Myocardial tissue characterization by combining late gadolinium enhancement imaging and percent edema mapping: a novel T2 map-based MRI method in canine myocardial infarction.

Background: Assessing the extent of ischemic and reperfusion-associated myocardial injuries remains challenging with current magnetic resonance imaging (MRI) techniques. Our aim was to develop a tissue characterization mapping (TCM) technique by combining late gadolinium enhancement (LGE) with our novel percent edema mapping (PEM) approach to enable the classification of tissue represented by MRI voxels as healthy, myocardial edema (ME), necrosis, myocardial hemorrhage (MH), or scar.

Methods: Six dogs underwent closed-chest myocardial infarct (MI) generation.

In the Absence of Central pre-B Cell Receptor Selection, Peripheral Selection Attempts to Optimize the Antibody Repertoire by Enriching for CDR-H3 Y101.

Sequential developmental checkpoints are used to "optimize" the B cell antigen receptor repertoire by minimizing production of autoreactive or useless immunoglobulins and enriching for potentially protective antibodies. The first and apparently most impactful checkpoint requires μHC to form a functional pre-B cell receptor (preBCR) by associating with surrogate light chain, which is composed of VpreB and λ5. Absence of any of the preBCR components causes a block in B cell development that is characterized by severe immature B cell lymphopenia.

Alterations in B cell development, CDR-H3 repertoire and dsDNA-binding antibody production among C57BL/6 ΔD-iD mice congenic for the lupus susceptibility loci sle1, sle2 or sle3.

Systemic lupus erythematosus (SLE) is an autoimmune disease that reflects a failure to block the production of self-reactive antibodies, especially those that bind double-stranded DNA (dsDNA). Backcrossing the lupus-prone NZM2410 genome onto C57BL/6 led to the identification of three genomic intervals, termed sle1, sle2 and sle3, which are associated with lupus susceptibility. We previously generated a C57BL/6 strain congenic for an immunoglobulin D locus (ΔD-iD) that enriches for arginine at dsDNA-binding positions.

HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence.

Complementarity Determining Region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen-binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection.

Age-independent myocardial infarct quantification by signal intensity percent infarct mapping in swine.

Purpose: To test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age.

Materials And Methods: Forty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.

Violation of an evolutionarily conserved immunoglobulin diversity gene sequence preference promotes production of dsDNA-specific IgG antibodies.

Variability in the developing antibody repertoire is focused on the third complementarity determining region of the H chain (CDR-H3), which lies at the center of the antigen binding site where it often plays a decisive role in antigen binding. The power of VDJ recombination and N nucleotide addition has led to the common conception that the sequence of CDR-H3 is unrestricted in its variability and random in its composition. Under this view, the immune response is solely controlled by somatic positive and negative clonal selection mechanisms that act on individual B cells to promote production of protective antibodies and prevent the production of self-reactive antibodies.

Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.

To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed.

The link between antibodies to OxLDL and natural protection against pneumococci depends on D(H) gene conservation.

Selection and physiological production of protective natural antibodies (NAbs) have been associated with exposure to endogenous antigens. The extent to which this association depends on germline NAb sequence is uncertain. Here we show that alterations in germline D(H) sequence can sever the association between the production of self-reactive NAbs and NAbs that afford protection against a pathogen.

Determination of infarct size in ex vivo swine hearts by multidetector computed tomography using gadolinium as contrast medium.

Objective: To demonstrate the feasibility of using multidetector computed tomography with gadolinium contrast (Gd-MDCT) for the quantification of myocardial infarct (MI).

Materials And Methods: MI was induced in male swine (n = 6). One week later, the animals received 0.

Quantification of myocardial viability distribution with Gd(DTPA) bolus-enhanced, signal intensity-based percent infarct mapping.

Introduction: A substantial, common shortcoming of the currently used semiautomated techniques for the quantification of myocardial infarct with delayed enhancement magnetic resonance imaging is the assumption that the whole myocardial slab that corresponds to the hyperenhanced tomographic area is 100% nonviable. This assumption is, however, incorrect. To resolve this conflict, we have recently proposed the signal intensity percent-infarct mapping method and validated it in an ex vivo, canine experiment.

Acute infarct selective MRI contrast agent.

To determine the infarct affinity of a low molecular weight contrast agent, Gd(ABE-DTTA), during the subacute phase of myocardial infarct (MI). Dogs (n = 7) were examined, using a closed-chest, reperfused MI model. MI was generated by occluding for 180 min the left anterior descending (LAD) coronary artery with an angioplasty balloon.

Percent infarct mapping for delayed contrast enhancement magnetic resonance imaging to quantify myocardial viability by Gd(DTPA).

Purpose: To demonstrate the advantages of signal intensity percent-infarct-mapping (SI-PIM) using the standard delayed enhancement (DE) acquisition in assessing viability following myocardial infarction (MI). SI-PIM quantifies MI density with a voxel-by-voxel resolution in clinically used DE images.

Materials And Methods: In canines (n= 6), 96 hours after reperfused MI and administration of 0.

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR.

Background: Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent.Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model.

Epigenetic reprogramming: a possible etiological factor in bladder pain syndrome/interstitial cystitis?

Purpose: The etiology of bladder pain syndrome/interstitial cystitis is poorly understood. The possibility that epigenetic reprogramming may have a role is discussed.

