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Handgrip strength is considered a biomarker of nutritional status and strength capacity, which are both linked to heart complications. However, it is not well understood how weakness, as measured by handgrip strength, factors into common heart conditions seen in aging adults such as chronic heart failure (CHF). The purpose of this study was to determine the association between weakness and incident CHF for aging Americans. Longitudinal-Panel. Physical measures were completed during enhanced face-to-face interviews. The core interview was typically conducted over the telephone. Data from 17,431 adults aged at least 50 years who identified as Black or White, completed interviews without a proxy, and participated in at least one wave of the 2006–2014 waves of the Health and Retirement Study were included. Handgrip strength was measured with a hand-held dynamometer. Healthcare provider diagnosed CHF was self-reported at each wave. Sex- and race-specific maximal handgrip strength cut-points were used for determining weakness (Black men

Discovering how certain health factors contribute to functional declines may help to promote successful aging. To determine the independent and joint associations of handgrip strength (HGS) and cognitive function with instrumental activities of daily living (IADL) and activities of daily living (ADL) disability decline in aging Americans. Data from 18,391 adults aged 50 years and over who participated in at least one wave of the 2006–2014 waves of the Health and Retirement Study were analyzed. A hand-held dynamometer assessed HGS and cognitive functioning was examined with a modified version of the Telephone Interview of Cognitive Status. IADL and ADL abilities were self-reported. Participants were stratified into four distinct groups based on their HGS and cognitive function status. Separate covariate-adjusted multilevel models were conducted for the analyses. Participants who were weak, had a cognitive impairment, and had both weakness and a cognitive impairment had 1.70 (95% confidence interval (CI) 1.57–1.84), 1.97 (CI 1.74–2.23), and 3.13 (CI 2.73–3.59) greater odds for IADL disability decline, respectively, and 2.26 (CI 2.03–2.51), 1.26 (CI 1.05–1.51), and 4.48 (CI 3.72–5.39) greater odds for ADL disability decline, respectively. HGS and cognitive functioning were independently and jointly associated with IADL and ADL disability declines. Individuals with both weakness and cognitive impairment demonstrated substantially higher odds for functional decline than those with either risk factor alone. Including measures of both HGS and cognitive functioning in routine geriatric assessments may help to identify those at greatest risk for declining functional capacity.

This paper reports re-crystallization behaviour of 60ZnO-30B2O3-10SiO2 pure glass. Influence of different fillers on the re-crystallization is also highlighted. Irrespective of the nature of the filler, glass transition temperature (Tg) remains the same as that of the pure glass at 570 °C. The onset crystallization temperature is enhanced by 15 to 25 °C owing to filler addition. The peak crystallization temperature corresponding to Zn3B2O6, ZnB2O4 and willemite occurs at 735, 810 and 851 °C for the pure glass. In the presence of alumina, gahnite emerges first at 700 °C followed by ZnB2O4 phase. With mullite as filler, initially ZnB2O4 and willemite formed at 700 °C and gahnite phase emerged only at 750 °C and peaks at 787 °C. In the presence of fused silica only ZnB2O4 and willemite phases were observed. The dielectric properties of the pure glass and that of the glass + fillers are also reported. Re-crystallization of various low K phases ensures good dielectric porpertis with reduced glass content after sintenring.

Adults with psychopathy have a high propensity for substance abuse, generally starting from a young age. This investigation tested hypotheses about differences in the neural responses associated with drug craving among high-risk young offenders with histories of abuse of stimulants and other drugs as a function of psychopathic traits. Fifty-four male adolescents (44 with a history of stimulant abuse and 10 controls) incarcerated at a maximum-security facility (M age = 17.08 years) completed a drug-cue exposure task while brain hemodynamic activity was monitored using functional magnetic resonance imaging (fMRI) with a mobile MRI scanner stationed at the facility. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). In the stimulant abuser group, drug cues elicited activity in classic reward circuitry. Consistent with studies of adult psychopathic traits and substance abuse, there was a negative association between PCL-YV scores and hemodynamic response related to drug craving in the amygdala and ACC in youth with a history of stimulant abuse. However, there were considerably more negative associations between the PCL:YV and hemodynamic response among youth than adults and this was primarily due to callous-unemotional traits rather than interpersonal or behavioral traits. The implications for how personality traits modulate motivations for drug-seeking behavior among adolescent offenders are discussed.

