bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue HHV6 and 7 determination in pediatric solid organ recipients − a pilot study
Authors: Gupta M. , Diaz‐Mitoma F. , Feber J. , Shaw L. , Forget C. , Filler G.
Published: November 2003

Abstract:  Herpes virus infections remain a major challenge in solid organ transplantation. HHV6 and 7 blood viral load was associated with pathology after renal transplantation. Little is known about the significance of tissue HHV6 and 7 infections. A total of 18 tissue biopsies (13 kidney, three GI and two BAL) from nine pediatric transplant patients (five kidney, two liver, one combined liver and kidney and one bone marrow transplant) were subjected to blood HHV6 IgG and IgM testing. In addition, tissue HHV6 and 7 semi‐quantitative PCR analysis with subsequent detection by ELISA and quantitative methods were applied to the same samples. We also studied four native kidney biopsies of children with other kidney disease. The results of the biopsies were correlated with clinical data. Of the transplant patients, 78% were HHV6 IgG positive. Six of nine had a positive IgM on at least one occasion, however, only two of nine transplant patients were symptomatic with a mixed CMV/EBV septic picture of multi‐organ failure. Only these two patients had a significant tissue viral load for HHV6. Additionally, a very significant tissue viral load for HHV6 was detected in an immunocompromised patient 3 wk after a roseola‐like febrile illness. The HHV6 copies were 31, 88 and 206 per 10 μL of DNA, respectively. In the patient who also had the fourth positive ELISA for HHV6 PCR product, the Multiplex PCR and restriction enzyme assay on its PCR product revealed a significant contribution by HHV7, while the HHV6‐B signal was rather weak. Significant tissue HHV6 loads can be found in tissue biopsies from organ recipients with significant illness and also in native kidneys after primary infection. This may explain the high prevalence of HHV6 in transplanted kidneys. Further studies on HHV6 and 7 using molecular techniques should be supported.
Challenges in conducting research with acutely ill hospitalized older patients
Authors: Hancock Karen , Chenoweth Lynn , Chang Esther
Published: November 2003

Abstract  The older population is the largest consumer of health care, yet little is known about their nursing needs during acute hospitalization. In undertaking a study to address this issue, the researchers faced many challenges that were related to the complexities of researching acutely ill hospitalized older patients. The purpose of the present discussion paper is to present some of the methodological and pragmatic factors that were encountered so that health professionals and researchers can be aware of the potential obstacles when researching this important area, and plan research accordingly. Potential barriers included the complexity of illness in the older person as a result of comorbidity and iatrogenesis; fatigue; normal age‐related processes such as visual/hearing impairment; frequent ward transfer or early discharge; delirium or dementia; and high staff turnover resulting in difficulties in coordinating the study. This paper raises the importance of balancing the need to maximize the rigor of research and the needs of participants. Recommendations for future research are made.
Clinicopathologic characteristics of Chinese hereditary non‐polyposis colorectal cancer
Authors: CUI Long , JIN Hei Ying , CHENG Hui Yu , YAN Yu Di , MENG Rong Gui , YU De Hong
Published: November 2003

OBJECTIVE:  The aim of the present study was to examine the clinicopathologic characteristics of Chinese patients with hereditary non‐polyposis colorectal cancer (HNPCC) and those with suspected (atypical) HNPCC.

METHODS:  Personal and family cancer histories were obtained by reviewing the charts and interviewing the proband and participating relatives. Families were identified and classified into three groups by either the Amsterdam or Japanese criteria for HNPCC. Clinical characteristics including onset, localization, stage of colorectal cancer (CRC), tumor multiplicity, survival and mucinous histology were evaluated.

RESULTS:  Ninety‐eight subjects comprising 92 CRC patients and six extracolonic cancer patients from 13 typical and 19 non‐typical HNPCC kindreds were enrolled. There were 53 patients with CRC, one with both CRC and extracolonic cancer and five with extracolonic cancer in the typical HNPCC group, and in the atypical group there were 38 patients with CRC and one with extracolonic cancer. The average onset age of typical HNPCC and atypical HNPCC was 48 and 50 years, respectively, without statistical difference. There were no statistical differences in sex, pathological type, stage, site distribution of the tumor or survival between typical HNPCC and atypical HNPCC groups. There were 11.1% (6/54) metachronous CRC in the typical HNPCC group, and 7.9% (3/38) metachronous and 2.6% (1/38) synchronous CRC in the atypical HNPCC group.

CONCLUSION:  The Amsterdam criteria are important, but inappropriate for the establishing the clinical diagnosis of HNPCC in Chinese patients, with some atypical families that did not fulfil all the Amsterdam criteria probably possessing similar clinicopathogical features and genetic alterations. It seems that HNPCC should be considered in some suspected cases.
Efficacy of a 1‐week rabeprazole triple therapy for eradicating Helicobacter pylori and ulcer healing: an ‘in‐clinical‐practice’ study
Authors: GOH KL , ROSAIDA MS , SALEM O , CHEAH PL , RANJEEV P , TAN YM , ROSMAWATI M , CHIN SC
Published: November 2003

OBJECTIVE:  To determine the efficacy and tolerability of a 1‐week treatment regimen consisting of rabeprazole and two antibiotics, clarithromycin and amoxicillin, in the eradication of Helicobacter pylori in an ‘in‐clinical‐practice’ setting.

