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6. Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan

Author

Khan,W., Rahman,A., Zaman,S., Kabir,M., Khan,R., Ali,W., Ahmad,S., Shabir,S., Jamil,S., and Ríos-Escalante,P. De los

Subjects
mosquito born viral disease, dengue fever, awareness, viral infection, endemic disease
Abstract

Dengue fever (DF) is increasingly recognized as one of the world’s major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Published
2023

7. Nonlinear radiative oblique stagnation point flow of viscoelastic fluid due to stretching cylinder with polymer processing applications.

Author

Abbasi, A., Farooq, W., Ghachem, Kaouther, Shabir, S., Elmonser, Hedi, Khan, Sami Ullah, and Kolsi, Lioua

Subjects
STAGNATION flow, STAGNATION point, VISCOELASTIC materials, FLUID flow, NON-Newtonian fluids, FINITE difference method
Abstract

The viscoelastic materials are a famous subclass of non-Newtonian fluids that present novel applications in various industrial processes. The most famous applications of viscoelastic fluid are observed in polymer processing. A major activity of the polymer processing industry is the production of thermoplastic polymer sheets and films. However, due to distinct rheology, a complete understanding of such materials is quite necessary for the polymer process. This continuation presents the rheological features of viscoelastic fluid with heat transfer phenomenon near the oblique stagnation point flow. The induced flow is accounted via stretched cylinder. The heat transfer analysis is also taken in the presence of non-linear heat flux. The problem is formulated using cylindrical coordinates in terms of non-linear coupled partial differential equations. Similarity transformation and normalized variables are used to convert the governing system into a set of ordinary differential equations. Due to the highly nonlinear model, the analytical solution of the system seems to be impossible therefore the approximate solution is obtained using the numerically stable and convergent finite difference method known as the Keller Box scheme. The simulated data via numerical algorithm is verified after comparing with already published investigations. The streamlines for the flow problem are presented. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases.

Author

Zhang, X, Singh, MP, Chakrabarty, R, Shabir, S, Yousuf, S, Obaid, AA, Moustafa, M, Al-Shehri, M, Al-Emam, A, Alamri, AS, Alsanie, WF, Alhomrani, M, Shkodina, AD, Singh, SK, Zhang, X, Singh, MP, Chakrabarty, R, Shabir, S, Yousuf, S, Obaid, AA, Moustafa, M, Al-Shehri, M, Al-Emam, A, Alamri, AS, Alsanie, WF, Alhomrani, M, Shkodina, AD, and Singh, SK

Abstract

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

Published
2022

12. Conhecimento, atitude e práticas em relação à dengue e seu vetor entre médicos na região de Malakand, Paquistão

Author

Khan, W., Rahman, A., Zaman, S., Kabir, M., Khan, R., Ali, W., Ahmad, S., Shabir, S., Jamil, S., and Ríos-Escalante, P. De los

Subjects
doença endêmica, mosquito born viral disease, dengue fever, conscientização, awareness, viral infection, doença viral transmitida por mosquito, dengue, endemic disease, infecção viral
Abstract

Dengue fever (DF) is increasingly recognized as one of the world’s major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control. Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

Published
2022

23. Fewer adverse events after reoperative parathyroidectomy associated with initial minimally invasive parathyroidectomy

Author

Nancy D. Perrier, James W. Suliburk, Lilah F. Morris, Carla L. Warneke, Elizabeth G. Grubbs, Minerva A. Romero Arenas, Jeffrey E. Lee, Shabir S. Abadin, and Sukhyung Lee

Subjects
Reoperation, Parathyroidectomy, medicine.medical_specialty, medicine.medical_treatment, Logistic regression, Postoperative Complications, medicine, Humans, Minimally Invasive Surgical Procedures, Adverse effect, Retrospective Studies, business.industry, General Medicine, Odds ratio, Hyperparathyroidism, Primary, medicine.disease, Confidence interval, Surgery, Logistic Models, Treatment Outcome, business, Complication, Body mass index, Primary hyperparathyroidism, Follow-Up Studies
Abstract