General circulation models frequently suffer from a substantial cold bias in equatorial Pacific sea surface temperatures (SSTs). For instance, the majority of the climate models participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5) have this particular problem (17 out of the 26 models evaluated in the present study). Here, we investigate the extent to which these equatorial cold biases are related to mean climate biases generated in the extra-tropics and then communicated to the equator via the oceanic subtropical cells (STCs). With an evident relationship across the CMIP5 models between equatorial SSTs and upper ocean temperatures in the extra-tropical subduction regions, our analysis suggests that cold SST biases within the extra-tropical Pacific indeed translate into a cold equatorial bias via the STCs. An assessment of the relationship between these extra-tropical SST biases and local surface heat flux components indicates a link to biases in the simulated shortwave fluxes. Further sensitivity studies with a climate model (CESM) in which extra-tropical cloud albedo is systematically varied illustrate the influence of cloud albedo perturbations, not only directly above the oceanic subduction regions but across the extra-tropics, on the equatorial bias. The CESM experiments reveal a quadratic relationship between extra-tropical Pacific albedo and the root-mean-square-error in equatorial SSTs—a relationship with which the CMIP5 models generally agree. Thus, our study suggests that one way to improve the equatorial cold bias in the models is to improve the representation of subtropical and mid-latitude cloud albedo.

Introduction: Cases of anaphylaxis in children are often not appropriately managed by caregivers. We aimed to develop and to test the effectiveness of an education tool to help pediatric patients and their families better understand anaphylaxis and its management and to improve current knowledge and treatment guidelines adherence. Methods: The GEAR (Guidelines and Educational programs based on an Anaphylaxis Registry) is an initiative that recruits children with food-induced anaphylaxis who have visited the ED at the Montreal Children's Hospital and at The Children's Clinic located in Montreal, Quebec. The patients and parents, together, were asked to complete six questions related to the triggers, recognition and management of anaphylaxis at the time of presentation to the allergy clinic. Participants were automatically shown a 5-minute animated video addressing the main knowledge gaps related to the causes and management of anaphylaxis. At the end of the video, participants were redirected to same 6 questions to respond again. To test long-term knowledge retention, the questionnaire will be presented again in one year's time. A paired t-test was used to compare the difference between the baseline score and the follow-up score based on percentage of correct answers of the questionnaire. Results: From June to November 2019, 95 pediatric patients with diagnosed food-induced anaphylaxis were recruited. The median patient age was 4.5 years (Interquartile Range (IQR): 1.6–7.4) and half were male (51.6%). The mean questionnaire baseline score was 0.77 (77.0%, standard deviation (sd): 0.16) and the mean questionnaire follow-up score was 0.83 (83.0%, sd: 0.17). There was a significant difference between the follow-up score and baseline score (difference: 0.06, 95% CI: 0.04, 0.09). There were no associations of baseline questionnaire scores and change in scores with age and sex. Conclusion: Our video teaching method was successful in educating patients and their families to better understand anaphylaxis. The next step is to acquire long-term follow up scored to determine retention of knowledge.

Solitary Pancreas (SPT) and simultaneous kidney-pancreas (SPKT) transplants carry a high risk of surgical complications that may lead to the loss of the pancreas graft and impact later kidney function. The purpose of this study was to investigate the role of MDCT in the diagnosis of early complications and its impact on kidney function.All patients receiving SPT or SPKT over 5 years were retrospectively included. Complications that occurred within the first 15 days were registered and MDCT data analyzed. Data regarding donor, transplant, and recipient characteristics as well as transplantation procedures were analyzed according to the occurrence of early complications. Kidney function at day 3 following MDCT was evaluated.One hundred and forty-one patients were included (85 men, 56 women; mean age 40.1 years, SD 7.7) with 119 SPKT and 22 SPT. Sixty-four complications were registered in 50 patients. Partial (P-) or complete venous thrombosis (C-VT) occurred in 12.1 % (n = 17), arterial thrombosis (AT) in 1.4 % (n = 2), and hemorrhage in 8.5 % (n = 12) of all patients. For venous thrombosis, the predominant risk factor was body mass index (BMI) for either recipients (P 0.05) or donors (P 0.01). Median time for venous thrombosis diagnosis with MDCT was 4 days. Kidney function was not altered following MDCT. Fourteen pancreatectomies were necessary. All patients with C-VT and AT had to undergo graftectomy.Vascular complications occurred early following grafting. Systematic early-enhanced MDCT at day 2-3 should be adequate to detect early thrombosis, especially if risk factors have been identified, without induced kidney function alteration.

In patients with diabetes, nerve injury is a common complication that leads to chronic pain, numbness and substantial loss of quality of life. Good glycemic control can decrease the incidence of diabetic neuropathy, but more than half of all patients with diabetes still develop this complication. There is no approved treatment to prevent or halt diabetic neuropathy, and only symptomatic pain therapies, with variable efficacy, are available. New insights into the mechanisms leading to the development of diabetic neuropathy continue to point to systemic and cellular imbalances in metabolites of glucose and lipids. In the PNS, sensory neurons, Schwann cells and the microvascular endothelium are vulnerable to oxidative and inflammatory stress in the presence of these altered metabolic substrates. This Review discusses the emerging cellular mechanisms that are activated in the diabetic milieu of hyperglycemia, dyslipidemia and impaired insulin signaling. We highlight the pathways to cellular injury, thereby identifying promising therapeutic targets, including mitochondrial function and inflammation.

