110 results on '"Parhar R"'
Search Results
2. Cannabinoid 2 receptor induction by IL-12 and its potential as a therapeutic target for the treatment of anaplastic thyroid carcinoma
- Author
-
Shi, Y, Zou, M, Baitei, E Y, Alzahrani, A S, Parhar, R S, Al-Makhalafi, Z, and Al-Mohanna, F A
- Published
- 2008
- Full Text
- View/download PDF
3. Cross-reactivities between date palm (Phoenix dactylifera L.) polypeptides and foods implicated in the oral allergy syndrome
- Author
-
Kwaasi, A. A. A, Harfi, H. A, Parhar, R. S, Saleh, S, Collison, K. S, Panzani, R. C, Al-Sedairy, S. T, and Al-Mohanna, F. A
- Published
- 2002
4. Calcium-dependent activation of naïve xenoendothelium by human naïve neutrophils under physiologic flow: absence of Galα1,3-Gal involvement
- Author
-
Sheikh, S., Parhar, R., and Al-Mohanna, F.
- Published
- 2001
5. Allergy to date fruits: characterization of antigens and allergens of fruits of the date palm (Phoenix dactylifera L.)
- Author
-
Kwaasi, A. A.A., Harfi, H. A., Parhar, R. S., Al-Sedairy, S. T., Collison, K. S., Panzani, R. C., and Al-Mohanna, F. A.
- Published
- 1999
6. Aeroallergens and viable microbes in sandstorm dust: Potential triggers of allergic and nonallergic respiratory ailments
- Author
-
Kwaasi, A. A. A., Parhar, R. S., Al-Mohanna, F. A. A., Harfi, H. A., Collison, K. S., and Al-Sedairy, S. T.
- Published
- 1998
7. SANDSTORM DUST CONTAINS POTENTIAL TRIGGERS OF RESPIRATORY AILMENTS: WS 008
- Author
-
Kwaasi, A.A. A., Parhar, R. S., Al-Mohanna, F. A., and Al-Sedairy, S. T.
- Published
- 1996
8. New agent, regenerating agent (RGTA) and bone marrow derived CD34+ lineage stem cells transplantation for the treatment of acute myocardial infarction
- Author
-
Mullangi C, Parhar R. Shahid, Kharabseh S., Al Sugair A, Al Dayal F, Al Mohanna F, and Al Halees Z
- Published
- 2006
- Full Text
- View/download PDF
9. 84TH ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION.
- Author
-
Laurberg, P., Berman, D.C., Pedersen, I.B., Andersen, S., Carlé, A., Chen, C., Hubbard, P., McLachlan, S.M., Murali, R., Rapoport, B., Aliesky, H., Banuelos, B., Ma, R., Latif, R., Davies, T.F., Shi, Y., Zou, M., Baitei, E., Al-Rijjal, R., and Parhar, R.
- Subjects
THYROID diseases ,THYROID cancer ,MEDICAL personnel ,PATIENTS' attitudes ,NON-alcoholic fatty liver disease ,REGULATORY T cells ,THYROID gland - Abstract
Recurrence was observed in 2.7% of patients with node negative disease, 5.3% of patients with N1a, and 13.1% of patients with N1b disease. Poster 52 I Thyroid Cancer Thursday Poster Clinical i B BILATERALITY IN PAPILLARY THYROID CARCINOMA: AN UPDATE WITH MORE THAN 2,000 CONSECUTIVE PATIENTS FROM A SINGLE INSTITUTE b We have previously reported that bilateral papillary thyroid carcinoma (PTC) presents with more advanced tumor stage and has a shorter disease-free survival than unilateral PTC in a cohort of 891 patients. Poster 67 I Thyroid Cancer Thursday Poster Clinical i B IMPROVING HEALTH CARE FOR THYROID CANCER PATIENTS - A PATIENT PARTNERSHIP APPROACH b In order to encourage patients' involvement in their own health care plans, some multi-disciplinary teams are choosing a proactive patient partnership approach instead of the traditional patient-centered approach. The patients with stable disease showed better progression free survival than patients with progressive disease (26 months vs. 47 months, p=0.070), but these patients with stable disease did not associate with better overall survival (p=0.42). [Extracted from the article]
- Published
- 2014
- Full Text
- View/download PDF
10. Impaired Cytotoxicity in Papillon-Lefèvre Syndrome.
- Author
-
Lundgren, T., Parhar, R. S., Renvert, S., and Tatakis, D. N.
- Subjects
KILLER cells ,PERIODONTITIS ,GENETIC disorders ,ETIOLOGY of diseases ,FLOW cytometry ,LYMPHOCYTES ,CELL-mediated cytotoxicity - Abstract
Papillon-Lefèvre syndrome (PLS), palmoplantar hyperkeratosis with periodontitis, has been genetically characterized. However, suspected associated immune dysfunctions remain elusive. The purpose of this study was to evaluate peripheral blood lymphocyte levels and natural killer (NK) cell cytotoxicity in PLS. Twenty patients and 20 healthy controls were examined. Peripheral blood lymphocytes were analyzed by flow cytometry for surface markers. NK cell cytotoxicity against K562 cells was determined by means of a
51 Cr release assay. White blood cell differential and proportions of B-, T-, T-helper, T-suppressor, and NK cells revealed only sporadic borderline variations from control values. In contrast, NK cell cytotoxicity was consistently and severely depressed (32-53% of control values) in all patients. To the best of our knowledge, this newly described impairment of NK cell cytotoxic function is the first consistent immune dysfunction reported in PLS. This suggests that the impaired NK cell cytotoxicity might contribute to the pathogenesis of PLS-associated periodontitis. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
11. Tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA is elevated in advanced stages of thyroid carcinoma.
- Author
-
Shi, Y, Parhar, R S, Zou, M, Hammami, M M, Akhtar, M, Lum, Z-P, Farid, N R, Al-Sedairy, S T, and Paterson, M C
- Subjects
- *
METALLOPROTEINASES , *MESSENGER RNA , *THYROID diseases , *CANCER - Abstract
Tumour cell invasion and metastasis is a multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of MMPs and thus prevent tumour cell invasion and metastasis by preserving extracellular matrix (ECM) integrity. In the present study we examined the expression of one member of TIMPs, TIMP-1, in 39 thyroid tumour specimens and two thyroid carcinoma cell lines (NPA and SW579). We also investigated the effect of high TIMP-1 expression on the invasive potential of NPA cells. Northern blot analysis showed that TIMP-1 mRNA levels correlated directly with tumour aggressiveness: the highest number of TIMP-1 transcripts was found in stages III and IV vs benign goitre (P < 0.0001). However, TIMP-1 expression was not increased in NPA and SW579 cells, both of which are derived from poorly differentiated thyroid tumours. Immunohistochemical study showed strong TIMP-1 staining in the stroma cells of advanced stages of carcinomas. Overexpression of TIMP-1 by gene transfer resulted in a significant suppression of the malignant phenotype of NPA cells as judged by an in vitro tumour invasion assay. These results suggest that high levels of TIMP-1 transcripts in advanced stages of thyroid carcinoma likely come from stroma rather than thyroid cancer cells, and TIMP-1 may function as a thyroid tumour invasion/metastasis suppressor. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF
12. Hyperplasia of mouse duodenal crypts and its control by NK cells during the initial phase of DMH carcinogenesis.
- Author
-
Altmann, G. G., Parhar, R. S., and Lala, P. K.
- Published
- 1990
- Full Text
- View/download PDF
13. Studies on clonal heterogeneity in two spontaneously metastasizing mammary carcinomas of recent origin.
- Author
-
Brodt, P., Parhar, R., Sankar, P., and Lala, P. K.
- Published
- 1985
- Full Text
- View/download PDF
14. Major allergens of date palm (<em>Phoenix dactylifera </em> L.) pollen.
- Author
-
Kwaasi, A. A. A., Parhar, R. S., Tipirneni, P., Harfi, H., and Al-Sedairy, S. T.
