- Urinary Bladder and Prostate Research
- Ion channel regulation and function
- Pelvic floor disorders treatments
- Urological Disorders and Treatments
- Ion Channels and Receptors
- Gastrointestinal motility and disorders
- Cardiac electrophysiology and arrhythmias
- Bladder and Urothelial Cancer Treatments
- Neuroscience of respiration and sleep
- Tissue Engineering and Regenerative Medicine
- Urinary Tract Infections Management
- Ion Transport and Channel Regulation
- Pain Mechanisms and Treatments
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Innovative Teaching Methods
- Cancer Immunotherapy and Biomarkers
- Photodynamic Therapy Research Studies
- Regulation of Appetite and Obesity
- interferon and immune responses
- Venomous Animal Envenomation and Studies
- Effects of Radiation Exposure
- Management of metastatic bone disease
Queen's University Belfast
2015-2024
Drexel University
2024
Centre for Cancer Biology
2000-2013
University of Surrey
2013
Belfast City Hospital
2010
University of Ulster
2010
University of Strathclyde
2002-2009
Queen's University
1999-2002
Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this was validated as predicting benefit from DNA-damaging chemotherapy. This defined by interferon signaling. In study, address the mechanism of immune response and its possible clinical significance. Methods: We used immunohistochemistry (IHC) to characterize infiltration in 184 cancer samples, which 65 were DDRD subtype. Isogenic cell lines,...
No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Aug 2002Kit Positive Cells In The Guinea Pig Bladder Karen D. McCloskey and Alison M. Gurney McCloskeyKaren GurneyAlison View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64752-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We describe the presence interstitial cells Cajal (ICC) throughout wall guinea pig bladder. Materials...
1 Collagenase dispersal of strips rabbit urethra yielded, in addition to normal spindle-shaped smooth muscle cells, a small proportion branched cells which resembled the interstitial Cajal dispersed from canine colon. These were clearly distinguishable their appearance under phase-contrast microscope, immunohistochemistry and ultrastructure. They had abundant vimentin filaments but no myosin, discontinuous basal lamina, sparse rough endoplasmic reticulum, many mitochondria well-developed...
No AccessJournal of UrologyInvestigative Urology1 Apr 2005MORPHOLOGY AND LOCALIZATION OF INTERSTITIAL CELLS IN THE GUINEA PIG BLADDER: STRUCTURAL RELATIONSHIPS WITH SMOOTH MUSCLE NEURONS ROSS A. DAVIDSON and KAREN D. McCLOSKEY DAVIDSONROSS McCLOSKEYKAREN View All Author Informationhttps://doi.org/10.1097/01.ju.0000146272.80848.37AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: In the current study...
Isolated interstitial (“pacemaker”) cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at −60 mV, these fired large spontaneous transient inward currents (STICs), averaging −860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous outward (STOCs) also observed fell into two categories, “fast” (<100 ms duration) “slow” (>1 duration). The latter coupled to STICs, suggesting that they shared same...
We investigated the 3-dimensional morphological arrangement of KIT positive interstitial cells Cajal in human bladder and explored their structural interactions with neighboring cells.Human biopsy samples were prepared for immunohistochemistry/confocal or transmission electron microscopy.Whole mount, flat sheet preparations labeled anti-KIT (Merck, Darmstadt, Germany) contained several immunopositive cell populations. A network stellate lamina propria made connections a cholinergic nerve...
Acetylcholine released from parasympathetic excitatory nerves activates contraction in detrusor smooth muscle. Immunohistochemical labeling of guinea pig with anti-c-Kit and anti-VAChT demonstrated a close structural relationship between interstitial cells Cajal (ICC) cholinergic nerves. The ability bladder ICC to respond the acetylcholine analog, carbachol, was investigated enzymatically dissociated cells, loaded Ca(2+) indicator fluo 4AM. fired transients response stimulation by carbachol...
No AccessJournal of UrologyInvestigative Urology1 Aug 2012Identification PDGFRα Positive Populations Interstitial Cells in Human and Guinea Pig Bladders Kevin P. Monaghan, Louise Johnston, Karen D. McCloskey MonaghanKevin Monaghan , JohnstonLouise Johnston McCloskeyKaren View All Author Informationhttps://doi.org/10.1016/j.juro.2012.03.117AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The...
