Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma

AbstractWe applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (I-IIA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.     

CD45-mediated signaling pathway is involved in Rhizoctonia bataticola lectin (RBL)-induced proliferation and Th1/Th2 cytokine secretion in human PBMC

We earlier reported the mitogenic and immunostimulatory activities of Rhizoctonia bataticola lectin (RBL), purified from phytopathogenic fungus R. bataticola in human PBMC. The lectin demonstrates specificity towards glycoproteins containing complex N-glycans. Since CD45-protein tyrosine phosphatase that abundantly expresses N-glycans is important in T-cell signaling, the study aimed to investigate the involvement of CD45 in the immunomodulatory activities of RBL. Flowcytometry and confocal microscopy studies revealed that RBL exhibited binding to PBMC and colocalized with CD45. The binding was comparable in cells expressing different CD45 isoforms-RA, -RB and -RO. CD45 blocking antibody reduced the binding and proliferation of PBMC induced by RBL. CD45-PTPase inhibitor dephostatin inhibited RBL-induced proliferation, expression of CD25 and pZAP-70. RBL-induced secretion of Th1/Th2 cytokines were significantly inhibited in presence of dephostatin. Also, dephostatin blocked phosphorylation of p38MAPK and STAT-5 that was crucial for the biological functions of RBL. The study demonstrates the involvement of CD45-mediated signaling in RBL-induced PBMC proliferation and Th1/Th2 cytokine secretion through activation of p38MAPK and STAT-5.     

Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans

We sought toexamine further the potential role of nitric oxide (NO) in the neurallymediated cutaneous vasodilation in nonacral skin during body heating inhumans. Six subjects were heated with a water-perfused suit whilecutaneous blood flow was measured by using laser-Doppler flowmetersplaced on both forearms. The NO synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) was given selectivelyto one forearm via a brachial artery catheter after marked cutaneousvasodilation had been established. During body heating, oraltemperature increased by 1.1 ± 0.1°C while heart rate increasedby 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascularconductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peakresponse to heating (P < 0.05 vs.pre-L-NMMA values) afterL-NMMA infusion. In somesubjects, L-NMMA caused CVC tofall by ~30%; in others, it had little impact on the cutaneouscirculation. CVC in the control arm showed a similar increase withheating, then stayed constant whileL-NMMA was given to thecontralateral side. These results demonstrate that NO contributesmodestly, but not consistently, to cutaneous vasodilation during bodyheating in humans. They also indicate that NO is not the only factorresponsible for the dilation.

     

Effects of heme on the structure of the denatured state and folding kinetics of cytochrome b562

Heme-linked proteins, such as cytochromes, are popular subjects for protein folding studies. There is the underlying question of whether the heme affects the structure of the denatured state by cross-linking it and forming other interactions, which would perturb the folding pathway. We have studied wild-type and mutant cytochrome b562 from Escherichia coli, a 106 residue four-alpha-helical bundle. The holo protein apparently refolds with a half-life of 4 micros in its ferrous state. We have analysed the folding of the apo protein using continuous-flow fluorescence as well as stopped-flow fluorescence and CD. The apo protein folded much more slowly with a half-life of 270 micros that was unaffected by the presence of exogenous heme. We examined the nature of the denatured states of both holo and apo proteins by NMR methods over a range of concentrations of guanidine hydrochloride. The starting point for folding of the holo protein in concentrations of denaturant around the denaturation transition was a highly ordered native-like species with heme bound. Fully denatured holo protein at higher concentrations of denaturant consisted of denatured apo protein and free heme. Our results suggest that the very fast folding species of denatured holo protein is in a compact state, whereas the normal folding pathway from fully denatured holo protein consists of the slower folding of the apo protein followed by the binding of heme. These data should be considered in the analysis of folding of heme proteins.     

Meiosis in garden roses

Summary Meiosis in 96 varieties of garden roses was studied. While the euploid numbers were most frequent, in exceptional cases, aneuploid numbers were recorded. Intervarietal variation in chromosome pairing is reflected in the varying degrees of expression of univalents, heteromorphic bivalents, bivalents with double secondary constrictions and multivalents. Supernumerary fragments in addition to the euploid chromosome complement were recorded in three varieties. Three varieties of floribundas and one of hybrid polyanthas were chromosome numerical mosaics.A part of Ph. D. thesis submitted by the senior author to the Post Graduate School, Indian Agricultural Research Institute, New Delhi, India.     

Pachytene analysis in oryza

Summary Pachytene analysis was undertaken in 4 japonica-indica rice hybrids. In all these hybrids, pairing was exceedingly abnormal lending evidence for structural hybridity. Earlier investigators who analysed metaphase-I and later stages of meiosis concluded that sterility is due to genic causes. The present investigation clearly points out the chromosomal causes of sterility and makes possible a reinterpretation of (1) non-recovery of recombinant phenotypes and (2) the occurrence of albina and other mutations in hybrid progenies.