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Dive into the research topics where Kathleen Nicol is active.

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Featured researches published by Kathleen Nicol.


The American Journal of Surgical Pathology | 2006

An immunohistochemical algorithm to facilitate diagnosis and subtyping of rhabdomyosarcoma: the Children's Oncology Group experience.

Raffaella A. Morotti; Kathleen Nicol; David M. Parham; Lisa A. Teot; Julie Moore; John R. Hayes; William H. Meyer; Stephen J. Qualman

Immunohistochemistry remains the current ancillary method of choice in the pathologic evaluation of small blue round-cell tumors. In at least 20% of cases of rhabdomyosarcoma (RMS), it is considered an essential factor in the final and/or differential diagnosis of the malignancy. Newer immunostains (antimyogenin, MyoD1) generated against intranuclear myogenic transcription factors offer pathologists the best hope for improving the sensitivity and specificity of RMS diagnosis. A large series of RMS (956) were studied consecutively from the intergroup rhabdomyosarcoma study and childrens oncology group files, along with multiple other malignant, benign or reactive lesions. A panel of antibodies to muscle-related antigens (myogenin, MyoD1, desmin, muscle-specific actin) was studied using formalin-fixed, paraffin-embedded tissue, an avidin-biotin/peroxidase complex immunohistochemical technique, antigen retrieval technique as appropriate, and automated immunostaining. Myogenin and MyoD1 were equally sensitive (positive for 97% of RMS cases), with both also showing similar specificity (90% vs. 91% of cases) for the diagnosis of RMS. Myogenin and MyoD1 staining were sometimes intact in areas of coagulative tumor necrosis, but negated by B5 fixation. Isolated, rare benign myogenin-positive nuclei were seen infrequently in reactive lymph nodes. Specifically, both myogenin and MyoD1 had significantly greater extent of expression for alveolar RMS (ARMS) than embryonal RMS (ERMS) (both with P<0.001). Similarly, both myogenin (P=0.001) and MyoD1 (P<0.001) had significantly higher expression for ARMS than RMS, not otherwise specified (NOS). They were never expressed in undifferentiated sarcomas; however, reactive or regenerative myocytes did show expression. Immunostains against intranuclear myogenic transcription factors are, at present, the best available markers for confirming the diagnosis of RMS. Their differential expression in reactive myogenic lesions, variability in ARMS versus ERMS, and absence in undifferentiated sarcomas suggest new biologic questions to be explored in future studies.


Journal of Immunology | 2007

Knockout of Mkp-1 Enhances the Host Inflammatory Responses to Gram-Positive Bacteria

Xianxi Wang; Xiaomei Meng; Joshua R. Kuhlman; Leif D. Nelin; Kathleen Nicol; B. Keith English; Yusen Liu

MAPK phosphatase (MKP)-1 is an archetypal member of the dual specificity protein phosphatase family that dephosphorylates MAPK. We have previously demonstrated that MKP-1 acts as a negative regulator of p38 and JNK in immortalized macrophages after stimulation with peptidoglycan isolated from Gram-positive bacteria. To define the physiological function of MKP-1 during Gram-positive bacterial infection, we studied the innate immune responses to Gram-positive bacteria using Mkp-1 knockout (KO) mice. We found that Mkp-1−/− macrophages exhibited prolonged activation of p38 and JNK, but not of ERK, following exposure to either peptidoglycan or lipoteichoic acid. Compared with wild-type (WT) macrophages, Mkp-1−/− macrophages produced more proinflammatory cytokines such as TNF-α and IL-6. Moreover, after challenge with peptidoglycan, lipoteichoic acid, live or heat-killed Staphylococcus aureus bacteria, Mkp-1 KO mice also mounted a more robust production of cytokines and chemokines, including TNF-α, IL-6, IL-10, and MIP-1α, than did WT mice. Accordingly, Mkp-1 KO mice also exhibited greater NO production, more robust neutrophil infiltration, and more severe organ damage than did WT mice. Surprisingly, WT and Mkp-1 KO mice exhibited no significant difference in either bacterial load or survival rates when infected with live S. aureus. However, in response to challenge with heat-killed S. aureus, Mkp-1 KO mice exhibited a substantially higher mortality rate compared with WT mice. Our studies indicate that MKP-1 plays a critical role in the inflammatory response to Gram-positive bacterial infection. MKP-1 serves to limit the inflammatory reaction by inactivating JNK and p38, thus preventing multiorgan failure caused by exaggerated inflammatory responses.


Transfusion | 2012

Immunosuppressive effects of red blood cells on monocytes are related to both storage time and storage solution

Jennifer A. Muszynski; Jyotsna Nateri; Kathleen Nicol; Kristin Greathouse; Lisa Hanson; Mark Hall

BACKGROUND: Reduced monocyte function is associated with adverse outcomes from critical illness. Red blood cells (RBCs) are thought to impair monocyte function but relationships between RBC storage solution and monocyte suppression are unknown. This study was designed to test the hypothesis that immunosuppressive effects of RBCs on monocytes are related to both storage time and preservative solution.


