Citations

SummaryIntroductionHigh‐performance liquid chromatography (HPLC) is a method commonly used for the detection of hemoglobin (Hb) variants. In addition to providing precise quantitation of Hb A2 and Hb F, the reported retention time and peak shape of a high number of hemoglobin (Hb) variants are very helpful for presumptive identification. However, there is a scarcity of summarized data in the literature of the mobility of Hb variants on this method.MethodsA total of 383 Hb variants were studied on the Bio‐Rad Variant ™ Classic HPLC instrument. Hb variant identification used a number of methods, including confirmation by DNA sequencing in at least one case for all alpha and beta chain Hb variants.ResultsRetention time data and the number of occurrences of each Hb variant were obtained. This showed that rare Hb variants can have similar retention times to the five most common alpha or beta chain Hb variants.ConclusionHPLC is a very powerful tool in the evaluation of Hb variants, particularly when combined with other methods. However, it should not be used as a stand‐alone method for definitive identification of Hb variants.

Abstract —Elevation of renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion increases sodium excretion. This natriuretic response is blunted by the nonspecific inhibition of the cyclooxygenase (COX) enzymes. The present study tested the hypothesis that the natriuretic response to increased RIHP during direct renal interstitial volume expansion is dependent on COX-1 but not COX-2. RIHP and fractional excretion of sodium (FE Na ) were measured before and after direct renal interstitial volume expansion in control rats (n=7), rats infused with the COX-1 inhibitor piroxicam (n=6, 1.5 mg/kg), and rats infused with the COX-2 inhibitors NS-398 (n=5, 1.5 mg/kg) and meloxicam (n=6, 0.3 mg/kg). In control animals, direct renal interstitial volume expansion significantly increased RIHP (Δ2.3±0.5 mm Hg, P <0.05) and FE Na (Δ1.1±0.3%, P <0.05). Likewise, in animals infused with NS-398 or meloxicam, direct renal interstitial volume expansion significantly increased RIHP (Δ1.8±0.6 mm Hg, P <0.05, and Δ1.7±0.3 mm Hg, P <0.05) and FE Na (Δ1.5±0.4%, P <0.05, and Δ1.1±0.3%, P <0.05), respectively. In contrast, infusion of piroxicam significantly blunted the natriuretic response to direct renal interstitial volume expansion (ΔFE Na 0.3±0.2%), even though RIHP was increased (Δ1.9±0.6 mm Hg, P <0.05). Infusion of piroxicam but not NS-398 or meloxicam blunted the natriuretic response to increased renal interstitial hydrostatic pressure, suggesting that the natriuretic response to increased blood pressure may be preserved during inhibition of COX-2.

AbstractPurpose: The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B- and T-cell malignancies. In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27.Experimental Design: The fully human mAb 1F5 was generated using human Ig transgenic mice and characterized by analytical and functional assays in vitro. Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. A pilot study of 1F5 was conducted in non-human primates to assess toxicity.Results: 1F5 binds with high affinity and specificity to human and macaque CD27 and competes with ligand binding. 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of 1F5 to cynomolgus monkeys was well tolerated without evidence of significant toxicity or depletion of circulating lymphocytes.Conclusions: Collectively, the data suggest that the human mAb 1F5, which has recently entered clinical development under the name CDX-1127, may provide direct antitumor activity against CD27-expressing lymphoma or leukemia, independent of its potential to enhance immunity through its agonistic properties. Clin Cancer Res; 18(14); 3812–21. ©2012 AACR.

Purpose. Women with ductal carcinomain situ(DCIS) are often candidates for breast-conserving therapy, and one option for radiation treatment is partial breast irradiation (PBI). This study evaluates the use of preoperative breast magnetic resonance imaging (MRI) for PBI selection in DCIS patients.Methods. Between 2002 and 2009, 136 women with newly diagnosed DCIS underwent a preoperative bilateral breast MRI at Mayo Clinic in Florida. One hundred seventeen women were deemed eligible for PBI by the NSABP B-39 (National Surgical Adjuvant Breast and Bowel Project, Protocol B-39) inclusion criteria using physical examination, mammogram, and/or ultrasound. MRIs were reviewed for their impact on patient eligibility, and findings were pathologically confirmed.Results. Of the 117 patients, 23 (20%) were found ineligible because of pathologically proven MRI findings. MRI detected additional ipsilateral breast cancer in 21 (18%) patients. Of these women, 15 (13%) had more extensive disease than originally noted before MRI, and 6 (5%) had multicentric disease in the ipsilateral breast. In addition, contralateral breast cancer was detected in 4 (4%).Conclusions. Preoperative breast MRI altered the PBI recommendations for 20% of women. Bilateral breast MRI should be an integral part of the preoperative evaluation of all patients with DCIS being considered for PBI.