bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel cell immunoassay to measure survival of motor neurons protein in blood cells
Authors: Kolb Stephen J , Gubitz Amelie K , Olszewski Robert F , Ottinger Elizabeth , Sumner Charlotte J , Fischbeck Kenneth H , Dreyfuss Gideon
Published: February 2006

Background

The motor neuron degenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN) gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples.

Methods

We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody.

Results

SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity.

Conclusion

SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials.
Visual fields in patients who have undergone vitrectomy for complications of diabetic retinopathy. A prospective study
Authors: Barsam Allon , Laidlaw Alistair
Published: February 2006

Backround

To determine the extent of visual field loss in patients who had required a pars plana vitrectomy secondary to complications of proliferative diabetic retinopathy.

Methods

Patients that had undergone a vitrectomy on at least one eye for treatment of either vitreous haemorrhage or tractional retinal detachment were selected for study. ETDRS acuity and Humphrey binocular Esterman visual field testing were performed and compared to the minimum standards for safe driving as defined by the Royal College of Ophthalmologists in 1999. In addition to this Goldman kinetic visual fields using a III4e and V4e stimulus size and central 24-2 threshold test with the SITA-fast strategy were performed on the vitrectomised eye.

Results

20 patients (n = 20) were recruited. Mean visual acuity in the eye being tested was 0.20 (Snellen 6/9.5). Results from the Humphrey field analyzer showed a mean number of abnormal stimulus locations of 71.2% (p < 0.005). 70% of patients had sufficient binocular acuity to drive and of these 71.4% were shown not to have a minimum visual field for safe driving on binocular Esterman field analysis.

Conclusion

Vitrectomy potentially allows retention/restoration of good visual acuity in patients with complications of proliferative diabetic retinopathy. However patients may be suffering from unrecognized visual impairment consequent upon extensive visual field loss which in over two thirds of patients may be sufficiently severe to preclude safe driving.
The effect of verbalization strategy on wisconsin card sorting test performance in schizophrenic patients receiving classical or atypical antipsychotics
Authors: Rossi Alessandro , Daneluzzo Enrico , Tomassini Annarita , Struglia Francesca , Cavallaro Roberto , Smeraldi Enrico , Stratta Paolo
Published: February 2006

Background

A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed.

The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST) remediation, in subjects on classical vs atypical antipsychotic (AP) treatment.

Methods

Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization) administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable) and AP treatment (i.e. atypical vs. classical).

Results

Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs.

Conclusion

Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.
Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber vertebral radiological and morphometric indices: Skeletal deformation associated with dysregulated systemic glucometabolism
Authors: Burkemper Katherine M , Garris David R
Published: February 2006

Background

Both diabetes and obesity syndromes are recognized to promote lumbar vertebral instability, premature osteodegeneration, exacerbate progressive osteoporosis and increase the propensity towards vertebral degeneration, instability and deformation in humans.

Methods

The influences of single-gene missense mutations, expressing either diabetes (db/db) or obese (ob/ob) metabolic syndromes on vertebral maturation and development in C57BL/KsJ mice were evaluated by radiological and macro-morphometric analysis of the resulting variances in osteodevelopment indices relative to control parameters between 8 and 16 weeks of age (syndrome onset @ 4 weeks), and the influences of low-dose 17-B-estradiol therapy on vertebral growth expression evaluated.

Results

Associated with the indicative genotypic obesity and hyper-glycemic/-insulinemic states, bothdb/dbandob/obmutants demonstrated a significant (P ≤ 0.05) elongation of total lumbar vertebrae column (VC) regional length, and individual lumbar vertebrae (LV1-5) lengths, relative to control VC and LV parameters. In contrast, LV1-5 width indices were suppressed in db/db and ob/ob mutants relative to control LV growth rates. Between 8 and 16 weeks of age, the suppressed LV1-5 width indices were sustained in both genotype mutant groups relative to control osteomaturation rates. The severity of LV1-5 width osteosuppression correlated with the severe systemic hyperglycemic and hypertriglyceridemic conditions sustained inob/obanddb/dbmutants. Low-dose 17-B-estradiol therapy (E2-HRx: 1.0ug/ 0.1 ml oil s.c/3.5 days), initiated at 4 weeks of age (i.e., initial onset phase ofdb/dbandob/obexpressions) re-established control LV 1–5 width indices without influencing VC or LV lengths in db/db groups.