METHODS:  Patients selected had unequivocal evidence of H. pylori infection based on urease test and histology of antral and corpus biopsies obtained at endoscopy. Patients with complicated ulcers were not included. Patients received rabeprazole 10 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by histology and urease test. Ulcer patients did not receive continued acid suppression therapy following the 1‐week course of treatment.

RESULTS:  The study recruited 205 patients of whom 25 were not compliant with the medications or defaulted on follow‐up and were therefore not included in the per‐protocol analysis. Eradication of H. pylori was successful in 166/180 of patients on per‐protocol analysis (92.2% [95% CI: 87.3, 95.7]) and in 169/205 patients on intention‐to‐treat analysis (82.4% [95% CI: 80.5, 90.2]; P = 1.000). There were 47 patients with active ulcers: DU 27, GU 18, DU/GU 2. Overall, ulcer healing was achieved in 42 of 44 (95.5%) patients who had successful eradication of H. pylori infection, but ulcers did not heal in any of the three patients (DU 2, GU 1) who did not eradicate the infection. Of the total group, 199 were assessed for compliance and side‐effects of treatment. Side‐effects were in general mild and tolerable. Of 14 patients who were not compliant with medication, 4 (2.0%) attributed it to side‐effects of treatment (increased abdominal pain, dizziness and taste disturbances) and the remaining 10 did not give specific reasons. The most common side‐effect was bitter taste, reported by 39.2% of patients. Other side‐effects, such as giddiness, increased abdominal pain, lethargy, loose bowel motions and skin rash, were mild and found in only a small percentage of patients.

CONCLUSIONS:  The rabeprazole 1‐week triple therapy with amoxicillin and clarithromycin is effective in eradicating H. pylori in an ‘in‐clinical‐practice’ setting. The treatment was well tolerated by patients. Good ulcer healing was achieved with short‐course H. pylori eradication therapy without the need for continued acid suppression.
Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation
Authors: Bolis Annalisa , Corbetta Sara , Cioce Antonella , De Curtis Ivan
Published: November 2003

Rac3 is one of the three known Rac GTPases in vertebrates. Rac3 shows high sequence homology to Rac1, and its transcript is specifically expressed in the developing nervous system, where its localization and function are unknown. By using Rac3‐specific antibodies, we show that the endogenous Rac3 protein is differentially expressed during mouse brain development, with a peak of expression at times of neuronal maturation and synaptogenesis. Comparison with Rac1 shows clear‐cut differences in the overall distribution of the two GTPases in the developing brain, and in their subcellular distribution in regions of the brain where both proteins are expressed. At P7, Rac3 staining is particularly marked in the deep cerebellar nuclei and in the pons, where it shows a discontinuous distribution around the neuronal cell bodies, in contrast with the diffuse staining of Rac1. Rac3 does not evidently co‐localize with pre‐ and post‐synaptic markers, nor with GFAP‐positive astrocytes, but it clearly co‐localizes with actin filaments, and with the terminal portions of calbindin‐positive Purkinje cell axons in the deep cerebellar nuclei. Our data implicate Rac3 in neuronal differentiation, and support a specific role of this GTPase in actin‐mediated remodelling of Purkinje cell neuritic terminals at time of synaptogenesis.
A quantitative and morphological study of projection neurons in lamina I of the rat lumbar spinal cord
Authors: Spike R. C. , Puskár Z. , Andrew D. , Todd A. J.
Published: November 2003

In the rat lumbar spinal cord the major supraspinal targets for lamina I projection neurons are the caudal ventrolateral medulla (CVLM), lateral parabrachial area (LPb) and periaqueductal grey matter (PAG). In this study we have estimated the number of lamina I neurons retrogradely labelled from each of these sites in the L4 segment, as well as the proportion that can be labelled by injecting different tracers into two separate sites. Our results suggest that this segment contains approximately 400 lamina I projection neurons on each side, and that approximately 85% of these can be labelled from either the CVLM or the LPb on the contralateral side. Around 120 lamina I cells in L4 project to the PAG, and over 90% of these cells can also be labelled from the CVLM or LPb. Most lamina I neurons projecting to CVLM or LPb are located in the contralateral dorsal horn, but in each case some cells were found to have bilateral projections. We also examined horizontal sections to investigate morphology and the expression of the neurokinin 1 (NK1) receptor in cells labelled from CVLM, LPb or PAG. There were no consistent morphological differences between these groups, however, while cells with strong or moderate NK1 receptor‐immunostaining were labelled from LPb or CVLM, they seldom projected to the PAG. These results suggest that many lamina I cells project to more than one site in the brain and that those projecting to PAG may represent a distinct subclass of lamina I projection neuron.
α2‐γ‐Aminobutyric acid (GABA)A receptors are the molecular substrates mediating precipitation of narcosis but not of sedation by the combined use of diazepam and alcohol in vivo
Authors: Täuber Marcus , Calame‐Droz Elisabeth , Prut Laetitia , Rudolph Uwe , Crestani Florence
Published: November 2003