Background This study compared reoperative complication rates after initial minimally invasive parathyroidectomy and standard cervical exploration. Methods Records from patients who underwent 1 reoperative parathyroidectomy at a single institution (1998 to 2012) were retrospectively reviewed. Results Seventy-seven patients were included; 74% underwent initial standard cervical exploration. Preoperative and operative characteristics were similar between groups; 74% underwent focused, unilateral reoperation. A significantly higher rate of postoperative complications occurred in the initial standard cervical exploration group (42% vs 15%, P = .03) that could not be explained by differences in the rates of symptomatic hypocalcemia ( P = .5). The type of prior parathyroidectomy was significantly associated with postoperative complications (odds ratio 4.1, 95% confidence interval 1.1 to 15.7, P = .04). In a multivariable logistic regression model that included body mass index, type of operation (for initial and reoperation), and initial operation performed prereferral as covariates, type of prior parathyroidectomy remained a significant predictor of postoperative complications. Conclusion Higher rates of postoperative sequelae after initial standard cervical exploration should be considered before performing routine 4-gland exploration.

Published
2014

24. S02. Pre-Implantation Genetic Diagnosis (PGD) in Ireland - from validation to introduction of a clinical service

Author

Morrison, PJ, Campbell, E, Kennedy, F, Russell, A, Smithson, WH, Parsons, L, Liggan, B, Irwin, B, Delanty, N, Hunt, SJ, Craig, J, Morrow, J, Dineen, T, Zhang, X, Flanagan, J, Kovacs, A, Mihart, R, O'Callaghan, J, Culligan, J, Daly, N, Waterstone, J, Magee, AC, Stewart, FJ, Dabir, TA, McConachie, M, McCoubrey, A, McConnell, VPM, Stack, D, O'Meara, E, Phelan, S, McDonagh, N, Kelly, L, Sciot, R, Debiec-Rychter, M, Morris, T, Cochrane, D, Sorensen, P, O'Sullivan, MJ, O'Byrne, JJ, Sweeney, M, Donnelly, D, Lambert, D, Beattie, D, Gervin, C, Graham, CA, Barton, DE, Lynch, SA, Whelan, CD, Hibar, DP, Stein, JL, Speed, D, Sisodiya, S, Ohnson, M, Goldstein, D, Medland, SE, Ranke, B, Thompson, PM, Cavalleri, G, Coleman, C, Quinn, EM, Ryan, AW, Anney, RJL, Trimble, V, Morris, DW, Donohoe, G, Conroy, J, Trynka, G, Wijmenga, C, Ennis, S, McManus, R, O'Halloran, ET, Magalhaes, TR, Cole, A, Cox, S, Jeong, C, Witonsky, D, Robbins, P, Montgomery, H, Ota, M, Hanaoka, M, Droma, Y, Beall, CM, Rienzo, A Di, Casey, J, McGettigan, P, Crushell, E, Hughes, J, Smyth, LJ, Kilner, JK, Benson, KA, Maxwell, AP, McKnight, AJ, Donnelly, DE, Jeffers, L, Hampton, S, Baillie, N, Cooke, S, O'Connell, SM, McDonald, A, O'Toole, N, Bradfield, A, Bradley, M, Hattersley, A, Ellard, S, Proks, P, Mattis, KK, Ashcroft, F, O'Riordan, SMP, Coyle, D, McDermott, M, O'Sullivan, M, Roche, E, Quinn, F, Cody, D, MacMahon, JM, Morrissey, R, Green, A, Thompson, AR, Kulkarni, A, Marks, KJ, Snape, K, Taylor, R, Bradley, L, Ramachandrappa, S, Pinto, CF, Dabir, T, Logan, P, Liew, S., Znaczko, A, Ryan, H., McDevitt, T, Higgins, M, Crowley, A, Rogers, M, Geoghegan, S, Shorto, J, Ramsden, S, O'Riordan, MP, Moore, M, Murphy, M, Irvine, A, Znaczko, Anna, Wilson, A, Stewart, F, Cather, MH, Young, IS, Nicholls, DP, O'Kane, M, Sharpe, P, Hanna, E, Hart, PJ, Savage, N, Humphreys, MW, Shaw-Smith, C, Osio, D, Collinson, MN, McKee, S, McNerlan, S, McGorrian, C, Galvin, J, O'Byrne, J, Stewart, S, Heggarty, SV, Hegarty, SP, McConnell, V, Turner, J, Ward, A, Kelly, R, Joyce, C, ó hIcí, B, Meaney, K, Gibson, L, Kelly, PM, Costigan, C, Gul, R, Byrne, S, Hughes, L, Ozaki, M, O'Sullivan, F, Parle-McDermott, A, Heavin, SB, McCormack, M, Slattery, L, Walley, N, Avbersek, A, Novy, J, Sinha, S, S, Alarts, N, Legros, B, Radtke, R., Sisodiya, Depondt, C, Cavalleri, GL, Connolly, S, Heron, EA, Irvine, MAG, Hughes, AE, Darlow, JM, Darlay, R, Hunziker, M, Kutasy, B, Green, AJ, Cordell, H, Puri, P, Chand, S, McCaughan, JA, Shabir, S, Chan, W, Kilner, J, Borrows, R, Douglas, AP, O'Neill, T, Shepherd, C, Hardy, R, Kenny, Molloy, B, Freeley, M, Quinn, E, McGinn, R, Long, A, Gahan, JM, Connolly, E, Byrne, MM, Gray, SG, Murphy, RT, Gui, H, Heinzen, E, Goldstein, D B, Petrovski, S, O'Brien, TJ, Cherny, S, Sham, PC, Baum, L, Duffy, S, Catherwood, N, McVeigh, TP, Sweeney, KJ, Miller, N, Kerin, MJ, and Weidhaas, JB