Conclusion

These data demonstrate that the abnormal systemic endometabolic states associated with the expression ofdb/dbandob/obgenomutation syndromes suppress LV 1–5 width osteomaturation rates, but enhanced development related VC and LV length expression, relative to control indices in a progressive manner similar to recognized human metabolic syndrome conditions. Therapeutic E2 modulation of the hyperglycemic component of diabetes-obesity syndrome protected the regional LV from the mutation-induced osteopenic width-growth suppression. These data suggest that these genotype mutation models may prove valuable for the evaluation of therapeutic methodologies suitable for the treatment of human diabetes- or obesity-influenced, LV degeneration-linked human conditions, which demonstrate amelioration from conventional replacement therapies following diagnosis of systemic syndrome-induced LV osteomaturation-associated deformations.
Single- versus two- layer intestinal anastomosis: a meta-analysis of randomized controlled trials
Authors: Shikata Satoru , Yamagishi Hisakazu , Taji Yoshinori , Shimada Toshihiko , Noguchi Yoshinori
Published: February 2006

Background

To compare single- with two- layer intestinal anastomosis after intestinal resection: a meta-analysis of randomized controlled trials.

Methods

Randomized controlled trials comparing single- with two-layer intestinal anastomosis were identified using a systematic search of Medline, Embase and the Cochrane Library Databases covering articles published from 1966 to 2004. Outcome of primary interest was postoperative leak. A risk ratio for trial outcomes and weighted pooled estimates for data were calculated. A fixed-effect model weighted using Mantel-Haenszel methods and a random-effect model using DerSimonian-Laird methods were employed.

Results

Six trials were analyzed, comprising 670 participants (single-layer group, n = 299; two-layer group, n = 371). Data on leaks were available from all included studies. Combined risk ratio using DerSimonian-Laird methods was 0.91 (95% CI = 0.49 to 1.69), and indicated no significant difference. Inter-study heterogeneity was significant (χ2 = 10.5, d.f. = 5, p = 0.06).

Conclusion

No evidence was found that two-layer intestinal anastomosis leads to fewer post-operative leaks than single layer. Considering duration of the anastomosis procedure and medical expenses, single-layer intestinal anastomosis appears to represent the optimal choice for most surgical situations.
The distribution of burden of dental caries in schoolchildren: a critique of the high-risk caries prevention strategy for populations
Authors: Batchelor Paul A , Sheiham Aubrey
Published: February 2006

Background

The 'high-risk approach' is a commonly adopted strategy recommended for the prevention of dental caries in populations. The scientific basis for the strategy has been questioned. The objective of this study is to assess the contribution that children identified at 'high-risk' made towards the total of new caries lesions over a 4-year period, by analysing the distribution of new lesions per 100 children.

Methods

Data are from the National Preventive Dentistry Demonstration Programme (NPDDP) in the United States. The analyses identified the distribution of new carious lesions over a 4-year period in four groups of 7 year-old children who received differing preventive regimes.

Results

The majority of new lesions occurred in those children classified at lowest caries risk at baseline. Irrespective of the preventive regime adopted and the initial caries levels, children classified as 'highest risk' contributed less than 6% of the total number of new lesions developing over 4 years.

Conclusion

These findings challenge the basis for the adoption of a high-risk strategy.
A survey of factors affecting clinician acceptance of clinical decision support
Authors: Sittig Dean F , Krall Michael A , Dykstra Richard H , Russell Allen , Chin Homer L
Published: February 2006

Background

Real-time clinical decision support (CDS) integrated into clinicians' workflow has the potential to profoundly affect the cost, quality, and safety of health care delivery. Recent reports have identified a surprisingly low acceptance rate for different types of CDS. We hypothesized that factors affecting CDS system acceptance could be categorized as relating to differences in patients, physicians, CDS-type, or environmental characteristics.

Methods

We conducted a survey of all adult primary care physicians (PCPs, n = 225) within our group model Health Maintenance Organization (HMO) to identify factors that affect their acceptance of CDS. We defined clinical decision support broadly as "clinical information" that is either provided to you or accessible by you, from the clinical workstation (e.g., enhanced flow sheet displays, health maintenance reminders, alternative medication suggestions, order sets, alerts, and access to any internet-based information resources).

Results

110 surveys were returned (49%). There were no differences in the age, gender, or years of service between those who returned the survey and the entire adult PCP population. Overall, clinicians stated that the CDS provided "helps them take better care of their patients" (3.6 on scale of 1:Never – 5:Always), "is worth the time it takes" (3.5), and "reminds them of something they've forgotten" (3.2). There was no difference in the perceived acceptance rate of alerts based on their type (i.e., cost, safety, health maintenance). When asked about specific patient characteristics that would make the clinicians "more", "equally" or "less" likely to accept alerts: 41% stated that they were more (8% stated "less") likely to accept alerts on elderly patients (> 65 yrs); 38% were more (14% stated less) likely to accept alerts on patients with more than 5 current medications; and 38% were more (20% stated less) likely to accept alerts on patients with more than 5 chronic clinical conditions. Interestingly, 80% said they were less likely to accept alerts when they were behind schedule and 84% of clinicians admitted to being at least 20 minutes behind schedule "some", "most", or "all of the time".

