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Stem cell treatment improves post stroke neurological outcomes:a comparative study in male and female rats

Stroke & Vascular Neurology 2021年第4期6卷 519-527,I0005-I0010页

作者： Koteswara Rao Nalamolu Bharath Chelluboina Casimir A Fornal Siva Reddy Challa david M Pinson david Z Wang jeffrey d klopfenstein Krishna Kumar Veeravalli Cancer Biology and Pharmacology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Pharmaceutical and Biomedical Sciences California Health Sciences UniversityClovisCaliforniaUSA Neurological Surgery University of Wisconsin-MadisonMadisonWisconsinUSA Health Sciences Education College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology Barrow Neurological InstitutePhoenixArizonaUSA Neurosurgery College of MedicineUniversity of IllinoisPeoriaIllinoisUSA OSF HealthCare Illinois Neurological Institute PeoriaIllinoisUSA Pediatrics College of MedicineUniversity of IllinoisPeoriaIllinoisUSA

Background and purpose The therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat *** results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells(MSC)in a rodent stroke *** hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females,despite any apparent sex differences in post stroke brain *** Transient focal cerebral ischaemia was induced in adult Sprague-dawley rats by occlusion of the middle cerebral *** the procedure,male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue *** groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests(Modified Neurological Severity Score assessment,adhesive tape removal,beam walk and rotarod).The tests were administered at regular intervals(at days 1,3,5,7 and 14)after reperfusion to determine the time course of neurological and functional recovery after *** The infarct volume and extent of swelling of the ischaemic brain were similar in males and *** similar pathological stroke lesions,the clinical manifestations of stroke were more pronounced in males than females,as indicated by the neurological scores and other *** treatment significantly improved the recovery of sensory and motor function in both sexes,and it demonstrated efficacy in both moderate stroke(females)and severe stroke(males).Conclusions despite sex differences in the severity of post stroke outcomes,MSC treatment promoted the recovery of sensory and motor function in male and female rats,suggesting that it may be a promising treatment for stroke.

关键词： neurological female rats

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Post-stroke mRNA expression profile of MMPs:effect of genetic deletion of MMP-12

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Stroke & Vascular Neurology 2018年第3期3卷 153-159页

作者： Koteswara Rao Nalamolu Bharath Chelluboina Ian B Magruder diane N Fru Adithya Mohandass Ishwarya Venkatesh jeffrey d klopfenstein david M Pinson Krishna M Boini Krishna Kumar Veeravalli department of Cancer Biology and Pharmacology University of Illinois College of MedicinePeoriaIllinoisUSA department of Neurosurgery University of Illinois College of MedicinePeoriaIllinoisUSA Comprehensive Stroke Center Illinois Neurological InstituteOSF HealthCare SystemSaint Francis Medical CenterPeoriaIllinoisUSA department of Pathology University of Illinois College of MedicinePeoriaIllinoisUSA department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTexasUSA department of Neurology University of Illinois College of MedicinePeoriaIllinoisUSA

background and purpose Recent reports from our laboratory demonstrated the post-ischaemic expression profile of various matrix metalloproteinases(MMPs)in rats and the detrimental role of MMP-12 in post-stroke brain *** hypothesise that the post-stroke dysregulation of MMPs is similar across species and that genetic deletion of MMP-12 would not affect the post-stroke expression of other *** tested our hypothesis by determining the pre-ischaemic and post-ischaemic expression profile of MMPs in wild-type and MMP-12 knockout *** Focal cerebral ischaemia was induced in wildtype and MMP-12 knockout mice by middle cerebral artery occlusion procedure by insertion of a monofilament *** hour after ischaemia,reperfusion was initiated by removing the *** day after reperfusion,ischaemic brain tissues from various groups of mice were collected,and total RNA was isolated and subjected to cdNA synthesis followed by PCR *** Although the post-stroke expression profile of MMPs in the ischaemic brain of mice is different from rats,there is a clear species similarity in the expression of MMP-12,which was found to be predominantly upregulated in both ***,the post-stroke induction or inhibition of various MMPs in MMP-12 knockout mice is different from their respective expression profile in wild-type ***,the brain mRNA expression profile of various MMPs in MMP-12 knockout mice under normal conditions is also different to their expression in wild-type *** In the ischaemic brain,MMP-12 upregulates several fold higher than any other *** derived with the genetic deletion of MMP-12 are constitutive and have altered MMP expression profile both under normal and ischaemic conditions.