- Subjects
DATE palm ,ALLERGENS ,ANTIGENS ,ENZYME-linked immunosorbent assay ,WESTERN immunoblotting ,IMMUNOBLOTTING - Abstract
The IgE-binding components of date palm (Phoenix dacrylifera L.) pollen were determined by ELISA and Western blotting in atopic patients in order to identify its major allergens. From a pool of previously identified allergenic fractions and sera from 15 skin-test-positive, atopic subjects, four components of 12, 14.4, 57, and 65-67 kDa were found to bind IgE in 80-93% of sera. Two other components of molecular masses 28-30 and 37-40 kDa also bound 60-80% of atopic sera. The immunologic specificity of date-pollen allergen that induced antibody response in sera of atopic patients was confirmed with ELISA. Furthermore, most of the reactivity in pooled positive atopic serum and antiserum raised in rabbits was eliminated after the sera were absorbed with the allergen. IgG immunoblot analyses showed varying degrees of cross-reactivity with common local allergens, notably Bermuda grass, but were generally of low intensity. These results indicate that date pollen has six major allergens with the 12, 14.4, 57, and 65-67 kDa bands binding 80-93%, and the 28-30 and 37-40 kDa bands 60-80% of atopic sera. We propose that these major allergens be assigned the notations "Pho d I" to "Pho d VI" in the order listed. [ABSTRACT FROM AUTHOR]
- Published
- 1993
- Full Text
- View/download PDF
15. Differential nm23 gene expression at the fetal-maternal interface.
- Author
-
Shi, Y, Parhar, RS, Zou, M, al-Sedairy, S, Farid, NR, Parhar, R S, and Farid, N R
- Published
- 1994
- Full Text
- View/download PDF
16. Mechanism of pentoxifylline mediated down-regulation of killer lineage cell functions.
- Author
-
Parhar, R. S., Ernst, P., Sheth, K., Einspenner, M., and Al-Sedairy, S.
- Published
- 1993
17. Treatment of subacute sclerosing panencephalitis with alpha interferon.
- Author
-
Gascon, Generoso G., Yamani, Soad, Cafege, A., Flock, L., Al-Sedairy, S., Parhar, R. S., Crowell, J., Nester, Michael, Kanaan, Imad, Jallu, Mohammed A., Gascon, G G, Yamani, S, Nester, M, Kanaan, I, and Jallu, M A
- Published
- 1991
- Full Text
- View/download PDF
18. 2-[18F]-fluoroisonicotinic acid hydrazide: biological evaluation in an acute infection model.
- Author
-
Amartey, J. K., Esguerra, C., Al-Otaibi, B., Parhar, R. S., and Al-Jammaz, I.
- Subjects
- *
FLUORINE , *ESCHERICHIA coli diseases , *HYDRATES , *RADIOCHEMICAL analysis - Abstract
We have synthesized 2-[18F]-fluoroisonicotinic acid hydrazide by nucleophilic displacement reaction on ethyl-2- (trimethylammonium)-isonicotinate precursor in acetonitrile. Kryptofix® 222 was used as the phase transfer catalyst. The intermediate fluorinated ethyl ester reacted with hydrazine hydrate to produce the hydrazide. Excellent radiochemical yield was attained with total synthesis time of approximately 60min. Biological evaluation was performed in bacterial cells and biodistribution in normal as well as E. coli infected CBA/J mice. It was found that the S. pneumoniae cells retained the radiotracer in an in vitro assay. The tracer showed positive localization at the infection/inflammation site in E. coli infected mice. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
19. Transcriptomal Insights of Heart Failure from Normality to Recovery.
- Author
-
Quttainah M, Raveendran VV, Saleh S, Parhar R, Aljoufan M, Moorjani N, Al-Halees ZY, AlShahid M, Collison KS, Westaby S, and Al-Mohanna F
- Subjects
- Animals, Echocardiography, Heart, Hypertrophy, Sheep, Heart Failure diagnosis, Ventricular Dysfunction, Left
- Abstract
Current management of heart failure (HF) is centred on modulating the progression of symptoms and severity of left ventricular dysfunction. However, specific understandings of genetic and molecular targets are needed for more precise treatments. To attain a clearer picture of this, we studied transcriptome changes in a chronic progressive HF model. Fifteen sheep ( Ovis aries ) underwent supracoronary aortic banding using an inflatable cuff. Controlled and progressive induction of pressure overload in the LV was monitored by echocardiography. Endomyocardial biopsies were collected throughout the development of LV failure (LVF) and during the stage of recovery. RNA-seq data were analysed using the PANTHER database, Metascape, and DisGeNET to annotate the gene expression for functional ontologies. Echocardiography revealed distinct clinical differences between the progressive stages of hypertrophy, dilatation, and failure. A unique set of transcript expressions in each stage was identified, despite an overlap of gene expression. The removal of pressure overload allowed the LV to recover functionally. Compared to the control stage, there were a total of 256 genes significantly changed in their expression in failure, 210 genes in hypertrophy, and 73 genes in dilatation. Gene expression in the recovery stage was comparable with the control stage with a well-noted improvement in LV function. RNA-seq revealed the expression of genes in each stage that are not reported in cardiovascular pathology. We identified genes that may be potentially involved in the aetiology of progressive stages of HF, and that may provide future targets for its management.
- Published
- 2022
- Full Text
- View/download PDF
20. Review of Palliative Radiation Therapy Patterns of Practice for Adrenal Metastases in British Columbia.
- Author
-
Parhar R, Livergant J, and Lefresne S
- Subjects
- Abdominal Pain etiology, Abdominal Pain radiotherapy, Adrenal Gland Neoplasms complications, Adrenal Gland Neoplasms mortality, Adrenal Gland Neoplasms secondary, Adult, Aged, Aged, 80 and over, Anorexia etiology, Back Pain etiology, Back Pain radiotherapy, British Columbia, Cancer Pain etiology, Cancer Pain radiotherapy, Dose Fractionation, Radiation, Female, Flank Pain etiology, Flank Pain radiotherapy, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, Male, Middle Aged, Nausea etiology, Nausea prevention & control, Palliative Care statistics & numerical data, Proportional Hazards Models, Quality of Life, Regression Analysis, Retrospective Studies, Adrenal Gland Neoplasms radiotherapy, Palliative Care methods, Practice Patterns, Physicians'
- Abstract
Purpose: The adrenal gland is a common site of metastasis in patients with advanced cancer, but it is rarely symptomatic. A subset of patients develop a complex pain syndrome with anorexia, nausea, and poorly localized visceral pain in the back, flank, or epigastric region. These symptoms can affect quality of life and are occasionally challenging to palliate. The role of palliative radiation therapy (PRT) in these patients is unclear. This population-based retrospective study evaluates PRT practices for patients with adrenal metastases and aims to describe treatment response and acute toxicity., Methods and Materials: Patients who received PRT to an adrenal metastasis between the years of 1985 and 2015 were identified in a provincial database. Patient demographics, tumor factors, symptom burden, radiation therapy prescriptions, and response to treatment were collected. Variables were summarized using descriptive statistics. The Kaplan-Meier test was used to assess survival. Factors associated with clinical response were evaluated using univariate and logistic regression analysis. Factors associated with survival were evaluated using univariate and Cox proportional hazards model., Results: One hundred patients who received 103 separate courses of PRT were identified. The majority had a lung primary (82%). The most common baseline symptoms were pain (90%) and gastrointestinal upset (13%). Prescriptions ranged from 600 cGy in a single fraction to 4500 cGy in 25 fractions. Seventy percent of patients experienced an improvement in pain (either a complete or partial response). Forty-three percent of patients developed acute toxicity from treatment. Median survival was 3 months., Conclusions: Compared with other anatomic sites, conventional PRT is uncommonly delivered to adrenal metastases. Despite heterogeneity in tumor histology and radiation therapy prescriptions, treatment was associated with an overall pain response of 70%. Prophylactic antiemetics to decrease radiation-induced nausea are required before treatment. Given the poor prognosis of this population, short fractionations are indicated., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
21. AGO2 Mediates MYC mRNA Stability in Hepatocellular Carcinoma.
- Author
-
Zhang K, Pomyen Y, Barry AE, Martin SP, Khatib S, Knight L, Forgues M, Dominguez DA, Parhar R, Shah AP, Bodzin AS, Wang XW, and Dang H
- Subjects
- Animals, Argonaute Proteins metabolism, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Heterografts, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Mice, Mice, Inbred NOD, Mice, Nude, Mice, SCID, Proto-Oncogene Proteins c-myc metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Transfection, Argonaute Proteins genetics, Carcinoma, Hepatocellular genetics, Genes, myc, Liver Neoplasms genetics, Proto-Oncogene Proteins c-myc genetics
- Abstract
Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the MYC transcript to promote HCC. Using mRNA and miRNA arrays from patients with HCC, we demonstrate that HCCs with elevated AGO2 levels are more likely to have the mRNA transcriptome deregulated and are associated with poor survival. Moreover, AGO2 overexpression stabilizes the MYC transcript independent of miRNAs. These observations provide a novel mechanism of gene regulation by AGO2 and provide further insights into the potential functions of AGO2 as an RBP in addition to RISC. IMPLICATIONS: Authors demonstrate that the RBP Argonaute 2 stabilizes the MYC transcript to promote HCC., (©2020 American Association for Cancer Research.)
