bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death
Authors: Kato Gregory J. , Wang Zeneng , Machado Roberto F. , Blackwelder William C. , Taylor 6th James G. , Hazen Stanley L. 
Published: March 2009

SummaryPulmonary hypertension (PH) in patients with sickle cell disease (SCD) is linked to intravascular haemolysis, impaired nitric oxide bioavailability, renal dysfunction, and early mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases (NOS), is associated with vascular disease in other populations. We determined the plasma concentrations for several key arginine metabolites and their relationships to clinical variables in 177 patients with SCD and 29 control subjects: ADMA, symmetric dimethylarginine (SDMA), NG‐monomethyl L‐arginine (L‐NMMA), N‐omega‐hydroxy‐L‐arginine (NOHA), arginine and citrulline. The median ADMA was significantly higher in SCD than controls (0·94  μmol/l vs. 0·31 μmol/l, P < 0·001). Patients with homozygous SCD had a remarkably lower ratio of arginine to ADMA (50 μmol/l vs. 237, P < 0·001). ADMA correlated with markers of haemolysis, low oxygen saturation and soluble adhesion molecules. PH was associated with high levels of ADMA and related metabolites. Higher ADMA level was associated with early mortality, remaining significant in a multivariate analysis. Subjects with homozygous SCD have high systemic levels of ADMA, associated with PH and early death, implicating ADMA as a functional NOS inhibitor in these patients. These defects and others converge on the nitric oxide pathway in homozygous SCD with vasculopathy.
Haemoglobin concentration and the risk of death in older adults: differences by race/ethnicity in the NHANES III follow‐up
Authors: Patel Kushang V. , Longo Dan L. , Ershler William B. , Yu Binbing , Semba Richard D. , Ferrucci Luigi , Guralnik Jack M. 
Published: March 2009

SummaryMildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non‐Hispanic whites, non‐Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988–94 US National Health and Nutrition Examination Survey who were ≥65 years of age were analyzed with mortality follow‐up through December 31, 2000. Mean haemoglobin in non‐Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non‐Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47·5%) participants died. Among non‐Hispanic whites and Mexican Americans, age‐ and sex‐adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut‐off points for anaemia. In contrast, the threshold for non‐Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non‐Hispanic blacks than in non‐Hispanic whites and Mexican Americans.
Naturally acquired inhibitory antibodies toPlasmodium vivaxDuffy binding protein are short-lived and allele-specific following a single malaria infection
Authors: Ceravolo I P , Sanchez B A M , Sousa T N , Guerra B M , Soares I S , Braga E M , McHenry A M , Adams J H , Brito C F A , Carvalho L H 
Published: March 2009

SummaryThe Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five cross-sectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBPII), we performed in vitro assays with mammalian cells expressing DBPII sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBPII are short-lived and biased towards a specific allele.
Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex
Authors: King M A , Covassin L , Brehm M A , Racki W , Pearson T , Leif J , Laning J , Fodor W , Foreman O , Burzenski L , Chase T H , Gott B , Rossini A A , Bortell R , Shultz L D , Greiner D L 
Published: March 2009

SummaryImmunodeficient non-obese diabetic (NOD)-severe combined immune-deficient (scid) mice bearing a targeted mutation in the gene encoding the interleukin (IL)-2 receptor gamma chain gene (IL2rγnull) engraft readily with human peripheral blood mononuclear cells (PBMC). Here, we report a robust model of xenogeneic graft-versus-host-like disease (GVHD) based on intravenous injection of human PBMC into 2 Gy conditioned NOD-scid IL2rγnull mice. These mice develop xenogeneic GVHD consistently (100%) following injection of as few as 5 × 106 PBMC, regardless of the PBMC donor used. As in human disease, the development of xenogeneic GVHD is highly dependent on expression of host major histocompatibility complex class I and class II molecules and is associated with severely depressed haematopoiesis. Interrupting the tumour necrosis factor-α signalling cascade with etanercept, a therapeutic drug in clinical trials for the treatment of human GVHD, delays the onset and progression of disease. This model now provides the opportunity to investigate in vivo mechanisms of xenogeneic GVHD as well as to assess the efficacy of therapeutic agents rapidly.
Reduced expression of IL‐3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones
Authors: De Frias Carvalho Vinicius , De Oliveira Barreto Emiliano , Farias‐Filho Francisco Alves , Gomes Leonardo Henrique Ferreira , De Lima Mendonça Leila , Cordeiro Renato Sérgio Balão , Martins Marco Aurélio , Silva Patrícia Machado Rodrigues e 
Published: March 2009