Conclusion

Even though a majority of our clinical decision support suggestions are not explicitly followed, clinicians feel they are of benefit and would be even more beneficial if they had more time available to address them.
Lactate production yield from engineered yeasts is dependent from the host background, the lactate dehydrogenase source and the lactate export
Authors: Branduardi Paola , Sauer Michael , De Gioia Luca , Zampella Giuseppe , Valli Minoska , Mattanovich Diethard , Porro Danilo
Published: February 2006

Background

Metabolic pathway manipulation for improving the properties and the productivity of microorganisms is becoming a well established concept. For the production of important metabolites, but also for a better understanding of the fundamentals of cell biology, detailed studies are required. In this work we analysed the lactate production from metabolic engineered Saccharomyces cerevisiae cells expressing a heterologous lactate dehydrogenase (LDH) gene. The LDH gene expression in a budding yeast cell introduces a novel and alternative pathway for the NAD+ regeneration, allowing a direct reduction of the intracellular pyruvate to lactate, leading to a simultaneous accumulation of lactate and ethanol.

Results

Four different S. cerevisiae strains were transformed with six different wild type and one mutagenised LDH genes, in combination or not with the over-expression of a lactate transporter. The resulting yield values (grams of lactate produced per grams of glucose consumed) varied from as low as 0,0008 to as high as 0.52 g g-1. In this respect, and to the best of our knowledge, higher redirections of the glycolysis flux have never been obtained before without any disruption and/or limitation of the competing biochemical pathways.

Conclusion

In the present work it is shown that the redirection of the pathway towards the lactate production can be strongly modulated by the genetic background of the host cell, by the source of the heterologous Ldh enzyme, by improving its biochemical properties as well as by modulating the export of lactate in the culture media.
Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines
Authors: Chavez-Blanco Alma , Perez-Plasencia Carlos , Perez-Cardenas Enrique , Carrasco-Legleu Claudia , Rangel-Lopez Edgar , Segura-Pacheco Blanca , Taja-Chayeb Lucia , Trejo-Becerril Catalina , Gonzalez-Fierro Aurora , Candelaria Myrna , Cabrera Gustavo , Duenas-Gonzalez Alfonso
Published: February 2006

Background

Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines.

Results

Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid.

Conclusion

Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.
Ecologists can enable communities to implement malaria vector control in Africa
Authors: Mukabana W Richard , Kannady Khadija , Kiama G Michael , Ijumba Jasper N , Mathenge Evan M , Kiche Ibrahim , Nkwengulila Gamba , Mboera Leonard , Mtasiwa Deo , Yamagata Yoichi , van Schayk Ingeborg , Knols Bart GJ , Lindsay Steven W , de Castro Marcia Caldas , Mshinda Hassan , Tanner Marcel , Fillinger Ulrike , Killeen Gerry F
Published: February 2006

Background

Integrated vector management (IVM) for malaria control requires ecological skills that are very scarce and rarely applied in Africa today. Partnerships between communities and academic ecologists can address this capacity deficit, modernize the evidence base for such approaches and enable future scale up.

Methods

Community-based IVM programmes were initiated in two contrasting settings. On Rusinga Island, Western Kenya, community outreach to a marginalized rural community was achieved by University of Nairobi through a community-based organization. In Dar es Salaam, Tanzania, Ilala Municipality established an IVM programme at grassroots level, which was subsequently upgraded and expanded into a pilot scale Urban Malaria Control Programme with support from national academic institutes.

Results

Both programmes now access relevant expertise, funding and policy makers while the academic partners benefit from direct experience of community-based implementation and operational research opportunities. The communities now access up-to-date malaria-related knowledge and skills for translation into local action. Similarly, the academic partners have acquired better understanding of community needs and how to address them.

