bluuebunny/crossref_metadata_2025 huggingface dataset:
IL‐15 converts human intestinal intraepithelial lymphocytes to CD94+ producers of IFN‐γ and IL‐10, the latter promoting Fas ligand‐mediated cytotoxicity
Authors: Ebert Ellen C.
Published: April 2005

Intestinal intraepithelial lymphocytes (IELs), T‐cell receptor αβ+ CD8+ T cells located between epithelial cells, are thought to contribute to Fas ligand (FL)‐mediated epithelial cell death in coeliac disease, a condition characterized by excess interleukin‐15 (IL‐15). This study evaluates the effects of prolonged IL‐15 stimulation on IELs. Human IELs were obtained from jejunal mucosa from gastric bypass operations for morbid obesity and cultured for 3 or 10 days with IL‐15. As the culture progressed, an increasing number of IELs became CD94+ and produced massive quantities of interferon‐γ (IFN‐γ) and IL‐10. There was a steady rate of transcription with no feedback regulation. Few chronically activated IELs produced IL‐2, IL‐4, or tumour necrosis factor‐α (ΤΝF‐α). To determine whether the accumulation of IL‐10 affected IEL functions, endogenous IL‐10 was neutralized by antibody during culture with IL‐15. This manipulation reduced expression of CD94, NKG2D, and FL as well as FL‐mediated killing of Jurkat cells by IELs. It did not affect perforin or TNF‐α expression or the associated cytotoxic activities. This study shows that IL‐15 induces the development of CD94+ IELs containing IFN‐γ and IL‐10, and that endogenous IL‐10 promotes FL‐mediated cytotoxicity.
Regulation of human neutrophil chemokine receptor expression and function by activation of Toll‐like receptors 2 and 4
Authors: Sabroe Ian , Jones Elizabeth C. , Whyte Moira K. B. , Dower Steven K.
Published: April 2005

Neutrophil chemokine receptor expression can be altered by exposure to Toll‐like receptor (TLR) agonists, a process that is thought to have the potential to localize neutrophils to sites of infection. In order to investigate this process in more detail, we examined the regulation of highly pure neutrophil CXCR1 and CXCR2 expression and function by selective agonists of TLR2 (Pam3CSK4) and TLR4 (lipopolysaccharide, LPS). CXCR1 and CXCR2 were down‐regulated by TLR engagement. CXCR2 loss was more rapid and showed a dependence upon soluble helper molecules (LPS binding protein and CD14) that was not evident for CXCR1, suggesting differential coupling of LPS signalling to CXCR1 and CXCR2 loss. However, TLR engagement in highly pure neutrophils did not result in complete loss of chemokine receptors, and LPS‐treated neutrophils remained able to mount a respiratory burst to CXCL8 and CXCL1, and were able to migrate towards CXCL8 in assays of under‐agarose chemotaxis. Thus, although treatment of purified human neutrophils with TLR2 and TLR4 agonists modifies chemokine receptor expression, remaining receptors remain functionally competent.
Effect of oestradiol on mouse uterine epithelial cell tumour necrosis factor‐α release is mediated through uterine stromal cells
Authors: Grant‐Tschudy Katherine S. , Wira Charles R.
Published: April 2005

Oestradiol‐17β (Oe2) stimulates uterine epithelial cell proliferation and is critical for normal uterine differentiation and secretory function. Oe2 can act directly on the epithelium via the epithelial oestrogen receptor (OR) or indirectly via the OR‐positive underlying stroma. A primary role for epithelial–stromal interactions has been established for mediating steroid hormone action in the uterus. This study was undertaken to determine the mode of Oe2 action in regulating epithelial cell cytokine release in the uterus. Mouse uterine epithelial and stromal cells were isolated and cultured separately. Transepithelial resistance (TER) was monitored with an EVOM voltohmmeter to determine monolayer polarity and integrity. Epithelial cells grown alone or in coculture with stromal cells were treated with Oe2. Supernatants collected were assayed for transforming growth factor‐β (TGF‐β) and tumour necrosis factor‐α (TNF‐α) by bioassay and enzyme‐linked immunosorbent assay, respectively. While Oe2 treatment of epithelial cells led to a significant decrease in TER, the amount of TNF‐α released was not altered. However, when epithelial cells were cocultured with stromal cells and treated with Oe2, apical TNF‐α release was significantly decreased, compared to cells not treated with hormone. As determined by oestrogen receptor antagonist studies, Oe2 primed epithelial cells for the action of the stromal paracrine factor(s). In contrast, TGF‐β release by epithelial cells was not affected by Oe2 when grown alone or in the presence of stromal cells. These studies indicate that Oe2 has both direct and indirect effects on the uterine epithelium. While epithelial monolayer integrity is directly influenced by Oe2, TNF‐α release in response to Oe2 is dependent on the presence of stromal cells, indicating that paracrine communication is necessary for steroid regulation of some but not all cytokines.
Immunology and mathematics: crossing the divide
Authors: Callard Robin E. , Yates Andrew J.
Published: April 2005

