

Myelofibrosis: response to busulfan after hydroxyurea failure.

We report a case of myelofibrosis with myeloid metaplasia (MMM) that responded dramatically to oral busulfan treatment after failure of hydroxyurea. Although busulfan treatment of this disease has fallen out of favour due to the favourable toxicity profile of hydroxyurea and reports of efficacy of interferon-alpha, our observation suggests there may still be a role for busulfan treatment of MMM in the setting of hydroxyurea or interferon failure or intolerance.

Alkylating Agents↗
PubMed2001

Milrinone echocardiographic viability test: a pilot study.

We assessed the utility of milrinone to predict recovery of function after surgical myocardial revascularization in patients with severe baseline left ventricular systolic dysfunction caused by coronary artery disease (CAD). Prediction of viable myocardial segments that will regain function after revascularization may help in the selection of patients who will benefit from coronary artery bypass graft surgery (CABG) as well as aid in the choice of target sites for coronary revascularization. We investigated 20 consecutive patients with CAD and left ventricular ejection fraction < or = 40% who had evidence of myocardial viability by either thallium scan or dobutamine viability test and were candidates for elective CABG. Left ventricular regional wall motion and global ejection fraction were assessed by transesophageal echocardiography in the operating room. Measurements were done before and 10 minutes after milrinone infusion, and immediately after CABG. Left ventricular wall motion score was derived by means of a 12-segment model. Functional improvement for each segment was defined as a wall motion change > 1. Baseline ejection fraction was 27% +/- 5% (mean +/- SD). Ejection fraction increased to 35% +/- 5% after milrinone infusion (P < .0001) and to 36% +/- 6% after CABG (P < .0001). Post-CABG ejection fraction was significantly correlated with postmilrinone ejection fraction (r = 0.65, P < .0001). Milrinone infusion resulted in augmentation of contraction in 98 of the 209 abnormal segments (wall motion score > or = 2); 91 (92.9%) of these improved after CABG. One hundred nine of the 111 segments that showed no improvement with milrinone did not improve after revascularization (98.2%). Seventy-three segments were akinetic or dyskinetic at baseline; 46 (63.0%) of these improved with milrinone. Improvement in regional wall motion after revascularization was detected in 84.8% of the segments that improved with milrinone versus only 3.7% of the segments that did not improve with milrinone. In patients with ischemic cardiomyopathy, improvement in left ventricular function (segmental wall motion and global ejection fraction) during milrinone infusion is highly predictive of improvement after CABG.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Requirement for Ca2+ signaling in the mechanism of thrombin-induced increase in endothelial permeability.

We compared the thrombin-activated responses in human umbilical vein endothelial cells (HUVECs) and a HUVEC-derived cell line, ECV304. Thrombin induced a 40-50% decrease in transendothelial monolayer electrical resistance and a twofold increase in 125I-albumin permeability in HUVECs, whereas it failed to alter the endothelial barrier function in ECV304 cells. Thrombin produced a brisk intracellular Ca2+ concentration transient and phosphorylation of 20-kDa myosin light chain in HUVECs but not in ECV304 cells. Thrombin-induced phosphoinositide hydrolysis was comparable in ECV304 cells and HUVECs, indicating the activation of thrombin receptors in both cell types. La3+ reduced both the thrombin-induced decrease in endothelial monolayer electrical resistance and the increase in 125I-albumin permeability in HUVECs. Because the absence of Ca2+ signaling could explain the impairment in the permeability response in ECV304 cells, we studied the effect of increasing intracellular Ca2+ concentration in ECV304 cells with thapsigargin. Exposure of ECV304 cells to thapsigargin caused decreased endothelial monolayer electrical resistance and increased 125I-albumin permeability. These results indicate that Ca2+ influx and activation of Ca2+-dependent signaling pathways are important determinants of the thrombin-induced increase in endothelial permeability.

Antigens, CD↗
PubMed2001

Synergistic effects of tumor necrosis factor-alpha and thrombin in increasing endothelial permeability.