Pediatric and Developmental Pathology | 2006

Distinguishing undifferentiated embryonal sarcoma of the liver from biliary tract rhabdomyosarcoma: A children's oncology group study

Kathleen Nicol; Van H. Savell; Julie Moore; Lisa A. Teot; Sheri L. Spunt; Stephen J. Qualman; Richard J. Andrassy; Carola Arndt; K. Scott Baker; Frederic G. Barr; W. Archie Bleyer; Philip P. Breitfeld; John C. Breneman; Julia A. Bridge; Ken M. Brown; Sarah S. Donaldson; Holcome E. Grier; Douglas S. Hawkins; Peter J. Houghton; Michael P. Link; Thom L. Lobe; Harold M. Maurer; William H. Meyer; Jeff M. Michalski; Charles N. Paidas; Alberto S. Pappo; David M. Parham; R. Beverly Raney; Leslie L. Robison; Eric Sandler

Morphologically, the distinction between undifferentiated embryonal sarcoma of the liver (UESL) and biliary tract rhabdomyosarcoma (RMS) can be uncertain because of some shared pathologic similarities. Patients with UESL have been consistently but erroneously enrolled in Childrens Oncology Group (COG) treatment protocols because UESL was equated with RMS, despite the differing primary treatment modalities of these entities. Review of COG pathology files yielded 20 cases of UESL that were compared to 25 cases of biliary tract RMS. Clinicopathologic features including immunohistochemical staining were examined. In the UESL cases, the male:female ratio was 1:1 and the median age was 10.5 years. Histologically, hyaline globules and diffuse anaplasia were consistently present. The cases of RMS had a male:female ratio of 1.8:1 with a median age of 3.4 years and routinely lacked diffuse anaplasia and hyaline globules. Polyclonal desmin and muscle-specific actin were variably immunoreactive in UESL and RMS; however, myogenin and myogenic regulatory protein D1 (MyoD1) were uniformly negative in UESL and routinely positive in the majority of biliary tract RMS. Myogenin, in particular, was highly significant (P = 0.0003) in distinguishing RMS from UESL. With a median follow-up of 8 months, 11 of 18 patients with UESL were still alive. The estimated 5-year survival for biliary tract RMS was 66%. Establishing the correct diagnosis of these distinct clinical and pathologic entities is important, as surgery alone may be curative in UESL, whereas initial chemotherapy is often recommended for the treatment of biliary tract RMS.


Shock | 2014

Innate immune function predicts the development of nosocomial infection in critically injured children.

Jennifer A. Muszynski; Ryan Nofziger; Kristin Greathouse; Jyotsna Nateri; Lisa Steele; Kathleen Nicol; Jonathan I. Groner; Gail E. Besner; Corey Raffel; Susan Geyer; Osama N. El-Assal; Mark Hall

ABSTRACT Background: Critical injury has been associated with reduction in innate immune function in adults, with infection risk being related to degree of immune suppression. This relationship has not been reported in critically injured children. Hypothesis: Innate immune function will be reduced in critically injured children, and the degree of reduction will predict the subsequent development of nosocomial infection. Methods: Children (⩽18 years old) were enrolled in this longitudinal, prospective, observational, single-center study after admission to the pediatric intensive care unit following critical injury, along with a cohort of outpatient controls. Serial blood sampling was performed to evaluate plasma cytokine levels and innate immune function as measured by ex vivo lipopolysaccharide-induced tumor necrosis factor &agr; (TNF-&agr;) production capacity. Results: Seventy-six critically injured children (and 21 outpatient controls) were enrolled. Sixteen critically injured subjects developed nosocomial infection. Those subjects had higher plasma interleukin 6 and interleukin 10 levels on posttrauma days 1–2 compared with those who recovered without infection and outpatient controls. Ex vivo lipopolysaccharide-induced TNF-&agr; production capacity was lower on posttrauma days 1–2 (P = 0.006) and over the first week following injury (P = 0.04) in those who went on to develop infection. A TNF-&agr; response of less than 520 pg/mL at any time in the first week after injury was highly associated with infection risk by univariate and multivariate analysis. Among transfused children, longer red blood cell storage age, not transfusion volume, was associated with lower innate immune function (P < 0.0001). Trauma-induced innate immune suppression was reversible ex vivo via coculture of whole blood with granulocyte-macrophage colony-stimulating factor. Conclusions: Trauma-induced innate immune suppression is common in critically injured children and is associated with increased risks for the development of nosocomial infection. Potential exacerbating factors, including red blood cell transfusion, and potential therapies for pediatric trauma-induced innate immune suppression are deserving of further study.