‘It's high time molecular biology became quantitative, it cries out to a physicist … for modeling. Modeling isn't a crutch, it's the opposite; it's a way of suggesting experiments to do, to fill gaps in your understanding.’ John Maddox, Editor of Nature 1966–73, and 1980–95.
The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games
Authors: Hehlgans Thomas , Pfeffer Klaus
Published: April 2005

The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunbiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed.
Veterinary pharmacovigilance. Part 1. The legal basis in the European Union
Authors: WOODWARD K. N.
Published: April 2005

Pharmacovigilance is a growing discipline and nowhere is this more true than in the context of the legislative requirements for veterinary pharmacovigilance within the European Union (EU), or more specifically, within the European Economic Area. Since 1995, the legislation governing the authorization of veterinary medicinal products in the EU has resulted in the older national procedures being replaced by the mutual recognition procedure and the centralized procedure. Also since 1995, the regulatory requirements for pharmacovigilance have developed and grown, as have the associated guidelines. The recent review of European veterinary medicines legislation, which concluded with the publication of an amending directive and a new regulation in March 2004, has introduced refinements to the pharmacovigilance system. This paper examines the EU legislation governing the authorization of veterinary medicinal products, including the elaboration of maximum residue limits, and the way in which this relates to the requirements of pharmacovigilance.
Candidal overgrowth in diabetic patients: potential predisposing factors
Authors: Belazi Maria , Velegraki Aristea , Fleva Alexandra , Gidarakou Ioanna , Papanaum Lucy , Baka Despina , Daniilidou Natasa , Karamitsos Dimitrios
Published: April 2005

This study was designed to investigate the potential factors that influence the prevalence of the oral carriage of Candida species in patients with type II diabetes mellitus. One hundred and twenty‐eight diabetic patients (68 males and 60 females, mean age 54 ± 7 years) were sequentially enrolled along with 84 (44 males and 40 females mean age 52 ± 8 years) healthy subjects. Samples were obtained by swabbing the oral mucosa of all participants. Yeast isolates were identified by germ tube test, with API 32 ID system, and by chlamydospore production on ‘cornmeal’ Tween‐80 agar. Candida spp. was recovered from the oral cavity of 64% of the diabetic group, in contrast to 40% of the control group. Candida albicans was the most frequently isolated species in both groups. Potential etiologic factors such as xerostomia, dentures, age, gender and diabetes on oral carriage of Candida spp. were evaluated. The oral carriage of Candida spp. was significantly higher in ‘diabetic’ patients compared with the healthy subjects but it seems that parameters such as xerostomia, dentures, age, gender and glycemic control cannot be directly associated with Candida growth in the oral cavity in the presence of diabetes.
Blastomycosis‐like pyoderma: Successful treatment with low‐dose acitretin
Authors: Nguyen Roland TD , Beardmore Graeme L
Published: April 2005

Blastomycosis‐like pyoderma typically presents as verrucous plaque(s) with a purulent discharge through multiple sinuses. Two patients with blastomycosis‐like pyoderma developing on significantly sun‐damaged skin are presented: an 84‐year‐old man with multiple painful nodules and plaques, and a 92‐year‐old woman with a solitary plaque on the left calf. Histopathology showed pseudoepitheliomatous hyperplasia with dermal foci of suppuration. Staphylococcus aureus was isolated from a biopsy specimen in the first patient, whereas the latter patient had Prevotella and Corynebacterium species. Investigations for fungi and mycobacteria yielded negative results. These microbiological findings further supported the clinicopathological diagnosis. Both patients failed to respond to oral doxycycline despite the in vitro susceptibility of the organisms. Treatment with low‐dose oral acitretin was successful in both patients after 3–4 months.
Risk and protective behaviours of bisexual minority women: a qualitative analysis
Authors: Champion J. D. , Wilford K. , Shain R. N. , Piper J. M.
Published: April 2005

Background  Public health messages urging women to seek health care services such as sexually transmitted diseases (STD) and cervical cancer screening or family planning services fail to address women who have sex with women (WSW). This negligence may have led to a false sense of security amongst WSW concerning sexual risk behaviour. Research has shown that WSW engaged in more high‐risk sexual behaviours than heterosexual women. WSW has been identified as an important vector in the spread of STDs in all populations because of bisexuality. To prevent and reduce transmission of STDs amongst WSW, perceptions of risk for STD amongst WSW need to be understood so that effective interventions may be developed.

Aim  To describe the relationship between sexual risk and protective behaviour and STD transmission amongst bisexual minority women with a history of STD.

Methods  Life history methods were used to interview 23 African‐American bisexual women with a history of STD.

Findings  Various themes unfolded during analysis of the patient interviews, including bisexual women's perceptions of STD risk, the context of sexual relationships with women and STD prevention, screening, and treatment practices.

