Search

Femoral vein catheterization can be undertaken easily and quickly by inexperienced physicians. However, accurate vein puncture is critical to reducing complications that include pseudoaneurysm and arteriovenous fistulae formation.

We describe an approach to generate multicomponent surface-immobilized patterns and gradients on the basis of the photochemically controlled covalent coupling of solution-phase biomolecules to benzophenone-modified substrates. Gradients were simply achieved by continuously varying the exposure to nondamaging UV light across the surface with the gradient profile controlled by biomolecule concentration and the spatial and temporal illumination of the surface. Sequential exposure of the same surface in the presence of different biomolecules resulted in overlapping patterns and gradients of proteins and carbohydrates. Finally, we preliminarily demonstrate that the resulting surfaces are suitable for generating model substrates to probe cell-substrate interactions.

Background and Purpose: To evaluate the impact of radiotherapy (RT) parameters on outcome in the SIOP/UKCCSG study of pre-RT chemotherapy for Supratentorial Primitive Neuro-ectodermal Tumours., Methods and Materials: Sixty-two patients aged 2.9-16.6 (median 6.4 years) were eligible. Forty-eight (77%) had non-pineal sites and 14 (23%) had pineal sites. Eleven were randomized to RT alone (6) and five to pre-RT Vincristine, Etoposide, Carboplatin and Cyclophosphamide. Fifty-one were not randomized, 15 receiving RT alone and 36 receiving pre-RT chemotherapy. Craniospinal RT (CSRT) 35 Gy/21 fractions were followed by 20 Gy/12 fractions to primary tumour., Results: Mean CSRT dose was 34.7 Gy and mean total primary dose was 53.4 Gy for those who received radiotherapy. Of 30 relapses, 18 (60%) were local only and 5 (16.7%) were combined local and leptomeningeal. There was no significant impact on Overall Survival (OS) or Event-Free Survival (EFS) of surgery-RT interval for patients treated by pre-RT chemotherapy or RT alone, or duration of RT (completing within 50 days). Planning films were received for 42/54 (77.8%) patients. Fourteen (33%) had one or more targeting deviations (10 cribriform fossa, 11 base of skull). There was a statistically significant increase in the risk of recurrence for patients with cribriform fossa targeting deviations (p=0.033), but not for patients with base of skull targeting deviations (p=0.242). There was no statistically significant difference in OS (p=0.0598) or EFS (p=0.0880) for patients who had one or more targeting deviations compared to those who had none., Conclusions: This study has not demonstrated a statistically significant impact of radiotherapy duration or targeting deviations on OS or EFS, possibly due to small patient numbers. However, multi-institutional SPNET trials should incorporate quality assurance programs including analysis of relapse pattern in relation to primary target volume coverage.

Since the 1930s, therapeutic recreation (TR) has been used in the UK to help young people cope with severe illness. This article surveys four systematic reviews and poses five questions that a paediatrician might ask: (1) How to select a TR experience and for which patient?; (2) Does TR augment brain injury rehabilitation?; (3) How do TR camps benefit children?; (4) Is TR cost-effective?; (5) What additional research is needed? Methodological weaknesses in research impair the strength of conclusions. There is little research about matching of TR experiences to individuals, disease groups or age groups, or about the effect of TR camps in brain injury rehabilitation. TR interventions enhance self-esteem, disease knowledge, emotional well-being, adaptation to illness and symptom control. Educationalists suggest that self-esteem is helped most in mid to late adolescence. Where studied, TR camps are safe, which reassures parents. There have been few studies on cost-effectiveness. We conclude that young people benefit from TR. However, better-quality research would help select and further develop these experiences for young people with ill health.

Background: To evaluate the metabolic effects of two weight loss diets differing in macronutrient composition on features of dyslipidemia and post-prandial insulin (INS) response to a meal challenge in overweight/obese individuals., Methods: This study was a parallel-arm randomized 4 mo weight loss trial. Adults (n = 50, 47 +/- 7 y) matched on BMI (33.6 +/- 0.6 kg/m2, P = 0.79) consumed energy restricted diets (deficit ~500 kcal/d): PRO (1.6 g.kg-1.d-1 protein and < 170 g/d carbohydrate) or CHO (0.8 g.kg-1.d-1 protein and > 220 g/d carbohydrate) for 4 mos. Meal challenges of respective diets were utilized for determination of blood lipids and post-prandial INS and glucose response at the beginning and end of the study., Results: There was a trend for PRO to lose more weight (-9.1% vs. -7.3%, P = 0.07) with a significant reduction in percent fat mass compared to CHO (-8.7% vs. -5.7%; P = 0.03). PRO also favored reductions in triacylglycerol (-34% vs. -14%; P < 0.05) and increases in HDL-C (+5% vs. -3%; P = 0.05); however, CHO favored reduction in LDL-C (-7% vs. +2.5%; P < 0.05). INS responses to the meal challenge were improved in PRO compared to CHO (P < 0.05) at both 1 hr (-34.3% vs. -1.0%) and 2 hr (-9.2% vs. +46.2%), an effect that remained significant after controlling for weight or fat loss (both P < 0.05)., Conclusion: A weight loss diet with moderate carbohydrate, moderate protein results in more favorable changes in body composition, dyslipidemia, and post-prandial INS response compared to a high carbohydrate, low protein diet suggesting an additional benefit beyond weight management to include augmented risk reduction for metabolic disease.

Directing the self-assembly of colloidal particles into nanostructures is of great interest in nanotechnology. Here, reversible end-to-end assembly of gold nanorods (GNR) is induced by pH-dependent changes in the secondary conformation of a disulfide-modified poly(L-glutamic acid) (SSPLGA). The disulfide anchoring group drives chemisorption of the polyacid onto the end of the gold nanorods in an ethanolic solution. A layer of poly(vinyl pyrrolidone) is adsorbed on the positively charged, surfactant-stabilized GNR to screen the surfactant bilayer charge and provide stability for dispersion of the GNR in ethanol. For comparison, irreversible end-to-end assembly using a bidentate ligand, namely 1,6-hexanedithiol, is also performed. Characterization of the modified GNR and its end-to-end linking behavior using SSPLGA and hexanedithiol is performed using dynamic light scattering (DLS), UV-vis absorption spectroscopy and transmission electron microscopy (TEM). Experimental results show that, in a colloidal solution of GNR-SSPLGA at a pH∼3.5, where the PLGA is in an α-helical conformation, the modified GNR self-assemble into one-dimensional nanostructures. The linking behavior can be reversed by increasing the pH (>8.5) to drive the conformation of the polypeptide to a random coil and this reversal with pH occurs rapidly within minutes. Cycling the pH multiple times between low and high pH values can be used to drive the formation of the nanostructures of the GNR and disperse them in solution.

