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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 controversial.Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells(MSC)in a rodent stroke model.We 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 injury.Methods Transient focal cerebral ischaemia was induced in adult Sprague-dawley rats by occlusion of the middle cerebral artery.Following 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 swelling.Additional 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 stroke.Results The infarct volume and extent of swelling of the ischaemic brain were similar in males and females.despite similar pathological stroke lesions,the clinical manifestations of stroke were more pronounced in males than females,as indicated by the neurological scores and other tests.MSC 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 damage.We 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 MMPs.We tested our hypothesis by determining the pre-ischaemic and post-ischaemic expression profile of MMPs in wild-type and MMP-12 knockout mice.Methods Focal cerebral ischaemia was induced in wildtype and MMP-12 knockout mice by middle cerebral artery occlusion procedure by insertion of a monofilament suture.One hour after ischaemia,reperfusion was initiated by removing the monofilament.One 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 analysis.results 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 species.Further,the post-stroke induction or inhibition of various MMPs in MMP-12 knockout mice is different from their respective expression profile in wild-type mice.Moreover,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 mice.Conclusions In the ischaemic brain,MMP-12 upregulates several fold higher than any other MMP.Mice 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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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 initiation.An 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 conditions.Experiments 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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Regression of recurrent granulosa cell tumor liver metastases following selective internal radiation therapy

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Hepatobiliary & Pancreatic diseases International 2023年第4期22卷 406-408页

作者： Omar A Mownah John d Leahy jeffrey Summers Stephen M Gregory Nigel d Heaton Institute of Liver Studies King’s Healthcare PartnersKing’s College Hospital NHS Foundation TrustDenmark HillLondon SE59RSUK department of Oncology Maidstone and Tunbridge Wells NHS TrustMaidstone ME169QQUK

Granulosa cell tumor(GCT)is the most common sex cordstromal tumor,comprising 5%of all ovarian malignancies[1].The disease course is indolent,and the majority of cases present at stage 1.However,metastases may develop with potential sites being peritoneum,lung,brain,liver and bone[2].due to the rarity of the disease,published evidence for management of granulosa cell tumor liver metastases(GCTLM)is limited.Surgical resection is the optimal treatment in instances where there is a high chance of achieving complete resection[3].With regards to unresectable GCTLM there is a paucity of evidence to guide treatment strategy.

关键词： metastases liver lung

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寓言历久弥新

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青年视觉 2024年第1期 132-145页

作者： jeffrey Art d'Egypte(图) 不详

在过去的六十多年间,大地艺术已完成几次悄然的转向:整体上,Robert Smithson《螺旋码头》式的在地创作仍在继续,信手来以呼应自然,也有越来越多的创作者借助更多元的材料、形式,思考全球化和地域文明、历史和当下——从2021年开始,每年... 详细信息

在过去的六十多年间,大地艺术已完成几次悄然的转向:整体上,Robert Smithson《螺旋码头》式的在地创作仍在继续,信手来以呼应自然,也有越来越多的创作者借助更多元的材料、形式,思考全球化和地域文明、历史和当下——从2021年开始,每年一度在埃及吉萨金字塔群举办的Forever Is Now展览,再次扩大和丰富了这个艺术门类的内涵,它将文化遗产、自然、当代装置、创作者和欣赏者共同纳入一个互动情境中,讲述一个历久弥新的寓言:其发散的意义生成取决于地缘和创作者,也取决于欣赏的视角。

关键词：互动情境大地艺术意义生成文化遗产地域文明金字塔历久弥新全球化

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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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Radiological determination of the cranial index of present-day Ghanaians

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Forensic Sciences Research 2022年第2期7卷 138-141页

作者： Benard Ohene Botwe jeffrey Nana Afari Boadu Kofi Adesi Kyei John d.Thompson department of Radiography University of Ghana School of Biomedical&Allied Health SciencesCollege of Health SciencesAccraGhana directorate of Radiography School of Health SciencesUniversity of SalfordSalfordUK