Conclusions  The contexts of sexual relationships including multiple or concurrent partner relationships with both men and women placed these women at high risk for STD. Regardless of the type of relationship or belief it is possible to get an STD, protection was often not used. These circumstances identify an extremely high‐risk population of women with need for more extensive research to identify strategies for health care interventions.
Jordanian married Muslim women's intentions to use oral contraceptives
Authors: Kridli S. A. , Newton S. E.
Published: April 2005

Background  High fertility rates and moderate to low contraceptive use in the Arab Islamic countries, and Jordan in particular, are issues of international nursing importance.

Aim  By using the Theory of Planned Behaviour (TPB) as the conceptual framework, the relationships between married Jordanian Muslim women's previous contraceptive use, type of experience, and intention to use oral contraceptives (OCs) were examined. The relationship between selected demographic variables and intention to use OCs was also examined.

Methods  The study was part of a large cross‐sectional survey. The Intention to Use Oral Contraceptive Tool was used to elicit participants’ intentions and beliefs regarding oral contraceptive use.

Sample  The study sample was composed of 245 Jordanian married Muslim women.

Results  Results revealed a significant relationship between previous oral contraceptive use and intention to use OCs. The relationships between type of experience, whether successful or unsuccessful, with previous OC use, and intention to use OCs were not significant.

Conclusion:  Nursing implications regarding the provision of family planning services that are sensitive to Jordanian Muslim women's religious preferences are discussed.
Nursing, midwifery and allied health education programmes in Afghanistan
Authors: Herberg P.
Published: April 2005

Background:  In 2001, Afghanistan was the centre of the world's attention. By 2002, following 23 years of internal conflict – including Soviet invasion, civil war and Taliban rule, plus 3 years of drought, the country was just beginning the process of re‐establishing its internal structures and processes. In the health sector, this included the revival of the Ministry of Health (MOH). The MOH was assisted in its efforts by multiple partners, including the UN, donor and aid agencies, and a variety of non‐governmental organizations. The author served as a consultant to the Aga Khan University School of Nursing, in partnership with the World Health Organization and the MOH, as it took on the work of strengthening nursing, midwifery and allied health education programmes for Afghanistan.

Aim:  This paper will focus on the initial assessment of that sector. It will describe the situation as it existed in 2002, by examining the Kabul Institute of Health Sciences (IHS) and then turn briefly to the current state of affairs.

Conclusions:  Despite the uncertainties of daily life in Afghanistan, the country has successfully initiated the reconstruction process. In the health sector, this can be seen in the work done at the Kabul IHS. Progress has been made in a number of areas, most notably in development and implementation of nursing and midwifery curricula. However, no one would deny that much more work is needed.
Iranian student nurses’ experiences of clinical placement
Authors: Peyrovi H. , Yadavar‐Nikravesh M. , Oskouie S. F. , Berterö C.
Published: April 2005

Background:  Nursing as a practice‐based profession requires that student nurses learn how to become professional in the clinical environment. Many studies have addressed student nurses’ clinical learning and related problems, but few have explored the whole clinical experience of being a student nurse.

Aim:  To understand and gain deeper insight into Iranian student nurses’ lived experience of clinical placement.

Method:  Five student nurses were interviewed about their clinical experience during clinical placement. The researchers analysed the verbatim transcripts using van Manen's phenomenological methodology, keeping in mind the recommended six research activities.

Findings:  Five themes emerged by which the phenomenon of clinical experience could be illustrated. These themes were: caring‐orientated relationships, attractive aspects of clinical experience, finding oneself in the clinical milieu, being supportive to classmates, and actualizing potential. Fourteen subthemes expanded and clarified the meaning of these themes.

Conclusion:  The attention paid and acknowledgement given to ‘caring’ and ‘knowledge’ by the student nurses showed that they are progressing toward their ultimate goal of being professional nurses. The student nurses’ awareness of ‘what is going on there?’ and also support from other significant people facilitates the students’ adaptation process and guarantees this progress.
Violence towards nursing staff in emergency departments in one Turkish city
Authors: Şenuzun Ergün F. , Karadakovan A.
Published: April 2005

Aim:  To determine the incidence of violence faced by nurses in emergency departments (ED) in a Turkish city, whether any of the incidents were reported and what legal action was taken. The second aim was to identify nurses’ attitudes towards these incidents and the relevance of their professional background.

Methods:  Data were collected by questionnaire from the nurses working in the ED of four major hospitals in Izmir, Turkey. The questionnaire consisted of 34 questions seeking socio‐demographic data, information on verbal and physical victimization and legal processes.

Results:  Sixty‐six nurses (72%) agreed to participate in the study. One third (34.8%) of participants were relatively new in the profession (0–5 years), and the majority of nurses (71.2%) had an ED experience of less than 5 years. The incidence of verbal violence (98.5%) was significantly more frequent than physical violence (19.7%). However, most incidents remained unreported (83.5%); most of the reported cases did not result in legal action (63.7%). Almost half of the nurses believed that possible explanations for the violent incidents they faced were because they were less competent and inexperienced in the profession than more senior colleagues.

