11C-diprenorphine binding in Huntington''s disease: a comparison of region of interest analysis with statistical parametric mapping

The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.     

A comparison of the antigen-presenting capabilities of class II MHC-expressing human lung epithelial and endothelial cells

Human lung alveolar epithelial cells constitutively express class II major histocompatibility complex (MHC). Human lung microvascular endothelial and small airway epithelial cells can be induced to express class II MHC by stimulation with the pro-inflammatory cytokine interferon-gamma. The levels of class II MHC on lung epithelial and endothelial cells were comparable to those seen on an Epstein-Barr virus (EBV)-transformed B-cell line. However, the costimulatory molecules B7-1 and B7-2 were not expressed. The ability of the class II MHC expressing human lung parenchymal cells to present alloantigen to CD4+ T lymphocytes was investigated. Freshly isolated human alveolar epithelial cells (type II pneumocytes) and monolayers of interferon-gamma-stimulated small airway epithelial and lung microvascular endothelial cells were co-cultured with allogeneic CD4+ T lymphocytes and proliferation determined by [3H]thymidine incorporation. A clear difference was observed between effects of the epithelial and endothelial cells on CD4+ T-lymphocyte activation. Alveolar and small airway epithelial cells failed to stimulate the proliferation of allogeneic CD4+ T lymphocytes whereas lung microvascular endothelial cells did stimulate proliferation. This difference could not be explained by the levels of class II MHC or the lack of B7-1 and B7-2 solely. Microvascular endothelial cells, and not alveolar or small airway epithelial cells, possess B7-independent costimulatory pathways.     

Neonatal diagnosis of familial hypercholesterolemia in newborns born to a parent with a molecularly defined heterozygous familial hypercholesterolemia

This study was designed to compare blood lipid levels in newborn individuals with molecularly defined heterozygous familial hypercholesterolemia [FH] to those in non-affected babies and to clarify the value of lipid determinations in assessment of diagnosis of FH at birth and 1 year of age. Twenty-five babies were born to 21 parents with DNA-documented heterozygous FH. Analysis of their cord blood samples revealed 11 newborns with the FH-North Karelia [FH-NK] mutation, 3 newborns with the FH-Helsinki [FH-HKI] mutation, and 11 nonaffected newborns. Cord serum total [TC] and LDL cholesterol [LDL-C] levels (mean +/- SD) in affected newborns (2.60 +/- 0.70 and 1.77 +/- 0.56, respectively) were significantly (P < .001) higher than those in nonaffected ones (1.54 +/- 0.23 and 0.78 +/- 0.15, respectively) and another cohort of 30 randomly selected control samples from apparently healthy newborns (1.84 +/- 0.46 and 1.03 +/- 0.30, respectively). However, there was overlapping of individual lipid levels in these three groups precluding the use of TC or LDL-C determinations in neonatal diagnosis of FH. In contrast, 1 year follow-up samples from 10 affected and 7 nonaffected individuals, as well as additional samples collected from another group of 8 affected and 9 nonaffected individuals, indicated that serum cholesterol levels showed much greater increment in children with FH. Thus, at the age of 1 year the mean serum TC and LDL-C levels in the affected infants (8.38 +/- 1.18 and 7.02 +/- 1.07, respectively) were much higher (P < .001) than the corresponding levels (4.40 +/- 0.66 and 2.89 +/- 0.68, respectively) in the nonaffected infants, and the individual ranges of TC and LDL-C levels were nonoverlapping in these two groups. Serum HDL cholesterol [HDL-C] levels in 1-year-old children with FH (0.95 +/- 0.14) were approximately 20% lower than those of their similar at birth. In conclusion, phenotypic expression of heterozygous FH, as defined by molecular analysis of genomic DNA, is evident in serum LDL-C (but not HDL-C) levels already at birth, but for diagnostic purposes blood lipid determinations carried out at the age of 1 year are highly superior to those performed at birth.     