SummaryRats turned diabetic by alloxan treatment are refractory to systemic anaphylactic shock, in a direct association with reduced intestinal haemorrhage and tissue response to antigen challenge. As diabetic rats show reduction in mast cell numbers in different body compartments, this study was undertaken to investigate the influence of alloxan diabetes on mast cell population as well as the expression of the mast cell growth factor interleukin (IL)‐3 in the small intestine of rats. We also analysed the putative involvement of endogenous insulin and glucocorticoid hormones in this phenomenon. There was a significant decrease in the number of mast cells present in the small intestine (ileum segment) of diabetic rats. Likewise, the immunohistochemical analysis revealed that IL‐3 labelling was markedly attenuated in diabetic rats, as compared with normal animals, a phenomenon which paralleled with a decreased mRNA expression as attested by Reverse transcriptase‐polymerase chain reaction technique. Treatment with insulin and with the steroid receptor antagonist RU 486 restored basal mast cell numbers, normal levels of IL‐3 labelling and mRNA expression for IL‐3 in the ileum of diabetic rats. In conclusion, our findings show that there is a causative relationship between down‐regulation of mast cell numbers and the expression of IL‐3 associated with diabetic state. In addition, as both parameters were suppressed by administration of insulin and RU 486, it indicates that an imbalance between the systemic levels of insulin and glucocorticoid hormones seems to be implicated in the reduction in intestinal mast cell population and refractoriness to antigen provocation in alloxan diabetes.
Dystroglycan patterns on the prostate of non‐obese diabetic mice submitted to glycaemic control
Authors: Cagnon Quitete Valéria Helena Alves , Fávaro Wagner José 
Published: March 2009

SummaryDystroglycan (DG) is an adhesion protein which plays a crucial role in the maintenance of tissue integrity. Diabetes has been pointed out as a disease which causes harmful effects on prostate function. Therefore, the main objective of this work was to verify DG distribution and structure features in diabetic mice with and without glycaemic control and to relate these parameters to prostate pathogenesis. Thirty mice (Nod and BALB/c) were divided into three groups after 20 days of diabetic state: the control group received a 5 ml/kg dose of physiological saline daily for 20 days; the diabetic group had the same treatment as the control group; the diabetic‐insulin group received 4–5 IU doses of Neutral Protamine Hagedorn (NPH) insulin daily for 20 days. After 20 days of treatment, all animals were killed and samples from the ventral prostate were processed for immunological and light microscopy analyses. The results showed diminished β‐ and α‐DG receptors in the diabetic group. However, there was a recovery of both β‐and α‐DG receptor immunolocalization after insulin administration. Epithelial and stromal morphological changes were verified in the diabetic group, which also presented recovery after insulin treatment. Thus, it could be concluded that diabetes disturbed prostate structure integrity and altered the occurrence of α and β‐DG receptors, indicating decreased cell‐matrix extracellular and cell‐basal membrane attachment. However, insulin treatment could partially restore glandular homeostasis. The decrease in epithelial–stromal interaction certainly predisposes this gland in diabetic mice to be a prostate disease target.
Megaoesophagus in Rassf1a‐null mice
Authors: Van Der Weyden Louise , Happerfield Lisa , Arends Mark J. , Adams David J. 
Published: March 2009

SummaryMegaoesophagus, or oesophageal achalasia, is a neuromuscular disorder characterized by an absence of peristalsis and flaccid dilatation of the oesophagus, resulting in the retention of ingesta in the dilated segment. The aetiology and pathogenesis of idiopathic (or primary) megaoesophagus are still poorly understood and very little is known about the genetic causes of megaoesophagus in humans. Attempts to develop animal models of this condition have been largely unsuccessful and although the ICRC/HiCri strain of mice spontaneously develop megaoesophagus, the underlying genetic cause remains unknown. In this report, we show that aged Rassf1a‐null mice have an enhanced susceptibility to megaoesophagus compared with wild‐type littermates (∼20%vs. ∼2% incidence respectively; P = 0.01). Histological examination of the dilated oesophaguses shows a reduction in the numbers of nerve cells (both ganglia and nerve fibres) in the myenteric plexus of the dilated mid and lower oesophagus that was confirmed by S100 immunohistochemistry. There was also a chronic inflammatory infiltrate and subsequent fibrosis of the myenteric plexus and the muscle layers. These appearances closely mimic the gross and histopathological findings in human cases of megaoesophagus/achalasia, thus demonstrating that this is a representative mouse model of the disease. Thus, we have identified a genetic cause of the development of megaoesophagus/achalasia that could be screened for in patients, and may eventually facilitate the development of therapies that could prevent further progression of the disease once it is diagnosed at an early stage.
Histological characteristics of human papilloma‐virus‐positive and ‐negative invasive and in situ squamous cell tumours of the penis
Authors: Krustrup Dorrit , Jensen Helle Lone , Van Den Brule Adriaan J.C. , Frisch Morten 
Published: March 2009