The radiological features of lobar and segmental liver atrophy and compensatory hypertrophy associated with biliary obstruction are important to recognise for diagnostic and therapeutic reasons. Atrophied lobes/segments reduce in volume and usually contain crowded dilated bile ducts extending close to the liver surface. There is often a “step” in the liver contour between the atrophied and non-atrophied parts. Hypertrophied right lobe or segments enlarge and show a prominently convex or “bulbous” visceral surface. The atrophied liver parenchyma may show lower attenuation on pre-contrast computed tomography (CT) and CT intravenous cholangiography (CT-IVC) and lower signal intensity on T1-weighted magnetic resonance imaging (MRI). Hilar biliary anatomical variants can have an impact on the patterns of lobar/segmental atrophy, as the cause of obstruction (e.g. cholangiocarcinoma) often commences in one branch, leading to atrophy in that drainage region before progressing to complete biliary obstruction and jaundice. Such variants are common and can result in unusual but explainable patterns of atrophy and hypertrophy. Examples of changes seen with and without hilar variants are presented that illustrate the radiological features of atrophy/hypertrophy.

Calling male field crickets (Gryllus spp.) are acoustically located and subsequently parasitized by the parasitoid fly, Ormia ochracea (Diptera: Tachinidae). Parasitism by O. ochracea results in cricket death. The reproductive compensation hypothesis posits that when a host's residual reproductive value decreases, it would be adaptive for that host to shift its resources into current reproduction. Reproductive compensation has not been observed in the cricket-fly system. Here we review the studies to date that have investigated reproductive compensation in the cricket-fly interaction, in an attempt to understand why crickets do not compensate for their future reproductive losses. We conclude that the cricket-fly interaction may not be an ideal system in which to investigate reproductive compensation and furthermore, that reproductive compensation has been poorly investigated in this system.

Mitochondrial-mediated oxidative stress in response to high glucose is proposed as a primary cause of dorsal root ganglia (DRG) neuron injury in the pathogenesis of diabetic neuropathy. In the present study, we report a greater number of mitochondria in both myelinated and unmyelinated dorsal root axons in a well-established model of murine diabetic neuropathy. No similar changes were seen in younger diabetic animals without neuropathy or in the ventral motor roots of any diabetic animals. These findings led us to examine mitochondrial biogenesis and fission in response to hyperglycemia in the neurites of cultured DRG neurons. We demonstrate overall mitochondrial biogenesis via increases in mitochondrial transcription factors and increases in mitochondrial DNA in both DRG neurons and axons. However, this process occurs over a longer time period than a rapidly observed increase in the number of mitochondria in DRG neurites that appears to result, at least in part, from mitochondrial fission. We conclude that during acute hyperglycemia, mitochondrial fission is a prominent response, and excessive mitochondrial fission may result in dysregulation of energy production, activation of caspase 3, and subsequent DRG neuron injury. During more prolonged hyperglycemia, there is evidence of compensatory mitochondrial biogenesis in axons. Our data suggest that an imbalance between mitochondrial biogenesis and fission may play a role in the pathogenesis of diabetic neuropathy.

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0–6andnbsp;Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72andnbsp;h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24andnbsp;h for all cell lines. Exposure to 750andnbsp;μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells.

BackgroundPro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities.MethodsWe examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks.ResultsIn vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF37 of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis of patient blood samples taken between 30 min and 24 h after intake of AT-101 showed a dose-dependent increase in plasma concentration with peak levels up to 300–700 ng/ml between 1.5 and 2.5 h after intake.ConclusionAT-101 is a competent enhancer of radiation-induced apoptosis in HNSCC in vitro. In addition, in vitro radiosensitization was observed at clinically attainable plasma levels. These finding support further evaluation of the combination of AT-101 with radiation in Bcl-2-overexpressing tumors.

A program of house dust sample collection and analysis has begun in Syracuse, New York, USA, in order to determine the feasibility of a geography-based exposure assessment for urban metals. The sampling program, and the protocols it employs, is described for two different types of wipe media, Ghost Wipes and Whatman Filters. Preliminary results show that strong spatial patterns of floor dust loading (mg dust per square foot) can be observed for data aggregated at a spatial scale of about 1600 m (approximately 2.5 km2). Floor dust metal concentrations were similar to those found in other urban environments, with some regional variation. The median floor dust Pb concentration was approximately 108 mg x kg(-1) for this initial data set of approximately 264 sampled residential locations, and varied from 50 to 1100 mg Pb x kg(-1).