Wear resistance of four luting agents as a function of marginal gap distance, cement type, and restorative material

This study investigated the effect of marginal gap width, luting cement, and restorative material on the wear resistance of the luting cement in areas where no occlusal contact is present. Three types of resin luting cement and one resin-modified glass-ionomer cement were used with two inlay systems, a resin composite, and an all-ceramic system. Bovine enamel represented tooth structure. Toothbrush abrasion was the wear modality. Three predetermined gap widths were selected: 240 +/- 30 microns, 150 +/- 30 microns, and 60 +/- 30 microns. All specimens were thermocycled. Regardless of the luting cement or the restorative material, there was a significant difference (P < 0.05) in wear resistance of the cement among the three gap distances at both the enamel and restoration interface. Vertical wear of the luting cement at the enamel interface increased linearly with marginal gap distance when all four cements were considered together (r2 > 0.51), regardless of type of restorative material used. The resin-modified glass-ionomer cement showed the least amount of wear for all variables considered. Significant differences in wear were found between the four luting cements at wide gap distances (240 microns) at the enamel interface, regardless of type of restorative material used. No significant differences were found between the two restorative materials at the enamel interface at the three gap distances.     

Inhibition by nociceptin of the light-evoked release of ACh from retinal cholinergic neurones

The retina possesses cholinergic amacrine cells which release acetylcholine (ACh) in response to flickering light. Using an eye-cup preparation in anaesthetized rabbits we found that when the retina was exposed to nociceptin, the light-evoked release of ACh was reduced in a concentration-dependent manner (IC50 = 100 nM), the maximum effect being 60% inhibition. Opioid receptors were not involved in the inhibitory effect of nociceptin because its action was not blocked by naloxone (1 microM) and furthermore mu-opioids enhanced the light-evoked release of ACh. Using rabbit retina homogenates we found that the retina possessed a substantial number of high-affinity binding sites for [3H]-nociceptin indicating the presence of ORL1-receptors. Since [des-Phe1]-nociceptin, which has no affinity for the ORL1-receptor, had no effect on the light-evoked release of ACh it is unlikely that the action of nociceptin was simply non-specific. We conclude that the inhibitory effect of nociceptin on retinal ACh release involves activation of the ORL1 receptors.     

A Bayesian approach to validating STR multiplex databases for use in forensic casework

A previous paper in this journal has described the conventional statistical analysis of three databases (Caucasian, Afro-Caribbean and Asians from the Indian subcontinent) where individuals are typed at six short tandem repeat (STR) loci. This paper presents a Bayesian analysis of the same data and the approach is centred on the concept of estimating coancestry coefficients from mixed databases. Posterior distributions for the three databases are presented and the discussed and the consequences of implementing bootstrap estimation procedures are also shown.     

Simulation of the enzyme reaction mechanism of malate dehydrogenase

A hybrid numerical method, which employs molecular mechanics to describe the bulk of the solvent-protein matrix and a semiempirical quantum-mechanical treatment for atoms near the reactive site, was utilized to simulate the minimum energy surface and reaction pathway for the interconversion of malate and oxaloacetate catalyzed by the enzyme malate dehydrogenase (MDH). A reaction mechanism for proton and hydride transfers associated with MDH and cofactor nicotinamide adenine dinucleotide (NAD) is deduced from the topology of the calculated energy surface. The proposed mechanism consists of (1) a sequential reaction with proton transfer preceding hydride transfer (malate to oxaloacetate direction), (2) the existence of two transition states with energy barriers of approximately 7 and 15 kcal/mol for the proton and hydride transfers, respectively, and (3) reactant (malate) and product (oxaloacetate) states that are nearly isoenergetic. Simulation analysis of the calculated energy profile shows that solvent effects due to the protein matrix dramatically alter the intrinsic reactivity of the functional groups involved in the MDH reaction, resulting in energetics similar to that found in aqueous solution. An energy decomposition analysis indicates that specific MDH residues (Arg-81, Arg-87, Asn-119, Asp-150, and Arg-153) in the vicinity of the substrate make significant energetic contributions to the stabilization of proton transfer and destabilization of hydride transfer. This suggests that these amino acids play an important role in the catalytic properties of MDH.     