Conclusion

Until sufficient evidence is provided, community-based IVM remains an operational research activity. Researchers can never directly support every community in Africa so community-based IVM strategies and tactics will need to be incorporated into undergraduate teaching programmes to generate sufficient numbers of practitioners for national scale programmes. Academic ecologists at African institutions are uniquely positioned to enable the application of practical environmental and entomological skills for malaria control by communities at grassroots level and should be supported to fulfil this neglected role.
An advanced expiratory circuit for the recovery of perfluorocarbon liquid from non-saturated perfluorocarbon vapour during partial liquid ventilation: an experimental model
Authors: Dunster Kimble R , Davies Mark W , Fraser John F
Published: February 2006

Background

The loss of perfluorocarbon (PFC) vapour in the expired gases during partial liquid ventilation should be minimized both to prevent perfluorocarbon vapour entering the atmosphere and to re-use the recovered PFC liquid.

Using a substantially modified design of our previously described condenser, we aimed to determine how much perfluorocarbon liquid could be recovered from gases containing PFC and water vapour, at concentrations found during partial liquid ventilation, and to determine if the amount recovered differed with background flow rate (at flow rates suitable for use in neonates).

Methods

The expiratory line of a standard ventilator circuit set-up was mimicked, with the addition of two condensers. Perfluorocarbon (30 mL of FC-77) and water vapour, at concentrations found during partial liquid ventilation, were passed through the circuit at a number of flow rates and the percentage recovery of the liquids measured.

Results

From 14.2 mL (47%) to 27.3 mL (91%) of the infused 30 mL of FC-77 was recovered at the flow rates studied. Significantly higher FC-77 recovery was obtained at lower flow rates (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). As a percentage of the theoretical maximum recovery, 64 to 95% of the FC-77 was recovered. Statistically significantly less FC-77 was recovered at 5 Lmin-1 (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). Amounts of perfluorocarbon vapour recovered were 47%, 50%, 81% and 91% at flow rates of 10, 5, 2 and 1 Lmin-1, respectively.

Conclusion

Using two condensers in series 47% to 91% of perfluorocarbon liquid can be recovered, from gases containing perfluorocarbon and water vapour, at concentrations found during partial liquid ventilation.
The proximal promoter region of mTert is sufficient to regulate telomerase activity in ES cells and transgenic animals
Authors: Pericuesta Eva , Ramírez Miguel Angel , Villa-Diaz Ana , Relaño-Gines Aroa , Maria Torres Juan , Nieto Marta , Pintado Belen , Gutiérrez-Adán Alfonso
Published: February 2006

Background

The reverse transcriptase of telomerase (Tert) controls telomerase activity maintaining the end of linear chromosomes in eukaryotic cells. Telomerase function is highly active in undifferentiated multipotent stem cells, decreases with cell differentiation and is generally absent from most somatic cells in the adult. Its absence is responsible of telomeres shortening in such somatic cells. Using an in vivo transgenic model and an in vitro culture differentiation of adult stem cells, we examined the elements of the mouse Tert (mTert) promoter that control telomerase activity.

Results

Three constructs comprising 1, 2 or 5 kb of the mTert promoter sequence coupled to the coding sequence of the green fluorescent protein (EGFP) were electroporated into embryonic stem (ES) cells. Transformed ES cells were able to mimic the expected mTert expression, which was associated to green fluorescence. One and 5 kb promoter produced the higher expression of EGFP, on ES cells. When ES cells were allowed to differentiate to embryoid bodies and to other cell types, they lost gradually the expression of mTert-EGFP as consequence of differentiation. No differences were found among the three constructs analyzed. We then generated transgenic mice with the three constructs. Expression of the reporter gene was monitored by reverse transcription-PCR analysis and EGFP visualization. The mRNA expression of the three constructs was lower than the endogenous mTert, but mimicked the endogenous mTert transcription pattern; however, no fluorescent expression of EGFP was detected in adult tissues. EGFP expression of the three constructs was visualized at the blastocysts stage and in new ES cells generated from them; in the germinal ring of E13 dpc foetuses; in ES-like colonies and in germinal stem cells generated from neonatal and adult testis cells; and in neuroesferes generated from E14 dpc foetuses' brain cells.

Conclusion

The 1 kb promoter upstream of the initiating ATG codon of mTert contains all the regulatory elements to control telomerase expression in ES cells during in vitro loss of pluripotency. The transgenic mouse lines generated represent an appropriate system to analyze the expression of mouse Tert gene under physiological condition and during establishment of stem cell lines generated from embryonic or adult tissues.
Identification, cloning and functional characterization of novel beta-defensins in the rat (Rattus norvegicus)
Authors: Yenugu Suresh , Chintalgattu Vishnu , Wingard Christopher J , Radhakrishnan Yashwanth , French Frank S , Hall Susan H
Published: February 2006

Background

beta-defensins are small cationic peptides that exhibit broad spectrum antimicrobial properties. The majority of beta-defensins identified in humans are predominantly expressed in the male reproductive tract and have roles in non-immunological processes such as sperm maturation and capacitation. Characterization of novel defensins in the male reproductive tract can lead to increased understanding of their dual roles in immunity and sperm maturation.