Classical benzodiazepines such as diazepam are widely used tranquillisers and hypnotics in various neuropsychiatric diseases including alcohol‐related disorders. One of the major drawbacks of benzodiazepine therapy, however, is an exacerbation of the sedative and hypnotic effects associated with alcohol intake, even at low doses. Even though the γ‐aminobutyric acid (GABA)A receptor complex is a common target for the actions of both classes of drugs, the molecular mechanisms underlying the enhanced pharmacological properties of the combined use of benzodiazepines and alcohol remain to be identified. The present experiments aimed at clarifying which of the GABAA receptor subtypes mediate the augmented hypnotic‐like and sedative effects of combined diazepam and alcohol using the righting reflex and motor activity assays, respectively, in histidine‐to‐arginine point mutated mice that possess diazepam‐insensitive α1‐, α2‐, α3‐ or α5‐GABAA receptors. The combination of diazepam (2 or 3 mg/kg) and ethanol (3 g/kg) induced loss of righting reflex with a significantly dose‐dependent increase of the latency to its full recovery in wild‐type, α1(H101R), α3(H126R) and α5(H105R) but not in α2(H101R) mice. A combined treatment with diazepam (1 mg/kg) and ethanol (2.5 g/kg) precipitated motor inhibition similarly in wild‐type and α2(H101R) mice. Responsiveness of the α2(H101R) mice to ethanol alone was similar to that of wild‐type mice. These results demonstrate that induction of loss of righting reflex by combined diazepam and alcohol is closely dependent on the activation of the α2‐GABAA receptors by the benzodiazepine whereas precipitation of sedation involves GABAA receptors other than the α2‐GABAA receptors.
Light‐induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6‐38 or PACAP immunoneutralization
Authors: Bergström A. L. , Hannibal J. , Hindersson P. , Fahrenkrug J.
Published: November 2003

Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are daily adjusted (entrained) by light via the retinohypothalamic tract (RHT). The RHT contains two neurotransmitters, glutamate and pituitary adenylate cyclase‐activating polypeptide (PACAP), which are believed to mediate the phase‐shifting effects of light on the clock. In the present study we have elucidated the role of PACAP in light‐induced phase shifting at early night in hamsters and shown that (i) light‐induced phase delay of running‐wheel activity was significantly attenuated by a specific PAC1 receptor antagonist (PACAP6‐38) or by immunoblockade with a specific anti‐PACAP antibody injected intracerebroventricularly before light stimulation; (ii) PACAP administered close to the SCN was able to phase‐delay the circadian rhythm of running‐wheel activity in a similar way to light; (iii) PACAP was present in the hamster RHT, colocalized with melanopsin, a recently identified opsin which has been suggested to be a circadian photopigment. The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP‐expressing cells of the RHT.
Complexity and temporal dynamics of frequency coding in the awake rat auditory cortex
Authors: Gaese Bernhard H. , Ostwald Joachim
Published: November 2003

Auditory cortical neurons are elements of a neuronal network that decomposes sounds into spectral and temporal information. In particular, their frequency selectivity has been investigated in great detail. Most studies used anaesthetized preparations and found mainly simple V‐shaped tuning. The few data available from awake animals indicate that more complex forms of spectral receptive fields, i.e. frequency response areas, can be found there. We investigated frequency response areas in the awake rat primary auditory cortex using statistical evaluation and found complex forms of frequency response areas with several separate subregions in many neurons, besides classical V‐shaped tuning. Response areas, as determined with narrow band noise, were very similar to those measured with pure tones. Their width was well correlated to the response strength to white noise stimulation. These results suggest that the excitatory subregions of frequency response areas were the neurons' predominant characteristic, relevant also for the processing of more complex types of stimuli. Investigating the spectrotemporal dynamics of frequency response areas revealed that approximately one‐third of the neurons showed long‐lasting excitatory or inhibitory components in addition to the typical ON‐response. Inhibition was usually of longer duration and occurred mainly in frequency ranges outside the range of initial excitatory responses. These results indicate that auditory cortical neurons in awake animals can represent spectrotemporal information of rather different complexity.
FLAIR‐FLOW 4: Synthesis report on obesity for health professionals
Authors: Goldberg Gail
Published: November 2003

