Search PubMed⌕ Search

Biomedical subjects

S Ali

Publications and source records attributed to S Ali.

At least 109 records · Page 6Linked to original sources
PubMed2000

Paraquat induces different pulmonary biochemical responses in Wistar rats and Swiss mice.

The paper presents results showing differential response to paraquat toxicity in Wistar rats and Swiss strain of mice. Paraquat-induced pulmonary biochemical responses in the two animal species were studied at different time point after giving a single intraperitoneal injection of the respective LD(10) doses of the herbicide paraquat to rats and mice. Paraquat induced different biochemical responses including different protective responses in the two animal species. As a protective response, NADPH-specific quinone reductase is induced in rats, while catalase is induced in mice. It is implied that an early induction of catalase in mice as opposed to rats may account for the resistance of Swiss mice to paraquat toxicity. Xanthine oxidase, which was induced in rats, remains unaffected in mice indicating that the enzyme contributes to paraquat toxicity only in Wistar rats. Time-course studies were also conducted to compare the differential responses of antioxidant enzymes and lipid peroxidation between the two species. The results of the study led us to suggest that the manifestation of paraquat toxicity involve distinct differences in early pulmonary biochemical responses in Wistar rats and Swiss mice.

Animals↗
PubMed2000

The impact of cytomegalovirus serology for 7-year graft survival in cadaveric kidney transplantation--the Newcastle experience.

To analyse the contribution of cytomegalovirus (CMV) serology to long-term graft survival in cadaveric kidney transplantation, 404 transplants from a single centre were divided into four subgroups with respect to the combination of donor and recipient CMV antibody status. Graft survival was estimated according to Kaplan-Meier for 1, 3, 5 and 7 years post-transplantation. The single-centre results confirm a negative impact of CMV-positive donor organs for initial graft survival in CMV-negative recipients within the first 3 years after transplantation. However, when 5- and 7-year long-term graft survival was studied, Donor +/Recipient - pairs showed a favourable long-term result, whilst D +/R - pairs had surprisingly a poorer outcome. Therefore, the concept of avoiding transplantation in the D +/R + CMV serology group should be ignored whereas attempts could be made to improve the poor long-term outcome of D +/R + pairs or to reduce its size by organ allocation.

Adolescent↗
PubMed2000

Development of Fasciolopsis buski (Trematoda : Fasciolidae) in Hippeutis umbilicalis and Segmentina trochoideus (Gastropoda : Pulmonata).

Sequential development and histopathologic effects of Fasciolopsis buski larvae were examined in two species of pulmonate snail, Hippeutis umbilicalis and Segmentina trochoideus. Miracidial attachment and penetration began 5 min post-exposure (PE). On day 2 PE, the sporocysts rapidly increased in size and over days 3-7 PE, they transformed into mother rediae which migrated to the ovotestis on day 10 PE. In both species of snail, daughter rediae were initially observed on day 17 PE, the first cercariae emerged on day 21 PE, and from that day onward daughter rediae were the dominant larval form occupying the ovotestis. Histopathologic changes were confined exclusively to the ovotestis and included lytic lesions due to mechanical damage, and disappearance of all cellular elements. No inflammatory responses were observed in the ovotestis, and no degenerated larvae of any kind were observed in the snails. Infected snails did not produce egg masses and lived no longer than 35 days. The lack of differences in miracidial recognition and penetration, and in the temporal, sequential, and spatial development of F. buski larvae in H. umbilicalis and S. trochoideus indicate that both these snail species are equally susceptible to F. buski.

Animals↗
PubMed2000

Intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and regulated on activation normal T cell expressed and secreted are expressed by human breast carcinoma cells and support eosinophil adhesion and activation.

Eosinophils are usually associated with parasitic and allergic diseases; however, eosinophilia is also observed in several types of human tumors, including breast carcinomas. In this study we examined several human breast carcinoma cell lines for adhesion molecule expression and the ability to bind and activate eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and this expression was enhanced by treatment with tumor necrosis factor-alpha (TNF-alpha). BT-20 and SK-BR-3 cells only expressed ICAM-1 or VCAM-1 after stimulation with TNF-alpha. Eosinophils constitutively bound to MDA-MB-435S cells, but not to BT-20 cells. Stimulation with TNF-alpha slightly enhanced eosinophil adhesion to MDA-MB-435S cells and dramatically increased adhesion to BT-20 cells. Greater than 80% of eosinophil adhesion to these cell lines was blocked with an anti-alpha4-integrin monoclonal antibody. Both MDA-MB-435S and BT-20 cells also released eosinophil activator(s). Supernatants from TNF-alpha-treated, but not control-treated, cell lines increased eosinophil adhesion to fibronectin and increased eosinophil transmigration across fibronectin-coated transwell plates. Enzyme-linked immunosorbent assays showed that TNF-alpha-stimulated breast carcinoma cells released the chemokine regulated on activation, T cell expressed and secreted (RANTES). Addition of an anti-RANTES antibody to breast carcinoma cell supernatants partially blocked eosinophil activation suggesting that RANTES in these supernatants was participating in eosinophil activation. These data show that TNF-alpha-stimulated breast carcinoma cells express mediators that can both bind and activate eosinophils, suggesting a mechanism for eosinophil localization to breast carcinoma sites.