Because activation of the coagulation cascade and the generation of thrombin coexist with sepsis and the release of tumor necrosis factor (TNF)-alpha, we determined the effects of TNF-alpha on the mechanism of thrombin-induced increase in endothelial permeability. We assessed Ca(2+) signaling in human umbilical vein endothelial cells. In human umbilical vein endothelial cells exposed to TNF-alpha for 2 h, thrombin produced a rise in the intracellular Ca(2+) concentration ([Ca(2+)](i)) lasting up to 10 min. In contrast, thrombin alone produced a rise in [Ca(2+)](i) lasting for 3 min, whereas TNF-alpha alone had no effect on [Ca(2+)](i.) Thrombin-induced inositol 1,4,5-trisphosphate generation was not different between control and TNF-alpha-exposed cells. In the absence of extracellular Ca(2+), thrombin produced similar increases in [Ca(2+)](i) in both control and TNF-alpha-exposed cells. In TNF-alpha-exposed cells, the thrombin-induced Ca(2+) influx after intracellular Ca(2+) store depletion was significantly greater and prolonged compared with control cells. Increased Ca(2+) entry was associated with an approximately fourfold increase in Src activity and was sensitive to the Src kinase inhibitor PP1. After TNF-alpha exposure, thrombin caused increased tyrosine phosphorylation of junctional proteins and actin stress fiber formation as well as augmented endothelial permeability. These results suggest that TNF-alpha stimulation of endothelial cells results in amplification of the thrombin-induced Ca(2+) influx by an Src-dependent mechanism, thereby promoting loss of endothelial barrier function.

Albumins↗
PubMed2000

G protein-coupled receptor kinase-5 regulates thrombin-activated signaling in endothelial cells.

We studied the function of G protein-coupled receptor kinases (GRKs) in the regulation of thrombin-activated signaling in endothelial cells. GRK2, GRK5, and GRK6 isoforms were expressed predominantly in endothelial cells. The function of these isoforms was studied by expressing wild-type and dominant negative (dn) mutants in endothelial cells. We determined the responses to thrombin, which activates intracellular signaling in endothelial cells by cleaving the NH(2) terminus of the G protein-coupled proteinase-activated receptor-1 (PAR-1). We measured changes in phosphoinositide hydrolysis and intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to thrombin as well as the state of endothelial activation. In the latter studies, the transendothelial monolayer electrical resistance, a measure of the loss of endothelial barrier function, was measured in real time. Of the three isoforms, GRK5 overexpression was selective in markedly reducing the thrombin-activated phosphoinositide hydrolysis and increased [Ca(2+)](i). GRK5 overexpression also inhibited the thrombin-induced decrease in endothelial monolayer resistance by 75%. These effects of GRK5 overexpression occurred in association with the specific increase in the thrombin-induced phosphorylation of PAR-1. In contrast to the effects of GRK5 overexpression, the expression of the dn-GRK5 mutant produced a long-lived increase in [Ca(2+)](i) in response to thrombin, whereas dn-GRK2 had no effect. These results indicate the crucial role of the GRK5 isoform in the mechanism of thrombin-induced desensitization of PAR-1 in endothelial cells.

Cells, Cultured↗
PubMed1999

Superiority of the combination of blood and agitated saline for routine contrast enhancement.

The purpose of this study was to evaluate the modification of the saline echo contrast method by mixing blood with agitated saline before intravenous injection. In 20 patients, contrast echocardiography was performed with a conventional technique from the apical 4-chamber view. We used 2 techniques: (1) the combination of blood (1 mL) withdrawn from the patients and air-agitated saline agitated, (2) air-agitated. In all patients, the blood combination technique was judged to make a greater contrast, with the agreement of all 3 reviewers. Peak echo intensity of the right ventricular cavity by the blood combination technique was significantly higher than that by agitated saline alone. In conclusion, the use of the combination of blood and agitated saline is superior to agitated saline alone for the opacification of the right atrium and ventricle in routine echocardiography.