To determine the accuracy of computed tomographic intravenous cholangiography (CT-IVC) for detection of choledocholithiasis. Sixty-five patients undergoing endoscopic retrograde cholangiography (ERC) underwent CT-IVC prior to ERC, using a single detector helical CT following intravenous infusion of 100 ml iotroxate. Patients with bilirubin levels3 times normal were excluded. ERC was indeterminate in three patients (4.7%) and CT-IVC in four (6.3%). Twenty-three patients had ductal calculi at ERC, and CT-IVC was positive in 22, with two false positives and one false negative: sensitivity 95.6%, specificity 94.3%. Stones were multiple in nine and solitary in 14. Of the 14 solitary stones, ten wereor=5 mm and eight wereor=4 mm. The bilirubin level in positive cases was within normal in 20. Maximum intensity projection (MIP) reformats showed stones in only 27% of cases and surface rendered (SR) reformats in none. CT-IVC is highly accurate for detection of ductal calculi, including single small calculi, with a normal or near normal serum bilirubin. Axial images should be used for interpretation rather than MIP or SR reformats.

Introduction: Children with moderate cellulitis are often treated with IV antibiotics in the hospital setting, as per recommendations. Previously in our hospital, a protocol using daily IV ceftriaxone with follow-up at the day treatment center (DTC) was used to avoid admission. In 2013, a new protocol was implanted and suggested the use of high dose (HD) oral cephalexin with follow-up at the DTC for those patients. The aim of this study was to evaluate the safety and efficacy of the HD cephalexin protocol to treat moderate cellulitis in children as outpatient. Methods: A retrospective chart review was conducted. Children were included if they presented to the ED between January 2014 and 2016 and were diagnosed with a moderate cellulitis sufficiently severe to request a follow up at DTC and who were treated according to the standard of care with the HD oral cephalexin (100 mg/kg/day) protocol. Descriptive statistics for clinical characteristics of patients upon presentation, as well as for treatment characteristics in the ED and DTC were analyzed. Treatment failure was defined as: need for admission at the time of DTC evaluation, change for IV treatment in DTC or return visit to the ED. Outcomes were compared to historic controls treated with IV ceftriaxone at the DTC, where admission was avoided in 80% of cases. Results: During the study period, 682 children with cellulitis were diagnosed in our ED. Of these, 117 patients were treated using the oral HD cephalexin outpatient protocol. Success rate was 89.5% (102/114); 3 patients had an alternative diagnosis at DTC. Treatment failure was reported in 12 cases; 10 patients (8.8%) required admission, one (0.9%) received IV antibiotics at DTC, and one (0.9%) had a return visit to the ED without admission or change to the treatment. This compares favorably with the previous study using IV ceftriaxone (success rate of 80%). No severe deep infections were reported or missed; 4 patients required drainage. The mean number of visits per patient required at the DTC was 1.6. Conclusion: Treatment of moderate cellulitis requiring a follow-up in a DTC, using an oral outpatient protocol with HD cephalexin is a secure and effective option. By reducing hospitalization rate and avoiding the need for painful IV insertion, HD cephalexin is a favourable option in the management of moderate cellulitis for pediatric patients, when no criteria of toxicity are present.

The genus Morus consists of trees and shrubs, which are distributed in temperate and subtropical regions. Commonly known as mulberry, a few of the Morus species are valued for their foliage, which constitutes the chief feed for mulberry silkworms. Steroids and isoprenoid compounds present in the foliage not only add nutritive factors to the feed but also contribute greatly to silkworm health and silk production. Mevalonate synthesis, which is the first step in isoprenoid biosynthesis, is catalyzed by the enzyme hydroxymethylglutaryl-CoAreductase (HMGR). A genomic clone, Mahmg1, was isolated from Morus alba and its expression characterized in mulberry and transgenic tobacco. In mulberry, Mahmg1 transcripts were highest in young leaves and flowers. The promoter region of the Mahmg1 gene was fused to the beta-glucuronidase (GUS) reporter gene and the fusion introduced into tobacco. In imbibed embryos, GUS expression was limited to the cotyledons, epicotyl, and root elongation zone. Later, GUS staining was observed in floral tissues, guard cells, and the heads of trichomes on the stem and petioles. Mahmg1::GUS activity increased 3-4-fold by treatment with 100 microM abscisic acid and 15-80-fold in dark-grown versus light-grown seedlings. These results show that expression of the Mahmg1 gene is differentially regulated by developmental and environmental cues, suggesting that its HMGR isozyme a may provide a precursor for synthesis of specific isoprenoids during mulberry growth and development.

