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Dive into the research topics where Kathleen H. Delaney is active.

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Featured researches published by Kathleen H. Delaney.


Journal of Neurocytology | 1998

MORPHOLOGICAL AND MORPHOMETRIC STUDIES OF THE DYSMYELINATING MUTANT, THE LONG EVANS SHAKER RAT

Jacek M. Kwiecien; Lawrence T. O'Connor; Brian D. Goetz; Kathleen H. Delaney; Fletch Al; Ian D. Duncan

The Long Evans shaker (les) rat is a recently identified CNS myelin mutant with an autosomal recessive mode of inheritance. Although scattered myelin sheaths are present in some areas of the CNS, most notably the ventral spinal cord in the young neonatal rat, this myelin is gradually lost, and 8-12 weeks little myelin is present throughout the CNS. Despite this severe myelin deficiency, some mutants may live beyond one year of age. Rare, thin myelin sheaths that are present early in development lack myelin basic protein (MBP) and on ultrastructural examination are poorly compacted and lack a major dense line. Many oligodendrocytes develop an accumulation of vesicles and membranous bodies, but no abnormal cell death is observed. In the optic nerve, cell kinetic studies show an increase in proliferation at early time points in les, while total glial cell counts are also increased in les from 2 months of age. In situ hybridization studies demonstrate that the numbers of mature oligodendrocytes are similar to controls early in life and increase with time compared to controls. There is both a progressive astrocyte hypertrophy and microgliosis. While les has a mutation in the myelin basic protein (mbp) gene, it is dissimilar in both genotype and phenotype to the previously described mbp mouse mutants, shiverer (shi) and shiverermld. Unlike shi and its allele, where myelin increases with time and oligodendrocytes become ultrastructurally normal, les oligodendrocytes are permanently disabled, continue to demonstrate cytoplasmic abnormalities, and fail to produce myelin beyond the first weeks of life.


Journal of Hypertension | 1995

Perindopril treatment prolonged the lifespan of spontaneously hypertensive rats.

Robert M.K. Vv. Lee; Kathleen H. Delaney; Mei Lu

Objective The effects of perindopril treatment on hypertension development and the lifespan of adult spontaneously hypertensive rats (SHR) were studied. Design Adult male SHR (aged 15 weeks) were given once a day treatment with 4 mg/kg perindopril by gavage for 12 weeks. Littermates given distilled water were used as controls. The blood pressure and lifespan of these rats were studied. Methods The systolic blood pressure (SBP), heart rate and body weight of these rats were measured at regular intervals until they died from natural causes. At necropsy macroscopic and microscopic examinations were made of various organs to determine the cause of death. Serum levels of creatinine, urea and protein were also measured. Results Perindopril treatment resulted in the normalization of SBP after 2 weeks of treatment. Withdrawal of the treatment after 12 weeks of treatment caused an elevation of SBP, but the blood pressure of the treated SHR had remained in the normotensive range (<1 50 mmHg). The heart rate and body weight of the SHR were not affected by the treatment. The average lifespan of the SHR was increased by 12 weeks compared with the control rats. The heart weight, brain lesions and arterial lesions were reduced by the treatment. Conclusion A 12-week treatment of adult SHR with perindopril was effective in causing a permanent prevention of hypertension, amelioration of some of the tissue damage associated with hypertension and an increase in the lifespan of these rats.


Neurologia I Neurochirurgia Polska | 2016

An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury

Jacek M. Kwiecien; Bożena Jarosz; Wendy Oakden; Michal Klapec; Greg J. Stanisz; Kathleen H. Delaney; Edyta Kotlinska-Hasiec; Rafal Janik; Radosław Rola; Wojciech Dabrowski

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125-2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125-2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process.