Summary  One of the activities of FLAIR‐FLOW Europe 4 (http://www.flair‐flow.com) is the production of synthesis reports. This report on obesity is the third in a series of six synthesis reports written for health professionals. Obesity is a condition in which abnormal or excessive fat accumulation in adipose tissue impairs health. Obesity is defined in adults as a body mass index above 30 (kg/m2). Obesity is one of the most visible, but until recently, most neglected public health problems. The current high prevalence (the percentage of the population who are obese) of obesity and the rapid increase in prevalence in the last 20 years has been referred to as an ‘epidemic’. ‘Globesity’ is now a major, worldwide public health problem and is a reflection of profound social, economic and cultural changes. Paradoxically, in many countries, the huge increase in the prevalence of obesity has occurred over the same time period that energy intakes have decreased, thus demonstrating increasingly sedentary lifestyles. The other fundamental cause of the obesity epidemic is the over‐consumption of high‐fat energy‐dense diets. However, not everyone exposed to this ‘obesigenic’ environment becomes obese. We do not yet know the aetiology of particular eating and lifestyle behaviours nor why the body's regulatory systems might respond more appropriately in some individuals than in others. Some of the factors may be genetic. The aim of this report, which focuses on obesity in adults, is to bring together in a user‐friendly format the progress and results of recent and ongoing European Union funded projects. To put this work in context, some background information of particular relevance to health professionals is also provided.
The “Employment‐first” Welfare State: Lessons from the New Deal for Young People
Authors: Finn Dan
Published: November 2003

New Labour is constructing an “employment‐first” welfare state. It plans through Jobcentre Plus to transform the passive culture of the benefit system by creating more explicit links between individual behaviour and engagement with labour market programmes. The New Deal for Young People (NDYP) has been at the forefront of these changes. This paper reports on the findings from four case studies that explored how the NDYP has changed young people's experience of the welfare state. It establishes that NDYP offers a mixture of employment assistance and “pressure” and has made progress in developing front‐line services and helping young long‐term unemployed people into work. NDYP does not, however, work for all. In areas of high unemployment and for some disadvantaged groups intermediate labour markets could enhance the New Deal and make real the offer of “employment opportunities for all”.
New Firms in Former Farms: A Process with Two Faces
Authors: Daalhuizen Femke , Van Dam Frank , Goetgeluk Roland
Published: November 2003

The number of farms in the Netherlands is decreasing. As a result, many agricultural buildings are losing their original function and designation. This article describes the re‐use of former agricultural buildings by non‐agricultural entrepreneurs. These new activities imply changes to the rural landscape, rural economy and rural society, which can be valued both as positive and as negative outcomes.
THE EGYPTIAN GREEN PIGMENT: ITS MANUFACTURING PROCESS AND LINKS TO EGYPTIAN BLUE*
Authors: Pagès‐Camagna S. , Colinart S.
Published: November 2003

The chemical and structural analysis of raw Egyptian blue and green pigment cakes and of 50 pigment samples taken from paintings kept in the Louvre Museum was performed using a set of analytical techniques (X‐ray powder diffraction, transmission and scanning electron microscopy, Raman microscopy and UV spectrophotometry). The structural and morphological study of modern samples prepared on the basis of these results has provided technological data that help to explain ancient procedures. The role of the firing temperature, the atmospheric conditions in the furnace and the cooling rate are considered. The difference between Egyptian blue and Egyptian green pigment is proved. Manufacturing processes for their deliberate synthesis are proposed.
Clinical effectiveness of different approaches to peritoneal dialysis catheter exit‐site care
Authors: Lockwood Craig , Hodgkinson Brent , Page Tamara
Published: November 2003

Executive summary

Objective  The objective of this review was to appraise and synthesise the best available evidence on the clinical effectiveness of peritoneal dialysis catheter exit‐site care.

Inclusion criteria  This review considered all randomised controlled trials that evaluated the effectiveness of peritoneal exit‐site care. In the absence of randomised controlled trials, other controlled research designs such as non‐randomised controlled trials were considered for inclusion in a narrative summary to enable the identification of current approaches and possible future strategies. Participants of interest were adults with chronic renal failure on maintenance peritoneal dialysis. Interventions of interest were those used to manage peritoneal catheter exit sites, and included types of dressings, frequency of dressings, types of skin care, and use of topical antiseptic or antimicrobial agents.

Search strategy  The search sought to find both published and unpublished studies. An initial limited search of MEDLINE and CINAHL databases was undertaken to identify key words contained in the title or abstract, and index terms used to describe relevant articles. A second extensive search was undertaken using all identified key words and index terms. The third step was a search of the reference lists and bibliographies of all relevant articles.

Methodological quality  All identified studies that met the inclusion criteria were assessed for methodological validity by two reviewers prior to inclusion in the review. Critical appraisal of studies focused on identifying bias in selection, performance, attrition and detection.

Results This review found few studies of sufficient quality to meet the inclusion criteria. The included studies often utilised historical control groups, potentially confounding measurement of their outcomes. The outcome measures varied considerably, thus meta‐analysis was not possible.