1. As a free radical, nitric oxide (NO) may be toxic to neurons through mechanisms that directly involve DNA damage. Lubeluzole, a novel benzothiazole compound, has recently been demonstrated to be neuroprotective through the signal transduction pathways of NO. We therefore examined whether neuroprotection by lubeluzole was dependent upon the molecular pathways of programmed cell death (PCD). 2. In primary hippocampal neurons, evidence of PCD was determined by hematoxylin and eosin (H&E) stain, transmission electron microscopy, and annexin-V binding. NO administration with the NO generators sodium nitroprusside (300 μM) or SIN-1 (300 μM) directly induced PCD. 3. Neurons positive for PCD increased from 22 ± 3% (untreated) to 72 ± 3% (NO) over a 24-hr period. Coadministration of NO and lubeluzole (750 nM), a neuroprotective concentration, actively decreased PCD expression on H&E stain from 72 ± 3% (NO only) to 25 ± 3% (NO and lubeluzole). Significant reduction in DNA fragmentation by lubeluzole also was evident on electron microscopy. Application of lubeluzole in concentrations that were not neuroprotective or administration of the biologically inactive R-isomer did not significantly alter NO-induced PCD, suggesting that neuroprotection by lubeluzole was intimately linked to the modulation of PCD. Lubeluzole also was able to prevent the initial stages of cellular membrane inversion labeled with annexin-V binding, an early and sensitive indicator of PCD. Interestingly, the critical period for lubeluzole to reverse PCD induction appeared to be within the first 4 hr following NO exposure. 4. Further investigation into the neuroprotective pathways that alter PCD may provide greater insight into the molecular mechanisms that ultimately determine neuronal injury.

Tropatepine is a compound with central anticholinergic properties that has been used in the treatment of neuroleptic-induced extrapyramidal syndrome. In this study, we report the plasma pharmacokinetics of tropatepine after intravenous and oral administration (20mg) in 8 healthy volunteers, after oral administration of different doses (10, 15 and 20mg) in 12 healthy volunteers, and following administration of multiple dosages of the drug (20mg/day) in 2 healthy volunteers. Pharmacokinetic parameters of tropatepine and the desmethylated active metabolite nortropatepine were estimated. Clearance following intravenous administration (19 \+- 4 L/h) and after multiple-dose oral administration (27 to 28 L/h) were stable given a bioavailability of 76.1 \+- 24%. A good correlation was found between dose (10, 15 and 20mg) and maximum plasma concentration (Cmax) [6.5 \+-4.5 \gmg/L, 8.5 \+- 6.2 \gmg/Land 18.2 \+- 8.2 \gmg/L, respectively] and total quantity of tropatepine excreted in urine over a period of 120 hours (200 \+- 67\gmg, 254 \+- 93\gmg and 351 \+- 139\gmg, respectively). Such a correlation and the stable clearance confirmed a good linearity in plasma concentrations. Time to reach Cmax (tmax) was 6 to 7 hours for tropatepine and nortropatepine. This delay and the half-life of tropatepine (around 40 hours) were long enough to allow daily administration. However, plasma concentrations varied from a Cmax of 29 \+- 1.4 \gmg/L to a Cmin of 13.8 \+- 1.1 \gmg/L. This doubling in concentration led to the fractionation of the daily dose. Divisible tablets of 5mg have been prepared by Diamant Laboratories. Since the half-life of nortropatepine is long (65.5 \+- 7.95 hours), the range of variations in plasma concentration was smaller than that of tropatepine, i.e. between a Cinmin of 6.5 \+-1.5 |J.g/L and a Cinmax of 9.5 \+- 3.2 \gmg/L. Tropatepine undergoes important metabolism, but nortropatepine is not the main metabolite. After multiple-dose administration, the ratio of urinary excretion of nortropatepine to tropatepine was higher (152%) than that after single-dose administration (62%).

Interaction between the fluorescent Lens culinaris agglutinin–fluorescein complex (LCA-FITC) and two glycoproteins, lactotransferrin (LTF) and serotransferrin (STF), was studied. The two glycoproteins have the same glycan structures, with one difference: the lactotransferrin glycans contain a fucose residue α-1,6-linked to the N-acetylglucosamine residue involved in the N-glycosylamine linkage. Fluorescence intensity quenching of the LCA-FITC complex shows that affinity between LCA and lactotransferrin is 50 times higher than that between LCA and serotransferrin, the fucose playing a major role in this high affinity (Ka is equal to 9.66 and 0.188 μM−1 for the LCA–LTF complex and LCA–STF complex, respectively). Time-resolved anisotropy decay indicates that the rotational correlation time of LCA (20 ns) does not change to a large extent whether the glycoproteins are bound to LCA or not. This suggests that there is no extended physical contact between LCA and the glycoproteins. The interaction between LCA and the glycoproteins occurs likely only via the carbohydrate chains, the STF and the LTF rotating almost-freely in the vicinity of LCA, with the glycans as an anchor.

The effect of thermal stresses in moulded components has been demonstrated by measuring the warpage of centre-gated discs which were injected in a mould, the two sides of which were regulated at different temperatures. Polypropylene discs exhibited larger warpage than polystyrene ones. The measured curvature increased with the difference in mould temperature, and decreased when the packing pressure increased. Thermal stresses and strains have been computed assuming an orthotropic thermo-elastic behaviour for the polymer. A three-dimensional finite element method was used. The different steps of the moulding process, and associated changes of boundary conditions, have been taken into account. The results are qualitatively in agreement with the measurements. Finally the calculation was applied to a box mould, leading to a characteristic box deformation in “diamond ace” form which is consistent with the experiments.