关键词： MMPs removing hypothesis

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Hematological changes during androgen deprivation therapy

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Asian Journal of Andrology 2012年第2期14卷 187-192页

作者： Mathis Grossmann jeffrey d Zajac department of Medicine Austin Health/Northern Health University of Melbourne Heidelberg Vic. 3084 Australia

Androgen deprivation therapy （AdT） has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of AdT is the development of anemia. Although anemia caused by AdT is rarely severe, AdT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. AdT-associated anemia may contribute to fatigue and reduced quality of life （QoL） in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of AdT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of AdT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the weli-descrihed actions of AdT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving AdT require further studies.

关键词： anemia androgen deprivation therapy (AdT) prostate cancer

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Pressure vessel priming analysis for a regulated liquid propulsion system

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Propulsion and Power Research 2020年第2期9卷 101-115页

作者： jeffrey d.Moore The Pennsylvania State University Altoona CollegeAltoonaPA16601USA

An investigation was performed to determine the pressure transient levels and time required to reach pressure equilibrium in a regulated liquid propulsion system due to the priming of a propellant tank during system *** experimental fluid flow test setup was designed and fabricated using a pressure vessel to house distilled water as a propellant simulant for liquid hydrazine and high-pressure gaseous nitrogen as the pressurant.A snubber orifice was installed downstream of the high-pressure gaseous nitrogen bottles to protect a regulator from high-pressure transients,prior to the regulation of incoming gas to beginning of life propulsion system propellant tank *** were conducted to measure pressure transients and time to pressure equilibrium by varying initial system pressures,snubber orifice diameter,and system ullage volume.A mathematical model was developed and compared against the experimental regulated system priming results to predict the system pressures and time to reach system pressure equilibrium during the pressurization period for regulated propulsion systems given initial conditions.

关键词： Priming event Regulated liquid propulsion system Pressure vessel Pressure transients Snubber orifice

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Src Is dephosphorylated at Tyrosine 530 in Human Colon Carcinomas

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Chinese Journal of Cancer Research 2011年第3期23卷 229-231页

作者： jeffrey d Bjorge donald J Fujita department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research InstituteUniversity of Calgary

Objective：Src is a protein tyrosine kinase that plays important roles in cancer development,and Src kinase activity has been found to be elevated in several types of ***,the cause of the elevation of Src kinase activity in the majority of human colon carcinomas is still largely *** aim at finding the cause of elevated Src kinase activity in human colon ***：We employed normal colon epithelial FHC cells and examined Src activation in human colon carcinoma specimens from 8 *** expression levels were determined by Western blotting,and the activity of Src kinase by kinase ***：Actin levels were different between tumor and normal tissues,demonstrating the complexities and inhomogeneities of the tissue *** kinase activities were increased in the majority of the colon carcinomas as compared with normal colon epithelial cells （range 13-29）.Src protein levels were reduced in the colon *** Y530 phosphorylation levels were reduced to a higher extent than protein levels in the ***：The results suggest that Src specific activities were highly increased in human colon carcinomas;phosphorylation at Src Y530 was reduced,contributing to the highly elevated Src specific activity and Src kinase activity.

关键词： Src Kinase activation dephosphorylation Colon carcinoma

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Human androgen deficiency： insights gained from androgen receptor knockout mouse models

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Asian Journal of Andrology 2014年第2期16卷 169-177,I0006页

作者： Kesha Rana Rachel A davey jeffrey d Zajac department of Medicine Austin Health University of Melbourne Heidelberg Victoria Australia.

The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.

关键词： androgen receptor androgen receptor knockout mouse model androgen deficiency

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卒中后基质金属蛋白酶的mRNA表达情况：基质金属蛋白酶-12基因敲除的作用

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英国医学杂志中文版 2018年第5期21卷 297-297页

作者：毛晨晖(译) 北京协和医院神经科

背景和目的我们实验室最近的报告显示大鼠缺血后各种基质金属蛋白酶（MMPs）的表达情况以及MMP-12住卒中后脑损伤中的有害作用。我们假设卒中后MMPs调节功能障碍在不同物种间类似存在。

关键词：卒中后基质金属蛋白酶蛋白酶-12基因

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Generalized megaviscera of lupus:Refractory intestinal pseudo-obstruction,ureterohydronephrosis and megacholedochus

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World Journal of Gastroenterology 2009年第28期15卷 3555-3559页