Conclusions This review suggests topical mupirocin may reduce the risk of exit‐site infection; however, the clinical effectiveness of any one antibiotic, antiseptic or dressing procedure was not established for the prevention or reduction of exit‐site infection rates or peritonitis. This review has underlined large gaps in the existing knowledge on the care of exit sites in patients on peritoneal dialysis.
The general case for redox control of wound repair
Authors: Sen Chandan K.
Published: November 2003

The orthodox view has been that reactive oxygen species are primarily damaging to cells. There is general agreement that while high (3%) doses of H2O2 may serve as a clinical disinfectant, its overall effect on healing is not positive. Current work shows that at very low concentrations, reactive oxygen species may regulate cellular signaling pathways by redox‐dependent mechanisms. Recent discoveries show that almost all cells of the wound microenvironment contain specialized enzymes that utilize O2 to generate reactive oxygen species. Numerous aspects of wound healing are subject to redox control. An understanding of how endogenous reactive oxygen species are generated in wound‐related cells may influence the healing process and could result in new redox‐based therapeutic strategies. Current results with growth factor therapy of wounds have not met clinical expectations. Many of these growth factors, such as platelet‐derived growth factor, rely on reactive oxygen species for functioning. Redox‐based strategies may serve as effective adjuncts to jump‐start healing of chronic wounds. The understanding of wound‐site redox biology is also likely to provide novel insights into the fundamental mechanisms that would help to optimize conditions for oxygen therapy. While a window of therapeutic opportunity seems to exist under conditions of low concentrations of reactive oxygen species, high levels may complicate regeneration and remodeling of nascent tissue. (WOUND REP REG 2003;11:431–438)
Use of hypoxia‐inducible factor signal transduction pathway to measure O2 levels and modulate growth factor pathways
Authors: Mogford Jon E. , Roy Nakshatra K. , Cross Kevin J. , Mustoe Thomas A.
Published: November 2003

Tissue PO2 levels are known to directly modulate numerous processes involved in the reparative response to cutaneous tissue injury, including cell differentiation and migration, extracellular matrix synthesis and maturation, and effectiveness of endogenous and exogenous growth factors. Oxygen is therefore likely the critical variable determining the healing capabilities of any tissue. Significant advances in the understanding of cutaneous wound healing progressed with advances in the measurement of tissue PO2, which has advanced over the past several decades from implantable probes to now include molecular tools such as the transcription factor hypoxia inducible factor‐1 (HIF‐1). HIF‐1 modulates the expression of genes that drive the cellular adaptive response to hypoxia and possess the HIF‐1 binding sequence named hypoxia response element within their promoter sequence. Molecular biology techniques are now allowing exploitation of the HIF‐1/hypoxia response element pathway to drive the expression of potential vulnerary ectopic genes. Here we show the utility of the hypoxia response element for hypoxia‐driven expression of the transforming growth factor‐β–signaling component Smad3 in vitro and the in vivo detection of ischemic hypoxia using luciferase. Smad3 is a positive effector of transforming growth factor‐β superfamily signal transduction. Such approaches are the latest evolution of work championed by Hunt and colleagues over the past 4 decades. (WOUND REP REG 2003;11:496–503)
From Authoritative Parenting Practices to an Authoritarian Context: Exploring the Person–Environment Fit
Authors: Mayseless Ofra , Scharf Miri , Sholt Michal
Published: November 2003

This study examined whether authoritarian or authoritative parenting practices best prepare youth for coping with an authoritarian context (i.e., the mandatory military service of 18‐year‐old men in Israel) with specific reference to the issue of person–environment fit. A year before their conscription, 85 male adolescents (M age=17.5) and their parents filled out questionnaires regarding their relationships; during basic training, they did so again regarding the new recruit's coping and adaptation. Two peers from each adolescent's basic training unit also rated their coping and adaptation. Findings demonstrated that authoritative parenting practices were advantageous with respect to coping and adaptation in an authoritarian context and that these associations were to some extent mediated through the adolescents' self‐esteem. These results are discussed in light of claims of limitations to the general benefit of the authoritative parenting style.
Self‐Mutilation and Homeless Youth: The Role of Family Abuse, Street Experiences, and Mental Disorders
Authors: Tyler Kimberly A. , Whitbeck Les B. , Hoyt Dan R. , Johnson Kurt D.
Published: November 2003

Self‐mutilation, which is the act of deliberately harming oneself, has been overlooked in studies of homeless and runaway youth. Given their high rates of abuse and mental health disorders, which are associated with self‐mutilation, homeless and runaway youth provide an ideal sample in which to investigate factors associated with self‐mutilation among a nonclinical population. Based on interviews with 428 homeless and runaway youth aged 16 to 19 years in 4 Midwestern states, the current study revealed widespread prevalence of self‐mutilation among these young people. Multivariate analyses indicated that sexual abuse, ever having stayed on the street, deviant subsistence strategies, and meeting diagnostic criteria for depression were positively associated with self‐mutilation. The findings are interpreted using stress theory and affect‐regulation models.
T‐cell costimulatory pathways in allograft rejection and tolerance
Authors: Rothstein David M. , Sayegh Mohamed H.
Published: November 2003