Subjects
Poster Presentations, Abstracts, Spoken Papers
Published
2014

25. Novel Statistically Designed Qbd Methodology for Quantitative Analysis of Nisoldipine in Pharmaceutical Dosage Forms

Author

Permender R, Anjoo K, and Shabir S

Subjects
Factorial, Bromocresol green, Operations research, Correlation coefficient, Factorial experiment, Quality by Design, Dosage form, chemistry.chemical_compound, Taguchi methods, chemistry, Statistics, medicine, Nisoldipine, Mathematics, medicine.drug
Abstract

The objective of the study was to develop superlative reproducible spectrophotometric estimation process of Nislodipine via BCG (Bromocresol green) solution using novel statistically Taguchi via factorial design methodology. Primarily, an L9 design array was experimented to find significant analytical variables and optimize their(s) best levels keeping drug amount constant. Additionally factorial i.e. Box-Behnken design (BBD) of better factors (X, Y & Z) levels at positive, null and negative spaces responses (R=absorbance) was studied to found better to best level. Moreover, polynomial quadratic equations for two and three dimensional models were designed to predict the best significant independent levels. The selected variable responses were statistically evaluated using ANOVA and showed correlation coefficient (r2=0.999) followed by good Beer’s (5-40 μg/ml) range at maximum absorption wavelength (420 nm) and was validated according to ICH guidelines. This robust novel statistically designed strategy can be considered as quality by design (QbD) quantitative methodology for Nisoldipine estimation in pharmaceutical’s.

Published
2016

26. The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

Author

Smalla, K.-H., Matthies, H., Langnase, K., Shabir, S., Bockers, T.M., Wyneken, U., Staak, S., Krug, M., Beesley, P. W., and Gundelfinger, E. D.