Abstract The simultaneous delivery of multiple cancer drugs in combination therapies to achieve optimal therapeutic effects patients can be challenging. This study investigated whether co-encapsulation the BH3-mimetic ABT-737 and topoisomerase I inhibitor camptothecin (CPT) PEGylated polymeric nanoparticles (NPs) was a viable strategy for overcoming their clinical limitations deliver both compounds at ratios. We found that thrombocytopenia induced by exposure diminished through its...
Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after shock, during which the bladder areflexic. NDO emergence and maintenance depend on profound plastic changes neuronal pathways regulating function. It that neurotrophins (NTs) are major regulators such changes. NGF best-studied NT in its role has already been established. Another very abundant neurotrophin BDNF. Despite being shown that, acting at level, BDNF key mediator...
The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and investigate their physiological significance contractility.KCNQ were examined at genetic, protein, cellular tissue level guinea pig using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, a panel activators inhibitors.KCNQ subtypes 1-5 muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous...
// Zenobia C. D’Costa 1 , Catherine Higgins Chee Wee Ong Gareth W. Irwin David Boyle Darragh G. McArt Karen McCloskey Niamh E. Buckley Nyree T. Crawford Lalitha Thiagarajan 3 James Murray 2 Richard D. Kennedy Karl A. Mulligan 4 Paul Harkin J.J. Waugh Chris J. Scott 5 Manuel Salto-Tellez Williams and B. Mullan Centre for Cancer Research Cell Biology, Queen’s University Belfast, UK Biomedical Science Institute, Trinity College Dublin, Green, Dublin 2, Ireland School of Biological...
Abstract Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) underactivity (DU)/underactive (UAB). The present article addresses proposal 1: “Are causes of damage leading to LUTD?” from the 2019 International Consultation on Incontinence—Research Society (ICI‐RS) meeting. Bladder animals humans is briefly described, along with proposed...
Urofacial, or Ochoa, syndrome (UFS) is an autosomal recessive disease featuring a dyssynergic bladder with detrusor smooth muscle contracting against undilated outflow tract. It also features abnormal grimace. Half of individuals UFS carry biallelic variants in
Freshly dispersed sheep mesenteric lymphatic smooth muscle cells were studied at 37 degrees C using the perforated patch-clamp technique with Cs(+)- and K(+)-filled pipettes. Depolarizing steps evoked currents that consisted of L-type Ca(2+) [I(Ca(L))] current a slowly developing current. The slow reversed 1 +/- 1.5 mV symmetrical Cl(-) concentrations compared 23.2 1.2 (n = 5) -34.3 3.5 4) when external was substituted either glutamate (86 mM) or I(-) (125 mM). Nifedipine (1 microM) blocked...
The presence of novel KCNQ currents was investigated in guinea pig bladder interstitial cells Cajal and their contribution to the maintenance resting membrane potential assessed.Enzymatically dispersed were patch clamped with K(+) filled pipettes voltage clamp current modes. Pharmacological modulators channels tested on potential.Cells stepped from -60 40 mV evoke dependent using a modified pipette solution containing ethylene glycol tetraacetic acid (5 mM) adenosine triphosphate (3...
Background and purpose: W/W v wild‐type murine bladders were studied to determine whether the phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is useful tool study function of bladder interstitial cells Cajal (ICC). Experimental approach: Immunohistochemistry, tension recordings microelectrode membrane potential performed on mutant bladders. Key results: Wild‐type detrusors contained c‐Kit ‐ vimentin‐immunopositive in comparable quantities, distribution...
The role of the calcium binding protein, Calbindin 2 (CALB2), in regulating response colorectal cancer (CRC) cells to 5-Fluorouracil (5-FU) was investigated. Real-time RT-PCR and Western blot analysis revealed that CALB2 mRNA protein expression were down-regulated p53 wild-type null isogenic HCT116 CRC cell lines following 48 h 72 5-FU treatment. Moreover, 5-FU-induced apoptosis significantly reduced LS174T which had been silenced. Further investigation translocated mitochondria treatment...