Methods

In silico rat genomic analyses were used to identify novel beta-defensins related to human defensins 118–123. RNAs isolated from male reproductive tract tissues of rat were reverse transcribed and PCR amplified using gene specific primers for defensins. PCR products were sequenced to confirm their identity. RT-PCR analysis was performed to analyze the tissue distribution, developmental expression and androgen regulation of these defensins. Recombinant defensins were tested against E. coli in a colony forming unit assay to analyze their antimicrobial activities.

Results

Novel beta-defensins, Defb21, Defb24, Defb27, Defb30 and Defb36 were identified in the rat male reproductive tract. Defb30 and Defb36 were the most restricted in expression, whereas the others were expressed in a variety of tissues including the female reproductive tract. Early onset of defensin expression was observed in the epididymides of 10–60 day old rats. Defb21-Defb36 expression in castrated rats was down regulated and maintained at normal levels in testosterone supplemented animals. DEFB24 and DEFB30 proteins showed potent dose and time dependent antibacterial activity.

Conclusion

Rat Defb21, Defb24, Defb27, Defb30 and Defb36 are abundantly expressed in the male reproductive tract where they most likely protect against microbial invasion. They are developmentally regulated and androgen is required for full expression in the adult epididymis.
Reservoir cells no longer detectable after a heterologous SHIV challenge with the synthetic HIV-1 Tat Oyi vaccine
Authors: Watkins Jennifer D , Lancelot Sophie , Campbell Grant R , Esquieu Didier , Mareuil Jean de , Opi Sandrine , Annappa Sylvie , Salles Jean-Pierre , Loret Erwann P
Published: February 2006

Background

Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using rabbits, different adjuvants authorized for human use to test on ELISA the recognition of Tat variants from the five main HIV-1 subtypes. A formulation was tested on macaques followed by a SHIV challenge with a European strain.

Results

Tat Oyi with Montanide or Calcium Phosphate gave rabbit sera able to recognize all Tat variants. Five on seven Tat Oyi vaccinated macaques showed a better control of viremia compared to control macaques and an increase of CD8 T cells was observed only on Tat Oyi vaccinated macaques. Reservoir cells were not detectable at 56 days post-challenge in all Tat Oyi vaccinated macaques but not in the controls.

Conclusion

The Tat Oyi vaccine should be efficient worldwide. No toxicity was observed on rabbits and macaques. We show in vivo that antibodies against Tat could restore the cellular immunity and make it possible the elimination of reservoir cells.
RNAi dependent epigenetic marks on a geminivirus promoter
Authors: Dogar Afzal Muhammad
Published: February 2006

Nicotiana benthamiana plants were stably transformed with an intron-spliced dsRNA producing construct cognate to bidirectional promoter of African cassava mosaic geminivirus (ACMV) DNA A. Transgenic lines expressed multiple siRNAs species upon ACMV infection. The de novo DNA methylation and an increased proportion of histone H3 Lysine-9 methylation (H3K9) at intergenic region (IGR) of ACMV DNA A were observed.
Energy expenditures & physical activity in rats with chronic suboptimal nutrition
Authors: Rising Russell , Lifshitz Fima
Published: February 2006

Background

Sub-optimally nourished rats show reduced growth, biochemical and physiological changes. However, no one has assessed metabolic rate adaptations in rats subjected to chronic suboptimal nutrition (CSN). In this study energy expenditure (EE; kcal/100 g body weight) and physical activity (PA; oscillations in weight/min/kg body weight) were assessed in rats subjected to three levels of CSN.