Deficient debrisoquine/sparteine type oxidation is inherited as an autosomal recessive trait. Of all Caucasians, 5-10% are poor metabolisers, due to the absence of cytochrome P4502D6. Extensive metabolisers (EMs) exhibit highly variable metabolic activity. We investigated the relationship between CYP2D6 activity and genotypes of the CYP2D locus in a large set of French Caucasian families. Genotypes concern both common mutations affecting the enzyme activity and linked BamHI polymorphisms of the locus. We found, like other authors, that in EMs part of the heterogeneity is explained by a subgroup of individuals heterozygous for a mutant allele. However, a second level of heterogeneity was detected among individuals not carrying mutations, and this was related to a polymorphic BamHI-defined DNA haplotype. Different combinations of haplotypes are associated with differences in CYP2D6 metabolic activity. This finding might help to clarify the conflicting data on the relation between CYP2D6 activity and susceptibility to lung cancer.

The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.

The interactions of horse heart apocytochromec with membrane interfaces were studied on membrane models including micelles of the anionic surfactant sodium dodecyl sulfate (SDS), the micelle forming lipid analogs dodecylphosphoglycol (Cl2PG), tetradecylphosphoglycol (Cl4PG), and dodecylphosphocholine (Cl2PN), and the negatively charged phospholipid 1-palmitoyl-2-oleoylsn-glycero phosphocholine (POPS) forming small unilamellar vesicles (SUV). The time-resolved fluorescence of the single tryptophan residue (Trp-59) emission was monitored to characterize the modifications of the conformational equilibrium and of the internal dynamics of the protein, which can be brought about by its binding to these model membranes. In most of the cases, as for the protein in solution, the excited state lifetime distribution of the Trp emission was described by four discrete classes, whose relative proportions and barycenters vary significantly in the different complexes formed. In the complex with POPS, however, the decay analysis showed only 3 lifetime classes: the long lifetime class displayed a bary-center value smaller than that observed for the protein in aqueous solution but with a much higher proportion, indicating a stabilization of this conformer in the membrane-bound form of the protein. A similar sensitivity of theTrp-59 excited state to deactivation by thermal collisions in water and in the protein/POPS complex was observed, indicating a probable location ofTrp-59 at the membrane/water interface. The effects of protein binding to C12PN, C12PG and C14PG micelles on the long life-time class proportion were similar to that of POPS but, in addition, there was a large contribution of a short lifetime component which was absent in POPS vesicles. The bary-center values of the excited state lifetime classes were comparable in these membrane systems, suggesting thatTrp-59 is not transferred to a non-polar environment. Binding of apocytochrome c to SDS micelles strongly reduced the lifetime class barycenters and, in contrast to the other membrane systems, strongly favored the contribution of the shortest lifetime class at the expense of the c3 class. This suggests an interaction of theTrp-59 with the sulfur containing head-group of this surfactant. The indole ring mobility is reduced at the interface contacts. A fastTrp-59 mobility with a large amplitude is suggested in the complex with POPS by an initial anisotropy value lower than the expected one of 0.295 measured in vitrified medium. These observations can be correlated with the induction of α-helical structure after interactions of apocytochromec with membrane model systems (de Jongh and de Kruijff 1990).

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI.

The molecular basis for DNA haplotype-dependent debrisoquine 4-hydroxylase (CYP2D6) expression was explored by sequencing all of the nine exons of the CYP2D6 gene. Two distinct exon sequence frameworks of the CYP2D6 gene were found, each associated with specific BamHI-defined DNA haplotypes of the CYP2D cluster. They corresponded to Arg296/Cys296 and Ser486/Thr486 amino acid polymorphisms in the CYP2D6 enzyme, and occurred in almost equal frequency among the Caucasians examined. These two major allozymes with amino acid differences in the presumed substrate recognition region and in the vicinity of the heme binding site could be the source of the observed DNA haplotype-dependent variation in phenotypic expression.

Photodegradation by sunlight is an important decomposition mechanism of polychlorinated biphenyls in the environment. Photodegradation of PCBs proceeds through successive dechlorination of the biphenyl nucleus and thus modify the proportions of the various congeners in a PCB mixture. The objectives of this work is to study the effects of sunlight on a typical PCB mixture such as Aroclor 1254, in a congener specific approach in order to observe the variations in the levels of these toxic congeners in the irradiated mixture.

The Comparison of Single Serum Antibody Values Against B. pertussis, C. pneumoniae , and M. pneumoniae Antigens in Active Duty American Soldiers in Korea Who Had Prolonged Cough Illnesses (Cases) with Similar Antibody Values in Sera from Well Active Duty Soldiers in Hawaii (Controls)

OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients with typical cat scratch disease (CSD).

The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is curently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (−6‡) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% \(V_{O_{2{\text{max}}} } \)) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.