- Published
- 2020
- Full Text
- View/download PDF
22. Intracellular calcium and NF- k B regulate hypoxia-induced leptin, VEGF, IL-6 and adiponectin secretion in human adipocytes.
- Author
-
Al-Anazi A, Parhar R, Saleh S, Al-Hijailan R, Inglis A, Al-Jufan M, Bazzi M, Hashmi S, Conca W, Collison K, and Al-Mohanna F
- Subjects
- Adipocytes cytology, Adipocytes drug effects, Cell Differentiation, Gene Expression Regulation drug effects, Humans, Signal Transduction drug effects, Adipocytes metabolism, Adiponectin metabolism, Calcium pharmacology, Hypoxia physiopathology, Interleukin-6 metabolism, Leptin metabolism, NF-kappa B pharmacology, Vascular Endothelial Growth Factor A metabolism
- Abstract
Aims: Hypoxia-induced adipokine release has been attributed mainly to HIF-1α. Here we investigate the role of intracellular calcium and NF-kB in the hypoxia-dependent release of leptin, VEGF, IL-6 and the hypoxia-induced inhibition of adiponectin release in human adipocytes., Main Methods: We used intracellular calcium imaging to compare calcium status in preadipocytes and in adipocytes. We subjected both cell types to hypoxic conditions and measured the release of adipokines induced by hypoxia in the presence and absence of HIF-1α inhibitor YC-1, NF-
κ B inhibitor SN50 and intracellular calcium chelator BAPTA-AM., Key Findings: We demonstrate reduced intracellular calcium oscillations and increased oxidative stress as the cells transitioned from preadipocytes to adipocytes. We show that differentiation of preadipocytes to adipocytes is associated with distinct morphological changes in the mitochondria. We also show that hypoxia-induced secretion of leptin, VEGF, IL-6 and hypoxia-induced inhibition of adiponectin secretion are independent of HIF-1α expression. The hypoxia-induced leptin, VEGF and IL-6 release are [Ca++ ]i dependent whereas adiponectin is NF-k B dependent., Significance: Our work suggests a major role for [Ca++ ]i in preadipocyte differentiation to adipocytes and that changes in mitochondrial morphology in the adipocytes might underlie the reduced calcium oscillations observed in the adipocytes. It also demonstrates that multiple signaling pathways are associated with the hypoxia-induced adipokine secretion., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
23. Data on hypoxia-induced VEGF, leptin and NF-kB p65 expression.
- Author
-
Al-Anazi A, Parhar R, Saleh S, Al-Hijailan R, Inglis A, Al-Jufan M, Bazzi M, Hashmi S, Conca W, Collison K, and Al-Mohanna F
- Abstract
The data set presented here is associated with the article "Intracellular calcium and NF-
k B regulate hypoxia-induced leptin, VEGF, IL-6 and adiponectin secretion in human adipocytes" (Al-Anazi et al., 2018). Data illustrate hypoxia-induced VEGF and leptin expression in human adipocytes treated with the calcium chelator BAPTA-AM (1 µM). It also shows NF-κB p65 induced expression by hypoxia. Preadipocytes were differentiated for 14 days and then subjected to 0.5-1.5% oxygen in the presence and absence of BAPTA-AM or the NF-κB inhibitor SN50 for 48 h prior to RNA isolation and PCR analysis.- Published
- 2018
- Full Text
- View/download PDF
24. Defective lipid metabolism associated with mutation in klf-2 and klf-3 : important roles of essential dietary salts in fat storage.
- Author
-
Ling J, Brey C, Schilling M, Lateef F, Lopez-Dee ZP, Fernandes K, Thiruchelvam K, Wang Y, Chandel K, Rau K, Parhar R, Al-Mohanna F, Gaugler R, and Hashmi S
- Abstract
Background: Dietary salts are important factors in metabolic disorders. They are vital components of enzymes, vitamins, hormones, and signal transduction that act synergistically to regulate lipid metabolism. Our previous studies have identified that Krüppel-like factor -3 (KLF-3) is an essential regulator of lipid metabolism. However, it is not known if KLF-2 also regulates lipid metabolism and whether KLF-2 and -3 mediate the effects of dietary salts on lipid metabolism., Methods: In this study, we used klf mutants [homozygous klf-2 (ok1043) V and klf-3 (ok1975) II mutants] to investigate the role of dietary salts in lipid metabolism. All gene expression was quantified by qRT-PCR. Localization of KLF-2 was analyzed by the expression of klf-2 :: gfp (in pPD95.75 vector) using a fluorescent microscope. Fat storage was measured by Oil Red O staining., Results: Klf-2 was identified to express in the intestine during all stages of Caenorhabditis elegans development with peak expression at L3 stage. Mutation of klf-2 increased fat accumulation. Under regular growth media free of Ca
2+, the expression of both klf-2 and - 3 was inhibited slightly; further their expression reduced significantly in WT worms fed on 10X Ca2+ diet. When klf-3 was mutated, the expression of klf-2 increased under 10X Ca2+ diet; but when klf-2 was mutated, the expression of klf-3 was not altered under 10X Ca2+ diet. Overall, Mg2+ and K+ were less effective on the gene expression of klfs . KLF target gene Ce -C/EBP-2 showed elevated expression in WT and klf-3 (ok1975) worms with changed Ca2+ concentrations but not in klf-2 (ok1043) worms. However, high Ca+2 diet exhibited inhibitory effect on Ce -SREBP expression in WT worms., Conclusion: Dietary Ca2+ is most effective on fat storage and klf-2 expression, wherein high Ca2+ diet decreased klf-2 expression and reduced fat buildup. Mechanistic study identified Ce -C/EBP (C48E7.3; lpd-2 ) and Ce-SREBP (Y47D3B.7; lpd-1 ) as the target genes of klf-2 and/or klf-3 to mediate lipid metabolism. This study identifies a new function of klf-2 in inhibiting fat buildup and reveals the interplay between dietary salts and klf-2 and klf-3 in lipid metabolism.- Published
- 2017
- Full Text
- View/download PDF
25. Progression of matrixin and cardiokine expression patterns in an ovine model of heart failure and recovery.
- Author
-
Quttainah M, Al-Hejailan R, Saleh S, Parhar R, Conca W, Bulwer B, Moorjani N, Catarino P, Elsayed R, Shoukri M, AlJufan M, AlShahid M, Ouban A, Al-Halees Z, Westaby S, Collison K, and Al-Mohanna F
- Subjects
- Animals, Cytokines biosynthesis, Disease Models, Animal, Disease Progression, Heart Failure metabolism, Heart Failure physiopathology, Immunoblotting, Matrix Metalloproteinases biosynthesis, Real-Time Polymerase Chain Reaction, Sheep, Sheep, Domestic, Cytokines genetics, Gene Expression Regulation, Heart Failure genetics, Matrix Metalloproteinases genetics, RNA genetics, Recovery of Function physiology, Ventricular Remodeling
- Abstract
Background: The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined., Objective: Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF)., Methods: Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff. A controlled and progressive increase of LV pressure was monitored echocardiographically. Endomyocardial biopsies were collected throughout the development of LVF and subsequent recovery after pressure unloading., Results: Thirteen sheep developed LVF with a subsequent recovery. Peak left ventricular hypertrophy (LVH) and dilatation (LVD) occurred at 31.5 ± 1.6 weeks and 102.7 ± 2.2 weeks post-banding respectively, with an increase in LV internal diameter in diastole (LVIDd 5.11 ± 0.12 compared to the control 3.37 ± 0.07 cm, p<0.001), with preserved LV ejection fraction (LVEF). Reduced LVEF became evident 116.5 ± 2.7 weeks post-banding. Clinical and echocardiographic improvements were observed following deflation of the aortic banding cuff. By 138.1 ± 3.1 weeks cardiac performance recovered with restoration of LVEF. Significant changes in the expression of matrix metalloproteinases (MMP)-1, -2, -3, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF)-2, interferon (INF)-α-2 and soluble CD40 ligand (sCD40L) were observed throughout the progression to failure and recovery., Conclusions: We used an ovine model to study reversible LV remodelling without interruption and found significant changes in matrixin and cardiokine expression during LV progression to failure and recovery., (Copyright © 2015. Published by Elsevier Ireland Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
26. Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice.