Discussion:  Victimized respondents mostly preferred to remain silent and did not report the incidents to the hospital administration since they believed that this would not result in legal action. It seems evident that our country lacks legal processes concerning job (workplace) violence. Effective legislative arrangements are necessary. Nurses and other ED staff also need continuing education concerning their rights and personal safety.
Extreme Spectra of Var Models and Orders of Near‐Cointegration
Authors: Ioannidis E. E. , Chronis G. A.
Published: April 2005

Abstract.  In this paper, we study the spectral properties of a bivariate vector autoregressive VAR(p) model when a root z0 = ρ0eiλ0 of the determinant of the model's characteristic matrix Φ(z) approaches the unit circle, the border of non‐stationarity. Let Φxx(z), Φxy(z), Φyx(z), Φyy(z) be the polynomial elements of Φ(z). We show that, depending on the relation of the order of z0 as root of  det(Φ(z)) with the orders of z0 as root of Φij(z), (i,j ∈ {x,y}), the two marginal spectra may tend to infinity at λ0, while the coherence may tend to unity at λ0. We investigate the conditions under which any of the above will occur, in detail. In the specific case where z0→1, the marginal series will be near‐integrated of certain orders of near‐integration, while there will eventually exist a linear combination of them with a lower order of near‐integration. We study the possible combinations of their orders of near‐integration. Finally, we develop a strategy with the help of which one may define a VAR(p) model with pre‐specified extreme spectral features and give some examples. Beyond the benefits of this latter for VAR model simulation, the analysis has, moreover, implications concerning the adequacy of VAR model fitting.
POSTMODERNISM AND HISTORY: MISSING THE MISSED CONNECTIONS
Authors: Roberts David D.
Published: April 2005

On the Future of History: The Postmodernist Challenge and Its Aftermath. By Ernst Breisach.
Hydrologic and geochemical controls on soluble benzene migration in sedimentary basins
Authors: ZHANG Y. , PERSON M. , MERINO E.
Published: April 2005

The effects of groundwater flow and biodegradation on the long‐distance migration of petroleum‐derived benzene in oil‐bearing sedimentary basins are evaluated. Using an idealized basin representation, a coupled groundwater flow and heat transfer model computes the hydraulic head, stream function, and temperature in the basin. A coupled mass transport model simulates water washing of benzene from an oil reservoir and its miscible, advective/dispersive transport by groundwater. Benzene mass transfer at the oil–water contact is computed assuming equilibrium partitioning. A first‐order rate constant is used to represent aqueous benzene biodegradation. A sensitivity study is used to evaluate the effect of the variation in aquifer/geochemical parameters and oil reservoir location on benzene transport. Our results indicate that in a basin with active hydrodynamics, miscible benzene transport is dominated by advection. Diffusion may dominate within the cap rock when its permeability is less than 10−19 m2. Miscible benzene transport can form surface anomalies, sometimes adjacent to oil fields. Biodegradation controls the distance of transport down‐gradient from a reservoir. We conclude that benzene detected in exploration wells may indicate an oil reservoir that lies hydraulically up‐gradient. Geochemical sampling of hydrocarbons from springs and exploration wells can be useful only when the oil reservoir is located within about 20 km. Benzene soil gas anomalies may form due to regional hydrodynamics rather than separate phase migration. Diffusion alone cannot explain the elevated benzene concentration observed in carrier beds several km away from oil fields.
Some virulence properties and characterization of motile Aeromonas species from milk and white cheese
Authors: YUCEL NIHAL , ERDEM BELGIN , KAYA DILEK
Published: April 2005

Three hundred and thirty‐eight samples of milk and milk products in Ankara were screened for the presence of motile Aeromonas species. The overall frequency of aeromonads in these samples was 27%. As expected, raw milk samples were more contaminated with aeromonads than were other products. Sixty‐five (49.2%) of the 132 bulk raw milk samples were contaminated with aeromonads. In 35 of these samples, populations of aeromonads from 1.5 × 102 to 3.0 × 103 cfu/mL were counted in ampicillin dextrin agar (ADA). Ten (40%) of the 25 raw milk samples sold in the street were contaminated with aeromonads. In eight of these samples, 1.2 × 102−3.0 × 103 cfu/mL were counted. Five (16%) of the 31 pasteurized milk and 12 (8%) of the 150 white cheese samples were contaminated with Aeromonas
spp., but no countable aeromonads population was noted in ADA. The incidence of A. hydrophila, A. sobria and A. caviae in all samples was found to be 90.2%, 4.3% and 5.4%, respectively. The majority of the strains identified as A. hydrophila and A. sobria were able to produce haemolysin, protease and DNase, while strains identified as A. caviae were only positive for DNase. All isolated Aeromonas species (A. hydrophila, A. sobria and A. caviae) were positive for uptake of Congo red dye. Nevertheless, only strains identified as A. hydrophila and A. sobria showed a high rate of positive results when tested for the production of the Voges–Proskauer reaction and lysine decarboxylase. The results of this work show that motile Aeromonas spp., especially A. hydrophila, are frequently found in these samples. As these products are usually commonly consumed in Ankara, they can pose a risk especially for children, the elderly and immunocompromised individuals.
Allosteric modulation of adenosine A1 receptor coupling to G‐proteins in brain
Authors: Childers Steven R. , Li Xinhui , Xiao Ruoyu , Eisenach James C.
Published: April 2005