The effect of gamma-radiation on the survival of microorganisms has been quantified for the natural population of two types of peat. Data for several microbial types have been separately determined by regular plating and by indirect statistical probability estimates including, a wholly enclosed ‘invertedbottle’ technique for higher dose levels to exclude any possibility of post-treatment contamination. The most persistent microorganisms at intermediate dosage (2.5–3.5 Mrad) were commonly a micrococcus (which closely resembledMicrococcus radiodurans) arthrobacter-like rods, myxobacteria and amoeboid forms. The persistent organisms all survived because of high resistance to γ-irradiation, not because of high initial numbers. The most numerous true bacteria (including sporeformers), actinomycetes, filamentous fungi and yeasts were all readily destroyed. Although the safety margin with the commercially recommended dose of 5 Mrad is low for some of the more resistant organisms, no change is justified at this stage since the organisms most likely to survive such a dose do not seem to seriously affect the subsequent growth and survival of rhizobia. Moreover there would be some risk of radiation-induced peat toxicity if higher doses were applied and some post-irradiation contamination will be difficult to avoid in commercial production.

The relative success of a commercial strain (TA1) competing with ineffective Uruguayan strains of Rhizobium trifolii for the colonisation of the root surface and in forming nodules has been tested with Trifolium subterraneum and T. vepens, and with a species indigenous to Uruguay (T. polymorphum). Competing pairs of strains were tested on hosts, raised from surface-sterilized seed and maintained on seedling agar in tube culture, so as to permit representation on the root surface and in each nodule to be determined. Relative nodulation success was estimated as a competitive index (C): the ratio of nodules formed by one strain to those formed by the other when equally represented on the root surface. On T. repens and T. subterraneum the effective strain (TA1) dominated the ineffective Uruguayan competitor (U73) so that CTA1:U73 ranged from 18 to greater than 94, and its success was very little dependent on relative representation on the root surface. On T. polymorphum, with which TA1 and U73 were both ineffective, the former was still superior (CTA1:U73=2–4), but was not as dominant as it was on the other two hosts; its success was more dependent on its root-surface representation. A mixture of several, all ineffective, Uruguayan strains narrowed the competitive advantage of strain TA1 and caused its relative nodulating success to become more dependent on representation on the root. The greater intrinsic nodulating competitiveness of strain TA1 was to some extent offset by its relatively poor colonisation of the root surface, where it could be outgrown by the Uruguayan strains, particularly when a medium or low level of inoculation permitted considerable growth. Delay in the addition of TA1 to an established population of U73 resulted in additional representation of the latter in nodules of T. subterraneum. However strain U73 was largely restricted to the earlier-formed nodules and the total, as distinct from the proportion, of TA1 nodules was largely unaffected by the start given its competitor. Nodules due to mixed infections were regularly encountered (up to 18%), particularly in the case of T. subterraneum. It was not possible to find in any of the strains' symbiotic properties a consistent explanation of their competitiveness in nodule formation. However it is perhaps significant that TA1 (the more successful strain) formed its first nodule slightly ahead of its competitors.

L’etude des coulees pyroclastiques sousmarines decouvertes en Iran revet un double interet. Tout d’abord, un interet regional car elles permettent d’expliquerpro parte l’origine des debris de verre argilises largement repandus dans les series sedimentaires eocenes de la zone de l’Iran Central, que les anciens auteurs appelaient tufs verts, boues tuffitiques ou, le plus souvent, series vertes. Un interet plus general ensuite car, contrairement au volcanisme basaltique, le volcanisme sous-marin acide est encore tres peu connu. Le dynamisme que nous proposons implique qu’a partir d’une lave acide sous-marine, fortement vesiculee et a phenocristaux automorphes, l’expansion des gaz engendre un facies vitroclastique a echardes, tandis que les phenocristaux sont fragmentes. L’ensemble forme un ecoulement gravitaire, riche en ponces, echardes, cristaux brises et gaz, de plus en plus turbulent vers l’aval et capable d’arracher au fond marin des lambeaux de sediments. Il evolue par la suite a la maniere d’un courant de turbidite.

The basaltic volcanism which finishes the eruptive activity of the Cantal volcano shows various patterns of the continuous transition from a lava flow to a pyroclastic flow. These sub-aerial deposits can exibit either a laminar or turbulent aspect. The affected lavas show neither mineralogical nor chemical differences from other basalts which did not present this behaviour. The outpouring was along fissures, in the central area of the volcano, as well as the margins; in this last case, it may have involved phreatomagmatic events. Study of the conditions of fragmentation is possible in the case of these basic lavas, because it was delayed until the magma reached the surface. It leads to a better understanding of a phenomenon that, for acid lavas, usually takes place in the feeding channel.

Rocket line immunoelectrophoresis was used to study the taxonomy ofAzotobacter andAzomonas assessed by reaction with antiserum to the AVO2 strain ofAzotobacter. Forty-five cultures, comprising seventeen species in five genera, showed that antigen “β”, like high-titer somatic agglutination, was restricted to all 11 strains ofAzotobacter vinelandii and to one strain which has been namedAzotobacter macrocytogenes (10EM). A thermoresistant antigen (“γ”) was found to be shared by all strains and species ofAzotobacter andAzomonas investigated.