- Author
-
Bhandarkar SS, Jaconi M, Fried LE, Bonner MY, Lefkove B, Govindarajan B, Perry BN, Parhar R, Mackelfresh J, Sohn A, Stouffs M, Knaus U, Yancopoulos G, Reiss Y, Benest AV, Augustin HG, and Arbiser JL
- Subjects
- Angiopoietin-2 physiology, Animals, Endothelial Cells metabolism, Hemangioma pathology, Intracellular Signaling Peptides and Proteins, Mice, NADPH Oxidase 4, NADPH Oxidases genetics, NADPH Oxidases physiology, Proteins genetics, Vascular Endothelial Growth Factor A antagonists & inhibitors, Cyclopentanes pharmacology, Enzyme Inhibitors pharmacology, Hemangioma drug therapy, NADPH Oxidases antagonists & inhibitors
- Abstract
Hemangiomas are the most common type of tumor in infants. As they are endothelial cell-derived neoplasias, their growth can be regulated by the autocrine-acting Tie2 ligand angiopoietin 2 (Ang2). Using an experimental model of human hemangiomas, in which polyoma middle T-transformed brain endothelial (bEnd) cells are grafted subcutaneously into nude mice, we compared hemangioma growth originating from bEnd cells derived from wild-type, Ang2+/-, and Ang2-/- mice. Surprisingly, Ang2-deficient bEnd cells formed endothelial tumors that grew rapidly and were devoid of the typical cavernous architecture of slow-growing Ang2-expressing hemangiomas, while Ang2+/- cells were greatly impaired in their in vivo growth. Gene array analysis identified a strong downregulation of NADPH oxidase 4 (Nox4) in Ang2+/- cells. Correspondingly, lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreased Ang2 mRNA levels and greatly impaired hemangioma growth in vivo. Using a structure-based approach, we identified fulvenes as what we believe to be a novel class of Nox inhibitors. We therefore produced and began the initial characterization of fulvenes as potential Nox inhibitors, finding that fulvene-5 efficiently inhibited Nox activity in vitro and potently inhibited hemangioma growth in vivo. In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function.
- Published
- 2009
- Full Text
- View/download PDF
27. A force-spectroscopy-based single-molecule metal-binding assay.
- Author
-
Cao Y, Er KS, Parhar R, and Li H
- Subjects
- Kinetics, Microscopy, Atomic Force, Protein Binding, Recombinant Proteins chemistry, Spectrophotometry, Ultraviolet, Thermodynamics, Metals chemistry, Proteins chemistry
- Abstract
Quantifying metal-binding by force: A quantitative single-molecule force-spectroscopy-based assay is developed to measure the binding affinity of metal ions to proteins. The method uses the unfolding force of a protein as a direct probe to distinguish the apo and metal-ion-bound forms of that protein and quantify the partitioning between the two forms (see figure).
- Published
- 2009
- Full Text
- View/download PDF
28. Recombinant Ov-ASP-1, a Th1-biased protein adjuvant derived from the helminth Onchocerca volvulus, can directly bind and activate antigen-presenting cells.
- Author
-
He Y, Barker SJ, MacDonald AJ, Yu Y, Cao L, Li J, Parhar R, Heck S, Hartmann S, Golenbock DT, Jiang S, Libri NA, Semper AE, Rosenberg WM, and Lustigman S
- Subjects
- Animals, Antigen Presentation immunology, Cytokines biosynthesis, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Membrane Glycoproteins immunology, Mice, Spike Glycoprotein, Coronavirus, Th2 Cells immunology, Toll-Like Receptor 2 immunology, Toll-Like Receptor 4 immunology, Viral Envelope Proteins immunology, Adjuvants, Immunologic, Antigen-Presenting Cells immunology, Antigens, Helminth immunology, Helminth Proteins immunology, Lymphocyte Activation immunology, Recombinant Proteins immunology, Th1 Cells immunology
- Abstract
We previously reported that rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based Ags. In this study, we further evaluated the adjuvanticity of rOv-ASP-1 and explored its mechanism of action. Consistently, recombinant full-length spike protein of SARS-CoV or its receptor-binding domain in the presence of rOv-ASP-1 could effectively induce a mixed but Th1-skewed immune response in immunized mice. It appears that rOv-ASP-1 primarily bound to the APCs among human PBMCs and triggered Th1-biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-1 is a novel potent innate adjuvant.
- Published
- 2009
- Full Text
- View/download PDF
29. Skin-homing CD8+ T lymphocytes show preferential growth in vitro and suppress CD4+ T-cell proliferation in patients with early stages of cutaneous T-cell lymphoma.
- Author
-
Thestrup-Pedersen K, Parhar R, Wu K, Bertilsson PA, Meyer B, Abu-Amero S, Hainau B, Aleisa A, Alfadley A, Hamadah I, Alajlan A, Al-Hussein K, and Al-Mohanna F
- Subjects
- Adolescent, Adult, Aged, CD4-Positive T-Lymphocytes pathology, CD8-Positive T-Lymphocytes pathology, Cell Cycle physiology, Female, Humans, Immunologic Surveillance, Interleukin-2 immunology, Interleukin-4 immunology, Lymphocyte Activation, Lymphoma, T-Cell, Cutaneous pathology, Male, Middle Aged, Neoplasm Staging, Receptors, Antigen, T-Cell, gamma-delta immunology, Skin Neoplasms pathology, X Chromosome Inactivation genetics, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Lymphoma, T-Cell, Cutaneous immunology, Skin Neoplasms immunology
- Abstract
A total of 27 T-lymphocyte cell strains were established from skin biopsies of 24 patients with various stages of cutaneous T-cell lymphoma (CTCL) by addition of the T-cell growth factors interleukin (IL)-2 and IL-4. Cellular proliferation and phenotypic changes were measured over 3 months in culture, and T-cell clones were studied using T-cell receptor-? re-arrangement techniques. An average outgrowth of 134 million T-lymphocytes from a 4-mm skin biopsy was observed over 2 months. Initially, most T-cells expressed the CD4+ phenotype. In 17 cell strains from patients with early CTCL a statistically significant predominance of CD8+ T-lymphocytes developed over 8-weeks' culture, indicating that CD8+ T-cells controlled the growth of CD4+ T cells, whereas CD4+ T-cells were predominant in cell strains from advanced CTCL (p <0.05). TCR-? re-arrangement studies revealed, on average, 12 T-cell clones per cell strain, which was reduced over time to 6 T-cell clones per cell strain. Lymphocytes from peripheral blood could kill lymphocytes from an autologous cell strain, suggesting the presence of autoreactive cytotoxic T-cells. Our study suggests how skin-homing CD8+ T-lymphocytes from patients with early stage CTCL can suppress the in vitro growth of skin-homing CD4+ T-lymphocytes, indicating immune surveillance.
- Published
- 2007
- Full Text
- View/download PDF
30. Synthesis and evaluation of radioiodinated substituted beta-naphthylalanine as a potential probe for pancreatic beta-cells imaging.
- Author
-
Amartey JK, Esguerra C, Al-Jammaz I, Parhar RS, and Al-Otaibi B
- Subjects
- Animals, CHO Cells, Cricetinae, Insulin-Secreting Cells metabolism, Isotope Labeling methods, Magnetic Resonance Spectroscopy, Mass Spectrometry, Mice, Mice, Inbred CBA, Radionuclide Imaging, Tissue Distribution, beta-Alanine chemistry, beta-Alanine metabolism, Insulin-Secreting Cells diagnostic imaging, Iodine Radioisotopes chemistry, Radiopharmaceuticals chemical synthesis, beta-Alanine analogs & derivatives
- Abstract
A non-invasive imaging technique capable of relating a signal from the beta-cells to their mass will be of immense value in understanding the progression of diabetes. Several molecular markers have indeed been identified and investigations are ongoing aimed at accomplishing the said goal. These include pancreatic islet antigen (IC-2), somatostatin receptors (SSTRs), and sulfonylurea receptors (SURs) on the pancreatic beta-cells. Therefore investigations exploiting the potential application of the radiolabeled ligands for these receptors for beta-cell imaging are receiving intensive research attention. Radioiodinated peptidomimetic based on beta-naphthylalanine and n-hexanediamine has been synthesized. The molecule was subjected to in vitro and in vivo evaluation. Radioligand binding studies on CHO cell line expressing the SSTR2 showed very low affinity. Nonetheless, biodistribution in normal mice showed significant uptake in the pancreas. There was partial blockage of the pancreatic uptake when excess of the peptidomimetic was coinjected. The result implies that the pancreatic uptake was receptor mediated but may not involve the SSTR2 and therefore warrants further investigation.
- Published
- 2006
- Full Text
- View/download PDF
31. Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed.