Summary:  The destiny of activated T cells is critical to the ultimate fate of immune response. After encountering antigen, naïve T cells receive signal 1 through the T‐cell receptor (TCR)‐major histocompatibility complex (MHC) plus antigenic peptide complex and signal 2 through ‘positive’ costimulatory molecules leading to full activation. ‘Negative’ T‐cell costimulatory pathways, on the other hand, function to downregulate immune responses. The purpose of this article is to review the current state of knowledge and recent advances in our understanding of the functions of the positive and negative T‐cell costimulatory pathways in alloimmune responses. Specifically, we discuss the functions of the CD28:B7 and the tumor necrosis factor receptor (TNFR):tumor necrosis factor (TNF) family of molecules in allograft rejection and tolerance. We address the following important questions: are T‐cell costimulatory pathways merely redundant or do they provide distinct and unique functions? What are the important and unique interactions between the various pathways? And, what are the effects and mechanisms of targeting of these pathways in different types and patterns of allograft rejection and tolerance models?
Alcohol‐Induced Suppression of Lung Chemokine Production and the Host Defense Response to Streptococcus pneumoniae
Authors: Boé Darren M. , Nelson Steve , Zhang Ping , Quinton Lee , Bagby Gregory J.
Published: November 2003

Background: Acute alcohol intoxication impairs neutrophil migration in response to intrapulmonary infection with Streptococcus pneumoniae, the most common bacterial cause of pneumonia. Many of the same host defense functions that are impaired in the alcohol‐intoxicated host are mechanistically associated with chemokines, a group of proinflammatory molecules that enhance neutrophil adhesion and direct neutrophil migration to sites of inflammation. The purpose of this study was to determine whether alcohol‐induced chemokine suppression is responsible for impaired neutrophil recruitment into the lung during infection of the alcohol‐intoxicated host.

Methods: S. pneumoniae was administered (107 colony‐forming units) intratracheally 30 min after intraperitoneal injection of 20% alcohol (5.5 g/kg) or saline. Four hours after bacterial challenge, bronchoalveolar lavage fluid (BALF) was collected, and the ability of BALF to induce neutrophil chemotaxis and adhesion molecule expression was measured by using chemotactic and flow cytometric assays. In another experiment, intratracheal challenge was performed by using recombinant macrophage inflammatory protein‐2 (MIP‐2), and BALF neutrophils were measured.

Results: BALF MIP‐2 and cytokine‐induced neutrophil chemoattractant were decreased by alcohol, and BALF from alcohol‐intoxicated animals had decreased chemotactic activity for neutrophils, as well as a decreased ability to up‐regulate neutrophil adhesion molecule expression, compared with controls. This decreased chemotactic activity was significantly increased in the alcohol group by repletion of chemokines to control levels. Alcohol also suppressed neutrophil recruitment after intrapulmonary challenge with MIP‐2, suggesting that mechanisms other than chemokine suppression contribute to the alcohol‐induced effect.

Conclusions: At least two mechanisms, suppressed chemokine production and impaired neutrophil adhesion molecule expression, likely work in concert in the alcohol‐intoxicated host to impair neutrophil adhesion and migration into the lung during pneumococcal infection. These alterations in neutrophil function likely increase the susceptibility of alcohol‐consuming hosts to pneumonia.
Ondansetron Reduces Mood Disturbance Among Biologically Predisposed, Alcohol‐Dependent Individuals
Authors: Johnson Bankole A. , Ait‐Daoud Nassima , Ma Jennie Z. , Wang Yanmei
Published: November 2003

Background: Early‐onset alcoholics (EOA) differ from late‐onset alcoholics (LOA) by developing problem drinking during youth, experiencing severe behavioral problems, having a familial disease history, and possessing a tendency toward subsyndromal mood disturbance, including symptoms of depression, anxiety, and hostility. Subsyndromal mood disturbance is, therefore, an important component of the early‐onset syndrome and may be mediated by serotonin dysfunction. Therefore, the serotonin‐3 antagonist ondansetron, which has been shown to be effective at improving drinking outcomes and promoting abstinence among EOA, presumably by ameliorating serotonin dysfunction, also may exert its beneficial effects by alleviating mood disturbance among EOA.

Methods: After one lead‐in week of single‐blind placebo administration, subjects underwent 11 weeks of double‐blind outpatient treatment using a 2 × 4 factorial design that examined age of onset (EOA versus LOA) and medication dose (placebo, or ondansetron 1, 4, or 16 μg/kg twice daily) combined with weekly standardized group cognitive‐behavioral therapy. The placebo lead‐in week was used to adjust for study entrance effects but not for excluding subjects. Assessments of mood were performed by using the overall score and subscales of the Profile of Mood States both at screening and at weekly intervals during the study.

Results: Subsyndromal mood disturbance was shown to be an important component of early‐onset alcoholism. Ondansetron (16 μg/kg twice daily) showed greater therapeutic efficacy at alleviating symptoms of overall mood disturbance, fatigue, vigor, confusion/bewilderment, and depression among EOA compared with LOA. EOA‐associated improvements in mood disturbance seemed to be independent of drinking behavior.