Three studies were conducted to evaluate the feeding value of slice alfalfa hay in feedlot diets. In Exp. 1, 108 steer calves (183.1 +/- 1.2 kg initial BW; 6 pens/treatment) were used in a completely randomized design to evaluate the effect of baling method on performance and morbidity of newly received calves. The study lasted 28 d. Treatments consisted of a 65% concentrate receiving diet containing 1) ground or 2) slice alfalfa hay. Steer calves were fed daily at 0800 h. Animals also received long-stem sudangrass hay the first 7 d. Steers were weighed on d 0, 16, and 28. Feed, sudangrass hay, or feed plus sudangrass hay intakes were not affected (P > 0.25) by treatment. Conversely, ADG from d 0 to 16 was greater (P < 0.001) for slice than ground (1.27 vs. 0.81 +/- 0.067 kg/d, respectively) and from d 0 to 28 (1.23 vs. 0.91 +/- 0.042 kg/d, respectively). In addition, G:F was greater (P < 0.001) for slice than ground hay from d 0 to 16 (0.39 vs. 0.25 +/- 0.021), and from d 0 to 28 (0.31 vs. 0.24 +/- 0.013 for slice and ground, respectively). Moreover, morbidity (40.5 +/- 3.9%; P = 0.20) and retreatment rates (30.7 +/- 7.5%; P = 0.14) were similar for slice and ground. In Exp. 2, 176 crossbred steers (393.9 +/- 10.8 kg initial BW) were used in an 84-d feeding experiment (4 pens/treatment) in a randomized complete block experimental design with a 2 x 2 factorial arrangement of treatments to evaluate effects of alfalfa baling method (ground or slice) and forage level (8 or 14%) on growth performance. Experimental diets were based on steam-flaked corn. Daily BW gain was greater (P = 0.10) for steers consuming ground compared with the slice hay diet. A baling method x forage level interaction (P = 0.07) was observed for DMI. Baling method did not (P = 0.98) influence DMI with 8% roughage level. But with 14% roughage, DMI was greater (P = 0.02) for steers consuming ground hay than the slice diet. The G:F ratio was affected (P = 0.03) only by forage level (0.194 vs. 0.182 +/- 0.003 for 8 and 14% roughage, respectively). In Exp. 3, 4 ruminally cannulated mixed-breed steers were used in a 4 x 4 Latin square design to evaluate effects on digestive function. No baling method effects (P >or= 0.16) were detected for DM, OM, CP, or NDF intakes or DM, OM, and NDF total tract digestibility. Digestibility of NDF and OM were greater (P

New gene expressed in prostate (NGEP) is a prostate-specific polytopic membrane protein found at high concentrations at cell:cell contact regions. To determine if NGEP is a useful target for antibody-based therapy of prostate cancer, we performed an immunohistochemical analysis of 126 human prostate carcinoma samples using polyclonal anti-NGEP sera and found that 91% of the cancers express NGEP protein. To elucidate the topology of NGEP and guide the development of monoclonal antibodies (mAb) reacting with the extracellular regions of NGEP, a hemagglutinin epitope tag was inserted at several positions within the NGEP sequence. The tagged proteins were expressed in 293T cells and locations of the tags were determined by immunofluorescence in intact or permeabilized cells. The results indicate that NGEP contains eight transmembrane domains with both the NH(2) and COOH termini of NGEP located inside the cell. We produced mAb to three regions that are predicted to be intracellular based on the epitope tag data (amino acids 1-352, 441-501, and 868-933), and as predicted, the mAb only detected the protein in permeabilized cells. NGEP is a glycoprotein with predicted glycosylation sites at N809 and N824. When these residues were converted to glutamine, glycosylation was abolished, confirming that the residues are extracellular. Our findings on the expression and the orientation of the NGEP protein serve as an important framework for the development of mAb targeting the extracellular regions of NGEP that could be used for prostate cancer immunotherapy.

Despite the inherent problems associated with in vivo animal models of tumor growth and metastases, many of the current in vitro brain tumor models also do not accurately mimic tumor-host brain interactions. Therefore, there is a need to develop such co-culture models to study tumor biology and, importantly, the efficacy of drug delivery systems targeting the brain. So far, few investigations of this nature have been published. In this paper we describe the development of a new model system and its application to drug delivery assessment. For our new model, a co-culture of DAOY cell brain tumor aggregates and organo-typic brain slices was developed. Initially, the DAOY aggregates attached to cerebellum slices and invaded as a unit. Single cells in the periphery of the aggregate detached from the DAOY aggregates and gradually replaced normal brain cells. This invasive behavior of DAOY cells toward organotypic cerebellum slices shows a similar pattern to that seen in vivo. After validation of the co-culture model using transmission electron microscopy, nanoparticle (NP) uptake was then evaluated. Confocal micrographs illustrated that DAOY cells in this co-culture model took up most of the NPs, but few NPs were distributed into brain cells. This finding corresponded with results of NP uptake in DAOY and brain aggregates reported elsewhere.

An historical and personal reflection on the function of the Benson-Calvin Cycle in isolated chloroplasts, the role of inorganic phosphate and the manner in which this might be best presented to students.

A useful route for the development of antitumour therapies is by creating improved methods for delivering therapeutic agents to tumour cells or subcellular compartments and increasing retention of drugs within target cells. In this study, we have characterized nanoparticle (NP) uptake and metabolism by DAOY cells, a human medulloblastoma cell line. NPs were formed from a novel polymer, poly (glycerol-adipate) (PGA), containing Rhodamine B Isothiocyanate (RBITC) as a fluorescent marker. It was observed that the cellular uptake of NPs depends on the incubation time and the concentration of NPs in the culture medium. The studies of retention and metabolism of NPs within cells indicated that 1) faster degradation of NPs within cells compared with that in cell culture medium in vitro; 2) a small fraction of NPs were recycled back to the outside of cell, whereas most NPs entered endosomes and lysosomes; and 3) recycled NPs were re-taken up in the following 2 h incubation time. These studies thus suggested that PGA NPs could be used for localising therapeutic agents into cells, and could provide prolonged drug effects because of their long sustained release in physiological conditions and their rapid release when taken up into cells.