2‐Amino‐4,5,6,7‐tetrahydrobenzo(β)thiophen‐3‐yl 4‐chlorophenylmethanone (T62) is a member of a group of allosteric modulators of adenosine A1 receptors tested in animal models of neuropathic pain to increase the efficacy of adenosine. To determine its mechanisms at the level of receptor‐G‐protein activation, the present studies examined the effect of T62 on A1‐stimulated [35S]guanosine‐5′‐O‐(γ‐thio)‐triphosphate ([35S]GTPγS) binding in brain membranes, and by [35S]GTPγS autoradiography using the A1 agonist, phenylisopropyladenosine (PIA), to activate G‐proteins. In hippocampal membranes, T62 increased both basal and PIA‐stimulated [35S]GTPγS binding. The effect of T62 was non‐competitive in nature, since it increased the maximal effect of PIA, with no effect on agonist potency. GTPγS saturation analysis showed that T62 increased the number of G‐proteins activated by agonist but had no effect on the affinity of activated G‐proteins for GTPγS. [35S]GTPγS autoradiography showed that the neuroanatomical localization of T62‐stimulated [35S]GTPγS binding was identical to that of PIA‐stimulated activity. The increase in PIA‐stimulated activity by T62 varied between brain regions, with areas of lower A1 activation producing the largest percent modulation by T62. These results suggest a mechanism of allosteric modulators to increase the number of activated G‐proteins per receptor, and provide a neuroanatomical basis for understanding potential therapeutic effects of such drugs.
Structural and functional analysis of cysteine residues in human glutamate decarboxylase 65 (GAD65) and GAD67
Authors: Wei Jianning , Wu Jang‐Yen
Published: April 2005

Previously, we have shown that brain glutamate decarboxylase (GAD) is greatly inhibited by sulfhydryl reactive reagent suggesting cysteine residue(s) may play an important role in GAD function. In this report, we determined the role of cysteine residues in the recombinant human 65‐kDa GAD isoform (hGAD65) and 67‐kDa GAD isoform (hGAD67), using a combination of matrix‐assisted laser desorption/ionization–time of flight (MALDI–TOF) mass spectrometry and site‐directed mutagenesis. Here, we report that cysteine 446 (C446) in hGAD65 is important for its activity and is present as free sulfhydryl group. This conclusion is based on the following observations: (i) mutation of C446 in hGAD65 to alanine reduced hGAD65 activity by more than 90%, (ii) MALDI–TOF analysis of the non‐reduced, trypsin‐digested GAD65 revealed that C446 is present as a free sulfhydryl group as indicated by a peak at m/z (mass/charge) 647.3446 (peptide 443–448) and, when GAD65 was treated with sulfhydryl reagent, N‐ethylmaleimide (NEM), the peak is shifted to m/z 772.3702,a mass increase of 125.1 daltons (Da) as a result of modification of cysteine by NEM. Parallel studies have also been conducted with hGAD67. Cysteine 455 was found to be important for GAD67 activity.
Neuropeptide Y stimulates neuronal precursor proliferation in the post‐natal and adult dentate gyrus
Authors: Howell Owain W. , Doyle Kharen , Goodman Jeffrey H. , Scharfman Helen E. , Herzog Herbert , Pringle Ashley , Beck‐Sickinger Annette G. , Gray William P.
Published: April 2005

Adult dentate neurogenesis is important for certain types of hippocampal‐dependent learning and also appears to be important for the maintenance of normal mood and the behavioural effects of antidepressants. Neuropeptide Y (NPY), a peptide neurotransmitter released by interneurons in the dentate gyrus, has important effects on mood, anxiety‐related behaviour and learning and memory. We report that adult NPY receptor knock‐out mice have significantly reduced cell proliferation and significantly fewer immature doublecortin‐positive neurons in the dentate gyrus. We also show that the neuroproliferative effect of NPY is dentate specific, is Y1‐receptor mediated and involves extracellular signal‐regulated kinase (ERK)1/2 activation. NPY did not exhibit any effect on cell survival in vitro but constitutive loss of the Y1 receptor in vivo resulted in greater survival of newly generated neurons and an unchanged total number of dentate granule cells. These results show that NPY stimulates neuronal precursor proliferation in the dentate gyrus and suggest that NPY‐releasing interneurons may modulate dentate neurogenesis.
Rat brain iron concentration is lower following perinatal copper deficiency
Authors: Prohaska Joseph R. , Gybina Anna A.
Published: April 2005