- Author
-
Al-Mohanna F, Saleh S, Parhar RS, Khabar K, and Collison K
- Subjects
- Animals, Antigens, Surface chemistry, Antigens, Surface immunology, Aorta cytology, Aorta immunology, Calcium Signaling immunology, Cells, Cultured, Chelating Agents pharmacology, Chemotaxis, Leukocyte immunology, Cytokines genetics, Disaccharides immunology, Enzyme Inhibitors pharmacology, Humans, Oligonucleotide Array Sequence Analysis, RNA, Messenger metabolism, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Sus scrofa, Transcriptional Activation immunology, Endothelial Cells immunology, Gene Expression Profiling, Gene Expression Regulation immunology, Graft Rejection immunology, Neutrophils immunology, Transplantation, Heterologous immunology
- Abstract
The role of innate immune cells in the recognition and activation of xenogeneic endothelium has always been considered secondary to the initial insult of xenoreactive natural antibodies (XNA) and complement. It was argued, however, that innate immune cells are capable of recognizing and activating xenogeneic endothelium in the absence XNA and complement. Here, we show that porcine aortic endothelial cells (PAECs) activate human neutrophils directly. This contact-dependent activation causes a transient calcium rise leading to increased reactive oxygen metabolite (ROM) production. Neutrophil gene-expression profiling using an adenylate uridylate-rich element-based microarray revealed a dramatic change in the neutrophil gene profiles upon exposure to PAECs. The PAEC-dependent neutrophil transcriptional activity was further confirmed by real-time polymerase chain reaction, which revealed a rapid increase in the mRNA message of a number of inflammatory cytokines. The activation of human neutrophils by PAECs was independent of galactose alpha1,3-galactose (Galalpha1,3-gal) structures, as inclusion of saturating concentrations of anti-Galalpha1,3-gal l antibodies had no significant effect. Furthermore, this activation was inhibited in the presence of the calcium chelator 1,2-bis(O-aminophenyl-ethane-ethane)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the ROM inhibitor diphelylene iodonium. Our data illustrate the direct activation of innate immune cells by PAECs in the absence of XNA and complement and suggest alternative recognition sites between PAECs and human innate immune cells.
- Published
- 2005
- Full Text
- View/download PDF
32. Prosthetic radioiodination of interleukin-8 ([(123/131)I]-IL-8): biological behavior in a mouse infection model.
- Author
-
Amartey JK, Esguerra C, Al-Otaibi B, Al-Jammaz I, Al-Qahtani M, and Parhar RS
- Subjects
- Animals, Cells, Cultured, Interleukin-8 chemistry, Iodine Radioisotopes chemistry, Iodine Radioisotopes pharmacokinetics, Isotope Labeling methods, Metabolic Clearance Rate, Mice, Mice, Inbred CBA, Organ Specificity, Radionuclide Imaging, Radiopharmaceuticals chemical synthesis, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, Escherichia coli Infections diagnostic imaging, Escherichia coli Infections metabolism, Interleukin-8 pharmacokinetics, Neutrophils diagnostic imaging, Neutrophils metabolism
- Abstract
Numerous molecular entities with diverse structures have been radiolabeled and investigated as potential infection and inflammation detection agents. However, none of these molecules have gained the acceptance of gallium citrate or radiolabeled autologous white blood cells. We have radioiodinated interleukin-8 using two different methods and tested the biological behavior of the products in mice. As expected, the direct radioiodinated material displayed extensive in vivo deiodination. The use of pyridine-based prosthetic label yielded a product with better kinetics than the direct radioiodination method and showed a better target to non-target ratio. Nonetheless, this method is not suited for labeling of bioactive peptides such as the title peptide because of the very high specific activity required to prevent cytotoxic effects in a human application.
- Published
- 2005
- Full Text
- View/download PDF
33. Immobilization of rolling NK cells on platelet-borne P-selectin under flow by proinflammatory stimuli, interleukin-12, and leukotriene B4.
- Author
-
Sheikh S, Parhar RS, Bakheet R, Saleh S, Collison K, and Al-Mohanna F
- Subjects
- Antibodies pharmacology, Blood Platelets metabolism, CD18 Antigens immunology, Cells, Cultured, Humans, Inflammation Mediators immunology, Interleukin-12 immunology, Killer Cells, Natural drug effects, Leukotriene B4 immunology, Leukotriene B4 pharmacology, Lymphocyte Function-Associated Antigen-1 immunology, Macrophage-1 Antigen immunology, Blood Platelets immunology, Cell Adhesion immunology, Chemotaxis, Leukocyte immunology, Inflammation Mediators pharmacology, Interleukin-12 pharmacology, Killer Cells, Natural immunology, P-Selectin immunology
- Abstract
Recruitment of leukocytes from bloodstream to extrahematic sites is tightly regulated by a variety of adhesion molecules that are expressed on the leukocytes and the vessel walls. In this manuscript, we describe the interactions between natural killer (NK) cells and activated, autologous platelets under physiologic flow. We found that surface-adherent human platelets are capable of recruiting human NK cells from flow and that this recruitment is characterized by an initial tethering followed by a rolling phase. Both phases were dependent on the adhesion molecule P-selectin and its counter-ligand on the NK cells (P-selectin glycoprotein ligand 1). Activation of rolling NK cells with inflammatory mediators commonly found in atherosclerotic plaques (interleukin-12 and leukotriene B4) causes immediate cessation of the rolling process and conversion to stationary adhesion. Blocking antibodies to the adhesion molecules membrane-activated complex-1 and leukocyte function antigen-1 inhibited this conversion. Our data suggest that platelets deposited at sites of vascular injury may provide an alternative substrate to endothelial cells for initial recruitment of NK cells to the vessel wall. This may result in extravasation of the NK cells if the appropriate chemotactic signal is applied. These data implicate the P-selectin and integrin family of adhesion molecules in the recruitment of NK cells to atherosclerotic sites.
- Published
- 2004
- Full Text
- View/download PDF
34. 2-[(18)F]-fluoroisonicotinic acid hydrazide: biological evaluation in an acute infection model.
- Author
-
Amartey JK, Esguerra C, Al-Otaibi B, Parhar RS, and Al-Jammaz I
- Subjects
- Animals, Disease Models, Animal, Humans, Hydrazines chemical synthesis, Isonicotinic Acids chemical synthesis, Mice, Mice, Inbred BALB C, Radionuclide Imaging, Escherichia coli Infections diagnostic imaging, Fluorine Radioisotopes, Infections diagnostic imaging, Tuberculosis, Pulmonary diagnostic imaging
- Abstract
We have synthesized 2-[(18)F]-fluoroisonicotinic acid hydrazide by nucleophilic displacement reaction on ethyl-2- (trimethylammonium)-isonicotinate precursor in acetonitrile. Kryptofix 222 was used as the phase transfer catalyst. The intermediate fluorinated ethyl ester reacted with hydrazine hydrate to produce the hydrazide. Excellent radiochemical yield was attained with total synthesis time of approximately 60 min. Biological evaluation was performed in bacterial cells and biodistribution in normal as well as E. coli infected CBA/J mice. It was found that the S. pneumoniae cells retained the radiotracer in an in vitro assay. The tracer showed positive localization at the infection/inflammation site in E. coli infected mice.
- Published
- 2004
- Full Text
- View/download PDF
35. Cytokines, matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 in gingival crevicular fluid from patients with Papillon-Lefèvre syndrome.
- Author
-
Ullbro C, Crossner CG, Nederfors T, Parhar R, Al Mohanna F, Meikle MC, Reynolds JJ, and Twetman S
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Gingival Pocket metabolism, Gingivitis metabolism, Humans, Interleukin-1 analysis, Interleukin-8 analysis, Male, Matrix Metalloproteinase 1 analysis, Matrix Metalloproteinase 3 analysis, Matrix Metalloproteinase 8 analysis, Matrix Metalloproteinase 9 analysis, Periodontitis metabolism, Tumor Necrosis Factor-alpha analysis, Cytokines analysis, Gingival Crevicular Fluid chemistry, Matrix Metalloproteinases analysis, Papillon-Lefevre Disease metabolism, Tissue Inhibitor of Metalloproteinase-1 analysis
- Abstract
The aim of the present study was to compare concentrations of cytokines, matrix metalloproteinases (MMPs) and a metalloproteinase inhibitor (TIMP-1) in gingival crevicular fluids (GCF) from sites with gingival inflammation in 28 young patients with Papillon-Lefèvre syndrome (PLS), and in age- and gender-matched controls. Each group consisted of 17 females and 11 males with a mean age of 11.0 years (range 4-22 years). In both groups, anterior upper sites with a clinical diagnosis of gingival inflammation and with pockets < or = 3 mm were selected for sampling of GCF, which was carried out with filter disks inserted into the gingival crevice until saturated. The concentrations of cytokines (IL-1alpha, IL-1beta, TNF-alpha, and IL-8), matrix metalloproteinases (MMP-1, MMP-3, MMP-8, and MMP-9), and their tissue inhibitor (TIMP-1) were analysed using commercial ELISA kits. Significantly higher levels of IL-1beta (P < 0.001) and MMP-8 (P < 0.05) were disclosed among the PLS patients compared with their controls, while the opposite was found for IL-8 (P < 0.05) and MMP-1 (P < 0.001). The individual variations were considerable in both groups. When comparing the expression of cytokines, MMPs, and TIMP-1 in PLS patients with clinically active and non-active periodontitis, the non-active PLS patients showed significantly higher values of IL-1beta than the patients with active periodontal disease (ANOVA, P < 0.01). In conclusion, this study was unable to demonstrate a clear-cut pathognomonic expression of cytokines or MMPs in patients with PLS, but further studies on cytokine and MMP output are warranted.