The SIOP PNET 3 study was designed to determine whether 10 weeks of moderately intensive chemotherapy given after surgery and before radiotherapy (RT) would improve the outcome for patients with primitive neuroectodermal tumours (PNETs) compared with RT alone. Patients with a histological diagnosis of supratentorial PNET (StPNET) and no radiological evidence of metastatic disease were initially eligible for randomisation to either chemotherapy followed by craniospinal RT 35 Gy in 21 fractions with a boost of 20 Gy in 12 fractions to the primary site, or RT alone. In respect of the increasing recognition that StPNET were high-risk tumours, randomisation for this group closed in November 1999. This analysis includes both randomised and non-randomised patients with StPNET entered into the study database. Sixty-eight patients aged 2.9-16.6 years (median 6.5 years) were included in the analysis (chemotherapy+RT: 44, RT alone: 24). Fifty-four patients (79%) had a non-pineal and 14 (21%) a pineal site. At a median follow-up of 7.4 years, for all patients overall survival (OS) at 3 and 5 years was 54.4% and 48.3%, respectively. Event-free survival (EFS) at 3 and 5 years was 50.0% and 47.0%, respectively. There was no statistically significant difference in OS or EFS according to treatment received. OS (P=0.05) and EFS (P=0.03) were significantly better for patients with pineal primary sites. EFS for pineal tumours were 92.9% at 3 years and 71.4% at 5 years and for non-pineal primaries 40.7% at 3 years and 40.7% at 5 years. This study confirmed the relatively good survival for non-metastatic pineal PNETs but poor survival of non-pineal StPNETs. There was no evidence that pre-radiation chemotherapy improved outlook. Future treatment programs should be directed at the particular natural history of these tumours, to further define prognostic factors and to explore further biological characteristics.

Calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) represent an important source of infection for susceptible cattle. We evaluated vaccine efficacy using calves PI with noncytopathic BVDV2a for the challenge and compared tests to detect BVDV in acutely or transiently infected calves versus PI calves. Vaccination with 2 doses of modified live virus vaccine containing BVDV1a and BVDV2a protected the calves exposed to the PI calves: neither viremia nor nasal shedding occurred. An immunohistochemistry test on formalin-fixed ear notches and an antigen-capture enzyme-linked immunosorbent assay on fresh notches in phosphate-buffered saline did not detect BVDV antigen in any of the acutely or transiently infected calves, whereas both tests had positive results in all the PI calves.

Diets with total protein intake >1.5 g.kg(-1).d(-1) and carbohydrate intake <150 g/d are effective for treatment of obesity, type 2 diabetes, and the Metabolic Syndrome. These diets improve body composition and enhance glycemic control. During weight loss, protein-rich diets reduce loss of lean tissue and increase loss of body fat. Specific mechanisms to explain each of these clinical outcomes remain to be fully elucidated. We propose that keys to understanding the relationship between dietary protein and carbohydrates are the relationships between the branched-chain amino acid leucine and insulin and glucose metabolism. Leucine is known to interact with the insulin signaling pathway to stimulate downstream signal control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Leucine also appears to modulate insulin signaling and glucose use by skeletal muscle. Whereas total protein is important in providing substrates for gluconeogenesis, leucine appears to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle. These mechanisms produce protein sparing and provide a stable glucose environment with low insulin responses during energy-restricted periods.

We have developed a new mammalian cell-based assay to screen for ligands of the estrogen receptor. A fluorescently tagged chimera between the glucocorticoid and the estrogen receptors, unlike the constitutively nuclear estrogen receptor, is cytoplasmic in the absence of hormone and translocates to the nucleus in response to estradiol. The chimera maintains specificity for estrogen receptor alpha ligands and does not show cross-reactivity with other steroids, providing a clean system for drug discovery. Natural and synthetic estrogen receptor alpha agonists as well as phytoestrogens effectively translocate the receptor to the nucleus in a dose-dependent manner. Antagonists of the estrogen receptor can also transmit the structural signals that result in receptor nuclear translocation. The potency and efficacy of high-affinity ligands can be evaluated in our system by measuring the nuclear translocation of the fluorescently labeled receptor in response to increasing ligand concentrations. The chimera is transcriptionally competent on transient and replicating templates, and is inhibited by estrogen receptor antagonists. Interestingly, the nucleoplasmic mobility of the chimera, determined by FRAP analysis, is faster than that of the wild type estrogen receptor, and the chimera is resistant to ICI immobilization. The translocation properties of this chimera can be utilized in high content screens for novel estrogen receptor modulators.

A major challenge in predicting Earth's future climate state is to understand feedbacks that alter greenhouse-gas forcing. Here we synthesize field data from arctic Alaska, showing that terrestrial changes in summer albedo contribute substantially to recent high-latitude warming trends. Pronounced terrestrial summer warming in arctic Alaska correlates with a lengthening of the snow-free season that has increased atmospheric heating locally by about 3 watts per square meter per decade (similar in magnitude to the regional heating expected over multiple decades from a doubling of atmospheric CO2). The continuation of current trends in shrub and tree expansion could further amplify this atmospheric heating by two to seven times.

Bovine viral diarrhea virus (BVDV) persistently infected (PI) calves represent significant sources of infection to susceptible cattle. The objectives of this study were to determine if PI calves transmitted infection to vaccinated and unvaccinated calves, to determine if BVDV vaccine strains could be differentiated from the PI field strains by subtyping molecular techniques, and if there were different rates of recovery from peripheral blood leukocytes (PBL) versus serums for acutely infected calves. Calves PI with BVDV1b were placed in pens with nonvaccinated and vaccinated calves for 35 d. Peripheral blood leukocytes, serums, and nasal swabs were collected for viral isolation and serology. In addition, transmission of Bovine herpes virus 1 (BHV-1), Parainfluenza-3 virus (PI-3V), and Bovine respiratory syncytial virus (BRSV) was monitored during the 35 d observation period. Bovine viral diarrhea virus subtype 1b was transmitted to both vaccinated and nonvaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to PI calves. There was evidence of transmission by viral isolation from PBL, nasal swabs, or both, and seroconversions to BVDV1b. For the unvaccinated calves, 83.2% seroconverted to BVDV1b. The high level of transmission by PI calves is illustrated by seroconversion rates of nonvaccinated calves in individual pens: 70% to 100% seroconversion to the BVDV1b. Bovine viral diarrhea virus was isolated from 45 out of 202 calves in this study. These included BVDV1b in ranch and order buyer (OB) calves, plus BVDV strains identified as vaccinal strains that were in modified live virus (MLV) vaccines given to half the OB calves 3 d prior to the study. The BVDV1b isolates in exposed calves were detected between collection days 7 and 21 after exposure to PI calves. Bovine viral diarrhea virus was recovered more frequently from PBL than serum in acutely infected calves. Bovine viral diarrhea virus was also isolated from the lungs of 2 of 7 calves that were dying with pulmonary lesions. Two of the calves dying with pneumonic lesions in the study had been BVDV1b viremic prior to death. Bovine viral diarrhea virus 1b was isolated from both calves that received the killed or MLV vaccines. There were cytopathic (CP) strains isolated from MLV vaccinated calves during the same time frame as the BVDV1b isolations. These viruses were typed by polymerase chain reaction (PCR) and genetic sequencing, and most CP were confirmed as vaccinal origin. A BVDV2 NCP strain was found in only 1 OB calf, on multiple collections, and the calf seroconverted to BVDV2. This virus was not identical to the BVDV2 CP 296 vaccine strain. The use of subtyping is required to differentiate vaccinal strains from the field strains. This study detected 2 different vaccine strains, the BVDV1b in PI calves and infected contact calves, and a heterologous BVDV2 subtype brought in as an acutely infected calf. The MLV vaccination, with BVDV1a and BVDV2 components, administered 3 d prior to exposure to PI calves did not protect 100% against BVDV1b viremias or nasal shedding. There were other agents associated with the bovine respiratory disease signs and lesions in this study including Mannheimia haemolytica, Mycoplasma spp., PI-3V, BRSV, and BHV-1.