Les structures phreatomagmatiques sont de deux types, maars et anneaux de tufs. Les donnees fournies par les descriptions de l’eruption du Capelinhos (Faial, Acores, 1957–1958), par les structures de la pointe ouest de l’ile de Faial, et par les breches palagonitiques du Velay et du Cantal (France), conduisent a relier anneaux de tufs hyaloclastiques et eruptions sub-aquatiques a faible profondeur («surt-seyennes»). Il est possible de preciser les causes, les caracteristiques, et le mecanisme de formation des anneaux de tufs.

De nombreux volcans resultant d’eruptions phreatomagmatiques engendrees par des magmas differencies ont ete etudies dans le Massif Central (France), dans les Champs Phlegreens (Italie), et l’ile de Sao miguel (Acores). Ils constituent une gamme de formes qui va du cratere d’explosion de type maar au cone de tufs hyaloclastiques. Un des traits essentiels de cette serie morphologique est la preponderance d’anneaux de tufs resultant d’eruptions subaeriennes. Les anneaux de tufs subaeriens lies aux magmas basiques sont beaucoup plus rare que les maars. Une approche thermodynamique montre que la quantite de chaleur fournie par les differents types de magmas et le rapport eau/magma sont le parametres principaux controlant l’activite, done la morphologie des appareils phreatomagmatiques.

The cell bodies of pyramidal cells in layers II and V of rat auditory cortex were quantitatively examined in groups of rats 3, 6, 15, 23, 27 and 34-36 months of age. The mean diameters of cell bodies of both layer II and layer V neurons, as measured in 1 micron plastic sections, increased between 3 and 15 months of age, then decreased to a diameter that was less in the 36-month-old than in the 3-month-old rats. Morphometry of the nuclei of the cells was done by measuring nuclear area and nuclear envelope length directly on electron micrographs. In the layer II cells, neither parameter changed with advancing age. In the layer V cells, the mean nuclear area decreased significantly in the old animals and the mean envelope length increased. Point-counting techniques were applied to electron micrographs of cell bodies to determine the relative volume of selected organelles, inclusions and ground substance in the perikaryal cytoplasm. In this part of the study the chronological pattern of change in layer II and layer V pyramidal cells was similar. The relative volume of dense bodies increased linearly with advancing age, with a slightly more accelerated rate in layer II cells. The relative volume of ground substance remained essentially constant through 27 months, and then at 34-36 months decreased to 83% and 89% of the three-month level in layer V and layer II, respectively. The relative volume of the rough endoplasmic reticulum (RER) did not change significantly until after 15 months, at which time it began to occupy increasingly a larger fraction of the perikaryal cytoplasm. Finally, the relative volumes of mitochondria, multivesicular bodies and Golgi apparatus did not show clear trends of change during the 33-month period.

The branching of clover root hairs was due to a factor (or factors) readily extracted from cells of Rhizobium trifolii and found in seedling solution supporting clover roots inoculated with this organism. Part of the active material was retained within a dialysis sac but a smaller, escaping fraction evoked the same response. The branching fraction was stable at 100°C and, partly, to nuclease and periodate, but was unstable when left in contact with the cells and when treated with trypsin. The dried residue of active filtrate contained 2% nucleic acid, 20% protein and about 34% carbohydrate which included antigenic lipopolysaccharide (approximately 1.6%). The branching response could not be attributed to either of these polysaccharides or to indole acetic acid. The capacity to cause branching was absent from all non-invasive mutants, but was increased in ineffective invasive forms, compared with the effective parent strain.

Paired rhizobial strains supplied in several proportions were used to study inter-strain competition in association with Macroptilium atropurpureum (DC) URB (siratro) and Stylosanthes guianensis (Aubl.) Swartz (Stylo, line I R I 1022). Plants raised from surface sterilized seed, were grown on agar in large cotton-wool plugged tubes, and populations and inter-strain ratios determined in the inoculum and on the root at several times after inoculation. The nodules were mapped in order of appearance and the strains they contained identified at harvest.

The plant-infection technique for the estimation of rhizobia, in which small-seeded hosts are grown on agar within test-tubes, is applicable to soils with a moderate rhizobial population (in the order of at least 100/g). Account might have to be taken of “skips” (less diluted: negative, when more diluted are positive) likely to result, at least in part, from unfavourable conditions for rhizobial survival, multiplication or nodulation. Because of such effects, a sparse population (in the order of (10/g) may not be detected even without dilution (1 g soil per plant tube). Localisation of rhizobia in the soil is likely to be important in determining contact with the plant roots in the dilution count and in sampling from the field. Difficulties with sparsely populated soils can be partly overcome by carefully conducted direct sowings of sterilised seed, preferably in the confines of cores, either left in the field or brought back to the glasshouse.