- Published
- 2004
- Full Text
- View/download PDF
36. Rapid static adhesion of human naïve neutrophil to naïve xenoendothelium under physiologic flow is independent of Galalpha1,3-gal structures.
- Author
-
Sheikh S, Parhar R, and Al-Mohanna F
- Subjects
- Animals, Aorta, Calcium Signaling physiology, Cell Adhesion drug effects, Cells, Cultured, Endothelium, Vascular drug effects, Humans, Neutrophils drug effects, Swine, Tumor Necrosis Factor-alpha pharmacology, Cell Adhesion physiology, Disaccharides physiology, Endothelium, Vascular physiology, Neutrophils physiology
- Abstract
Adhesion interactions under flow have long been known to depend on applied wall shear stress. We investigated the ability of human naïve neutrophils to adhere to xenogeneic endothelial cells under static and flow conditions. We demonstrate that human naïve neutrophils bind to xenogeneic endothelial cells under flow conditions. This binding is dependent on the applied stress and is independent of Galalpha1,3-gal structures, ICAM-1, or its counter ligands LFA-1alpha and Mac-1. The binding was rapid and is characterized by stationary attachment with no obvious rolling or change in morphology. This binding leads to a transient increase in intracellular-free calcium levels in xenogeneic but not allogeneic-endothelial cells with occasional oscillations that persist long after the initial contact between the two cell types. Previous activation of xenoendothelium by autologous serum or human TNF-alpha augments binding of human naïve neutrophils to the endothelial cells. Our data suggest novel interaction sites between the xenogeneic endothelial cells and human naïve neutrophils.
- Published
- 2002
37. Detection of xenoantibodies using a simple flow cytometric assay.
- Author
-
Al-Hussein K, Al-Mukhalafi Z, Pyle HR, Parhar RS, Al-Mohanna F, and Lee J
- Subjects
- Adult, Animals, Aorta, Cells, Cultured, Disaccharides immunology, Epitopes immunology, Flow Cytometry methods, Humans, Middle Aged, Swine, Antibodies, Heterophile blood, Cell Survival, Endothelium, Vascular cytology
- Abstract
Higher primates, including humans, have high levels of pre-existing naturally circulating antibodies that predominantly recognize the epitope Gal (1,3-Gal), which is highly expressed on the surface of xenogenic cells. Deposition of these antibodies on the endothelial cell surface of vascularized xenografts leads to an activation of the classical pathway of the complement system, resulting in tissue ischemia and necrosis with rapid demise of the xenograft. This hyperacute rejection (HAR) is always a major barrier in xenograft transplantation and should be minimized by accurately monitoring the naturally occurring antibodies. In the present study, we utilized a simple and rapid flow cytometric (FCM) assay to monitor the presence of these naturally occurring antibodies. We found that the FCM assay is very effective in measuring human antibodies bound to the xenogenic cells, which cause cytotoxicity. This assay could be useful in the pre- and post-xenotransplantation monitoring of xenoantibodies, thus, helping in the development of strategies to block the binding of preformed human antibodies to the xenograft in order to overcome the problem of HAR.
- Published
- 2001
- Full Text
- View/download PDF
38. Synthesis and preliminary evaluation of Tc-99m-labeled somatostatin analog (RC-160) using "3+1" mixed ligand approach.
- Author
-
Amartey JK, Parhar RS, and Al-Jammaz I
- Subjects
- Animals, Breast Neoplasms metabolism, Female, Humans, Ligands, Mice, Radioligand Assay, Somatostatin analogs & derivatives, Somatostatin pharmacokinetics, Technetium Compounds chemistry, Tissue Distribution, Tumor Cells, Cultured metabolism, Radiopharmaceuticals chemical synthesis, Somatostatin chemical synthesis
- Abstract
The success of (111)In-pentetreotide as a cancer-imaging agent has given impetus to the search for other peptide-based radiopharmaceuticals. The labeling with Tc-99m has become even more attractive because of the ready availability and near ideal physical properties. Additionally, the kinetics of the peptide-receptor interactions favors the radiolabeling with technetium-99m. A somatostatin analog RC-160 has been labeled with Tc-99m using the "3+1" mixed ligand approach utilizing the NNS/S coordination sites. The ternary complex was formed in greater than 95% within 30 min by simultaneous reduction and complexation of technetium-99m pertechnetate. The Tc-99m and the surrogate rhenium complexes showed similar chromatographic behavior. The complex was evaluated by in vitro receptor binding studies carried out on HTB-121 breast cancer cell line and biodistribution studies performed in normal mice. Our findings suggest that RC-160 can be labeled by the mixed ligand approach with the complex retaining its biological activity and warrants further studies.
- Published
- 2001
- Full Text
- View/download PDF
39. Vaccinia virus complement control protein is capable of protecting xenoendothelial cells from antibody binding and killing by human complement and cytotoxic cells.
- Author
-
Al-Mohanna F, Parhar R, and Kotwal GJ
- Subjects
- Animals, Antibody-Dependent Cell Cytotoxicity drug effects, Aorta cytology, Cytotoxicity, Immunologic, Graft Rejection prevention & control, Humans, Swine, Transplantation, Heterologous immunology, Endothelium, Vascular cytology, T-Lymphocytes, Cytotoxic immunology, Viral Proteins pharmacology
- Abstract
Background: Vaccinia virus complement control protein (VCP) was the first secretory microbial protein shown to have structural similarity to the family of complement control proteins. VCP can block both the classical and alternate complement pathways. Recently, VCP has been shown to bind to heparin, and this property contributes to separate functions, making the molecule a multifunctional protein., Methods: VCP prepared from a natural infection of RK-13 cells with vaccinia virus was purified to homogeneity. Cultured pig aortic endothelial cells (PAECs) were mixed with human serum, anti-Gal alpha1,3 Gal antibody, neutrophils, or natural killer (NK) cells in the presence or absence of VCP and either direct binding of FITC-labeled antibody or killing by cytotoxic cells was estimated., Results: Our cell culture studies demonstrate that VCP blocks complement-mediated killing of PAECs by human serum in a dose-dependent manner. We also demonstrate that VCP is capable of blocking Gal alpha1,3 Gal binding sites on PAECS. Surprisingly, VCP effectively blocked interactions between PAECs and cytotoxic cells such as human naive neutrophils and NK cells., Conclusion: VCP is a novel protein amongst the complement control protein family and can, not only block xenorejection by inhibiting complement but also by blocking killing by cytotoxic cells.
- Published
- 2001
- Full Text
- View/download PDF
40. Ca(2+)-dependent production of reactive oxygen metabolites by human neutrophils in response to fluorinated propranolol analogues.
- Author
-
Saleh S, Aboul-Enein HY, Parhar R, Collison K, and Al-Mohanna F
- Subjects
- Actins metabolism, Fluorine chemistry, Homeostasis drug effects, Humans, In Vitro Techniques, Neutrophils metabolism, Oxidants chemistry, Oxidants pharmacology, Propranolol analogs & derivatives, Propranolol chemistry, Calcium metabolism, Neutrophils drug effects, Propranolol pharmacology, Reactive Oxygen Species metabolism
- Abstract
Fluorinated analogues of propranolol, namely trifluoroethyl propranolol (F3), pentafluoropropyl propranolol (F5), and heptafluorobutyl propranolol (F7), were found to induce reactive oxygen metabolite (ROM) production in human neutrophils in a dose-dependent manner. Preincubation of neutrophils with the calcium chelator BAPTA-AM or the tyrosine kinase inhibitor genistein inhibited this ROM production. Direct measurements of intracellular calcium revealed that these analogues caused a transient increase in intracellular calcium. In addition, these fluorinated analogues of propranolol caused a transient increase in actin polymerization. The effects of these compounds were found to be dependent upon the degree of fluorination of the parent compound. Propranolol, on the other hand, had no direct effect on ROM, calcium, or actin polymerization when added alone to neutrophils, although it did modify responses of cells to various stimuli. Whereas ROM production induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was enhanced in a dose-dependent manner, the response to the particulate stimulus, latex beads, was abolished.