Experiments performed with Holtzman rats demonstrated that brain iron (Fe) was lower by postnatal day 13 (P13) in pups born and nursed by dams that began copper‐deficient (–Cu) treatment at embryonic day 7. Transcardial perfusion of P24–P26 males and females to remove blood Fe contamination revealed that brain Fe was still 20% lower in –Cu than +Cu rats. Estimated blood content of brain for –Cu rats was greater than for +Cu rats; for all groups, values ranged between 0.43 and 1.03%. Using group‐specific data and regression analyses, r = 0.99, relating blood Fe to hemoglobin, brain Fe in non‐perfused rats in a replicate study was lower by 33% at P13 and 39% at P24 in –Cu rats. Brain extracts from these rats and from P50 rats from a post‐weaning model were compared by immunobloting for transferrin receptor (TfR1). P24 brain –Cu/+Cu TfR1 was 3.08, suggesting that brains of –Cu rats were indeed Fe deficient. This ratio in P13 rats was 1.44, p < 0.05. No change in P50 –Cu rat brain TfR1 or Fe content was detected despite a 50% reduction in plasma Fe. The results suggest that brain Fe accumulation depends on adequate Cu nutriture during perinatal development.
Smoking, a weak predictor of periodontitis in older adults
Authors: Persson Rigmor E. , Kiyak Asuman H. , Wyatt Chris C. I. , MacEntee Michael , Persson G. Rutger
Published: April 2005

Background: The impact of smoking habits on periodontal conditions in older subjects is poorly studied.

Aims: To assess if a history of smoking is associated with chronic periodontitis and medical history in older subjects.

Material and Methods: The medical and dental history was collected from 1084 subjects 60–75 years of age. Smoking history information was obtained from self‐reports. Periodontal variables [clinical probing depth (PD)5.0 mm, clinical attachment levels (CALs) 4.0 mm], and radiographic evidence of alveolar bone loss were assessed.

Results: 60.5% had never smoked (NS), 32.0% were former smokers (FS) (mean smoke years: 26.1 years, SD±13.1), and 7.5% were current smokers (CS) (mean smoke years 38.0 years, (SD±12.1). The proportional distribution of CAL 4.0 mm differed significantly by smoking status (NS and CS groups) (mean difference: 12.1%, 95% confidence interval (CI): 1.5–22.6, p<0.02). The Mantel–Haenszel common odds ratio between smoking status (CS+FS) and periodontitis (>20% bone loss) was 1.3 (p<0.09, 95% CI: 0.9–2.0) and changed to 1.8 (p<0.02, 95% CI: 1.3–2.7) with 30 years of smoking as cutoff. A weak correlation between number of years of smoking and CAL4.0 mm was demonstrated (r2 values 0.05 and 0.07) for FS and CS, respectively. Binary logistic forward (Wald) regression analysis demonstrated that the evidence of carotid calcification, current smoking status, gender (male), and the number of remaining teeth were explanatory to alveolar bone loss.

Conclusions: A clinically significant impact on periodontal conditions may require 30 years of smoking or more. Tooth loss, radiographic evidence of carotid calcification, current smoking status, and male gender can predictably be associated with alveolar bone loss in older subjects.
Pyoderma gangrenosum
Authors: Conrad Curdin , Trüeb Ralph M.
Published: April 2005

Pyoderma gangrenosum (PG) is a non‐infectious reactive neutrophilic dermatosis which typically starts with pustules which rapidly evolve to painful ulcers of variable size and depth with undermined violaceous borders. Since its first description in 1930, the pathogenesis of PG has remained elusive even as an ever‐widening range of systemic diseases has been described in association with it. The diagnosis of PG is based on clinical and pathologic features and requires exclusion of other conditions that produce ulcerations, since misdiagnosis exposes patients to risks associated with treatment. Critical to proper management are correct diagnosis, identification and treatment of any underlying disorder, and the appropriate choice of topical and systemic therapy. PG has four distinctive clinical and histologic variants, and the specific clinical features of the lesion may provide a clue to the associated disease. The most common associated diseases are inflammatory bowel disease, rheumatological or hematological disease or malignancy. Although there is no single successful treatment for PG, certain type of PG lesions are recognized to respond more readily to accepted therapies than others. Local treatment may be sufficient for mild disease, while systemic immunosuppressive therapy is necessary for severe cases. The treatments with the best clinical evidence are oral or pulse intravenous corticosteroids, and cyclosporine. Surgical therapy is useful in selected cases in conjunction with immunosuppression. Wound stabilization is obtained only through control of the systemic and local inflammatory process. Emerging therapies include use of platelet‐derived growth factor and cell culture grafts when re‐epithelialization is slow, and the TNF‐alpha blocking agent infliximab for refractory disease. Despite advances in therapy, the long‐term outcome for patients with PG remains unpredictable, because relapses are common.
USE OF RADIOGRAPHY IN COMBINATION WITH COMPUTED TOMOGRAPHY FOR THE ASSESSMENT OF NONCARDIAC THORACIC DISEASE IN THE DOG AND CAT
Authors: Prather Andrew B. , Berry Clifford R. , Thrall Donald E.
Published: April 2005