Antigens, CD↗
PubMed2000

A differential scanning calorimetry study of phosphocholines mixed with paclitaxel and its bromoacylated taxanes.

High sensitivity differential scanning calorimetry (DSC) was used to investigate the thermotropic phase properties of binary mixtures of disaturated phosphocholines (PCs) and alpha-bromoacyl taxane derivatives. The alpha-bromoacyl taxanes were synthesized as hydrolyzable hydrophobic prodrugs of paclitaxel. The PCs used were 1, 2-dimyristoyl-sn-glycero-3-phosphatidyl-choline (DMPC), 1, 2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1, 2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). The bromoacyl chain lengths of the taxane prodrugs were varied from 6 to 12 or 16 carbons. For comparison, paclitaxel and PC mixtures were also examined. DSC data from DPPC and bromoacyl taxane mixtures showed a complete abolition of the pretransition and significant broadening of the main phase transition with increasing amounts of bromoacyl taxane prodrugs. The effects were more pronounced with the long-chain compared to the short-chain prodrugs. Under equivalent DSC conditions, the short-chain DMPC showed greater changes in thermotropic phase behavior than with DPPC on taxane addition, suggesting an enhanced degree of association with the fluid-type bilayers. Under similar conditions, the long-chain DSPC bilayers showed a far less significant change in phase behavior on taxane addition than DPPC. These changes were also chain length-dependent for both the PCs and the taxane prodrugs. In contrast, PC and paclitaxel (lacking the acyl chain) mixtures under similar conditions showed insignificant changes in the endotherms, suggesting only slight insertion of the molecule into the PC bilayers. From the DSC data it is apparent that taxane prodrugs solvated in DMPC bilayers more than in DPPC and DSPC bilayers, and taxane prodrugs with longer acyl chains were able to associate with PCs better than those with shorter chain prodrugs. DSC data also suggest that paclitaxel was poorly associated with any of the PCs. In general, the amount of taxane association with bilayers decreased in order: DMPC > DPPC >> DSPC. In contrast, the transition enthalpy (DeltaH) of DMPC, DPPC, and DSPC mixtures with paclitaxel showed significantly lower enthalpies than with taxane prodrugs. Taken together, the DSC data suggest that the acyl chains of paclitaxel prodrugs have some access into the bilayers via alignment with the acyl chain of the PC component.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Benzophenones of Garcinia pseudoguttifera (Clusiaceae).

Four biogenetically related benzophenones have been isolated from the Fijian Garcinia pseudoguttifera. They are: 6-hydroxy-2,4-dimethoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (myrtiaphenone-A); 2,2-dimethyl-8-benzoyl-7-hydroxy-5-methoxy-6-(3-methyl-2-butenyl)benzopy ran (myrtiaphenone-B); 2,6-dihydroxy-4-methoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (vismiaphenone-C) and a new benzophenone, 2,2-dimethyl-8-benzoyl-3,7-dihydroxy-5-methoxy- 6-(3-methyl-2-butenyl)-3,4-dihydrobenzopyran (pseudoguttiaphenone-A). Pseudoguttiaphenone-A could be biogenetically derived from vismiaphenone-C. The major component of G. pseudoguttifera was identified as eupha-8,24-dien-3 beta-ol.

Benzophenones↗
PubMed2000

Nardostachys jatamansi protects against liver damage induced by thioacetamide in rats.