- Published
- 2001
- Full Text
- View/download PDF
41. Cultivar-specific IgE-epitopes in date (Phoenix dactylifera L.) fruit allergy. Correlation of skin test reactivity and ige-binding properties in selecting date cultivars for allergen standardization.
- Author
-
Kwaasi AA, Harfi HA, Parhar RS, Collison KS, Al-Sedairy ST, and Al-Mohanna FA
- Subjects
- Adult, Allergens chemistry, Allergens immunology, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Female, Food Hypersensitivity blood, Food Hypersensitivity epidemiology, Fruit immunology, Humans, Immunoblotting, Immunoglobulin E blood, Male, Molecular Weight, Plant Extracts analysis, Plant Extracts immunology, Saudi Arabia epidemiology, Skin Tests, Allergens analysis, Epitopes immunology, Food Hypersensitivity etiology, Fruit adverse effects, Immunoglobulin E immunology
- Abstract
Background: Date fruits are allergenic and standardized extracts are required for diagnosis and therapy of this allergy. Since there are several cultivars of dates, this study was carried out to assess the allergenicity of different cultivars in order to select suitable source material for standardization., Methods: The protein profiles of 18 of the most commonly sold varieties were compared by SDS-PAGE and their relative allergenicity assessed by SPT and IgE-based ELISA and immunoblotting. Thirty-two date fruit-sensitive patients were skin tested with a pooled extract from all the cultivars. Six of the patients with high SPT results (> or =3+) who volunteered were further tested with the 18 cultivars and their sera used in ELISA and immunoblotting., Results: Six of the cultivars gave high SPT-positive reactions in > or =4 of patients. Five of these high SPT-reactive cultivars gave high IgE ELISA scores (> or =0.58) but individual cultivars varied in their number of IgE immunoblot bands. Cultivar-specific IgE-binding patterns indicated that only certain cultivars bound IgE at molecular weights of < or =14.3 and 27-33 kDa whilst all cultivars bound to a 54-58 kDa doublet. Cultivars that bind to the < or =14.3 and 27-33 kDa bands appeared to form the majority of the high SPT-reactive cultivars. When individual sera of 24 of the 32 SPT-positive patients were used in IgE immunoblots with the pooled cultivar extract, all sera bound IgE at < or =14.3 and 27-33 kDa and about 60% of sera bound to a 54-58 kDa doublet bands., Conclusions: These results indicate that allergenicity of date fruits is a cultivar-specific phenomenon. Sixty to 100% of sera from date fruit-allergic patients bind IgE to three major allergens of < or =14.3, 27-33 and 54-58 kDa. Five of the cultivars that evoke high SPT reactions, high IgE ELISA scores and bind IgE to the major allergens, can be selected for the preparation of 'in-house' allergen extracts and for allergen standardization.
- Published
- 2000
- Full Text
- View/download PDF
42. Alpha-gal-independent dual recognition and activation of xenogeneic endothelial cells and human naïve natural killer cells.
- Author
-
Sheikh S, Parhar R, Kwaasi A, Collison K, Yacoub M, Stern D, and Al-Mohanna F
- Subjects
- Animals, Antibodies blood, Calcium metabolism, Cell Transplantation, Galactose immunology, Humans, Lymphocyte Activation drug effects, Papio, Sheep, Swine, Endothelium, Vascular cytology, Galactose pharmacology, Killer Cells, Natural cytology, Killer Cells, Natural transplantation, Transplantation, Heterologous pathology
- Abstract
Background: Interaction between vascularized xenograft and host immune system is thought to occur via Galactose alpha (1,3) Galactose (Gala 1,3 gal) structures decorating the xenograft., Methods: We raised anti-Gala 1,3 gal-BSA polyclonal antibodies in baboons and investigated effect(s) of these antibodies as well as soluble Gala 1,3 gal-BSA on human naive natural killer (NK) cell interactions with porcine aortic endothelial cells., Results: We demonstrate that human naive (unstimulated) NK cells recognize xenogeneic endothelial cells under conditions where binding to the Gala 1,3 gal structures is minimized by the presence of blocking anti-Gala 1,3 gal IgG or soluble Gala 1-3 gal and in the absence of xenoreactive natural antibodies and complement. After xenogeneic encounter both endothelial cells and human NK cells are activated. Endothelial cell activation is rapid and is manifested initially by an intraendothelial calcium transient and subsequently by expression of P-selectin and vascular endothelial cell adhesion molecule-1 on the xenoendothelium surface. NK cell activation is manifested by increased expression of perforin and increased cytotoxicity towards the xenoendothelium. Neither recognition nor activation of the xenoendothelium was affected by the introduction of either anti-Gala 1,3 gal IgG or soluble Gala 1-3 gal., Conclusion: Our data provide evidence that innate immune cells, such as NK cells, recognize and activate xenoendothelial cells independently of Gala 1-3 gal structures and raise the possibility of novel interactive sites on both human naive NK cells and discordant xenogeneic endothelium.
- Published
- 2000
- Full Text
- View/download PDF
43. Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human neutrophils.
- Author
-
Collison K, Saleh S, Parhar R, Meyer B, Kwaasi A, Al-Hussein K, Al-Sedairy S, and Al-Mohanna F
- Subjects
- Actins metabolism, Calcium physiology, Humans, Interleukin-12 metabolism, Neutrophil Activation drug effects, Neutrophils drug effects, Neutrophils immunology, Phosphorylation drug effects, Polymers metabolism, Protein Binding immunology, Signal Transduction drug effects, Tyrosine physiology, Calcium metabolism, Interleukin-12 physiology, Neutrophils metabolism, Signal Transduction immunology, Tyrosine metabolism
- Abstract
The cytokine IL-12 is proposed to play a bridging role between innate and adaptive immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This binding leads to a transient increase in 1) intracellular free calcium due to its release from membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by neutralizing Abs to IL-12. Inhibition of either calcium transient or tyrosine phosphorylation causes inhibition of reactive oxygen metabolite production. However, inhibition of actin polymerization enhances IL-12-induced oxidase activation. Our data suggest 1) a direct role for IL-12 in the activation of human neutrophils, and 2) a calcium-dependent signaling pathway for IL-12.
- Published
- 1998
44. Presence of leukemia inhibitory factor and interleukin-12 in human follicular fluid during follicular growth.
- Author
-
Coskun S, Uzumcu M, Jaroudi K, Hollanders JM, Parhar RS, and al-Sedairy ST
- Subjects
- Cells, Cultured, Chorionic Gonadotropin pharmacology, Female, Fertilization in Vitro, Granulosa Cells metabolism, Growth Inhibitors analysis, Humans, Infertility, Female therapy, Leukemia Inhibitory Factor, Lymphokines analysis, Ovarian Follicle metabolism, Pregnancy, Follicular Fluid metabolism, Growth Inhibitors biosynthesis, Interleukin-2 biosynthesis, Interleukin-6, Lymphokines biosynthesis
- Abstract
Problem: Cytokines have been shown to be present in human follicular fluid and have regulatory functions on follicular maturation. The presence of leukemia inhibitory factor (LIF) and interleukin (IL)-12 in human follicular fluid obtained at different stages of maturation was investigated., Method of Study: Follicular fluids and granulosa cells were obtained from preovulatory and immature follicles. Follicular fluids from both groups were assayed for IL-12 and LIF by enzyme-linked immunosorbent assay. Granulosa cells from preovulatory and immature follicles were treated with human chorionic gonadotropin (hCG) in vitro and subsequent LIF and IL-12 production were measured., Results: The average concentration of LIF was significantly higher in preovulatory follicles (7.6 +/- 1.3 pg/ml, n = 24) than in immature follicles (2.0 +/- 1.3 pg/ml, n = 6). The concentration of IL-12 was significantly higher in follicular fluid obtained from immature follicles (10.9 +/- 5.0 pg/ml) than in preovulatory follicles (1.3 +/- 0.4 pg/ml). hCG only stimulated LIF production from mature granulosa cells; it had no effect on IL-12 production., Conclusions: IL-12 and LIF are present in follicular fluid and their levels are regulated differently during follicular maturation. hCG stimulates LIF production from granulosa cells in vitro.
