p63 immunostaining in destained bronchoscopic cytological specimens.

The p53 homologous squamous stem-cell regulatory protein p63 is expressed in squamous carcinomas but is not characteristically detected in small-cell carcinomas (SCCs). A panel of thyroid transcription factor (TTF) 1 and p63 has been shown to be useful in distinguishing SCCs from poorly differentiated squamous carcinoma of the lung (PDSLC) in small biopsies and cytological cell blocks. Because tumor samples frequently are limited to cytological smears, we attempted to detect p63 in destained slides from a spectrum of pulmonary malignancies.

Spatially-localized correlation of dGEMRIC-measured GAG distribution and mechanical stiffness in the human tibial plateau.

The concentration of glycosaminoglycan (GAG) in articular cartilage is known to be an important determinant of tissue mechanical properties based on numerous studies relating bulk GAG and mechanical properties. To date limited information exists regarding the relationship between GAG and mechanical properties on a spatially-localized basis in intact samples of native tissue. This relation can now be explored by using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC--a recently available non-destructive magnetic resonance imaging method for measuring glycosaminoglycan concentration) combined with non-destructive mechanical indentation testing.

Fine needle aspiration.

Fine needle aspiration (FNA) has been widely used as a diagnostic tool for the past half century. Differing from large bore cutting needle biopsy, FNA utilizes 22- to 27-gauge needles. The cell samples aspirated from a lesion are characteristically smeared on glass slides for immediate microscopic evaluation.

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma.

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms.

In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction.

The therapeutic potential of administering stem cells to promote angiogenesis and myocardial tissue regeneration after infarction has recently been demonstrated. Given the advantages of using embryonic stem cells and mouse models of myocardial infarction for furthering the development of this therapeutic approach, the purpose of this study was to determine if embryonic stem cells could be loaded with superparamagnetic iron oxide (SPIO) particles and imaged in a mouse model of myocardial infarction over time using MRI. Mouse embryonic stem cells were labeled with SPIO particles.

A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer's disease.

Among the earliest invariant neuropathological changes in Alzheimer's disease (AD) is the degeneration of vulnerable hippocampal CA1 and subicular pyramidal neurons. Semaphorin 3A (Sema3A) is a secreted protein that functions in signaling growth cone collapse, chemorepulsion and neuronal apoptosis during early development of the central nervous system. In this report we show that accumulation of an internalized form of Sema3A is associated with degeneration of neurons in vulnerable fields of the hippocampus during AD.

Ectopic expression of murine diphosphoinositol polyphosphate phosphohydrolase 1 attenuates signaling through the ERK1/2 pathway.

Signals from several receptor tyrosine kinases are transduced by activation of the Ras family of GTP-binding proteins. Activation of Ras initiates a kinase cascade that culminates in activation of the mitogen-activated protein kinases (MAPKs). The MAPKs include the c-jun NH(2)-terminal protein kinases (JNKs) and extracellular signal-regulated kinases (ERKs), both of which phosphorylate Elk-1/TCF, a factor that activates transcription of the c-fos gene.

T2 of articular cartilage in the presence of Gd-DTPA2-.

T(2) information and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are both used to characterize articular cartilage. They are currently obtained in separate studies because Gd-DTPA(2-) (which is needed for dGEMRIC) affects the inherent T(2) information. In this study, T(2) was simulated and then measured at 8.

Perfusion MRI of U87 brain tumors in a mouse model.

Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue:blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue.

Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and hashimoto's thyroiditis: A stem cell hypothesis of papillary carcinoma oncogenesis.

Most models suggest that the cell of origin of papillary carcinoma is the mature thyroid follicular epithelial cell. In a recent study, p63 was detected in papillary carcinoma, Hashimoto's thyroiditis, and in squamoid aggregates and solid cell nests (SCNs), embryonic remnants found sporadically in the fully developed thyroid. In the present study, the relationship between solid cell nests and papillary carcinoma was investigated further.

Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction.

Ischemia resulting from myocardial infarction (MI) promotes VEGF expression, leading to vascular permeability (VP) and edema, a process that we show here contributes to tissue injury throughout the ventricle. This permeability/edema can be assessed noninvasively by MRI and can be observed at the ultrastructural level as gaps between adjacent endothelial cells. Many of these gaps contain activated platelets adhering to exposed basement membrane, reducing vessel patency.

T2 and T1rho MRI in articular cartilage systems.

T2 and T1rho have potential to nondestructively detect cartilage degeneration. However, reports in the literature regarding their diagnostic interpretation are conflicting. In this study, T2 and T1rho were measured at 8.

Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): potential clinical applications.

Objective: We sought to describe a range of in vivo observations of glycosaminoglycan distribution in knee cartilage using the delayed gadolinium-enhanced MRI of cartilage technique.

Conclusion: The index of glycosaminoglycan distribution, T1(Gd), can exceed 500 msec (denoting high glycosaminoglycan) or can be less than 300 msec, with focal areas as low as 240 msec. Compartmental differences, as well as focal defects within the knee, were observed in patients who had sustained injuries to the ligaments and menisci of the knee or who had chronic osteoarthritis.

Assessment of early osteoarthritis in hip dysplasia with delayed gadolinium-enhanced magnetic resonance imaging of cartilage.