The aim of this study was to determine the outcome for patients with Chang stage M2-3 medulloblastoma (MB) treated with surgery and pre-radiotherapy (RT) chemotherapy (CT). Between 1992 and 2000, 68 patients aged 2.8-16.4 years (median 7.8 years) with M2-3 MB were treated with CT comprising vincristine, etoposide, carboplatin and cyclophosphamide. For 61 patients, CT was followed by craniospinal RT 35 Gy/21 fractions with a posterior fossa (PF) boost, 20 Gy/12 fractions. Twenty-four (35%) irradiated patients received a metastatic boost (mean dose to metastases 47.4 Gy, range 40.0-55.1 Gy). With 7.2-years of median follow-up, overall survival (OS) rates at 3 and 5 years were 50.0% (95% Confidence Interval (CI): 38.1-61.9%) and 43.9% (95% CI: 32.0-55.7%), respectively, event-free survival (EFS) rates at 3 and 5 years were 39.7% (95% CI: 28.1-51.3%) and 34.7% (95% CI: 23.2-46.2%), respectively. Univariate analysis did not demonstrate an impact of age, gender, M stage, extent of resection, RT duration or metastatic boost. For patients commencing RT within 110 days of surgery, EFS was significantly (P=0.04) worse than for those who commenced RT later than this. Response to pre-RT CT was assessable from institutional reports for 44 (65%) patients, and 17 (39%) had a complete response (CR), 15 (34%) a partial response (PR), 4 (9%) stable disease (SD) and 8 (18%) progression. Although CT improved outcome for M0-1 patients in the primitive neuroectodermal tumour (PNET-3) randomised study, and resulted in a high response rate in this study, there has been no apparent improvement in outcome for M2-3 patients when compared with earlier multi-institutional series. Newer approaches such as more intensive CT and RT need to be explored.

Patients with complete or partial edentulism who have insufficient bone for endosseous dental implant treatment present a challenge for the dental practitioner. Alveolar distraction osteogenesis is a technique for creating bone and soft tissue, without the need for bone grafting and its potential complications. In this article, alveolar distraction osteogenesis is compared with traditional bone grafting techniques. A case is presented to illustrate successful bilateral mandibular vertical distraction osteogenesis with creation of adequate bone volume for endosseous implant-supported dental restoration.

Progesterone receptor (PR), a member of the nuclear receptor superfamily, is a key regulator of several processes in reproductive function. We have studied the dynamics of the interaction of PR with a natural target promoter in living cells through the use of fluorescence recovery after photobleaching (FRAP) analysis and also have characterized the dynamics of the interaction of PR with the mouse mammary tumor virus (MMTV) promoter reconstituted into chromatin in vitro. In photobleaching experiments, PR in the presence of the agonist R5020 exhibits rapid exchange with the MMTV promoter in living cells. Two PR antagonists, RU486 and ZK98299, have opposite effects on receptor dynamics in vivo. In the presence of RU486, PR binds to the promoter and is exchanged more slowly than the agonist-activated receptor. In contrast, PR bound to ZK98299 is not localized to the promoter and exhibits higher mobility in the nucleoplasm than the agonist-bound receptor. Significantly, PR bound to R5020 or RU486 can recruit the SWI/SNF chromatin remodeling complex to the promoter, but PR activated with ZK98299 cannot. Furthermore, we found ligand-specific active displacement of PR from the MMTV promoter during chromatin remodeling in vitro and conclude that the interaction of PR with chromatin is highly dynamic both in vivo and in vitro. We propose that factor displacement during chromatin remodeling is an important component of receptor mobility and that ligand-specific interactions with remodeling complexes can strongly influence receptor nuclear dynamics and rates of exchange with chromatin in living cells.

The development of green fluorescent protein (GFP) technology combined with live cell microscopy techniques have revealed the dynamic properties of GFP-tagged proteins in the nucleus. The mobility of a GFP-tagged protein can be assessed using a quantitative photobleaching technique, fluorescence recovery after photobleaching (FRAP) analysis. FRAP experiments demonstrate that many nuclear proteins are highly mobile within the nucleus. However, the factors within the nucleus that regulate this mobility are not known. This is partly due to an absence of protocols that can be used to identify such nuclear mobility factors. We developed a novel in situ assay that combines a biochemical permeabilization and extraction procedure with a quantitative FRAP technique, a method we used to uncover a new functional role for molecular chaperones in the nuclear mobility of steroid receptors. This assay can readily be adapted to identify and characterize other nuclear mobility factors.

Objective: The objective of this study was to evaluate the routine use of gradient-refocused echo MRI sequences in the detection of cortical cerebral microbleeding suggestive of cerebral amyloid angiopathy in elderly patients (> 70 years old)., Conclusion: The addition of gradient-refocused echo sequences to routine brain MRI resulted in the identification of cerebral amyloid angiopathy-related microbleeding in 15.5% of elderly patients. In most (86.7%) of these patients with positive findings, cerebral amyloid angiopathy was not suspected clinically, and 46.7% of these patients were undergoing anticoagulant or aspirin therapy, placing them at an increased risk of recurrent intracranial hemorrhage and catastrophic stroke.

An ultrafast UV laser crosslinking assay has provided novel insights into the progression of the SWI/SNF-mediated chromatin-remodeling reaction and transcription factor binding in real time. We demonstrate site-specific crosslinking between the glucocorticoid receptor (GR), the hSWI/SNF chromatin-remodeling complex, and the mouse mammary tumor virus (MMTV) promoter assembled in an array of correctly positioned nucleosomes. GR first demonstrates rapid binding to the promoter and then is actively displaced from the template during the remodeling reaction. This displacement reaction requires the hSWI/SNF complex and ATP, is specific to the nucleoprotein template, and is accompanied by a core histone rearrangement. The hSWI/SNF complex associates with random positions on the chromatin template in the absence of GR but is recruited specifically to the B/C region when GR is included. These results indicate that enhancement of hSWI/SNF-mediated factor accessibility, a hallmark of chromatin remodeling, is in some cases transient, reversible, and periodic.