Results

Body weight gain was diminished (76.7 ± 12.0 and 61.6 ± 11.0 g) in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight (148.5 ± 32.3 g). The rats fed 80% gained weight similarly to controls (136.3 ± 10.5 g). Percent Fat-free body mass was reduced (143.8 ± 8.7 and 142.0 ± 7.6 g) in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 ± 17.5 g) as compared with controls (201.6 ± 33.4 g). Body fat (g) decreased in rats fed 80% (19.7 ± 5.3), 70% (15.3 ± 3.5) and 60% (9.6 ± 2.7) of ad-libitum in comparison to controls (26.0 ± 6.7). EE and PA were also altered by CSN. The control rats increased their EE and PA during the dark periods by 1.4 ± 0.8 and 1.7 ± 1.1 respectively, as compared with light the period; whereas CSN rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the dark periods as compared with the light period EE(7.5 ± 1.4 and 7.8 ± 0.6 vs. 9.0 ± 1.2 and 9.7 ± 0.8; p < 0.05, respectively), PA(3.1 ± 0.8 and 1.6 ± 0.4 vs. 4.1 ± 0.9 and 2.4 ± 0.4; p < 0.05) and RQ (0.87 ± 0.04 and 0.85 ± 0.5; vs. 0.95 ± 0.03 and 0.91 ± 0.05 p < 0.05). In contrast, both light (7.1 ± 1.4) and dark period (6.2 ± 1.0) EE and PA (3.4 ± 0.9 and 2.5 ± 0.5 respectively) were reduced in rats fed 60% of ad-libitum energy intake.

Conclusion

CSN rats adapt to mild energy restriction by reducing body fat, EE and PA mainly during the dark period while growth proceeds and lean body mass is preserved. At higher levels of energy restrictions there is decreased growth, body fat and lean mass. Moreover EE and PA are also reduced during both light and dark periods.
Globalization, migration health, and educational preparation for transnational medical encounters
Authors: Koehn Peter H
Published: February 2006

Unprecedented migration, a core dimension of contemporary globalization, challenges population health. In a world of increasing human mobility, many health outcomes are shaped by transnational interactions among care providers and care recipients who meet in settings where nationality/ethnic match is not an option. This review article explores the value of transnational competence (TC) education as preparation for ethnically and socially discordant clinical encounters. The relevance of TC's five core skill domains (analytic, emotional, creative, communicative, and functional) for migration health and the medical-school curriculum is elaborated. A pedagogical approach that prepares for the transnational health-care consultation is presented, with a focus on clinical-clerkship learning experiences. Educational preparation for contemporary medical encounters needs to include a comprehensive set of patient-focused interpersonal skills, be adaptable to a wide variety of service users and global practice sites, and possess utility in addressing both the quality of patient care and socio-political constraints on migration health.
Serum level of semicarbazide-sensitive amine oxidase in children with ADHD
Authors: Roessner Veit , Uebel Henrik , Becker Andreas , Beck Georg , Bleich Stefan , Rothenberger Aribert
Published: February 2006

Background

The objective of this study was to analyze the extracellularly acting semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD for the first time. SSAO is known to show deviations from normal in various somatic disorders and to interplay with the intracellularly active MAO. In humans two forms of SSAO a circulating form in plasma and a membrane-bound form are involved in monoaminergic metabolism.

Methods

We analyzed serum levels of SSAO in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV criteria of ADHD combined type by HPLC method and fluorimetric detection. A group of 42 healthy volunteers within the same age range (7.0 – 14.0 years) served as controls.

Results

No significant differences between children with ADHD (SSAO activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further, stimulant medication status had no influence on the result (F = 2.52; p > 0.11).

Conclusion

There is no evidence for a deviation of SSAO serum activity in ADHD. Hence, extracellularly acting SSAO does not seem to be a promising factor for further research in ADHD. But progress in knowledge of its physiologic role and of the relationship between the membrane-bound and the circulating serum form may open new avenues for research on SSAO in ADHD.
Exploration of auditory P50 gating in schizophrenia by way of difference waves
Authors: Arnfred Sidse M
Published: February 2006

Electroencephalographic measures of information processing encompass both mid-latency evoked potentials like the pre-attentive auditory P50 potential and a host of later more cognitive components like P300 and N400.

Difference waves have mostly been employed in studies of later event related potentials but here this method along with low frequency filtering is applied exploratory on auditory P50 gating data, previously analyzed in the standard format (reported in Am J Psychiatry 2003, 160:2236-8). The exploration was motivated by the observation during visual peak detection that the AEP waveform was different in the patient group, although this was not reflected by the peak measures. The sample included un-medicated schizophrenia spectrum patients (n = 17) and healthy controls (n = 24). The patients had an attenuated difference P50. This attenuation was primarily seen in the sub-sample of patients with severe negative symptoms. The difference attenuation was due to low amplitude at the first stimulus. This suggests an abnormality in readiness more than an abnormality in gating in the patient group.
Work life of persons with asthma, rhinitis, and COPD: A study using a national, population-based sample
Authors: Yelin Edward , Katz Patricia , Balmes John , Trupin Laura , Earnest Gillian , Eisner Mark , Blanc Paul
Published: February 2006

Objective

To estimate the duration of work life among persons reporting a physician's diagnosis of COPD, asthma, or rhinitis compared to those with select non-respiratory conditions or none and to delineate the factors associated with continuance of employment.