Nardostachys jatamansi is a medically important herb of Indian origin used for centuries in Ayurvedic and Unani systems of medicine for the treatment of various ailments. In the present paper, a 50% ethanolic extract of the rhizomes of N. jatamansi is shown to possess hepatoprotective activity. Pretreatment of rats with the extract (800 mg/kg body wt, orally) for three consecutive days significantly ameliorated the liver damage in rats exposed to the hepatotoxic compound thioacetamide. Elevated levels of serum transaminases (aminotransferases) and alkaline phosphatase, observed in thioacetamide alone treated group of animals, were significantly lowered in N. jatamansi pretreated rats. Pretreatment of the animals with the extract also resulted in an increase in survival in rats intoxicated with LD90 dose of the hepatotoxic drug.

Animals↗
PubMed2000

Estrogen receptor alpha in human breast cancer: occurrence and significance.

Estrogens have long been recognized as being important for stimulating the growth of a large proportion of breast cancers. Now it is recognized that estrogen action is mediated by two receptors, and the presence of estrogen receptor alpha (ER alpha) correlates with better prognosis and the likelihood of response to hormonal therapy. Over half of all breast cancers overexpress ER alpha and around 70% of these respond to anti-estrogen (for example tamoxifen) therapy. In addition, the presence of elevated levels of ER alpha in benign breast epithelium appears to indicate an increased risk of breast cancer, suggesting a role for ER alpha in breast cancer initiation, as well as progression. However, a proportion of ER alpha-positive tumors does not respond to endocrine therapy and the majority of those that do respond eventually become resistant. Most resistant tumors remain ER alpha-positive and frequently respond to alternative endocrine treatment, indicative of a continued role for ER alpha in breast cancer cell proliferation. The problem of resistance has resulted in the search for and the development of diverse hormonal therapies designed to inhibit ER alpha action, while research on the mechanisms which underlie resistance has shed light on the cellular mechanisms, other than ligand binding, which control ER alpha function.

Alternative Splicing↗
PubMed2000

The antagonism of interferon-gamma (IFN-gamma) by heparin: examination of the blockade of class II MHC antigen and heat shock protein-70 expression.

IFN-gamma is a pleiotropic cytokine that is primarily involved in the regulation of immune cell activation and the development of tissue inflammation. It is capable of activating a range of non-immune cells, including those of the vascular endothelium. These cells respond by increasing the expression of intracellular and cell-surface molecules such as class II MHC antigens and adhesion molecules that, together, increase the tendency for interaction with immune cells. It is known that IFN-gamma can bind cell surface and extracellular heparan sulphate. Furthermore, soluble heparin can inhibit the function of this cytokine, presumably by competitive displacement from the cell surface, resulting in the failure of normal receptor signal transduction. In this study it is shown that heparin can prevent normal induction of the class II transactivator and heat shock cognate protein-70 in an IFN-gamma-treated endothelial cell line. Both of these molecules are dependent on the activation of intracytoplasmic STAT-1, which is the most receptor proximal component of their respective induction pathways. This provides further evidence for the blockade by heparin of ligand activation of the specific IFN-gamma receptor.

Cell Line↗
PubMed2000

Scandinavian test of artificial neural network for classification of myocardial perfusion images.

Artificial neural networks are systems of elementary computing units capable of learning from examples. They have been applied to automated interpretation of myocardial perfusion images and have been shown to perform even better than experienced physicians. It has been shown that physicians interpreting myocardial perfusion images benefit from the advice of such networks. These networks have been developed and validated in the same hospital. However, widespread use of neural networks will only take place if the networks can maintain a high accuracy in other hospitals, i.e. hospitals using different gamma cameras, different acquisition techniques, different study protocols, etc. The purpose of this study was to develop a neural network in one hospital and test it in another. An artificial neural network was trained to detect coronary artery disease using myocardial perfusion scintigrams from 135 patients at a Swedish hospital. Thereafter, this network was tested using scintigrams from 68 patients at a Danish hospital and compared to six criteria based on expert physician analysis and quantitative analysis by the CEqual program. The sensitivity of the network was significantly higher than that of one of the physician criteria (0. 92 versus 0.71) and two of the CEqual-based criteria (0.94 versus 0. 63 and 0.96 versus 0.65) compared at equal specificities. It was concluded that an artificial neural network can maintain high accuracy in a hospital other than the one where it was developed.

Coronary Disease↗
PubMed2000

Regulation of T-cell apoptosis: a mixed lymphocyte reaction model.