Subjects
Glycoproteins -- Research, Biochemistry -- Research, Prosencephalon -- Physiological aspects, Proteins -- Research, Neuroplasticity -- Analysis, Immunocytochemistry -- Analysis, Science and technology
Abstract

Neuroplastin-65 and -55 (previously known as gp65 and gp55) are glycoproteins of the Ig superfamily that are enriched in rat forebrain synaptic membrane preparations. Whereas the two-Ig domain isoform neuroplastin-55 is expressed in many tissues, the three-lg domain isoform neuroplastin-65 is brain-specific and enriched in postsynaptic density (PSD) protein preparations. Here, we have assessed the function of neuroplastin in long-term synaptic plasticity, Immunocytochemical studies with neuroplastin-65-specific antibodies differentially stain distinct synaptic neuropil regions of the rat hippocampus with most prominent immunoreactivity in the CA1 region and the proximal molecular layer of the dentate gyrus. Kainate-induced seizures cause a significant enhancement of neuroplastin-65 association with PSDs, Similarly, long-term potentiation (LTP) of CA1 synapses in hippocampal slices enhanced the association of neuroplastin-65 with a detergent-insoluble PSD-enriched protein fraction. Several antibodies against the neuroplastins, including one specific for neuroplastin-65, inhibited the maintenance of LTP. A similar effect was observed when recombinant fusion protein containing the three extracellular Ig domains of neuroplastin-65 was applied to hippocampal slices before LTP induction. Microsphere binding experiments using neuroplastin-[F.sub.c] chimeric proteins show that constructs containing Ig1-3 or Ig1 domains, but not Ig2-3 domains mediate homophilic adhesion. These data suggest that neuroplastin plays an essential role in implementing long-term changes in synaptic activity, possibly by means of a homophilic adhesion mechanism.

Published
2000

34. Interstitial Fibrosis and Tubular Atrophy (IFTA), Antibody Mediated Rejection (ABMR) and Recurrent Disease as the Major Causes of Late Renal Allograft Loss.

Author

Horgan, P., primary, Huhn, L., additional, Atkinson, D., additional, Chand, S., additional, Shabir, S., additional, Krishnan, H., additional, Robinson, K., additional, Williams, A., additional, Ball, S., additional, Neill, D., additional, Skordilis, K., additional, Vydianath, B., additional, Briggs, D., additional, McCloskey, M., additional, and Borrows, R., additional

Published
2014
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42. Transplantation: clinical studies