The National Cancer Data Base report on race, age, and region variations in prostate cancer treatment

BACKGROUND: Patterns of care for prostate cancer patients in the United States have changed as early detection has improved. The National Cancer Data Base of the American College of Surgeons Commission on Cancer provides information about the treatment of patients in all age, race, and regional groups from institutions that represent cancer care at the community level as well as in medical centers. METHODS: Data on 251,416 prostate cancer patients diagnosed between 1992 and 1994 were studied. Patient and disease characteristics, including age, race, the geographic region from which a case was reported, American Joint Committee on Cancer stage, and tumor grade were related to the primary pattern of treatment. Stage-standardized comparisons were made among different age groups, race groups, and regional groups. RESULTS: Stage and tumor grade varied little across age, race, and regional classifications. African American patients were more likely than white patients to have Stage IV prostate cancer at the time of diagnosis. Men older than 75 years had greater proportions than younger men of both the earliest and the most advanced stages of cancer. Overall, 24.6% of patients received no cancer-directed therapy, 11.6% were treated with hormones or endocrine surgery, 28.6% received radiation therapy, 28.3% underwent radical prostatectomy, and 6.9% were treated by other modalities or combinations of modalities. Treatment patterns varied markedly by age. The selection of radical prostatectomy relative to no treatment and radiation therapy varied by race and region. CONCLUSIONS: The results of this study showed that prostate cancer treatment varies by patient age, race, and geographic region. The reasons for some of these variations are not well understood and deserve further investigation.     

The comparison of postoperative multiple organ failure with arterial disease to that with gastrointestinal cancer]

The clinical features of 22 postoperative multiple organ failure (MOF) patients, comprised of 8 with arterial disease (A-MOF) and 14 with gastrointestinal cancer (G-MOF), were investigated. Differences in the operative time, blood loss, and mortality were not significant. The initial organ impaired was the lungs in 78.6% of G-MOF patients and the heart or kidneys in all A-MOF patients. Infection developed in over 80% of both groups. In many A-MOF patients, the pneumonia or septicemia developed secondary to organ failure, while intraabdominal infection triggered respiratory failure in many G-MOF patients. Our organisms in infected specimens and their antibiotic sensitivities was valuable for the early administration of effective antibiotics. Upper gastrointestinal tract bleeding was important in the prognosis of both groups and occurred more frequently in A-MOF than in G-MOF patients. Consumption coagulopathy in A-MOF patients and DIC induced by infection in G-MOF patients mainly caused such bleeding. Preoperative administration of heparin was effective in improving coagulopathy. Furthermore, measurement of intramural pH with tonometer in the stomach and gastric irrigation with oxygenated perfluorochemicals were effective in the prediction and prevention of gastrointestinal bleeding.     

Children's decoding of emotion in expressive body movement: The development of cue attunement.

Little research has focused on children's decoding of emotional meaning in expressive body movement; none has considered which movement cues children use to detect emotional meaning. The current study investigated the general ability to decode happiness, sadness, anger, and fear in dance forms of expressive body movement and the specific ability to detect differences in the intensity of anger and happiness when the relative amount of movement cue specifying each emotion was systematically varied. Four-year-olds (n?=?25), 5-year-olds (n?=?25), 8-year-olds (n?=?29), and adults (n?=?24) completed an emotion contrast task and 2 emotion intensity tasks. Decoding ability exceeding chance levels was demonstrated for sadness by 4-year-olds; for sadness, fear, and happiness by 5-year-olds; and for all emotions by 8-year-olds and adults. Children as young as 5 years were shown to rely on emotion-specific movement cues in their decoding of anger and happiness intensity. The theoretical significance of these effects across development is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)