Background: The efficacy of surgical and medical treatment of osteoarthritis is difficult to assess because of the lack of a noninvasive, sensitive measure of cartilage integrity. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) was designed to specifically examine glycosaminoglycan changes in articular cartilage that occur during the development of osteoarthritis. Our primary goal was to compare this technique with measurement of the joint space width on conventional radiographs in patients with hip dysplasia.

Expression of p63 in papillary thyroid carcinoma and in Hashimoto's thyroiditis: a pathobiologic link?

p63 proteins are p53 homologs that are postulated to regulate squamous stem cell commitment. An immunohistochemical survey of p63 expression in normal thyroid and in reactive, neoplastic, and inflammatory thyroid disorders was performed. Sections from routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid, pH 6.

The nested variant of urothelial carcinoma: clinicopathology of 2 cases.

The nested variant of urothelial carcinoma is a recently described bladder tumor entity with a rare incidence. Two cases of this disease are presented in this report; the patients in both cases were elderly men, with a predominant involvement of the trigone region. Histologically, the tumor cells were arranged in ill-defined nests and had low-grade nuclear features.

Detection of HPV DNA in cervical specimens collected in cytologic solution by ligation-dependent PCR.

Objective: To determine the feasibility and sensitivity of detecting human papillomavirus (HPV) in specimens collected in Cytyc PreservCyt fluid (Boxborough, Massachusetts, U.S.A.

Magnetic resonance imaging of patched heterozygous and xenografted mouse brain tumors.

Experimental mouse models are emerging as useful systems for the study of human brain tumors. Nuclear magnetic resonance imaging (MRI) methods can noninvasively provide images of complex heterogeneous tissues such as experimental brain tumors. The current report demonstrates the feasibility of longitudinal high-resolution MRI in two mouse brain tumor models: patched heterozygous (ptc +/-) mice with spontaneously arising posterior fossa tumors that resemble human medulloblastoma, and homozygous nude mice implanted with intracerebral xenografts of human medulloblastoma cell lines.

p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung.

We studied the usefulness of p63 and thyroid transcription factor-1 (TTF-1) immunostains for differentiating poorly differentiated squamous cell carcinoma (PDSCC) from small cell lung carcinoma (SCLC). We used monoclonal antibodies reactive to p63 or TTF-1 to stain 4-microns-thick sections from 30 formalin-fixed, paraffin-embedded lung biopsy and resection specimens and 7 alcohol-fixed, formalin-postfixed, paraffin-embedded cell blocks from lung fine-needle aspirations (FNAs). For p63, we used a streptavidin-biotin kit, diaminobenzidine as the chromogen, and a hematoxylin counterstain.

Differential recovery of glycosaminoglycan after IL-1-induced degradation of bovine articular cartilage depends on degree of degradation.

In the present study we examined cartilage matrix repair following IL-1-induced matrix depletion. Previous data indicated that, in some cases, chondrocytes can synthesize macromolecules to establish a functional extracellular matrix in response to a matrix-damaging insult or when placed in a three-dimensional environment with inadequate matrix. However, the conditions under which such 'repair' can occur are not entirely clear.

Immunohistochemical visualization of histone H1 phosphorylation in squamous intraepithelial lesions of the gynecologic tract.

Immunohistochemical staining was performed on gynecologic tract squamous intraepithelial lesions using a novel phosphorylation-specific monoclonal antibody (designated 12D11) that detects histone H1 when phosphorylated at a cyclin-dependent kinase (CDK)-responsive epitope. Findings were compared to immunostaining by MIB-1, an extensively studied antibody probe of proliferation. Routinely fixed and processed archival sections were subjected to distinct antigen retrieval and staining protocols for each antibody and were processed for immunodetection of either Ki-67 (with MIB-1) or phosphohistone H1, using a streptavidin-biotin kit and diaminobenzidine as chromagen.

Can MTR be used to assess cartilage in the presence of Gd-DTPA2-?

Magnetization transfer (MT) and T(1) and T(2) relaxation of normal, trypsinized, and interleukin-1beta (IL-1beta)-treated cartilage were measured in the absence and presence of Gd-DTPA(2-). Without the addition of Gd-DTPA(2-), neither T(1) nor T(2) showed any significant change with cartilage damage. However, with Gd-DTPA(2-), trypsinized cartilage exhibited substantially shorter T(1) than normal cartilage, as expected due to the glycosaminoglycan (GAG) loss in these samples, and associated increased Gd-DTPA(2-) concentration.

Relaxivity and diffusion of gadolinium agents in cartilage.

Prior work indicates that the distribution of Gd(DTPA)(2-) (as measured by T(1)) is a good surrogate measure of the distribution of gycosaminoglycan (GAG) in cartilage. In addition to the measured T(1) in the presence of Gd(DTPA)(2-), the precision of the measurement of Gd(DTPA)(2-) concentration depends on the T(1) without Gd(DTPA)(2-) (T(o)(1)), and the relaxivity (r) of Gd(DTPA)(2-) in cartilage, parameters that are influenced by cartilage composition. These parameters were measured in native and GAG-depleted cartilage in order to estimate the bounds on the values one might expect for cartilage in arbitrary states of degeneration.