The cranial index(CI)of Ghanaians is currently unknown.The aim of this study was to measure the CI in a population of Ghanaians in order to classify them against pre-determined CI categories.A systematic random sampling method was used to select 300 normal computed tomography(CT)head scans of adult Ghanaians from the largest hospital in Ghana.All patients were deemed to have a normal cranial image configuration based on the radiological report.The biparietal diameter(BPd,width)and the occipitofrontal diameter(OFd,length)were measured on transaxial CT images using a workstation with a calibrated measurement calliper tool.The CI ratio was calculated as the BPd multiplied by 100 and divided by the OFd.Mean,standard deviation(Sd)and range were calculated for BPd,OFd and CI.differences in measurements between demographic groups were compared using an unpaired t-test,with testαset at 0.05.Of the population of Ghanaians included in this study,165(55%)were male and 135(45%)were female.The mean CI was 77.3±3.6 in males and 79.0±3.3 in females,placing both genders in the mesocephalic category.However,the difference between males and females was found to be statistically significant(P=0.02).The study indicated that most Ghanaian adults belong to the mesocephalic category of CI.Females also had a higher CI,which could be used to differentiate gender groups.This information can be useful for forensic medicine,plastic surgeries for clinical and research purpose.

关键词： Forensic sciences cranial index CI sexual dimorphism computed tomography CT

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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 cancers.However,the cause of the elevation of Src kinase activity in the majority of human colon carcinomas is still largely unknown.We aim at finding the cause of elevated Src kinase activity in human colon carcinomas.Methods：We employed normal colon epithelial FHC cells and examined Src activation in human colon carcinoma specimens from 8 patients.Protein expression levels were determined by Western blotting,and the activity of Src kinase by kinase assay.Results：Actin levels were different between tumor and normal tissues,demonstrating the complexities and inhomogeneities of the tissue samples.Src 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 carcinomas.Src Y530 phosphorylation levels were reduced to a higher extent than protein levels in the carcinomas.Conclusion：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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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 codes.One method is for sequential configurations,where the air code module in invoked over some time interval prior to the sea module.The other method is for concurrent setups,in which the air and sea modules run in parallel.The focus is the temporal representation of air-sea fluxes.The methods we study conserve moments of the fluxes,with an arbitrary order of accuracy possible in time.different step sizes are allowed for the two fluid codes.An a posteriori stability indicator is defined,which can be computed efficiently on-the-fly over each coupling interval.For a model of two coupled fluids with natural heat convection,using finite elements in space,we prove the sufficiency of our stability indicator.Under certain conditions,we also prove that stability can be enforced by iteration when the coupling interval is small enough.In 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 parameter.This is a sharper result than what has been shown previously for related algorithms with finite element methods.Computational 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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depilatory double-disc mouse model for evaluation of vesicant dermal injury pharmacotherapy countermeasures

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Animal Models and Experimental Medicine 2023年第1期6卷 57-65页

作者： Tomas L.Roldan Shike Li jeffrey d.Laskin dayuan Gao Patrick J.Sinko department of Pharmaceutics Rutgers University Ernest Mario School of PharmacyPiscatawayNew JerseyUSA department of Environmental and Occupational Health Rutgers University School of Public HealthPiscatawayNew JerseyUSA CounterACT Center of Excellence Rutgers UniversityPiscatawayNew JerseyUSA

Background:Sulfur mustard(SM)is a chemical warfare vesicant that severely injures exposed eyes,lungs,and skin.Mechlorethamine hydrochloride(NM)is widely used as an SM surrogate.This study aimed to develop a depilatory double-disc(ddd)NM skin burn model for investigating vesicant pharmacotherapy countermeasures.Methods:Hair removal method(clipping only versus clipping followed by a depilatory),the effect of acetone in the vesicant administration vehicle,NM dose(0.5-20μmol),vehicle volume(5-20μl),and time course(0.5-21 days)were investigated using male and female Cd-1 mice.Edema,an indicator of burn response,was assessed by biopsy skin weight.The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation.The optimized ddd model was validated using an established reagent,NdH-4338,a cyclooxygenase,inducible nitric oxide synthase,and acetylcholinesterase inhibitor prodrug.Results:Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible(18-fold lower%CV)compared to clipping alone.Acetone did not affect edema formation.Peak edema occurred 24-48 h after NM administra-tion using optimized dosing methods and volume.Ideal partial-thickness burns were achieved with 5μmol of NM and responded to treatment with NdH-4338.No dif-ferences in burn edematous responses were observed between males and females.Conclusion:A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures.This model pro-vides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.

关键词： edema mice skin vesicant

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