Computed tomography (CT) of the thorax was performed in 28 dogs and five cats and findings were compared with previous thoracic radiographs. The sample population included all animals that had thoracic radiographs and a CT study within 5 days of each other, where the complete imaging studies were available for review. Thoracic radiographs were considered indeterminate in 31 patients and CT examinations were done to acquire additional information. The presence of additional information from CT relating to presence of pathology, location of pathology, extent of pathology, and involvement of mediastinal structures was recorded. Whether there was a change in diagnosis based on the CT findings was also recorded. In only 4/33 animals (all dogs) did CT fail to provide any new information for the parameters evaluated when compared with survey thoracic radiographs. Additional information about the pathology that was present was gained by CT in 5/5 cats and 21/28 dogs. New information on compartmental location of pathology was seen in 4/5 cats and 19/28 dogs. New information on pathology extent was noted in 5/5 cats and 20/28 dogs. Additional information regarding involvement of mediastinal structures was obtained in 2/5 cats and 10/28 dogs. A change in diagnosis was made in 3/5 cats and 13/28 dogs. In conclusion, CT is a valuable tool for evaluating intrathoracic disease. CT provides additional cross‐sectional anatomic information that can aid in anatomic localization and evaluation of the extent of the pathology in question.
Diagnosis and Management of Pediatric Urinary Tract Infections
Authors: Zorc Joseph J. , Kiddoo Darcie A. , Shaw Kathy N.
Published: April 2005

Urinary tract infection (UTI) is among the most commonly diagnosed bacterial infections of childhood. Although frequently encountered and well researched, diagnosis and management of UTI continue to be a controversial issue with many challenges for the clinician. Prevalence studies have shown that UTI may often be missed on history and physical examination, and the decision to screen for UTI must balance the risk for missed infections with the cost and inconvenience of testing. Interpretation of rapid diagnostic tests and culture is complicated by issues of contamination, false test results, and asymptomatic colonization of the urinary tract with nonpathogenic bacteria. The appropriate treatment of UTI has been controversial and has become more complex with the emergence of resistance to commonly used antibiotics. Finally, the anatomic evaluation and long-term management of a child after a UTI have been based on limited evidence, and newer studies question some of the tenets of prior recommendations. The goal of this review is to provide an up-to-date summary of the literature with particular attention to practical questions about diagnosis and management for the clinician.
AN UNSUPERVISED KERNEL BASED FUZZY C-MEANS CLUSTERING ALGORITHM WITH KERNEL NORMALISATION
Authors: ZHOU SHANG-MING , GAN JOHN Q.
Published: April 2005

In this paper, a novel procedure for normalising Mercer kernel is suggested firstly. Then, the normalised Mercer kernel techniques are applied to the fuzzy c-means (FCM) algorithm, which leads to a normalised kernel based FCM (NKFCM) clustering algorithm. In the NKFCM algorithm, implicit assumptions about the shapes of clusters in the FCM algorithm is removed so that the new algorithm possesses strong adaptability to cluster structures within data samples. Moreover, a new method for calculating the prototypes of clusters in input space is also proposed, which is essential for data clustering applications. Experimental results on several benchmark datasets have demonstrated the promising performance of the NKFCM algorithm in different scenarios.
Enhanced expression of EGF receptor in a model of salt-sensitive hypertension
Authors: Ying Wei-Zhong , Sanders Paul W.
Published: April 2005

Chronic kidney disease in the Dahl/Rapp salt-sensitive (S) rat is related to an arteriolopathic process that occurs following the onset of hypertension and involves vascular smooth muscle cell (VSMC) hyperplasia and luminal constriction. Because previous studies have shown that activation of the epidermal growth factor receptor (EGFR) produces a mitogenic stimulus in VSMC and the EGFR participates integrally in the vasoconstrictor responses of renal arterioles, the present study analyzed the expression of EGFR in these animals. Compared with Sprague-Dawley (SD) rats, renal cortical expression of EGFR was increased in both prehypertensive and hypertensive S rats. Immunohistochemistry using a polyclonal antibody to EGFR demonstrated that EGFR expression was prominent in the renal vasculature, particularly in the media of afferent and efferent arterioles and the aorta of S rats. When examined, primary cultures of VSMC from S rats showed increased expression of EGFR, compared with VSMC from SD and Dahl/Rapp salt-resistant rats. Following addition of EGF, autophosphorylation of the EGFR was enhanced in cells from S rats, as was the downstream signaling events that included activation of p42/44 MAPK and Akt pathways. Thus in vivo and in vitro studies demonstrated augmented expression and functional activity of the EGFR in S rats.
Effects of capsaicin and nitric oxide synthase inhibitor on increase in cerebral blood flow induced by sensory and parasympathetic nerve stimulation in the rat
Authors: Ayajiki Kazuhide , Fujioka Hideyuki , Shinozaki Kazuya , Okamura Tomio
Published: April 2005