Author

Crespo, M., primary, Collado, S., additional, Mir, M., additional, Hurtado, S., additional, Cao, H., additional, Barbosa, F., additional, Serra, C., additional, Hidalgo, C., additional, Faura, A., additional, Garcia de Lomas, J., additional, Montero, M., additional, Horcajada, J. P., additional, Puig, J. M., additional, Pascual, J., additional, Ulusal Okyay, G., additional, Uludag, K., additional, Sozen, H., additional, Arman, D., additional, Dalgic, A., additional, Guz, G., additional, Fraile, P., additional, Garcia-Cosmes, P., additional, Rosado, C., additional, Gonzalez, C., additional, Tabernero, J. M., additional, Costa, C., additional, Saldan, A., additional, Astegiano, S., additional, Terlizzi, M. E., additional, Messina, M., additional, Bergallo, M., additional, Segoloni, G., additional, Cavallo, R., additional, Schwarz, A., additional, Grosshennig, A., additional, Heim, A., additional, Broecker, V., additional, Haller, H., additional, Linnenweber, S., additional, Liborio, A. B., additional, Mendoza, T. R., additional, Esmeraldo, R. M., additional, Oliveira, M. L. M. B., additional, Nogueira Paes, F. J. V., additional, Silva Junior, G. B., additional, Daher, E. F., additional, Hodgson, K., additional, Baharani, J., additional, Fenton, A., additional, Mjoen, G., additional, Hartmann, A., additional, Reisaeter, A., additional, Midtvedt, K., additional, Dahle, D. O., additional, Holdaas, H., additional, Shabir, S., additional, Lukacik, P., additional, Bevins, A., additional, Basnayake, K., additional, Bental, A., additional, Hughes, R. G., additional, Cockwell, P., additional, Burrows, R., additional, Hutchison, C. A., additional, Varma, P., additional, Kumar, A., additional, Hooda, A., additional, Badwal, S., additional, Barrios, C., additional, Crespo, M., additional, Fumado, L., additional, Frances, A., additional, Arango, O., additional, Pawlik, A., additional, Chudek, J., additional, Kolonko, A., additional, Wilk, J., additional, Jalowiecki, P., additional, Wiecek, A., additional, Teplan, V., additional, Kralova-Lesna, I., additional, Mahrova, A., additional, Racek, J., additional,  tollova, M., additional, Maggisano, V., additional, Caracciolo, V., additional, Solazzo, A., additional, Montanari, M., additional, Della Grotta, F., additional, Nakazawa, D., additional, Nishio, S., additional, Nakagaki, T., additional, Ishikawa, Y., additional, Ito, M., additional, Shibazaki, S., additional, Shimoda, N., additional, Miura, M., additional, Morita, K., additional, Nonomura, K., additional, Koike, T., additional, Locsey, L., additional, Seres, I., additional, Sztanek, F., additional, Harangi, M., additional, Padra, J., additional, Asztalos, L., additional, Paragh, G., additional, Rodriguez-Reimundes, E., additional, Soler-Pujol, G., additional, Diaz, C. H., additional, Davalos-Michel, M., additional, Vilches, A. R., additional, Laham, G., additional, Stavem, K., additional, Norby, G., additional, Tutal, E., additional, Canver, B., additional, Can, S., additional, Sezer, S., additional, Colak, T., additional, Paschoalin, R., additional, Barros, X., additional, Duran, C., additional, Torregrosa, J. V., additional, Tellez, E., additional, Marin, M., additional, Smalcelj, R., additional, Smalcelj, A., additional, Claes, K., additional, Petit, T., additional, Bammens, B., additional, Kuypers, D., additional, Naesens, M., additional, Vanrenterghem, Y., additional, Evenepoel, P., additional, Gerhart, M. K., additional, Colbus, S., additional, Seiler, S., additional, Grun, O., additional, Fliser, D., additional, Heine, G. H., additional, Vincenti, F., additional, Grinyo, J., additional, Larsen, C., additional, Medina Pestana, J., additional, Dong, Y., additional, Thomas, D., additional, Charpentier, B., additional, Luna, E., additional, Martinez, R., additional, Cerezo, I., additional, Ferreira, F., additional, Cubero, J., additional, Villa, J., additional, Martinez, C., additional, Garcia, C., additional, Rodrigo, E., additional, Santos, L., additional, Pinera, C., additional, Quintela, E., additional, Ruiz, J. C., additional, Fernandez-Fresnedo, G., additional, Palomar, R., additional, Gomez-Alamillo, C., additional, Martin de Francisco, A. L., additional, Arias, M., additional, Nainan, G., additional, del Carmen Rial, M., additional, Steinberg, S., additional, Kamar, N., additional, Durrbach, A., additional, Becker, T., additional, Florman, S., additional, Lang, P., additional, Schnitzler, M., additional, Duan, T., additional, Block, A., additional, Sawosz, M., additional, Cieciura, T., additional, Durlik, M., additional, Perkowska, A., additional, Sikora, P., additional, Beck, B., additional, De Mauri, A., additional, Brambilla, M., additional, Stratta, P., additional, Chiarinotti, D., additional, De Leo, M., additional, Attou, S., additional, Arzour, H., additional, Boudrifa, N., additional, Mekhlouf, N., additional, Gaouar, A., additional, Merazga, S., additional, Kalem, K., additional, and Haddoum, F., additional

Published
2011
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48. Cytomegalovirus-Associated CD4+CD28nullCells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction

Author

Shabir, S., Smith, H., Kaul, B., Pachnio, A., Jham, S., Kuravi, S., Ball, S., Chand, S., Moss, P., Harper, L., and Borrows, R.

Abstract

Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4+T cells lacking costimulatory CD28 (CD4+CD28nullcells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4+CD28nullcells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4+CD27−CD28nullcells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4+CD28nullcell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4+CD28nullcell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes.