Pediatric Blood & Cancer | 2008

Congenital amegakaryocytic thrombocytopenia: The diagnostic importance of combining pathology with molecular genetics

Melissa J. Rose; Kathleen Nicol; Micah Skeens; Thomas G. Gross; Bryce A. Kerlin

Congenital Amegakaryocytic Thrombocytopenia (CAMT) is a rare bone marrow failure syndrome that presents with isolated thrombocytopenia within the first year of life. Classic diagnostic bone marrow findings reveal absent or significantly decreased megakaryocytes with otherwise normal marrow cellularity. We present a newborn with thrombocytopenia whose initial bone marrow aspirate showed an appropriate number of megakaryocytes. CAMT was subsequently diagnosed after molecular testing demonstrated a mutation in the thrombopoietin receptor. The presence of a normal number of megakaryocytes on an initial bone marrow aspirate should not exclude CAMT from the differential diagnosis of thrombocytopenia within the first year of life. Pediatr Blood Cancer 2008;50:1263–1265.


Transfusion | 2017

Transfusion‐related immunomodulation: review of the literature and implications for pediatric critical illness

Jennifer A. Muszynski; Philip C. Spinella; Jill M. Cholette; Jason P. Acker; Mark W. Hall; Nicole P. Juffermans; Daniel P. Kelly; Neil Blumberg; Kathleen Nicol; Jennifer L. Liedel; Allan Doctor; Kenneth E. Remy; Marisa Tucci; Jacques Lacroix; Philip J. Norris

Transfusion‐related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions.


Transfusion | 2015

Supernatants from stored red blood cell (RBC) units, but not RBC-derived microvesicles, suppress monocyte function in vitro.

Jennifer A. Muszynski; Justin Bale; Jyotsna Nateri; Kathleen Nicol; Yijie Wang; Valerie P. Wright; Clay B. Marsh; Mikhail A. Gavrilin; Anasuya Sarkar; Mark D. Wewers; Mark W. Hall

We have previously shown that critically ill children transfused with red blood cells (RBCs) of longer storage durations have more suppressed monocyte function after transfusion compared to children transfused with fresher RBCs and that older stored RBCs directly suppress monocyte function in vitro, through unknown mechanisms. We hypothesized that RBC‐derived microvesicles (MVs) were responsible for monocyte suppression.


Transfusion | 2015

Red blood cell transfusion and immune function in critically ill children: a prospective observational study

Jennifer A. Muszynski; Elfaridah Frazier; Ryan Nofziger; Jyotsna Nateri; Lisa Steele; Kathleen Nicol; Philip C. Spinella; Mark Hall

Our previous in vitro work showed that stored red blood cells (RBCs) increasingly suppress markers of innate immune function with increased storage time. This multicenter prospective observational study tests the hypothesis that a single RBC transfusion in critically ill children is associated with immune suppression as a function of storage time.


The Annals of Thoracic Surgery | 2010

Thrombotic Risk of Recombinant Factor Seven in Pediatric Cardiac Surgery: A Single Institution Experience

Todd Karsies; Kathleen Nicol; Mark Galantowicz; Julie A. Stephens; Bryce A. Kerlin

BACKGROUND Recombinant activated factor seven (rFVIIa) is increasingly being used as a hemostatic adjunct in pediatric cardiac surgery. We evaluated the thrombotic safety profile of rFVIIa in pediatric congenital heart disease (CHD) surgery. METHODS This was a retrospective matched case-control study over six years at a single institution. Patients who received rFVIIa after CHD surgery were matched to controls based on age, diagnosis, and procedure. We compared thrombosis, hemorrhage, transfusions, length of stay, and repeat procedures between groups. RESULTS Twenty-five patients received rFVIIa (mean dose: 70 mcg/kg); 50 controls were matched. There was no significant difference in the rate of thrombosis between patients who received rFVIIa and controls (8% vs 4%). After rFVIIa, there was a significant reduction in transfusion volume (median 77.1 mL/kg vs 14.6 mL/kg; p < 0.001) as well as a significant decrease in hemorrhagic chest tube output (8.3 +/- 1.6 mL/kg/hour vs 1.4 +/- 0.3 mL/kg/hour; mean +/- standard error of the mean; p < 0.001). No difference was seen in intensive care unit or hospital length of stay or mortality between patients receiving rFVIIa and controls. CONCLUSIONS The rFVIIa therapy did not increase thrombotic complications when used as rescue therapy after CHD surgery but did appear to decrease bleeding complications in this small cohort.

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Dive into the Kathleen Nicol's collaboration.

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Don Hayes

Nationwide Children's Hospital

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Thomas J. Preston

Nationwide Children's Hospital

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Jennifer A. Muszynski

Nationwide Children's Hospital

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Mark Hall

Nationwide Children's Hospital

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Jyotsna Nateri

Nationwide Children's Hospital

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Philip C. Spinella

Washington University in St. Louis

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Andrew R. Yates

Nationwide Children's Hospital

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Joseph D. Tobias

Nationwide Children's Hospital

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