Following a hormone signal, steroid/nuclear receptors bind regulatory elements in chromatin and initiate the recruitment of a variety of multi-protein complexes to promoter sequences. These complexes ultimately lead to the recruitment of general transcription factors and the initiation of transcription. Traditional models suggest that these factors remain statically bound to each other and to chromatin until other signals are received to reduce transcription. Recent findings demonstrate that the processes and actions involved are much more complex than traditional models convey, and that the movement of receptors and coactivators is remarkably dynamic. Transcription factors are highly mobile in the nuclear environment, and interact only briefly with target sites in the nucleus. As a result of these transient interactions, promoters move through many states during activation and repression. Two general concepts emerge from current data: (1) Various transcription factors appear to follow "ordered recruitment" to promoters on a time scale of minutes to hours in response to a stimulus. During this response, the proteins that interact with chromatin may cycle on and off the promoter multiple times. (2) During these ordered recruitment cycles, the individual molecules that form functional complexes often exchange rapidly on a time scale of seconds. This rapid exchange of molecules within a formed complex occurs independently of long-term cycling on chromatin. Several processes are implicated in rapid nuclear dynamics, including potential roles for molecular chaperones, the proteasome degradation machinery and chromatin remodeling complexes.

Purpose: To analyze the impact of radiotherapy (RT) parameters on outcome in a randomized study of pre-RT chemotherapy for M0-M1 medulloblastoma., Methods and Materials: Patients were randomized to RT alone or RT preceded by chemotherapy with vincristine, etoposide, carboplatin, and cyclophosphamide. RT consisted of craniospinal RT, 35 Gy in 21 fractions, followed by a posterior fossa (PF) boost of 20 Gy in 12 fractions. The accuracy of cribriform fossa, skull base, and PF field placement was assessed., Results: Between 1992 and 2000, 217 patients were randomized, of whom 179 were eligible for analysis. At a median follow-up of 5.4 years, the 3- and 5-year overall survival rate was 79.5% and 70.7%, respectively. The 3- and 5-year event-free survival (EFS) rate was 71.6% and 67.0%, respectively. EFS was significantly better for the chemotherapy plus RT group (3-year EFS rate 78.5% vs. 64.8%, p = 0.0366). Overall survival and EFS were significantly better for patients completing RT within 50 days compared with those taking >50 days to complete RT (3-year overall survival rate 84.1% vs. 70.9%, p = 0.0356, 3-year EFS rate 78.5% vs. 53.7%, p = 0.0092). Multivariate analysis identified the use of chemotherapy (p = 0.0248) and RT duration (p = 0.0100) as predictive of better EFS. Planning films were reviewed for 131 (74.4%) of 176 patients. Sixty-five (49.6%) had no targeting deviations and 58 (44.3%) had one or more deviations. PF recurrence occurred in 11 (34.4%) of 32 with a PF targeting deviation compared with 13 (16.3%) of 80 without (p = 0.043). No statistically significant impact of other targeting deviations on recurrence risk or EFS were found., Conclusion: The results of this study have confirmed the importance of the duration of RT for medulloblastoma. Also, attention to detail when planning RT is important, as illustrated in the case of PF field placement.

Live cell imaging has revealed the rapid mobility of steroid hormone receptors within nuclei and their dynamic exchange at transcriptionally active target sites. Although a number of other proteins have been shown to be highly mobile within nuclei, the identity of soluble factors responsible for orchestrating nuclear trafficking remains unknown. We have developed a previously undescribed in situ subnuclear trafficking assay that generates transcriptionally active nuclei, which are depleted of soluble factors required for the nuclear mobility of glucocorticoid (GR) and progesterone receptors (PR). Using this system and a fluorescence recovery after photobleaching technique, we demonstrate that nuclear mobility of GR recovered on incubation with reticulocyte lysate was inhibited by geldanamycin, a drug that blocks the chaperone activity of heat-shock protein 90. Direct proof of molecular chaperone involvement in steroid receptor subnuclear trafficking was provided by the ATP-dependent recovery of nuclear mobility of GR and PR on incubation with various combinations of purified chaperone and/or cochaperone proteins. Additionally, for both receptors, the inclusion of hormone during the recovery period leads to a retardation of nuclear mobility. Thus, our results provide a description of soluble nuclear mobility factors and furthermore demonstrate a previously unrecognized role for molecular chaperones in the regulation of steroid receptor function within the nucleus.

The somatotrophic axis is the main endocrine system regulating postnatal growth; however, prenatal growth is independent of growth hormone (GH). Fetal development relies on the coordinated actions of a range of hormones, including insulin-like growth factors (IGF), and prolactin (PRL), in the control of differentiation, growth and maturation. In the sheep the abundance peaks for liver IGF-II and PRL receptors occur during late gestation while that for IGF-I receptor occurs at birth. All receptors, with the exception of GH receptor subsequently decrease by age 6 months. It has been proposed that maternal undernutrition during gestation regulates the maturation of the fetal hypothalmic-pituitary-adrenal axis and endocrine sensitivity. Critically, the timing of the nutritional insult may affect the magnitude of reprogramming. Maternal malnutrition during early to mid-gestation (3.2-3.8 MJ/d (60% total metabolisable energy requirements) v. 8.7-9.9 MJ/d (150% total metabolisable energy requirements) between 28 and 80 d of gestation) had no effect on body or liver weight. Nutrient-restricted (NR) fetuses sampled at 80 d (mid-gestation) showed up-regulation of hepatic PRL receptor, but following refeeding the normal gestational rise in PRL and GH receptors did not occur. Hepatic IGF-II receptor was down regulated in NR fetuses at both mid- and late gestation. Conversely, 6-month-old offspring showed no difference in the abundance of either GH receptor or PRL receptor, while IGF-II mRNA was increased. Offspring of ewes malnourished during late gestation (9.1 MJ/d (60% total metabolisable energy requirements) v. 12.7 MJ/d (100% total metabolisable energy requirements) from 110 d of gestation to term) showed reduced abundance of hepatic GH and PRL receptor mRNA. In conclusion, maternal undernutrition during the various stages of gestation reprogrammed the PRL-GH-IGF axis. Nutritional regulation of cytokine receptors may contribute to altered liver function following the onset of GH-dependent growth, which may be important in regulating endocrine adaptations during subsequent periods of nutritional deprivation.