Materials And Methods: A literature search was performed with the Entrez-PubMed(R) database using the key words urinary bladder, epigenetics, epigenetic mechanisms, interstitial cystitis, diagnosis, etiology, urothelial cells, mast cells, nerve fibers, nerves, nerve growth factor, recurrent injury, stem cells, inflammatory mediators and demethylases.

Virtual in vivo biopsy map of early prostate neoplasm in TRAMP mice by MRI.

Background: The noninvasive, early detection of Prostate Intraepithelial Neoplasia (PIN), a precancerous neoplasia of the prostate, would be highly desirable. In our experiments, we used TRAMP mice to model PIN in the range of grade 1 through grade 4.

Methods: Contrast enhanced pixel-by-pixel R1 mapping of the prostate was used to detect areas with the different prostate neoplasia grades.

Head-to-head comparison between delayed enhancement and percent infarct mapping for assessment of myocardial infarct size in a canine model.

Purpose: To compare a novel method, percent-infarct-mapping (PIM), with conventional delayed enhancement (DE) of contrast for accurate myocardial viability assessment. Contrary to signal intensity (SI), the longitudinal relaxation-rate enhancement (DeltaR1) is an intrinsic parameter linearly proportional to the concentration of contrast agent (CA). Determining DeltaR1 voxel-by-voxel, after administering an infarct-avid CA, allows determination of per-voxel percentage of infarcted tissue.

In vivo myocardial tissue kinetics of Gd(ABE-DTTA), a tissue-persistent contrast agent.

The phenomenological tissue kinetics of Gd(ABE-DTTA) was investigated in myocardial infarction (MI). Reperfused infarction was generated by balloon catheter in closed-chest canines (N=11). Forty-eight hours thereafter, inversion-recovery (IR)-prepared fast gradient-echo control images were acquired with varying inversion times (TIs).

SIRT1 is significantly elevated in mouse and human prostate cancer.

Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1).

A combined method for the determination of myocardial perfusion in experimental animals using microspheres and CMR.

A convenient method is introduced for myocardial perfusion research by combining multislice short-axis cine cardiovascular magnetic resonance (MSA-CMR) and colored microspheres (CM). In canine control-ischemia-reperfusion (n = 11), Cardiac output (CO) was measured using MSA-CMR (COMSA), Phase Contrast CMR (PC-CMR, COPC) and CM (from reference blood samples, COmicro) in 3 experimental periods per animal. COmicro significantly and systematically overestimated COMSA (median deviation: 291 mL/min, p < 0.

Cancer progression in the transgenic adenocarcinoma of mouse prostate mouse is related to energy balance, body mass, and body composition, but not food intake.

Calorie restriction can inhibit or delay carcinogenesis, reportedly due to a reduction in calorie intake rather than by concurrent changes in body mass and/or composition. Our objective was to test the hypothesis that body mass and/or composition have an important effect, independent of energy intake, on the benefits or hazards associated with calorie restriction or overeating, respectively. In the first experiment, transgenic mice that spontaneously develop prostate cancer [transgenic adenocarcinoma of mouse prostate (TRAMP)] were housed at 27 degrees C or 22 degrees C and pair fed the same diet for 21 weeks (95% of ad libitum intake at 27 degrees C).

Percent infarct mapping: an R1-map-based CE-MRI method for determining myocardial viability distribution.

Viability detection is crucial for the management of myocardial infarction (MI). Signal intensity (SI)-based MRI methods may overestimate infarct size in vivo. In contrast to SI, the longitudinal relaxation-rate enhancement (DeltaR1) is an intrinsic parameter that is linearly proportional to the concentration of contrast agent (CA).

Gd(ABE-DTTA), a novel contrast agent, at the MRI-effective dose shows absence of deleterious physiological effects in dogs.

The physiological effects of a novel MRI contrast agent, Gd(ABE-DTTA), were investigated in dogs, monitoring parameters in blood samples. Each animal (n = 8 in the short-term, n = 4 in the long-term group) underwent isoflurane anesthesia followed by the generation of myocardial infarction and received a contrast agent at the MRI effective dose. Blood samples were collected 24 and 48 h, and 7, 14, 28, 35, 49 and 56 days after contrast agent administration.

beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts.

The cells' ability to proliferate in response to growth factor stimulation is significantly altered during cancer progression. To investigate the mechanisms underlying these alterations in prostate cancer, the role and expression of beta1A integrin and type 1 insulin-like growth factor receptor (IGF-IR), known to contribute to cell proliferation and transformation, were analyzed. Using small interfering RNA oligonucleotides to down-regulate beta1A, we show that beta1A expression is required for IGF-IR-mediated prostate cancer cell proliferation and anchorage-independent growth.

Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP).

Studies in vitro suggest that osteopontin (OPN), an extracellular matrix protein secreted by macrophages infiltrating prostate tumors, and by tumor cells, may have a role in the transition from clinically insignificant tumors to metastatic prostate cancer (PC). Latent PC occurs at equal rates in Western and Asian men, but the incidence of advanced PC is many-fold higher in Western men. Our earlier studies in TRAnsgenic Mouse Prostate adenocarcinoma (TRAMP) mice showed that genistein, an isoflavone found in soybeans, lowered the incidence of advanced PC.