Methods

Persons ages 55 to 75 reporting a physician's diagnosis of COPD, asthma, or rhinitis as well as those without any of these conditions were identified by random-digit dialing (RDD) in the continental U.S and administered a structured survey. We used Kaplan-Meier life table analysis to estimate the duration of work life among persons with and without the three conditions and Cox proportional hazard regression to examine the role of demographic and work characteristics in the proportion leaving employment in each time interval.

Results

Persons with COPD, asthma, and rhinitis were no less likely than the remainder of the population to have ever worked, but those with COPD were less likely to be working when interviewed or as of age 65, whichever came first. As of age 55, only 62 percent of persons with COPD continued to work versus 72 and 78 percent of persons with asthma and rhinitis, respectively. Persons with COPD, asthma, and rhinitis all had an elevated risk of leaving work prior to age 65 relative to those without chronic conditions, with and without adjustment for demographic and work characteristics.

Conclusion

COPD and to a lesser extent asthma and rhinitis were associated with a substantially shortened work life, an effect not due to demographic and work characteristics.
Identification of major cell types in paraffin sections of bovine tissues
Authors: Niku Mikael , Ekman Anna , Pessa-Morikawa Tiina , Iivanainen Antti
Published: February 2006

Background

Identification of cell types in bovine tissue sections is complicated by the limited availability of anti-bovine antibodies, and by antigen retrieval treatments required for formalin-fixed tissue samples. We have evaluated an antibody and lectin panel for identifying major cell types in paraffin-embedded bovine tissue sections, and report optimized pretreatments for these markers.

Results

We selected 31 useful antibodies and lectins which can be used to identify cell types of epithelia, connective tissue, muscle, and nervous tissue, as well as cell proliferation and apoptosis.

Conclusion

The panel of markers allows the identification of all major cell types in paraffin-embedded cattle tissue sections by immunohistochemistry or lectin histochemistry. Heat-induced epitope retrieval methods are required for most antibodies.
Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease
Authors: Meerts Peter , Misinzo Gerald , Lefebvre David , Nielsen Jens , Bøtner Anette , Kristensen Charlotte S , Nauwynck Hans J
Published: February 2006

Background

In a previous study, it was demonstrated that high replication of Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence of PCV2-neutralizing antibodies. The aim of the present study was to investigate if this correlation could also be found in SPF pigs in which PMWS was experimentally reproduced and in naturally PMWS-affected pigs.

Results

When looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals seroconverted at the same time point, and titres in PMWS-affected animals were only slightly lower compared to those in healthy animals. In healthy animals, the evolution of PCV2-neutralizing antibodies coincided with that of total antibodies. In PMWS-affected animals, neutralizing antibodies could either not be found (sera from field studies) or were detected in low titres between 7 and 14 DPI only (sera from experimentally inoculated SPF pigs). Differences were also found in the evolution of specific antibody isotypes titres against PCV2. In healthy pigs, IgM antibodies persisted until the end of the study, whereas in PMWS-affected pigs they quickly decreased or remained present at low titres. The mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower in PMWS-affected pigs compared to their healthy group mates at the end of each study.

Conclusion

This study describes important differences in the development of the humoral immune response between pigs that get subclinically infected with PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4 experiments led to the development of PMWS. These observations may contribute to a better understanding of the pathogenesis of a PCV2-infection.
Identifying repeat domains in large genomes
Authors: Zhi Degui , Raphael Benjamin J , Price Alkes L , Tang Haixu , Pevzner Pavel A
Published: February 2006

We present a graph-based method for the analysis of repeat families in a repeat library. We build a repeat domain graph that decomposes a repeat library into repeat domains, short subsequences shared by multiple repeat families, and reveals the mosaic structure of repeat families. Our method recovers documented mosaic repeat structures and suggests additional putative ones. Our method is useful for elucidating the evolutionary history of repeats and annotating de novo generated repeat libraries.
Differential expression of leukocyte-associated Ig-like receptor-1 during neutrophil differentiation and activation
Authors: Verbrugge Annelies , de Ruiter Talitha , Geest Christian , Coffer Paul J , Meyaard Linde
Published: February 2006