A winter grazing/feedlot performance experiment repeated over 2 yr (Exp. 1) and a metabolism experiment (Exp. 2) were conducted to evaluate effects of grazing dormant native range or irrigated winter wheat pasture on subsequent intake, feedlot performance, carcass characteristics, total-tract digestion of nutrients, and ruminal digesta kinetics in beef cattle. In Exp. 1, 30 (yr 1) or 67 (yr 2) English crossbred steers that had previously grazed native range (n = 38) or winter wheat (n = 59) for approximately 180 d were allotted randomly within previous treatment to feedlot pens (yr 1 native range = three pens [seven steers/pen], winter wheat = two pens [eight steers/pen]; yr 2 native range = three pens [eight steers/pen], winter wheat = four pens [10 or 11 steers/pen]). As expected, winter wheat steers had greater (P < 0.01) ADG while grazing than did native range steers. In contrast, feedlot ADG and gain efficiency were greater (P < 0.02) for native range steers than for winter wheat steers. Hot carcass weight, longissimus muscle area, and marbling score were greater (P < 0.01) for winter wheat steers than for native range steers. In contrast, 12th-rib fat depth (P < 0.64) and yield grade (P < 0.77) did not differ among treatments. In Exp. 2, eight ruminally cannulated steers that had previously grazed winter wheat (n = 4; initial BW = 407 +/- 12 kg) or native range (n = 4; initial BW = 293 +/- 23 kg) were used to determine intake, digesta kinetics, and total-tract digestion while being adapted to a 90% concentrate diet. The adaptation and diets used in Exp. 2 were consistent with those used in Exp. 1 and consisted of 70, 75, 80, and 85% concentrate diets, each fed for 5 d. As was similar for intact steers, restricted growth of cannulated native range steers during the winter grazing phase resulted in greater (P < 0.001) DMI (% of BW) and ADG (P < 0.04) compared with winter wheat steers. In addition, ruminal fill (P < 0.01) and total-tract OM digestibility (P < 0.02) were greater for native range than for winter wheat steers across the adaptation period. Greater digestibility by native range steers early in the finishing period might account for some of the compensatory gain response. Although greater performance was achieved by native range steers in the feedlot, grazing winter wheat before finishing resulted in fewer days on feed, increased hot carcass weight, and improved carcass merit.

Purpose: To determine whether preradiotherapy (RT) chemotherapy would improve outcome for Chang stage M0-1 medulloblastoma when compared with RT alone. Chemotherapy comprised vincristine 1.5 mg/m2 weekly for 10 weeks and four cycles of etoposide 100 mg/m2 daily for 3 days, and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.5 g/m2., Patients and Methods: Patients aged 3 to 16 years inclusive were randomly assigned to receive 35 Gy craniospinal RT with a 20 Gy posterior fossa boost, or chemotherapy followed by RT., Results: Of 217 patients randomly assigned to treatment, 179 were eligible for analysis (chemotherapy + RT, 90 patients; RT alone, 89 patients). Median age was 7.67 years, and median follow-up was 5.40 years. Overall survival (OS) at 3 and 5 years was 79.5% and 70.7%, respectively. Event-free survival (EFS) at 3 and 5 years was 71.6% and 67.0%, respectively. EFS was significantly better for chemotherapy and RT (P =.0366), with EFS of 78.5% at 3 years and 74.2% at 5 years compared with 64.8% at 3 years and 59.8% at 5 years for RT alone. There was no statistically significant difference in 3-year and 5-year OS between the two arms (P =.0928). Multivariate analysis identified use of chemotherapy (P =.0248) and time to complete RT (P =.0100) as having significant effect on EFS., Conclusion: This is the first large multicenter randomized study to demonstrate improved EFS for chemotherapy compared with RT alone. It is anticipated that this regimen could reduce ototoxicity and nephrotoxicity compared with cisplatin-containing schedules. The importance of avoiding interruptions to RT has been confirmed.

Dan Arnon, Bob Whatley, Mary Belle Allen, and their colleagues, were the first to obtain evidence for 'complete photosynthesis by isolated chloroplasts' albeit at rates which were 1% or less of those displayed by the intact leaf. By the 1960s, partly in the hope of confirming full functionality, there was a perceived need to raise these rates to the same order of magnitude as those displayed by the parent tissue. A nominal figure of 100 mumol/mgcchlorophyll/h (CO(2) assimilated or O(2) evolved) became a target much sought after. This article describes the contributions that Dick Jensen and Al Bassham [(1966) Proc Natl Acad Sci USA 56: 1095-1101], and my colleagues and I, made to the achievement of this goal and the way in which it led to a better understanding of the role of inorganic phosphate in its relation to the movement of metabolites across chloroplast envelopes.

Through the use of photobleaching techniques, we examined the dynamic interaction of three members of the transcription apparatus with a target promoter in living cells. The glucocorticoid receptor (GR) interacting protein 1 (GRIP-1) exhibits a half maximal time for fluorescent recovery (tau(R)) of 5 s, reflecting the same rapid exchange as observed for GR. In contrast, the large subunit (RPB1) of RNA polymerase II (pol II) required 13 min for complete fluorescence recovery, consistent with its function as a processive enzyme. We also observe a complex induction profile for the kinetics of GR-stimulated transcription. Our results indicate that GR and GRIP-1 as components of the activating complex are in a dynamic equilibrium with the promoter, and must return to the template many times during the course of transcriptional activation.

Three experiments were conducted to determine effects of restricting intake of the final finishing diet as a means of dietary adaptation compared with diets increasing in grain over a period of 20 to 22 d on overall cattle performance, carcass characteristics, digestibility, digesta kinetics, and ruminal metabolism. In Exp. 1, 84 Angus x Hereford yearling steers (initial BW = 418 +/- 29.0 kg) were fed for 70 d. Restricting intake during adaptation had no effect (P > 0.10) on overall ADG:DMI, but decreased (P < 0.05) DMI compared with ad libitum access to adaptation diets, which resulted from differences during the initial 28 d of the experiment. In Exp. 2, 150 mixed crossbred steer calves (initial BW = 289 +/- 22.9 kg) were fed for an average of 173 d. Restricting intake decreased (P < 0.01) overall daily gain (1.51 vs 1.65 kg/d) and DMI (8.68 vs 9.15 kg/d) compared with ad libitum fed steers; however, ADG:DMI was not influenced (P > 0.10) by adaptation method. Experiment three used eight ruminally and duodenally fistulated steers (initial BW = 336 +/- 20 kg) in a completely random design. Total tract digestibility, digesta kinetics and ruminal metabolism were determined. Restricting intake reduced (P < 0.10) daily DMI variation from d 1 through 7, 8 through 14, and 22 through 28 compared with ad libitum feeding of three adaptation diets. Restricted steers had reduced (adaptation method x period interaction, P < 0.05) intakes and fecal excretions of ADF and greater OM digestibilities on d 4 through 7, 11 through 14, and 18 through 21. Digesta kinetics and ruminal metabolism were generally not affected (P > 0.10) by adaptation method. Our results suggest that restricted-feeding of the final diet as a means of dietary adaptation can be used in finishing cattle with few problems from acidosis or related intake variation. In light-weight steers (Exp. 2), disruptions in intake during the adaptation period might have resulted in restriction for an extended period, which decreased (P < 0.01) hot carcass weight compared with calves fed ad libitum. Effects of limit feeding during the initial 28 d of the feeding period on site and extent of digestion, digesta kinetics, and ruminal metabolism were minimal, supporting few differences in performance across the finishing period for yearling cattle.