Conclusions: Ondansetron has been shown to be an effective treatment for early‐onset alcoholism. Ondansetron's ability to improve symptoms of depression, anxiety, and hostility among EOA may make an additional contribution to its therapeutic effect. Mechanistic studies are needed to delineate more clearly the relationship between serotonin dysfunction and pathophysiology among various subtypes of alcohol‐dependent individuals.
Analyses of Quantitative Trait Loci Contributing to Alcohol Preference in HAD1/LAD1 and HAD2/LAD2 Rats
Authors: Carr Lucinda G. , Habegger Kirk , Spence John , Ritchotte Aimee , Liu Lixiang , Lumeng Lawrence , Li Ting‐Kai , Foroud Tatiana
Published: November 2003

Background: The high‐alcohol‐drinking (HAD1/HAD2) and low‐alcohol‐drinking (LAD1/LAD2) rat lines, derived from the N/NIH rat, were developed by using a within‐family selection and rotational breeding design for alcohol preference and alcohol consumption. Previously, a 20‐cM genome screen identified quantitative trait loci (QTLs) on chromosomes 5, 10, 12, and 16 by using F2 progeny from HAD1 and LAD1 animals.

Methods: A total of 459 F2 HAD1 × LAD1 animals had been previously genotyped, and 428 HAD2 × LAD2 F2 animals were genotyped for microsatellite markers within the identified QTL regions. Linkage analyses were performed with the program QTL Express, a recently developed Web‐based interface that implements a least‐squares method.

Results: The linkage peaks previously identified in the HAD1 × LAD1 genome scan relied on one or two markers. Placement of additional markers in and around the QTL regions provided further support for each of the QTLs. Two of the QTLs on chromosomes 10 and 16 were confirmed in the replicate line; these QTLs exhibited linkage in both the HAD1/LAD1 and HAD2/LAD2 studies.

Conclusions: This study demonstrated the importance of confirmation of QTLs in a replicate line, as well as the complexity of the genetic contribution to alcohol preference. Assessing these QTL regions in the inbred HAD/LAD animals will further facilitate characterization of these regions.
Prevalence of Escherichia coli O157 on the hands of food‐workers
Authors: Kerr K.G. , Seale K. , Walbran S. , Rajgopal A. , Bentham D.
Published: November 2003

A total of 94 food handlers working at 25 premises in the city of Bradford were examined to determine the prevalence of carriage of Escherichia coli O157:H7 on their hands. A total of 50 clerical workers who did not handle food on a professional basis were recruited as controls. All subjects made palmar impressions on 225mm2 plates containing modified cefixime‐tellurite sorbitol MacConkey agar. In contrast with earlier studies, which examined only abattoir workers, none of the food‐handlers or controls in this investigation carried the bacterium on their hands.
Measuring distributive and procedural justice: An exploratory investigation of the fairness of retailer‐supplier relationships in the UK food industry
Authors: Duffy R. , Fearne A. , Hornibrook S.
Published: November 2003

A report on UK supermarkets published by the Competition Commission in October 2000 concluded that there was evidence that multiple food retailers were abusing their position of power and engaging in practices that adversely affected the competitiveness of suppliers. To address these adverse effects it was recommended that a code of practice be introduced to govern retailer‐supplier relationships. The International Institute for Environment and Development (IIED) is co‐ordinating a project that is designed to monitor the extent to which multiple retailers are complying with the principles set out in the code of practice. This paper presents the findings of exploratory research, conducted as part of this project, to investigate suppliers’ current perceptions of the fairness of their trading relationships with the multiple retailers.
Relationship marketing: case studies of personal experiences of eating out
Authors: Rashid Tahir
Published: November 2003

This paper explains relationship marketing (RM) and discusses the benefits to customers and firms applying RM. Nine dimensions central to making RM successful are assessed. These are: trust, commitment, social bonding, empathy, experiences, fulfilment of promise, customer satisfaction, internal relationship marketing, and communication. The researcher then describes three personal experiences of eating out in three different restaurants and discusses good RM techniques applied deliberately or otherwise by these establishments.
Early Allelic Selection in Maize as Revealed by Ancient DNA
Authors: Jaenicke-Després Viviane , Buckler Ed S. , Smith Bruce D. , Gilbert M. Thomas P. , Cooper Alan , Doebley John , Pääbo Svante
Published: November 2003

Maize was domesticated from teosinte, a wild grass, by ∼ 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete.
A Superconducting Reversible Rectifier That Controls the Motion of Magnetic Flux Quanta
Authors: Villegas J. E. , Savel'ev Sergey , Nori Franco , Gonzalez E. M. , Anguita J. V. , García R. , Vicent J. L.
Published: November 2003

We fabricated a device that controls the motion of flux quanta in a niobium superconducting film grown on an array of nanoscale triangular pinning potentials. The controllable rectification of the vortex motion is due to the asymmetry of the fabricated magnetic pinning centers. The reversal in the direction of the vortex flow is explained by the interaction between the vortices trapped on the magnetic nanostructures and the interstitial vortices. The applied magnetic field and input current strength can tune both the polarity and magnitude of the rectified vortex flow. Our ratchet system is explained and modeled theoretically, taking the interactions between particles into consideration.
Crown profile equations for stand-grown western hemlock trees in northwestern Oregon
Authors: Marshall David D , Johnson Gregory P , Hann David W
Published: November 2003

