Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells

The adoptive transfer of donor T cells that have been genetically modified to recognize leukemia could prevent or treat leukemia relapse after allogeneic HSCT (allo-HSCT). However, adoptive therapy after allo-HSCT should be performed with T cells that have a defined endogenous TCR specificity to avoid GVHD. Ideally, T cells selected for genetic modification would also have the capacity to persist in vivo to ensure leukemia eradication. Here, we provide a strategy for deriving virus-specific T cells from CD45RA(-)CD62L(+)CD8(+) central memory T (T(CM)) cells purified from donor blood with clinical grade reagents, and redirect their specificity to the B-cell lineage marker CD19 through lentiviral transfer of a gene encoding a CD19-chimeric Ag receptor (CAR). Virus-specific T(CM) were selectively transduced by exposure to the CD19 CAR lentivirus after peptide stimulation, and bi-specific cells were subsequently enriched to high purity using MHC streptamers. Activation of bi-specific T cells through the CAR or the virus-specific TCR elicited phosphorylation of downstream signaling molecules with similar kinetics, and induced comparable cytokine secretion, proliferation, and lytic activity. These studies identify a strategy for tumor-specific therapy with CAR-modified T cells after allo-HSCT, and for comparative studies of CAR and TCR signaling.     

In vitro analysis of alpha-adrenoceptor interactions with the myogenic response in resistance vessels.

The interaction of alpha 1- and alpha 2-adrenoceptor constriction of isolated rat cremaster small arteries (mean diameter +/- SEM, 114 +/- 5 microns) with the myogenic mechanism was examined with in vitro videomicroscopy. Microdissected vessels were double-cannulated with glass micropipets in a tissue bath, and intraluminal pressure was set at 65 mm Hg baseline pressure. Norepinephrine (NE) concentration-response curves were obtained alone and in the presence of prazosin or rauwolscine to establish the concentration of NE required to selectively stimulate alpha 1- or alpha 2-adrenoceptors. A bimodal response was produced by NE alone, indicating interaction with more than one receptor population. Rauwolscine and prazosin each produced dextral displacement at low (< 0.1 microM) NE concentrations. However, while prazosin exhibited competitive antagonism, rauwolscine did not antagonize NE at concentrations > or = EC50 value. Thus, both alpha 1- and alpha 2-adrenoceptors mediate constriction at low NE concentrations, but only alpha 1-receptors contributed to constriction at intermediate and high concentrations. These data are in contrast to previous findings for the same vessels studied in vivo. Diameter responses to increases and decreases in transmural pressure from baseline were examined in the relaxed (passive) state with nitroprusside present, during spontaneous intrinsic tone, and during induced alpha 1- or alpha 2-tone (EC20 concentration of NE plus rauwolscine or prazosin). Myogenic constriction during increases in lumen pressure and myogenic inhibition of tone during decreases in pressure were greatest during alpha 2-tone, less during intrinsic tone and least during alpha 1-tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive flow evaluations of coronary artery bypass grafting using dynamic cardiac CT

We aimed to investigate the correlation of graft flow measurements between transit-time flow measurement (TTFM) during coronary artery bypass grafting (CABG) surgery and dynamic cardiac CT after the surgery.Fourteen patients underwent CABG with TTFM and postoperative dynamic cardiac CT; 11 internal thoracic artery (ITA) grafts and 15 saphenous venous grafts (SVGs) were included for analysis. Pearsons correlation analysis was performed for the comparisons of the TTFM and cardiac dynamic CT flow parameters.TTFM was not significantly correlated with the CT flow of the ITA grafts (r = −0.23, P = .49), but it had a very strong correlation with the CT flow of the SVGs (r = 0.83, P < .01).In patients who underwent CABG surgery, dynamic cardiac CT enabled quantitative evaluation of SVG flow, with good correlation with TTFM.     

Thermoregulatory sympathetic nervous system activity and diet‐induced waist‐circumference reduction in obese Japanese women

The present study is designed to investigate how and to what extent sympathovagal behavior in a balanced low‐calorie diet relates to favorable changes of body mass, waist circumference, and/or metabolic risk factors. The study involved 28 mildly obese women without clinical complications, who underwent an 8‐week calorie restriction program using a 1,200‐kcal daily diet with an adequate nutrient content; including two regular meals, and one formula meal replacement. All subjects were examined before and after the dietary intervention. We measured anthropometric parameters, blood pressure, and biochemical blood profiles for lipid metabolism. Autonomic nervous system activity was evaluated by heart rate variability power spectral analysis. The dietary intervention induced moderate, but significant reduction of waist circumference (?5.3% ± 0.8%), body fat percentage (?5.8% ± 0.8%), and body mass (?6.6% ± 0.5%). Linear regression analysis showed that Δvery low frequency (VLF) power reflecting energy metabolic‐ and thermoregulatory sympathetic function significantly correlated to Δwaist circumference (r = ?0.53, P < 0.01), Δbody fat percentage (r = ?0.39, P < 0.05), Δbody mass (r = ?0.43, P < 0.05), ΔHDL‐cholesterol/total cholesterol ratio (HDL‐C/TC) (r = 0.62, P < 0.001), and Δnonesterified fatty acids (NEFA) (r = 0.56, P < 0.01). A stepwise multiple regression analysis additionally revealed that Δwaist circumference (P = 0.024), ΔHDL‐C/TC (P = 0.013), and ΔNEFA (P = 0.016) were significant and independent factors, which contributing to the variance in ΔVLF power (r² = 0.61). Although causes and consequences of obesity continue to elude researchers, the present study indicates that thermoregulatory sympathetic activity relates to moderate waist‐circumference reduction together with favorable changes of blood lipid profiles after short‐term dietary modification in mildly obese women. Am. J. Hum. Biol. 2009. © 2009 Wiley‐Liss, Inc.     

Effects of dual-energy subtraction chest radiography on detection of small pulmonary nodules with varying attenuation: receiver operating characteristic analysis using a phantom study

Purpose  

The aim of this study was to investigate the detectability of simulated pulmonary nodules with different X-ray attenuation by flat-panel detector (FPD) chest radiography using a dual-exposure dual-energy subtraction (DES) technique.     

Topical immunology of nasal allergy and mucosal IgE antibodies

Summary In the present study, the in vitro tissue-radioallergosorbent test (t-RAST) was performed in two groups of patients: one with perennial attacks of sneezing, serous hypersecretion and nasal congestion, the other with nasal congestion only. The results obtained were compared with those obtained by a series of conventional allergy tests. We then found that t-RAST provided objective data comparable to those obtained with serum-RAST and that the t-RAST is a reliable means of quantitatively detecting specific IgE antibodies in the nasal mucosa. t-RAST is of special value to diagnosticians because it is able to discern unequivocally and easily those patients with localized nasal allergy.     

Mucosal pathology of the eustachian tube after exposure to sulfur dioxide

Summary We studied the mucosal pathology present in the eustachian tubes of guinea pigs following exposure to sulfur dioxide. Secretory sthenia but with slight deterioration of ciliary activity was observed in the mucosal samples examined. Our data have shown that 24-h exposure to 300 ppm sulfur dioxide does not cause otitis media with effusion in the guinea pig since active ciliary function will prevent any secretions produced from stagnating in the tympanic cavity.