- Published
- 1998
- Full Text
- View/download PDF
45. Prostanoid production in the umbilicoplacental arterial tree relative to impaired glucose tolerance.
- Author
-
Saldeen P, Olofsson P, Parhar RS, and al-Sedairy S
- Subjects
- Cohort Studies, Culture Techniques, Diabetes Mellitus, Type 2 metabolism, Diabetes, Gestational metabolism, Female, Glucose Intolerance metabolism, Glucose Tolerance Test, Humans, Pregnancy, Pregnancy Trimester, Third, Reference Values, Umbilical Arteries anatomy & histology, Umbilical Arteries cytology, 6-Ketoprostaglandin F1 alpha biosynthesis, Diabetes Mellitus, Type 2 embryology, Diabetes, Gestational embryology, Glucose Intolerance embryology, Placenta blood supply, Thromboxane A2 biosynthesis, Umbilical Arteries metabolism
- Abstract
The purpose of this study was to investigate prostanoid synthesis in different segments of the umbilicoplacental vascular tree and its relationship to impaired maternal glucose tolerance. Segments from the umbilical artery and vein, allantochorionic artery branches, and the cotyledon artery from 21 women with diabetes or impaired glucose tolerance and 10 healthy women were studied. Production of prostacyclin (PGI2) and thromboxane (TxA2) metabolites was determined. The Mann-Whitney U test, Wilcoxon signed-ranks matched-pairs test, Kruskal-Wallis test, analysis of variance, and simple linear regression analysis were used. A two-tailed P value of < 0.05 was considered statistically significant. From the umbilical artery distal to the cotyledon artery, the PGI2 synthesis decreased and the TxA2 synthesis increased gradually towards the periphery in normal pregnancy. The PGI2/TxA2 ratio was more than 200 times higher in the umbilical artery than in the cotyledon artery. The TxA2 production tended in general to be higher in the diabetic group than in the control group, resulting in significantly lower PGI2/TxA2 ratios in some vessels. The prostanoid production was not significantly correlated to maternal HbA1c or cord C-peptide concentrations. The balance between vascular prostacyclin and thromboxane synthesis in the umbilicoplacental arterial tree changed gradually towards the periphery: the more peripheral, the lower the prostacyclin and the higher the thromboxane production. The physiological role of this phenomenon is unknown, but may be of importance for the equilibration of vascular tone between arteries of different calibers. The altered prostanoid balance found in diabetic pregnancy was not directly attributable to the degree of maternal glycemic control, but may reflect increased free radical activity and peroxide production in diabetes.
- Published
- 1998
- Full Text
- View/download PDF
46. The effect of antibodies against cell-surface adhesion molecules (LFA-1 alpha and ICAM-1) on the migration and localization of 99mTc-labeled leukocytes in acute infection.
- Author
-
Amartey JK, Parhar RS, and al-Sedairy ST
- Subjects
- Acute Disease, Animals, Antibodies immunology, Cell Movement, Female, Mice, Mice, Inbred CBA, Escherichia coli Infections diagnosis, Intercellular Adhesion Molecule-1 physiology, Leukocytes physiology, Lymphocyte Function-Associated Antigen-1 physiology, Technetium
- Abstract
The deficiency of adhesion molecules on leukocytes could severely impair their ability to migrate and perform effective immunological functions leading to clinical situation such as LAD (leukocyte adhesion deficiency) syndrome. We investigated the effects of blocking anti-LFA-1 alpha and ICAM-1 antibody-treated 99mTc-labeled leukocytes on the migration and localization to the site of E. coli-induced acute infection in CBA/J mice. A significant inhibition of migration and localization of antibody-treated leukocytes to the site of infection was observed, reaffirming the vital role of these adhesion molecules, especially during scintigraphic examination of patients for deep infections or abscess using labeled leukocytes.
- Published
- 1997
- Full Text
- View/download PDF
47. Activation of naive xenogeneic but not allogeneic endothelial cells by human naive neutrophils: a potential occult barrier to xenotransplantation.
- Author
-
al-Mohanna F, Collison K, Parhar R, Kwaasi A, Meyer B, Saleh S, Allen S, al-Sedairy S, Stern D, and Yacoub M
- Subjects
- Animals, Aorta cytology, Calcium metabolism, Cell Adhesion genetics, Cell Adhesion immunology, Cytotoxicity, Immunologic genetics, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Graft Rejection etiology, Graft Rejection genetics, Humans, Killer Cells, Natural immunology, Molecular Sequence Data, Sheep, Swine, Transplantation, Homologous, Umbilical Veins cytology, Endothelium, Vascular immunology, Neutrophils immunology, Transplantation, Heterologous adverse effects
- Abstract
Here we demonstrate that human neutrophils, the predominant circulating leukocytes in intimate contact with endothelial cells lining the vasculature, directly recognize xenogeneic endothelium independently of xenoreactive natural antibody and complement. A rapid and calcium-dependent activation of native (unstimulated) xenogenic endothelial cells by human neutrophils leads to 1) translocation of P-selectin from the Wiebel-Palade bodies to the surface of xenogeneic endothelial cells, 2) increased synthesis and expression of vascular cell adhesion molecule-1 on the xenogeneic endothelial cells, and 3) enhanced killing of the xenogeneic endothelium by natural killer cells. Our data directly implicate naive neutrophils as major early participants in xenograft recognition and endothelial activation independent of xenoreactive natural antibodies and complement.
- Published
- 1997
48. Prostanoid production in umbilical vessels and its relation to glucose tolerance and umbilical artery flow resistance.
- Author
-
Saldeen P, Olofsson P, Parhar RS, and al-Sedairy S
- Subjects
- C-Peptide metabolism, Drug Tolerance, Epoprostenol metabolism, Female, Fetal Blood metabolism, Glycated Hemoglobin metabolism, Humans, Laser-Doppler Flowmetry, Pregnancy, Pulsatile Flow, Thromboxane A2 metabolism, Pregnancy in Diabetics metabolism, Prostaglandins biosynthesis, Umbilical Arteries physiology, Umbilical Veins metabolism, Vascular Resistance
- Abstract
Objective: To study prostanoid synthesis in umbilical vessels relative to maternal glucose tolerance and umbilical artery blood flow resistance., Study Design: Umbilical artery pulsatility index was determined by Doppler velocimetry in 21 women with diabetes or impaired glucose tolerance and 10 healthy women. Segments from the umbilical artery and vein were incubated and prostacyclin (PGI2) and thromboxane (TxA2) metabolites determined. Statistical analyses with the Mann-Whitney U test, Kruskal-Wallis test, Wilcoxon signed-ranks matched-pairs test, contingency table analysis, Fisher's exact test, and simple linear regression analysis were used and a two-tailed P value of < 0.05 considered statistically significant., Results: No significant difference in PGI2 or TxA2 production was found in umbilical vessels between the women with diabetes/impaired glucose tolerance and controls, but the PGI2/TxA2 ratio in the vein was significantly lower in the diabetes/impaired glucose tolerance group. The umbilical artery pulsatility index was positively correlated to the PGI2/TxA2 ratio in cord vessel segments and to cord plasma TxA2 concentration. The cord plasma TxA2 concentration was significantly higher in cases with a high umbilical artery pulsatility index. The prostanoid production was not correlated to maternal HbA1c or cord plasma C-peptide concentrations., Conclusions: In association with diabetes, an increased 'peroxide vascular tone' and an enhanced 'endoperoxide shift' between platelets and vascular endothelium may explain the unexpected positive correlation found between the umbilical artery pulsatility index and the vascular PGI2/TxA2 synthesis ratio.
- Published
- 1996
- Full Text
- View/download PDF
49. Intrathymic inoculations of donor leukocytes evoke differential cellular immune responses during cardiac allogenic and xenogenic transplant.
- Author
-
Parhar RS, Fotopoulos V, Einspenner M, and al-Sedairy ST
- Subjects
- Animals, B-Lymphocytes immunology, Cricetinae, Hyaluronan Receptors biosynthesis, Immunity, Cellular, Immunosuppression Therapy methods, Intercellular Adhesion Molecule-1 biosynthesis, Lymphocyte Culture Test, Mixed, Lymphocyte Function-Associated Antigen-1 biosynthesis, Mesocricetus, Rabbits, Rats, Rats, Inbred WF, Rats, Sprague-Dawley, Receptors, Interleukin-2 biosynthesis, T-Lymphocytes immunology, Thymus Gland, Antilymphocyte Serum therapeutic use, Heart Transplantation immunology, Lymphocyte Transfusion, Transplantation, Heterologous immunology, Transplantation, Homologous immunology
- Published
- 1996
50. Pentoxifylline (PTX) selectively potentiates cyclosporine (CsA)-mediated suppression of cell-mediated lymphocytotoxicity. Median-effect analysis for the drug dose reductions in PTX and CsA combination treatment.
- Author
-
Khabar KS, Dzimiri M, Parhar RS, Siddiqui S, Einspenner M, Al-Humaidan A, and Al-Sediary ST
- Subjects
- Drug Synergism, Humans, Lymphocytes immunology, Cyclosporine pharmacology, Cytotoxicity, Immunologic drug effects, Immunosuppressive Agents pharmacology, Lymphocytes drug effects, Pentoxifylline pharmacology, Phosphodiesterase Inhibitors pharmacology
- Published
- 1996
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.