Three experiments were conducted to examine the effect of dietary vitamin E on receiving performance and health and on finishing performance of beef cattle. One hundred twenty beef steers (Exp. 1; initial BW = 173 kg) and 200 beef heifers (Exp. 2; initial BW = 204 kg) were assigned randomly to one of three treatment diets formulated to supply 285, 570, or 1,140 IU/animal daily of supplemental vitamin E during the receiving period. Average daily gain, gain:feed, and DMI were calculated every 14 d, with pen as the experimental unit. Morbidity and retreatment data were analyzed using a nonparametric procedure. After the receiving period, cattle were assigned to a grazing period followed by a finishing program and fed until slaughter. In Exp. 3, 17 beef steers were used to evaluate effects of the same three vitamin E levels on humoral immune response to an ovalbumin vaccine given on d 0 and 14. Jugular blood samples were collected on d 0, 7, 14, and 21. In Exp. 1, vitamin E did not affect (P > 0.10) ADG, DMI, or gain:feed for d 0 to 14, 14 to 28, or 0 to 28. No effects were noted for percentage of morbidity; however, cattle receiving 1,140 IU/d had a numerically (P = 0.15) lower incidence of retreatment. During the 91-d finishing phase, a quadratic effect (P < 0.08) was noted for DMI, ADG, backfat thickness, longissimus muscle area, and yield grade. In Exp. 2, a tendency for a linear (P = 0.10) increase in ADG was observed for the first 14 d of receiving; however, ADG decreased linearly (P = 0.06) with vitamin E concentration thereafter. For the 28-d period, ADG and DMI did not differ among treatments, but gain:feed decreased linearly (P < 0.05) for d 14 to 28 and for d 0 to 28. No effects on percentage morbidity were noted in Exp. 2, and no differences were detected for ADG, gain:feed, or DMI for the 98-d finishing period. There was a linear increase in yield grade (P < 0.05) and a linear (P < 0.08) decrease in longissimus muscle area with increasing vitamin E. Heifers receiving 570 IU of vitamin E during the receiving period tended to have a higher (P < 0.09) dressing percentage at slaughter. In Exp. 3, no significant differences were detected in serum IgG titers to ovalbumin on d 0, 7 or 14; however, on d 21, a linear increase (P = 0.07) in serum IgG titers was noted with supplemental vitamin E. Supplemental vitamin E had limited effects on performance; however, effects on humoral immune response and recovery from respiratory disease warrant further research.

The Z-scheme is considered in the context of personal recollections of events during the time that it was conceived and an evaluation of its enduring importance.

The Hill reaction, its elucidation, and significance is briefly described. Hill oxidants, the role of the methemoglobin reducing factor and its relation to ferredoxin, and the part played by chloroplast envelopes are discussed.

There is little evidence about the efficacy of Cognitive Behavioural Therapy (CBT) in the older adult population. Research highlights that the preferred treatment for this group appears to be medication. This study compares an older adult mental health service with a younger adult service in terms of range of referrals, outcomes, attendance rates and length of time in therapy. The range of disorders referred was a wide mix of anxiety disorders and depression. There were no significant differences in therapy outcomes apart from home adjustment measures where older adults showed greater improvement. Younger adults showed significantly higher rates of non- attendance (DNA) and had higher dropout rates. Possible reasons for this are discussed. CBT appeared effective in both age groups, however older adults were treated more quickly due to a higher attendance rate.

The formation of adducts of tris(pentafluorophenyl)borane with strongly coordinating anions such as CN(-) and [M(CN)(4)](2)(-) (M = Ni, Pd) is a synthetically facile route to the bulky, very weakly coordinating anions [CN[B(C(6)F(5))(3)](2)](-) and [M[CNB(C(6)F(5))(3)](4)](2-) which are isolated as stable NHMe(2)Ph(+) and CPh(3)(+) salts. The crystal structures of [CPh(3)][CN[B(C(6)F(5))(3)](2)] (1), [CPh(3)][ClB(C(6)F(5))(3)] (2), [NHMe(2)Ph](2)[Ni[CNB(C(6)F(5))(3)](4)].2Me(2)CO (4b.2Me(2)CO), [CPh(3)](2)[Ni[CNB(C(6)F(5))(3)](4)].2CH(2)Cl(2) (4c.2CH(2)Cl(2)), and [CPh(3)](2)[Pd[CNB(C(6)F(5))(3)](4)].2CH(2)Cl(2) (5c.2CH(2)Cl(2)) are reported. The CN stretching frequencies in 4 and 5 are shifted by approximately 110 cm(-1) to higher wavenumbers compared to the parent tetracyano complexes in aqueous solution, although the M-C and C-N distances show no significant change on B(C(6)F(5))(3) coordination. Zirconocene dimethyl complexes L(2)ZrMe(2) [L(2) = Cp(2), SBI = rac-Me(2)Si(Ind)(2)] react with 1, 4c or 5c in benzene solution at 20 degrees C to give the salts of binuclear methyl-bridged cations, [(L(2)ZrMe)(2)(mu-Me)][CN[B(C(6)F(5))(3)](2)] and [(L(2)ZrMe)(2)(mu-Me)](2)[M[CNB(C(6)F(5))(3)](4)]. The reactivity of these species in solution was studied in comparison with the known [[(SBI)ZrMe](2)(mu-Me)][B(C(6)F(5))(4)]. While the latter reacts with excess [CPh(3)][B(C(6)F(5))(4)] in benzene to give the mononuclear ion pair [(SBI)ZrMe(+).B(C(6)F(5))(4)(-)] in a pseudo-first-order reaction, k = 3 x 10(-4) s(-1), [(L(2)ZrMe)(2)(mu-Me)][CN[B(C(6)F(5))(3)](2)] reacts to give a mixture of L(2)ZrMe(mu-Me)B(C(6)F(5))(3) and L(2)ZrMe(mu-NC)B(C(6)F(5))(3). Recrystallization of [Cp' '(2)Zr(mu-Me)(2)AlMe(2)][CN[B(C(6)F(5))(3)](2)] affords Cp' '(2)ZrMe(mu-NC)B(C(6)F(5))(3) 6, the X-ray structure of which is reported. The stability of [(L(2)ZrMe)(2)(mu-Me)](+)X(-) decreases in the order X = [B(C(6)F(5))(4)] > [M[CNB(C(6)F(5))(3)](4)] > [CN[B(C(6)F(5))(3)](2)] and increases strongly with the steric bulk of L(2) = Cp(2) << SBI. Activation of (SBI)ZrMe(2) by 1 in the presence of AlBu(i)(3) gives extremely active ethene polymerization catalysts. Polymerization studies at 1-7 bar monomer pressure suggest that these, and by implication most other highly active ethene polymerization catalysts, are strongly mass-transport limited. By contrast, monitoring propene polymerization activities with the systems (SBI)ZrMe(2)/1/AlBu(i)(3) and CGCTiMe(2)/1/AlBu(i)(3) at 20 degrees C as a function of catalyst concentration demonstrates that in these cases mass-transport limitation is absent up to [metal] approximately 2 x 10(-5) mol L(-1). Propene polymerization activities decrease in the order [CN[B(C(6)F(5))(3)](2)](-) > [B(C(6)F(5))(4)](-) > [M[CNB(C(6)F(5))(3)](4)](2-) >> [MeB(C(6)F(5))(3)](-), with differences in activation barriers relative to [CN[B(C(6)F(5))(3)](2)](-) of DeltaDeltaG = 1.1 (B(C(6)F(5))(4)(-)), 4.1 (Ni[CNB(C(6)F(5))(3)](4)(2-)) and 10.7-12.8 kJ mol(-)(1) (MeB(C(6)F(5))(3)(-)). The data suggest that even in the case of very bulky anions with delocalized negative charge the displacement of the anion by the monomer must be involved in the rate-limiting step.