Inhibitory receptors containing immunoreceptor tyrosine-based inhibitory motifs play an important regulatory role in immune cell activation. In addition, several studies suggest that these receptors are involved in the regulation of hematopoietic cell differentiation. Here, we have investigated the expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), an inhibitory receptor expressed on most peripheral blood leukocytes and on CD34+ hematopoietic progenitor cells, in neutrophil differentiation and activation. We found that although LAIR-1 was expressed on peripheral blood eosinophils, cell-surface expression on mature neutrophils was low, suggesting that LAIR-1 expression is regulated during granulocyte differentiation. Indeed, the promyeloid cell line HL-60 expressed LAIR-1, but the expression decreased during chemical-induced differentiation toward neutrophils. Similarly, in bone marrow-derived neutrophil precursors, the most immature cells expressed LAIR-1, and loss of LAIR-1 expression was associated with neutrophil maturation. LAIR-1 was re-expressed rapidly on the membrane of mature neutrophils upon stimulation with tumor necrosis factor α, granulocyte macrophage-colony stimulating factor, or N-formyl-methionyl-leucyl-phenylalanine, indicating that LAIR-1 may also regulate neutrophil effector function. Our studies suggest that LAIR-1 may play a regulatory role in differentiation and function of human granulocytes.
Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-γ
Authors: Doni Andrea , Michela Mosca , Bottazzi Barbara , Peri Giuseppe , Valentino Sonia , Polentarutti Nadia , Garlanda Cecilia , Mantovani Alberto
Published: February 2006

The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1β and was suppressed by dexamethasone, 1α, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-γ (IFN-γ). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4.3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1β were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor α mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-γ and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.
Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation
Authors: Li Chong Hui , Wang Jiang Huai , Redmond H Paul
Published: February 2006

Tolerance to bacterial cell-wall components may represent an essential regulatory mechanism during bacterial infection. We have demonstrated previously that the inhibition of nuclear factor (NF)-κB and mitogen-activated protein kinase activation was present in bacterial lipoprotein (BLP) self-tolerance and its cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP-induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent upstream signaling pathway for NF-κB activation in vitro was examined further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant cells had a significant reduction in tumor necrosis factor α (TNF-α) production in response to a high-dose BLP (86±12 vs. 6042±245 ng/ml, P<0.01) or LPS (341±36 vs. 7882±318 ng/ml, P<0.01) stimulation. The expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as confirmed by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant cells, although IRAK-1 mRNA expression remained unchanged as revealed by real-time reverse transcriptase-polymerase chain reaction analysis. Furthermore, decreased MyD88-IRAK immunocomplex formation, as demonstrated by immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total and phosphorylated inhibitor of κB-α (IκB-α) expression, which was not up-regulated by subsequent BLP or LPS stimulation. These results demonstrate that in addition to the down-regulation of TLR2 expression, BLP tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK association, and IκB-α phosphorylation. These findings further elucidate the molecular mechanisms underlying bacterial peptide tolerance.
Elevated Glucose and Diabetes Promote Interleukin-12 Cytokine Gene Expression in Mouse Macrophages
Authors: Wen Yeshao , Gu Jiali , Li Shu-Lian , Reddy Marpadga A. , Natarajan Rama , Nadler Jerry L.
Published: February 2006

Inflammation is emerging as an important mechanism for micro- and macrovascular complication of diabetes. The macrophage plays a key role in the chronic inflammatory response in part by generating particular cytokines. IL-1β, IL-6, IL12, IL-18, TNFα, and interferon-γ are produced primarily in macrophages and have been associated with accelerated atherosclerosis and altered vascular wall function. In this study, we evaluated the effect and mechanism of high glucose (HG) on gene expression of these cytokines in mouse peritoneal macrophages (MPM). HG led to a 2-fold increase in the mRNA expression of these cytokines, with IL-12 showing the highest activation (5.4-fold) in a time-dependent (3–12 h) and dose-dependent (10, 17.5, and 25 mmol/liter) manner. The effects were specific to HG because mannitol and 3-O-methyl-glucose had no effect on cytokine mRNA expression. HG also increased IL-12 protein accumulation from MPM. We also explored the role of induced and spontaneous diabetes on inflammatory cytokine expression in MPM. Increases in expression in MPM of multiple inflammatory cytokines, including a 20-fold increase in IL-12 mRNA, were observed in streptozotocin-induced type 1 diabetic mice as well as type 2 diabetic db/db mice, suggesting that cytokine gene expression is increased by hyperglycemia in vivo. We next explored potential mechanisms of HG-induced increases in IL-12 mRNA. HG increased the activity of protein kinase C, p38 MAPK (p38), c-Jun terminal kinase, and inhibitory-κB kinase in MPM. Furthermore, inhibitors of these signaling pathways significantly reduced HG-induced IL-12 mRNA expression in MPM. These results provide evidence for a potentially important mechanism linking elevated glucose and diabetes to inflammation.