CD34-positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform

Acute promyelocytic leukemia (APL) has a favorable prognosis. Current therapy includes chemotherapy used in combination with all-trans-retinoic acid (ATRA). Although the differentiating effects of ATRA on promyelocytes have been well established, in vitro studies have shown that less-differentiated APL blasts (CD34(+)) demonstrate a variable responsiveness to ATRA. To assess the clinical relevance of this finding, we analyzed a cohort of 38 patients with t(15;17) and/or PML-RARalpha APL to determine the incidence and laboratory features of CD34(+) APL. Thirty-two percent (12/38) of cases were CD34(+). There was a difference in WBC at presentation between CD34(+) and CD34(-) cases (34.6 +/- 9.2, mean +/- standard error vs. 5.4 +/- 2.0, P = 0.009). Patients with CD34(+) APL demonstrated a micro/hypogranular phenotype (75%) (P = 0.001), co-expression of CD2(+) (83%) (P = 0.001), and the bcr3 isoform (100%) (P = 0.017). In contrast, CD34(-) cases demonstrated hypergranular morphology (65%), CD2(+) (15%), and the bcr1 isoform (50%). A high presenting WBC count (\G10 x 10(9)/L) was associated with an inferior overall survival (Log rank = 0.0047). Patients with CD34(+) APL demonstrated an incidence of early mortality of 50%. Despite a marked correlation between CD34 positivity and increased WBC count, overall survival of CD34(+) and CD34(-) cases did not differ significantly in our small cohort. Immunophenotypic analysis for CD34 expression should be included in future large APL trials to determine if detection of CD34(+) blasts represents an independent adverse prognostic factor.     

Subcompartmentalization of HIV-1 quasispecies between seminal cells and seminal plasma indicates their origin in distinct genital tissues

The mononuclear cells and plasma components of semen from HIV-infected subjects have been shown to contain HIV-1. However, there is very little information as to whether distinct HIV-1 population are present in these two seminal compartments or as to their tissue of origin. Phylogenetic analysis of nucleotide sequences of the C2-V5 region of the HIV-1 gp120 from HIV-1 RNA isolated from seminal cells and seminal plasma of five subjects indicates that the HIV-1 population derived from seminal plasma was distinct from that present in seminal cells. Such subcompartmentalization of HIV-1 between seminal cells and seminal plasma was detected as early as 3 months after seroconversion and persisted up to 38 months following seroconversion. Furthermore, comparison of HIV-1 sequences between testis and prostate tissues showed distinct HIV-1 populations in these tissue compartments. In situ real-time (Taqman) PCR analysis of prostate and testis tissues indicated that T lymphocytes were the predominant cells infected with HIV-1 in both of these tissues. Since seminal plasma is derived from prostate and most of the seminal cells originate from the rete testis and epididymis, these results are consistent with the idea that HIV-1 in seminal plasma is derived from the prostate, while HIV-1-infected cells in semen originate mostly from the rete testis and epididymis. These findings provide for the first time evidence of subcompartmentalization of HIV-1 in male genital organs and suggest that intervention strategies such as vasectomy may not prevent sexual transmission.     

Collaborative study to assess risk of lung disease in Pi MZ phenotype subjects

We studied 143 Pi MZ heterozygous (MZ) subjects from random populations that had been examined previously for alpha 1-antitrypsin phenotype. Each Pi MZ subject was closely matched with a Pi M control subject from the same population at each of 6 centers. An expanded National Heart, Lung and Blood Institute (NHLBI) respiratory symptom questionnaire was completed by each subject. Pulmonary function tests designed to detect established as well as early obstructive airway abnormalities were administered. Multivariate analysis of the variance of data from the questionnaire and pulmonary function tests corrected for age, race, sex, and smoking history showed no significant difference (p less than 0.05) between subjects of Pi MZ and Pi M phenotype. The size of the populations studied and number of observations made for each variable were sufficient to assure that small differences could be detected with 95% power. We conclude that MZ phenotype alone carries no greater risk of developing lung disease than M phenotype.     

In vivo response times for a heated skin surface CO2 electrode during rest and exercise

The continuous, noninvasive estimation of arterial carbon dioxide tension (PaCO2) by heated skin surface electrodes has recently become available for pediatric patients. Skin surface (PsCO2) electrodes can enhance the safety of procedures such as intubation, bronchoscopy, ventilator changes, sleep studies, or measurement of the ventilatory response to CO2 or hypoxia. However, clinical situations that include rapid changes in PaCO2 demand knowledge of the in vivo response time. We compared the response of a heated PsCO2 electrode to end tidal CO2 (PetCO2) during abrupt changes in inspired CO2 from room air to 7% CO2 and back to room air. We obtained 54 curves on nine healthy subjects. There was an initial lag time with less than a 10% change in PsCO2. Then PsCO2 approached PetCO2 exponentially. For subjects at rest changing from breathing room air to 7% CO2, the initial lag time was 40 +/- 2 seconds and the 50% response time of the exponential portion was 46 +/- 3 seconds. Thus, it took 86 seconds for the electrode to record a 60% response to an abrupt increase in inspired CO2. The initial lag and 50% response time were considerably shorter during exercise (30 +/- 2 and 33 +/- 2 seconds) and even shorter when switched from breathing 7% CO2 to room air (23 +/- 2 and 21 +/- 2 seconds). Exercise did not further reduce the response time when CO2 was initially elevated, suggesting the faster response time was due to vasodilation of the skin due to elevated CO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxyntomodulin suppresses appetite and reduces food intake in humans

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.