Despite the capacity for antigen-specific activation and rapid clonal expansion, homeostatic mechanisms ensure that the mature immune system contains a relatively stable number of T cells. In recent years, it has become apparent that this stability is a consequence of apoptotic death of most of the specific T cells generated during an immune response. Clearly this process must be tightly regulated in order to retain sufficient T-cell progeny to mediate an effective response, whilst allowing the rapid deletion of these cells at the end of the response to prevent lymphadenopathy and cross-reactive autoimmunity. In this study, the factors that regulate the sensitivity of T cells to apoptosis were investigated in vitro after the induction of primary T-cell activation within a mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly acquire the expression of both Fas and Fas ligand (FasL) on their surface and contain high levels of the precursor form of the pro-apoptotic enzyme, caspase 8 (FLICE). However, these T cells were resistant for up to 5 days to apoptosis following the stimulation of Fas; a maximal apoptotic response was observed after 7 days. This time point coincided with a marked reduction in expression of the FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points beyond day 7, the number of viable cells in the MLR decreased further despite a reduction in the expression of FasL. However, the expression of interleukin-2 (IL-2) at these late time points was low, resulting in a decrease in expression of the anti-apoptotic protein Bcl-2. This can produce apoptosis by allowing leakage of cytochrome-c from mitochondria resulting in direct activation of the caspase cascade. In this study, it is shown that T cells are resistant to apoptosis for the first 5 days after activation as a consequence of insensitivity of the Fas pathway and the presence of intracellular Bcl-2. After between 5 and 7 days, the cells become sensitive to Fas-mediated apoptosis while retaining Bcl-2 expression. At later time points, Fas ligation is reduced but the cells respond to a decreased availability of IL-2 by reducing Bcl-2 expression; this encourages further apoptosis by allowing the direct activation of caspase enzymes.

Adult↗
PubMed2000

Short-term results after aortic valve replacement with stentless xenografts in elderly patients.

OBJECTIVE: Our aim was to chart the short-term results of the first 75 of our patients who had undergone first-time aortic valve replacement (AVR) with stentless xenografts. DESIGN: Our study included a complete follow-up (mean/max. 1.5/3.7 years) of the first 75 patients (42 males, 33 females; mean age 74, range 61-84 years) who underwent a first AVR with stentless xenografts. RESULTS: Forty-three percent of patients were in functional class II and 57% in classes III-IV preoperatively. Coronary artery bypass grafting (CABG) was performed in 33 patients. Early mortality (< or = 30 days) was 6.7%, with no significant relation to CABG or age. Crude survival was 81% (95% confidence interval, CI: 71-91 %) at 3 years. Using a multivariate analysis, we identified a low left ventricular ejection fraction as a predictor of early and late mortality. Late survival (early mortality excluded) was comparable with the survival of a matched Danish background population. There were six embolic events (all cerebral: 3 minor, 1 major, 2 fatal), while two patients underwent redo-AVR because of either endocarditis (fatal) or aortic regurgitation caused by malaligned commissures. There were no other valve-related complications. Cumulative freedom was 89% (95% CI: 79-99%) for embolism and 86% (95% CI: 76-96 %) for all complications at 3 years. At the end of the study, 64% of the survivors were in functional class I, 34% were in class II and 2% in class III. CONCLUSIONS: Considering the age composition of our patients, and compared with international results, our early mortality rates were acceptable. The absence of late excess mortality compared with the background population and the functional status at end-of-study may indicate the potential haemodynamic advantages of stentless aortic valves, at least in the short term.

Aged↗
PubMed2000

Secretor polymorphism and human immunodeficiency virus infection in Senegalese women.

The FUT2 gene encodes the enzyme alpha (1,2) fucosyltransferase, which determines expression of blood-group antigens on mucosal epithelial cell surfaces and in secretions. Homozygotes for a specific stop mutation in FUT2 (nonsecretors) cannot produce this enzyme and thus are unable to express blood group antigens. Nonsecretor status is associated with a decreased risk of several respiratory viral infections. By use of molecular genotyping, 2 populations of Senegalese women were examined for polymorphisms of the FUT2 gene. Among Senegalese commercial sex workers, absence of FUT2 (nonsecretor genotype) was associated with reduced risk of human immunodeficiency virus (HIV) type 1 infection (odds ratio [OR] adjusted for cervical and vaginal infection, 0.18; 95% confidence interval [CI], 0.04-0.90) and HIV-2 infection (adjusted OR, 0.43; 95% CI, 0.13-1.39), although the latter was not statistically significant. Modification of cell surface carbohydrates at mucosal surfaces determined by the FUT2 gene may underlie the protective association against heterosexual HIV infection.

Adult↗
PubMed2000

Gene therapy strategies for intracranial tumours: glioma and pituitary adenomas.