Crown profile equations were developed for stand-grown western hemlock (Tsuga heterophylla (Raf.) Sarg.) in northwest Oregon. The profile model uses a segmented approach, dividing the crown into an upper and lower portion at the point of the largest crown width (LCW). The model explains about 86% of the variation in crown width when LCW is known but only 66% when LCW is predicted using a model developed from a larger data set collected in the same area as the data for developing the crown profile models were collected. The model can be adjusted using measurements or predictions of LCW for western hemlock in other populations. Comparisons are made with the crown form of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco).
Emergence and survival of Populus tremula seedlings under varying moisture conditions
Authors: Latva-Karjanmaa Tarja , Suvanto Leena , Leinonen Kari , Rita Hannu
Published: November 2003

Aspen produces large numbers of seeds, even though it mainly reproduces asexually with root suckers. The aim of this study was to find out how different moisture conditions affect emergence and survival of Populus tremula L. seedlings. This was studied with a sowing experiment (totally randomized factorial design). There were altogether 10 blocks, each containing 16 microsites and three treatments (sowing time, watering, sowing shelter) replicated twice in each block. Seedlings emerged on 56% of microsites. Sowing time affected seedling emergence. Both the proportion of microsites with seedlings and the number of seedlings per microsite were lower after first than after second sowing, when the weather was rainier. Watering increased the number of seedlings per microsite, but the proportion of micro sites with at least one seedling was not affected. Sowing shelter had a negative effect on the seedling emergence, especially after second sowing. The survival of seedlings was low (10%) and strongly dependent on watering. The effect of block and its interactions with treatments indicated that seedling emergence and survival depended also on seedbed conditions. We conclude that sexual reproduction of aspen may occur in nature, but it is rare. The seeds also maintained their germinability longer than earlier observed.
Strategic reserve design in the central coast of British Columbia: integrating ecological and industrial goals
Authors: Gonzales Emily K , Arcese Peter , Schulz Rueben , Bunnell Fred L
Published: November 2003

Few conservation reserves worldwide have been created in ways that are likely to promote the persistence of species, ecosystems, and ecological processes regarded as being representative of biological diversity. We demonstrate the application of newer approaches to systematic reserve design that could help stakeholders find designs that maximize simultaneously ecological, societal, and industrial goals. We created example reserve designs using the simulated annealing algorithm of SITES 1.0 and then contrasted these designs with a proposed reserve design negotiated as a multi stakeholder process for British Columbia's central coast. Our strategic approach recommended reserve designs that included greater proportions of key conservation elements identified by stakeholders without increasing the land area or timber volume in reserves currently under consideration for protection. Our examples demonstrate that strategic approaches to reserve design can facilitate the repeatable and efficient allocation of land to conservation and development and, therefore, represent an improvement on ad hoc methods. Readily available software facilitates the exploration of alternative conservation and societal values, incorporate the interests of multiple stakeholders, and provides a focus and catalyst for discussion at the planning table.
Evaluating ecological representation within differing planning objectives for the central coast of British Columbia
Authors: Wells R W , Bunnell F L , Haag D , Sutherland G
Published: November 2003

Maintaining representation of a full range of ecosystem types is a widely accepted strategy to conserve biodiversity in protected areas. We evaluated representation in the central coast region of British Columbia, a forested landbase containing a complex mix of management options, administrative and ownership types, and disparate ecological and economic objectives. We found that most ecosystem types were well represented outside areas subject to management activities, but a minority were poorly represented. When we examined areas under consideration for protection or special management, we found that they failed to represent many of the most poorly represented ecosystem types and incorporated limited amounts of the remainder. Because these poorly represented types were relatively limited in area, it should be possible to adjust proposed reserve areas to improve representation of these types with limited impact on other values. Failing to do so will result in increased opportunity costs to improve representation in the future. Despite the limitations of ecological classification systems to represent biodiversity, they are an improvement over strictly ad hoc approaches because they employ a systematic, repeatable approach in selecting reserve areas.
The influence of decomposing logs on soil biology and nutrient cycling in an old-growth mixed coniferous forest in Oregon, U.S.A.
Authors: Spears J DH , Holub S M , Harmon M E , Lajtha K
Published: November 2003

This study investigated the effect of coarse woody debris (CWD) on mineral soils at the H.J. Andrews Experimental Forest in the central Cascade Range of Oregon, U.S.A. Nutrients in CWD leachates were compared with (i) forest floor (control) leachates, (ii) over a decay chronosequence, and (iii) among CWD of four species. There were few differences among CWD leachates and forest floor leachates. Soils under CWD were warmer but not wetter than control soils. Water-soluble organic carbon was higher in soils under CWD than in controls at 515 cm depth (p < 0.02), but soil C concentrations did not differ. Gross N mineralization was faster in control soils. We found no differences in N, P, microbial biomass, Biolog plate assays, or enzyme activity in soils. Nutrient leachate differences among CWD species were small. Differences in solutions and in soils among CWD and controls were largest during the middle decay classes. This study suggests that either (i) CWD has no long-term effect and does not contribute large amounts of organic matter to the soil profile or (ii) the effect of CWD is so prolonged that no spatial affect is noticeable because all soils have been affected by CWD at some time.