Published
2016
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49. The importance of Rho-associated kinase-induced Ca2+ sensitization as a component of electromechanical and pharmacomechanical coupling in rat ureteric smooth muscle.

Author

Borysova, Lyudmyla, Shabir, S., Walsh, Michael P., and Burdyga, Theodor

Subjects
PROTEIN kinases, CALCIUM, URETERS, SMOOTH muscle, LABORATORY rats, MUSCLE contraction, URODYNAMICS, CELLULAR signal transduction, PHOSPHORYLATION
Abstract

Abstract: Ureteric peristalsis, which occurs via alternating contraction and relaxation of ureteric smooth muscle, ensures the unidirectional flow of urine from the kidney to the bladder. Understanding of the molecular mechanisms underlying ureteric excitation–contraction coupling, however, is limited. To address these knowledge deficits, and in particular to test the hypothesis that Ca2+ sensitization via activation of the RhoA/Rho-associated kinase (ROK) pathway plays an important role in ureteric smooth muscle contraction, we carried out a thorough characterization of the electrical activity, Ca2+ signaling, MYPT1 (myosin targeting subunit of myosin light chain phosphatase, MLCP) and myosin regulatory light chain (LC20) phosphorylation, and force responses to membrane depolarization induced by KCl (electromechanical coupling) and carbachol (CCh) (pharmacomechanical coupling). The effects of ROK inhibition on these parameters were investigated. We conclude that the tonic, but not the phasic component of KCl- or CCh-induced ureteric smooth muscle contraction is highly dependent on ROK-catalyzed phosphorylation of MYPT1 at T855, leading to inhibition of MLCP and increased LC20 phosphorylation. [Copyright &y& Elsevier]

Published
2011
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50. Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative histomorphometric assessment and serum creatinine.

Author

Day CJ, Howie AJ, Nightingale P, Shabir S, Adu D, Savage CO, Hewins P, Day, Clara J, Howie, Alec J, Nightingale, Peter, Shabir, Shazia, Adu, Dwomoa, Savage, Caroline O, and Hewins, Peter

Abstract

Background: Clinical and pathologic features that predict outcome have important potential application in patients with pauci-immune necrotizing glomerulonephritis (usually antineutrophil cytoplasmic antibody-associated vasculitis). This study examines the predictive value of simple quantitative renal histologic measurements in a large cohort with extended follow-up.Study Design: Cohort study.Setting& Participants: 390 consecutive patients with pauci-immune necrotizing glomerulonephritis at a single hospital (1983-2002); 90 patients underwent repeated kidney biopsy during follow-up.Predictors: Age and serum creatinine concentration at biopsy, antineutrophil cytoplasmic antibody specificity, percentage of normal glomeruli, percentage of glomeruli with active lesions, and index of chronic damage (quantitative measurement of established cortical damage) in the initial kidney biopsy for all patients. The same factors were assessed in both biopsy specimens for patients undergoing an additional biopsy.Outcomes& Measurements: End-stage renal disease and patient survival.Results: Mortality at 1 and 5 years was 23% and 40%, respectively: standardized mortality ratio, 4.74 (95% CI, 3.62-6.32). End-stage renal disease was reached by 14% and 18% at 1 and 5 years, respectively. In multivariable analysis, serum creatinine level at biopsy and percentage of normal glomeruli in the initial biopsy specimen were the best predictors of kidney survival. C Statistics were 0.80 for creatinine level alone and 0.83 for creatinine level with normal glomeruli. In patients undergoing an additional biopsy, rapid progression in the index of chronic damage and serum creatinine level at the second biopsy were associated with kidney survival in multivariable analysis.Limitations: Retrospective analysis. External validity of the index of chronic damage requires further assessment. Selection bias may influence repeated biopsy analyses.Conclusions: Serum creatinine level at biopsy best predicts kidney survival in patients with pauci-immune necrotizing glomerulonephritis overall. [ABSTRACT FROM AUTHOR]

Published
2010
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