SummaryA high prevalence of cervical cancer associated high‐risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from 145 patients with invasive (n = 116) or in situ (n = 29) penile squamous cell carcinoma were subjected to systematic histological evaluation and were PCR‐tested for 14 hrHPV types and 23 low‐risk HPV types. Around half (52%) of invasive and nine‐tenths (90%) of in situ lesions were positive for an hrHPV type, of which HPV 16 was by far the predominant type (91% of hrHPV‐positive lesions). In relation to histological characteristics, hrHPV positivity was statistically significantly more common in high‐grade tumours, lesions dominated by small tumour cells, lesions with a high number of multinucleated cells and mitoses, and lesions with a small amount of parakeratosis. In conclusion, about half of invasive penile squamous carcinomas in this study were hrHPV‐positive, most notably to HPV 16, and probably arose through in situ lesions whereas the other half of invasive penile lesions appeared to be unrelated to hrHPV. A number of histological characteristics differed significantly between hrHPV‐positive and ‐negative invasive penile carcinomas.
The effects of colonization, extinction and competition on co‐existence in metacommunities
Authors: Hunt Julia J.F.G. , Bonsall Michael B. 
Published: March 2009

SummaryThe co‐existence of competitors in heterogeneous landscapes depends on the processes of colonization, extinction and spatial scale. In this study, we explore the metapopulation dynamics of competitive interactions.Rather than simply evaluating the outcome of interspecific competition in the traditional manner, we focus on both the local population dynamic effects and the regional metapopulation processes affecting species co‐existence.We develop a theoretical model of regional co‐existence to generate a set of predictions on the patterns of colonization necessary for co‐existence and the regional processes that can lead to competitive exclusion. We empirically test these predictions using metacommunity microcosms of the interaction between two bruchid beetles (Callosobruchus chinensis,Callosobruchus maculatus).Using well‐replicated time series of the interaction between the bruchids and statistical methods of model fitting, we show how the qualitative and quantitative pattern of interspecific competition between the bruchid beetles is shaped by the structure of the metacommunity.In unlimited dispersal metacommunities, the global exclusion of the inferior competitor is shown to be influenced more by the processes associated with extinction rather than low colonization ability. In restricted dispersal metacommunities, we show how the co‐existence of competitors in a spatially heterogeneous habitat (patches connected through limited dispersal) is affected by Allee effects and life‐history [colonization (dispersal) – competition] trade‐offs.
Putting a break on protein translocation: metabolic regulation of mitochondrial protein import
Authors: Herrmann Johannes M. 
Published: March 2009

SummarySequence‐inherent targeting information directs polypeptides synthesized in the cytosol to their respective cellular compartment. Some proteins use ambiguous sorting signals or specific folding properties to be dually distributed between the cytosol and mitochondria. A study published in this issue of Molecular Microbiology shows that in the case of fumarase this distribution is controlled by the metabolic state of yeast cells. The metabolite‐dependent distribution of fumarase represents an exciting example of regulated protein import into mitochondria that shows that eukaryotes can adapt the intracellular protein distribution to their physiological conditions.
Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients
Authors: Berge M. , Guillemain R. , Boussaud V. , Pham M.‐H. , Chevalier P. , Batisse A. , Amrein C. , Dannaoui E. , Loriot M.‐A. , Lillo‐Le Louet A. , Billaud E.M. 
Published: March 2009

Background. Aspergillosis is a high‐risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug–drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels.Methods. VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 ± 0.5 – C2 : 4.0 ± 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data.Results. The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 ± 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 ± 2.6, n=31/VRZ versus 1.7 ± 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of the drug–drug interactions and adjustment requirements.Conclusions. TDM is required because VRZ levels are often undetectable in treated CF lung transplant patients, supporting the use of antifungal drug combinations until achievement of VRZ C0 at a steady state between 1 and 2 mg/L. Plasma VRZ concentrations should be determined for the quantitative, individualized management of drug–drug interactions in lung transplant patients, in particular immunosuppressant such as tacrolimus, considering VRZ to be both a target and an inhibitor of CYP3A4.
Population density of Diabrotica virgifera virgifera LeConte beetles in Serbian first year and continuous maize fields
Authors: Sivcev I. , Stankovic S. , Kostic M. , Lakic N. , Popovic Z. 
Published: March 2009