Current land-cover classifications used for global modelling portray Arctic tundra as one or two classes. This is insufficient for analysis of climate-vegetation interactions. This paper presents a simple three-level vegetation-map legend system useful for modelling at global, regional, and landscape scales. At the highest level (global scale: 10 7 -10 8  km 2 ) the Tundra Zone is divided into four subzones based on vegetation response to temperature along the latitudinal temperature gradient from north to south: (1) Cushion-forb, (2) Prostrate Dwarf-shrub, (3) Erect Dwarf-shrub, and (4) Low Shrub subzones. The boundaries follow a modification of Yurtsev's phytogeographic subzones. Parent material and topography are also major considerations at global, regional, and landscape scales. Soil pH is a key variable for many ecosystem responses, and a division into acidic (pH 5.5 or less) and nonacidic soils is used. A conceptual mesotopographic gradient is used to characterize the influence of soil-moisture and snow regimes. The example legend framework focuses on the Northern Alaska floristic subprovince, and could be expanded to other floristic provinces using local expert knowledge and available literature. Dominant plant functional types within each habitat type within the four subzones are also presented. Modellers could include or ignore different levels of resolution depending on the purpose of the model. The approach resolves conflicts in terminology that have previously been encountered between the Russian, North American, and Fennoscandian approaches to Arctic zonation.

Two experiments were conducted to determine the effect of degree of corn processing on urinary ammonia and urea N concentrations, serum metabolite and insulin concentrations, and feedlot performance of steers. Corn was processed by either dry rolling to .54 kg/L bulk density (DR42; 42 lb/bushel) or steam flaking to a bulk density of .36 or .26 kg/L (28 [SF28] and 20 [SF20] lb/bushel, respectively). Degrees of processing were selected to generate final products with 25, 50, or 75% enzymatically available starch. Available starch, expressed as a percentage of total starch for DR42, SF28, and SF20, averaged 24.5, 56.4, and 81.1% in Exp. 1 and 22.4, 60.1, and 80.1% in Exp. 2. In Exp. 1, 29 steers were housed in individual outdoor pens and adapted to a 90% concentrate diet over 21 d. Whole blood and urine were collected before feeding and at 4 and 8 h after feeding on d 0, 7, 14, 21, 28, 84, and 140. Daily DMI decreased linearly (P < .03) as degree of processing increased, whereas water intake did not differ (P > .42) among treatments. Average daily gain, ADG:DMI, and hot carcass weight responded quadratically (P < .04) to an increasing degree of processing. Urinary ammonia and urea N concentrations were not influenced (P > .30) by degree of processing. Whole blood packed cell volume, serum glucose, creatinine, D(-)-lactate, L(+)-lactate, and lactate dehydrogenase activity did not differ (P > .15) among treatments. For insulin data, ME intake on the day of sample collection was evaluated as a covariate. On d 28, serum insulin (2.49, 2.95, and 1.80+/-.33 ng/mL) responded quadratically (P = .04) as degree of processing increased. Serum insulin did not differ (P = .52) on d 84, whereas insulin (5.77, 7.51, and 4.12+/-.98 ng/mL) responded quadratically (P = .02) on d 140. In Exp. 2,216 steers were blocked by BW into two blocks (18 pens; 12 steers/pen) and assigned to the same treatments used in Exp. 1. Daily DMI and carcass weight responded quadratically (P < .05), whereas ADG and ADG:DMI increased linearly (P < .04) with increasing degree of processing. Results suggest that the degree of corn processing influences serum insulin concentrations of feedlot steers; however, serum metabolites, urinary nitrogen composition, and carcass characteristics were generally not affected by degree of corn processing.

Primitive neuroectodermal tumours are amongst the most common paediatric tumours of the central nervous system. These tumours are composed of undifferentiated cells and a variable component of more differentiated cell types. Most analysis of these tumours has focused on molecules normally found in the differentiated cells or those found in all primitive neuronal precursors. In this article we describe recent advances in understanding of the molecular processes involved in normal neurogenesis. We discuss the relevance of these data to the biology of neuronal tumours and describe strategies we and others have adopted to investigate the usefulness of molecules found in undifferentiated neuronal tissues in understanding the events which underlie oncogenesis in this tumour type.

Our objective was to determine the effects of preshipping (PRE) vs. arrival (ARR) medication with tilmicosin phosphate (MIC; Exp. 1 and 2) and feeding chlortetracycline (CTC; 22 mg/kg of BW from d 5 to 9; Exp. 2) on health and performance of beef calves received in the feedlot. Ninety-six steers (Exp. 1; pay weight 236 kg) and 240 (Exp. 2; average pay weight 188 kg) steer and bull calves were used. For Exp. 1, treatments included no MIC (CON), PRE, and ARR. For Exp. 2, treatments were arranged in a 3x2 factorial. Treatments included CON, PRE, and ARR, either with CTC or without CTC. For Exp. 2, serum concentrations of immunoglobulin (Ig)G and alpha-1-acid glycoprotein (AGP) were determined on samples collected on d 0, 5, 10, and 28 and d 0, 5, and 10, respectively. No MIC x CTC interactions were observed. No differences were noted among MIC or CTC treatments in any of the experiments for ADG, daily DMI, or gain:feed ratio for the overall receiving periods. For Exp. 1, percentage of steers treated for bovine respiratory disease (BRD) was decreased (P<.05) for MIC-treated animals vs CON (71.9, 45.2, and 46.9 for CON, PRE, and ARR, respectively), and the week that calves were treated for BRD differed (P<.10) among treatments. For Exp. 2, the number of calves treated for BRD was decreased (P<.01) for MIC-treated steers vs CON and decreased (P<.05) for ARR vs. PRE (40.0, 18.7, and 7.5% for CON, PRE, and ARR, respectively). Averaged across days, serum IgG was decreased (P<.05) for MIC-treated steers vs. CON, with no differences noted among treatments for AGP. Results suggest that preshipping medication programs are no more effective than arrival medication programs using tilmicosin phosphate.