Intracranial tumours such as brain gliomas and pituitary adenomas pose a challenging area of research for the development of gene therapy strategies, both from the point of view of the severity of the diseases, to the physiological implication of gene delivery into the central nervous system and pituitary gland. On the one hand, brain gliomas are very malignant tumours, with a life expectancy of six months to a year at the most after the time of diagnosis, in spite of advances in treatment modalities which involve chemotherapy, surgery and radiotherapy. Gene therapy for these tumours is therefore a very attractive therapeutic modality which due to the severity of the disease is already in clinical trials. On the other hand, pituitary tumours are usually benign, and in most cases, treatment is successful. Nevertheless, there are some instances, especially with the macroadenomas and some invasive tumours in which treatment fails. Gene therapy strategies for these adenomas therefore needs to progress substantially in terms of safety, adverse side effects and physiological impact on the normal pituitary gland before clinical implementation. In this paper, we will review gene delivery systems both viral and non-viral and several therapeutic strategies which could be implemented for the treatment of these diseases. These include cytotoxic approaches both conditional and direct, immune-stimulatory strategies, anti-angiogenic strategies and approaches which harness pro-apoptotic and tumour suppressor gene targets. We will also review the models which are currently available in which these gene therapy strategies can be tested experimentally. This new therapeutic modality holds enormous promise, but we still need substantial improvements both from the delivery, efficacy and safety stand points before it can become a clinical reality.

Adenoma↗
PubMed2000

Detection of cytomegalovirus (CMV) antigens in kidney biopsies and transplant nephrectomies as a marker for renal graft dysfunction.

Chronic rejection accounts for the greatest loss of renal allografts. HLA mismatching has been minimised by organ allocation and new immunosuppressive drugs have been employed, but the average cadaveric graft survival still does not exceed 12 years. Though the aetiology is multifactorial, one contributory factor for this condition is cytomegalovirus (CMV). Detection of CMV in kidney biopsies and sera can diagnose and monitor this inflammatory event and define its role in chronic nephropathy. Twenty five biopsies taken at the time of transplantation, 10 biopsies for graft dysfunction and tissue blocks from 20 explanted kidney grafts were collected and investigated for CMV antigens by immunohistochemistry. Tissue samples were snap frozen and cryostat sections were incubated with monoclonal antibodies for CMV antigens followed by immunoperoxidase staining. In 12 out of 20 transplant nephrectomies CMV antigens were found. Only two of these patients had clinical CMV disease. Time 0 biopsies from CMV seronegative donors (n = 11) and CMV seropositive donors (n = 14) were negative for CMV antigens. The prevalence of CMV antigens in grafts lost due to chronic rejection was 60%. These antigens were not found within the time 0 biopsies, but were detected in 30% of biopsies taken at the time of clinical graft dysfunction. CMV appears to contribute to chronic rejection even without clinical disease.

Antigens, Viral↗
PubMed2000

Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7.

Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction of TFIIH with AF2, the activation function located in the ligand binding domain (LBD) of ERalpha. This interaction involves (1) the integrity of helix 12 of the LBD/AF2 and (2) p62 and XPD, two subunits of the core TFIIH. These findings are suggestive of a novel mechanism by which nuclear receptor activity can be regulated by ligand-dependent recruitment of modifying activities, such as kinases.

Amino Acid Motifs↗
PubMed1999

SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor.

Suppressors of cytokine signaling, SOCS-1, SOCS-2 and SOCS-3, are non-transmembrane proteins with Src-homology-2 (SH2) domain, involved in negative regulation of the Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway. Using transient overexpression system the role of SOCS proteins in regulating prolactin receptor intracellular mediators leading to gene activation was analyzed. Overexpression of SOCS-1 led to a significant reduction in PRLR-mediated tyrosyl phosphorylation of Jak2, PRLR, Stat5 and the cytoplasmic protein tyrosine phosphatase SHP2. Overexpression of SOCS-3 however, led to selective inhibition in PRLR-mediated tyrosyl phosphorylation of Jak2, the PRLR as well as SHP2. On the other hand, overexpression of SOCS-2 had no inhibitory effects on the tyrosyl phosphorylation status of the PRLR, Jak2, Stat5 or SHP2 in response to PRLR activation. Finally, the role of SOCS proteins in regulating the biological activity of the PRLR was investigated. Unlike SOCS-2, both SOCS-1 and SOCS-3 abolished the ability of the PRLR to induce beta-casein gene promoter activation. These results demonstrate that SOCS-1, SOCS-2 and SOCS-3 are differentially implicated in PRLR signaling to gene activation.

Animals↗