AbstractA 5‐year field survey examined western corn rootworm (WCR) (Diabrotica virgifera virgifera LeConte) beetle density in Serbia from 2002 to 2006. First‐, second‐, third‐, fourth‐ and fifth‐year maize fields were sampled; they represented 64.61%, 21.66%, 9.45%, 3.53% and 0.75% of all sampled fields respectively. Results showed that the mean WCR beetle population density from 794 maize fields differed depending on cropping history. Minimum mean WCR/trap/day was 0.0 in the first‐year maize fields in 2002 and 2006. Maximum mean WCR/trap/day was registered in the fourth‐year and the fifth‐year maize fields (27.8 and 21.2 respectively). Mean population density of WCR adults increased with the number of years of continuous maize from 1.17, 4.61, 6.41, 10.30 up to 13.53 WCR/trap/day for first‐fifth‐year maize fields respectively. Mean WCR/trap/day ± SE exceeded the economic population threshold of >6 WCR/trap/day in third‐year continuous maize fields. Out of 794 maize fields, 697 (87.78%) registered a mean population density below the <6 beetles/trap/day threshold. In only 97 fields was WCR population density >6 beetles/trap/day, a finding that predicts a risk of economic damage to a subsequent maize planting. These data are representative of the Serbian situation from 2002 to 2006; they indicate that WCR are well dispersed across commercial maize fields in Serbia. These results provide new insight into the current low WCR population densities in maize fields managed by crop rotation, a finding that can help in creating long‐term management strategy.
Prepenetration Stages of Guignardia psidii in Guava: Effects of Temperature, Wetness Duration and Fruit Age
Authors: Escanferla Maria Eugenia , Moraes Sylvia Raquel Gomes , Salaroli Renato Barbosa , Massola Jr Nelson Sidnei 
Published: March 2009

AbstractThis study examined the effects of temperature and wetness duration in vitro and in vivo as well as the effects of fruit age on germination and appressoria formation by conidia of Guignardia psidii, the causal agent of black spot disease in guava fruit. The temperatures tested for in vitro and in vivo experiments were 10, 15, 20, 25, 30, 35 and 40°C. The wetness periods studied were 6, 12, 24, 36 and 48 h in vitro and 6, 12 and 24 h in vivo. Fruit 10, 35, 60, 85 and 110‐days old were inoculated and maintained at 25°C, with a wetness period of 24 h. Temperature and wetness duration affected the variables evaluated in vitro and in vivo. All variables reached their maximum values at between 25 and 30°C with a wetness duration of 24 h in vivo and 48 h in vitro. These conditions resulted in 31.3% conidia germination, 33.6% appressoria formation and 32.5% appressoria melanization in vitro, and 50.4% conidia germination and 9.5% appressoria formation in vivo. Fruit age also influenced these factors. As fruit age increased, conidia germination and appressoria formation gradually increased. Conidia germination and appressoria formation were 10.8% and 2.3%, respectively, in 10‐day‐old fruits. In 110‐day‐old fruits, conidia germination and appressoria formation were 42.5% and 23.2% respectively.
Strain E26 of Agrobacterium vitis, a Biological Control Agent of Grapevine Crown Gall, Does Not Contain virA and virG Pathogenic Determinants
Authors: Wei Qing , Li Jin‐Yun , Wang Jian‐Hui , Wang Hui‐Min 
Published: March 2009

AbstractRisk assessment of biological control agents (BCAs) for the control of plant diseases in the field and/or laboratories has now become a necessary procedure before developing and producing novel BCAs. Agrobacterium vitis strain E26 is a promising potential biocontrol agent of grapevine crown gall disease. However, much less is understood about its safety or environmental risks. In this study, polymerase chain reaction (PCR) and Southern blot analyses were used to determine whether five essential virulence genes (virA, virG, iaaH, iaaM and ipt) were present in strain E26. Primers and probes were designed based on the conserved regions of each gene. The overall results obtained indicated that A. vitis strain E26 does not contain the virA and virG determinants, suggesting that this strain would be unlikely to elicit crown gall symptoms in either host or non‐host plants. It seems that the iaaH, iaaM, or ipt gene were not present in strain E26 either. An applicable new approach combining PCR and Southern blot analyses to examine the pathogenicity of potential BCAs, particularly BCAs from the genus of Agrobacterium spp. was described.