作者： Frederick d Park jeffrey K Lee Ganga d Madduri Pradipta Ghosh department of Medicine University of California San Diego San Diego California 92103 United States division of Gastroenterology and Hepatology University of California San Diego San Diego California92103 United States

dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus （SLE）. Chronic intestinal pseudoobstruction （CIPO） resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation （megacholedochus）. While the molecular pathogenesis is largely unknown, observed histopathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis. High dose immunosuppression usually results in resolution of symptoms with recovery of smooth muscle function, indicative of an autoimmune etiology. We report a patient with SLE who presented with intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus, and present images that illustrate megaviscera simultaneously involving all 3 visceral organs. Since the co-manifestation of all 3 is unusual and has been reported only once previously, we have termed this rare clinical syndrome generalized megaviscera of lupus （GML）. Although the SLE disease-activity parameters responded to aggressive immunomodulative therapy in our patient, clinical evidence of peristaltic dysfunction persisted in all involved viscera. This is a variation from the favorable outcomes reported previously in SLE patients with GML and we attribute this poor clinical outcome to disease severity and, most importantly, delayed clinical presentation. Since inflammation followed by atrophy and fibrosis are key aspects in the pathogenesis and natural history of GML, the poor response in our patient who presented late in the clinical course may be the result of ＇burnt out＇ inflammation with irreversible end-stage fibrosis. Thus, early recognition and timely initiation of treatment may be the key to recover visceral peristaltic function in patients with GML.

关键词： Systemic lupus erythematosus Intestinalpseudo-obstruction Biliary tract diseases Hydroureter Hydronephrosis Smooth muscle Autoimmune myositis

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Stability of Two Conservative,High-Order Fluid-Fluid Coupling Methods

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Advances in Applied Mathematics and Mechanics 2019年第6期11卷 1287-1338页

作者： jeffrey M.Connors Robert d.dolan University of Connecticut Department of MathematicsStorrsCT 06269USA

This paper investigates two methods of coupling fluids across an interface,motivated by air-sea interaction in application *** method is for sequential configurations,where the air code module in invoked over some time interval prior to the sea *** other method is for concurrent setups,in which the air and sea modules run in *** focus is the temporal representation of air-sea *** methods we study conserve moments of the fluxes,with an arbitrary order of accuracy possible in *** step sizes are allowed for the two fluid *** a posteriori stability indicator is defined,which can be computed efficiently on-the-fly over each coupling *** a model of two coupled fluids with natural heat convection,using finite elements in space,we prove the sufficiency of our stability *** certain conditions,we also prove that stability can be enforced by iteration when the coupling interval is small *** particular,for solutions in a certain class,we show that the step size scaling is no worse than O(h)in three dimensions of space,where Oh is a mesh *** is a sharper result than what has been shown previously for related algorithms with finite element *** examples illustrate the behavior of the algorithms under a wide variety of configurations.

关键词： Air-sea atmosphere-ocean fluid-fluid partitioned time stepping conservative coupling

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Strengthening nanocomposite magnetism through microemulsion synthesis

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Nano Research 2018年第8期11卷 4133-4141页

作者： Yijun xie Alexandre H. Vincent Haeun Chang jeffrey d. Rinehart Materials Science and Engineering Program University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA department of Chemistry and Biochemistry University of Cafifomia San Diego 9500 Gilman Drive La Jolla CA 92093 USA

The magnetic strength and versatility of heterostructures generated via a simple microemulsion cluster-formation technique is demonstrated. This approach allows optimization of individual component magnetic nanoparticles prior to heterostructuring, expediting the discovery and optimization of hybrid magnetic materials. The efficacy of this method is validated through a magnetic study of nanoparticle clusters combining antiferromagnetic CoO and superparamagnetic CoFe204 nanoparticles with tunable particle ratio and size. An enhancement of coercivity compared with pure CoFe204 nanoparticles indicates that close interparticle contacts are achieved. Upon annealing, an exchange bias field of 0.32 T was observed--over twice that achieved in any other colloidally-synthesized system. Additionally, the unique microstructure is defined during cluster formation and thus protects magnetic coercivity during the annealing process. Overall, this work demonstrates a general approach for quickly exploring magnetic parameter space, designing interparticle functionality, and working towards the construction of high-value bulk magnets with low materials and processing cost.

关键词： nanoparticle cluster microemulsion exchange bias exchange interaction coercivity

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