Oncogene | 2018

BMI1 is a therapeutic target in recurrent medulloblastoma

David Bakhshinyan; Chitra Venugopal; Ashley Adile; Neha Garg; Branavan Manoranjan; Robin M. Hallett; Xin Wang; Sujeivan Mahendram; Parvez Vora; Thusyanth Vijayakumar; Minomi Subapanditha; Mohini Singh; Michelle Kameda-Smith; Maleeha Qazi; Nicole McFarlane; Aneet Mann; Olufemi Ajani; Blake Yarascavitch; Vijay Ramaswamy; Hamza Farooq; Sorana Morrissy; Liangxian Cao; Nadiya Sydorenko; Ramil Baiazitov; Wu Du; Josephine Sheedy; Marla Weetall; Young-Choon Moon; Chang-Sun Lee; Jacek M. Kwiecien

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor, representing 20% of newly diagnosed childhood central nervous system malignancies. Although advances in multimodal therapy yielded a 5-year survivorship of 80%, MB still accounts for the leading cause of childhood cancer mortality. In this work, we describe the epigenetic regulator BMI1 as a novel therapeutic target for the treatment of recurrent human Group 3 MB, a childhood brain tumor for which there is virtually no treatment option beyond palliation. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naive tumors will provide limited clinical benefit since recurrent metastatic MBs are highly genetically divergent from their primary tumor. Using a small molecule inhibitor against BMI1, PTC-028, we were able to demonstrate complete ablation of self-renewal of MB stem cells in vitro. When administered to mice xenografted with patient tumors, we observed significant reduction in tumor burden in both local and metastatic compartments and subsequent increased survival, without neurotoxicity. Strikingly, serial in vivo re-transplantation assays demonstrated a marked reduction in tumor initiation ability of recurrent MB cells upon re-transplantation of PTC-028-treated cells into secondary recipient mouse brains. As Group 3 MB is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious targeted agent would be rapidly transitioned to clinical trials.


International Journal of Dentistry | 2017

Osseointegration of a 3D Printed Stemmed Titanium Dental Implant: A Pilot Study

James Tedesco; Bryan E.J. Lee; Alexander Lin; Dakota Marie Binkley; Kathleen H. Delaney; Jacek M. Kwiecien; Kathryn Grandfield

In this pilot study, a 3D printed Grade V titanium dental implant with a novel dual-stemmed design was investigated for its biocompatibility in vivo. Both dual-stemmed (n = 12) and conventional stainless steel conical (n = 4) implants were inserted into the tibial metaphysis of New Zealand white rabbits for 3 and 12 weeks and then retrieved with the surrounding bone, fixed, dehydrated, and embedded into epoxy resin. The implants were analyzed using correlative histology, microcomputed tomography, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The histological presence of multinucleated osteoclasts and cuboidal osteoblasts revealed active bone remodeling in the stemmed implant starting at 3 weeks and by 12 weeks in the conventional implant. Bone-implant contact values indicated that the stemmed implants supported bone growth along the implant from the coronal crest at both 3- and 12-week time periods and showed bone growth into microporosities of the 3D printed surface after 12 weeks. In some cases, new bone formation was noted in between the stems of the device. Conventional implants showed mechanical interlocking but did have indications of stress cracking and bone debris. This study demonstrates the comparable biocompatibility of these 3D printed stemmed implants in rabbits up to 12 weeks.


The Journal of Neuroscience | 1999

Insertion of a Retrotransposon in Mbp Disrupts mRNA Splicing and Myelination in a New Mutant Rat

Lawrence T. O’Connor; Brian D. Goetz; Jacek M. Kwiecien; Kathleen H. Delaney; Andrew L. Fletch; Ian D. Duncan


Human Gene Therapy | 1998

Delivery of Recombinant Gene Product to Canines with Nonautologous Microencapsulated Cells

M. A. Peirone; Kathleen H. Delaney; J. Kwiecin; A. Fletch; Patricia L. Chang


Journal of Laboratory and Clinical Medicine | 2003

Delivery of recombinant gene product to canine brain with the use of microencapsulation.

Susan C Barsoum; William Milgram; William A. MacKay; Craig L. Coblentz; Kathleen H. Delaney; Jacek M. Kwiecien; Stephen A. Kruth; Patricia L. Chang


Laboratory Animal Science | 1995

Familial dysmyelination in a Long Evans rat mutant.

Kathleen H. Delaney; Jacek M. Kwiecien; Wegiel J; Wisniewski Hm; Percy Dh; Fletch Al


Comparative Medicine | 2000

Neuropathology of bouncer Long Evans, a novel dysmyelinated rat.

Jacek M. Kwiecien; Blanco M; Fox Jg; Kathleen H. Delaney; Fletch Al

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Brian D. Goetz

University of Wisconsin-Madison

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Ian D. Duncan

University of Wisconsin-Madison

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