Aged↗
PubMed1998

Echocardiographic detection of Kaposi's sarcoma causing cardiac tamponade in a patient with acquired immunodeficiency syndrome.

Pericardial effusions are common in patients with acquired immunodeficiency syndrome (AIDS). The differential diagnosis is diverse, and in most cases the etiology cannot be established. A cardiac tamponade was diagnosed in a 32-year-old male with AIDS and systemic Kaposi's sarcoma. Transthoracic echocardiography revealed a large pericardial effusion with right atrial collapse and a mobile multilobular mass at the apex protruding into pericardial space. Autopsy showed that this mass was Kaposi's sarcoma confined to the epicardial fat. This is the first case of cardiac Kaposi's sarcoma detected premortem by echocardiography.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Synthesis and opioid activity of novel tetrapeptides analogous to sequence (1-4) of dermorphin.

Seven new tetrapeptides analogous to (1-4) sequence of dermorphin were synthesized and evaluated for their opioid activity. The peptides were synthesized by the solution phase method. Their opioid activity revealed that peptides II and V were the most potent in the analgesia test as well as in the peripheral assays. Peptide II was most active in the guinea pig ileum assay, whereas peptide VI was 2763 times more selective for mu-receptors.

Amino Acid Sequence↗
PubMed1998

Structure-activity relationship studies of dynorphin A and related peptides.

An up-to-date review is presented covering all the available information concerning the isolation, discovery, synthesis, conformation, receptor binding characteristics, pharmacological properties and SAR studies of dynorphin A and related peptides. The potential of dynorphin A and its analogs has yet to be fully realized.

Analgesia↗
PubMed1995

Immunomodulatory activity of met-enkephalin and its two potent analogs.

The effects of Met-enkephalin (Met-Enk), a delta receptor binding opioid peptide, and its more stable synthetic analogs, Tyr-D-Ala-Gly-MePhe-Met-NHC3H7-iso (1), Tyr-D-Ala-Gly-MePhe-Gly-NHC3H7-iso (2) and Tyr-D-Ala-Gly-MePhe-Gly-NHCH2C6H5 (3), on human T-cell transformation and natural killer (NK) cell cytotoxicity have been evaluated. Analogs 1 and 2 have been found to be as potent as Met-Enk in stimulating T-cell transformation and augmenting NK cell cytotoxicity. Analog 3 had no effect on T-cell transformation and NK cell cytotoxicity. Proliferative response was measured by 3H-thymidine uptake after 5 days of incubation. The kinetics of the T-cell transformation response (peak 5th day) is similar to those for in vitro T-cell responses to specific antigens rather than via polyclonal activation.

Adjuvants, Immunologic↗
PubMed1993

von Willebrand factor and endothelial damage in essential hypertension.

The relationship between von Willebrand factor antigen (vWFAg, a specific endothelial cell product) and hypertension was examined. Circulating vWFAg levels were measured in serum from patients attending a hypertension clinic and in normotensive controls. The vWFAg was higher in those patients with uncontrolled hypertension at 131 +/- 34 IU/dl than in controls (90 +/- 30 IU/dl) and in those whose hypertension was controlled 104 +/- 29 IU/dl (P < 0.001). Levels of vWFAg correlated with both SBP (r = 0.42, P < 0.0002) and DBP (r = 0.25, P < 0.05), but serum from neither group of patients was more cytotoxic to cultured endothelial cells in vitro than was serum from controls. Neither symptoms of cardiovascular or peripheral vascular disease or two of its risk factors (hypercholesterolaemia or smoking, alone or in combination) appeared to further increase vWFAg in patients with uncontrolled hypertension. However, vascular disease and the same risk factors did increase vWFAg to 133 +/- 36 IU/dl in those patients with controlled hypertension (P < 0.001). These data indicate a relationship between vWFAg and hypertension and suggest that endothelial damage may indeed be important in the vascular complications of hypertension.

Adult↗