Effects of electrical stimulation of the nerve bundles including sensory and parasympathetic nerves innervating cerebral arteries on cerebral blood flow (CBF) and mean arterial blood pressure (MABP) were investigated with a laser-Doppler flowmeter and a blood pressure monitoring system in anesthetized rats pretreated with and without capsaicin. The electrode was hooked on the nerve bundles including the distal nasociliary nerve from trigeminal nerve and parasympathetic nerve fibers from sphenopalatine ganglion. In control rats, the nerve stimulation for 30 s increased CBF in the ipsilateral side and MABP. Hexamethonium attenuated the increase in CBF and abolished that in MABP. Under treatment with hexamethonium, NG-nitro-l-arginine (l-NNA, 1 mg/kg) significantly attenuated the stimulation-induced increase in CBF, which was restored by the addition of l-arginine. Although the dose of l-NNA was raised up to 10 mg/kg, the stimulation-induced increase in CBF was not further inhibited and was never abolished. In capsaicin-pretreated rats, magnitudes of the stimulation-induced increases in CBF and MABP were lower than those in control rats. Hexamethonium attenuated the increase in CBF and abolished that in MABP. Under treatment with hexamethonium, l-NNA abolished the stimulation-induced increase in CBF in capsaicin-pretreated rats. In conclusion, nitric oxide released from parasympathetic nerves and neuropeptide(s) released antidromically from sensory nerves may be responsible for the increase in CBF in the rat. The afferent impulses by nerve stimulation may stimulate the trigeminal nerve and lead to the rapid increase in MABP, which partly contributes to the increase in CBF.
Barometric whole body plethysmography in mice
Authors: Schwarze J. , Hamelmann E. , Gelfand E. W.
Published: April 2005

There has been significant utilization of the technique described by Hamelmann et al. ( Am J Respir Crit Care Med 156: 766–775, 1997) in which a parameter, enhanced pause (Penh), related to airways responsiveness is noninvasively measured by unrestrained plethysmography (UP). Investigating this technique, we sought to answer these questions: 1) How do changes in Penh compare with changes in traditional plethysmographic and lung mechanical parameters? 2) How do UP parameters perform in two different mouse strains? Awake immunized and control BALB/c ( n = 16) and C57BL/6 ( n = 14) mice were placed in the UP chamber and exposed to doses of aerosolized methacholine while the following parameters were measured at each concentration: inspiratory time (Ti), expiratory time (Te), total time (Ttot), Ti/Ttot, peak inspiratory pressure, peak expiratory pressure, Pause, Penh, tidal volume (Vt), Vt/Ti, Vt/Te, and Vt/Ttot. The next day, lung resistance (Rl) and compliance (Cl) were invasively measured in the same animals. For the BALB/c, the parameters with the highest magnitude of correlation coefficient vs. Rl are (in order) 1) Cl, 2) Pause and Penh, 3) parameters of breathing frequency (Te, Ttot, Ti), and 4) parameters related to Vt (inspiratory pressure, expiratory pressure). Flow parameters (Vt/Ttot, Vt/Te, Vt/Ti) and duty cycle parameters (Ti/Ttot) had insignificant correlations. This ordering is significantly different in C57BL/6 mice, in which the parameters with the largest correlations are 1) Cl, 2) parameters of breathing frequency, and 3) flow parameters. Pause, Penh, Vt, and duty cycle parameters had insignificant correlations. These data show that Penh is problematic in the sense that it is strain specific; it behaves very differently in BALB/c and C57BL/6 mice. We suggest that UP parameters largely originate as part of reflex control of breathing processes, rather than in the lung mechanics and conclude that it is inappropriate to use UP parameters in general, and Penh specifically, as substitute variables for invasive mechanical indexes such as Rl.
Activation of Spinal D1/D5 Receptors Induces Late-Phase LTP of C-Fiber–Evoked Field Potentials in Rat Spinal Dorsal Horn
Authors: Yang Hong-Wei , Zhou Li-Jun , Hu Neng-Wei , Xin Wen-Jun , Liu Xian-Guo
Published: April 2005

Long-term potentiation (LTP) of C-fiber–evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has shown that the late phase of the spinal LTP is protein synthesis–dependent. Considerable evidence has accumulated that dopamine D1/D5 receptors are important for late-phase LTP in hippocampus. In this study, the role of D1/D5 receptors in LTP of C-fiber–evoked field potentials in spinal dorsal horn was evaluated in urethan-anesthetized Sprague-Dawley rats. We found the following. 1) Spinal application of SKF 38393, a D1/D5 receptor agonist, induced a slowly developed LTP of C-fiber–evoked field potentials, lasting for >10 h, and the effect was blocked by the D1/D5 antagonist SCH 23390, whereas a D2 receptor agonist (quinpirole) induced depression of C-fiber responses, lasting for 2 h. 2) The potentiation produced by D1/D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. 3) SCH 23390 selectively depressed the late-phase LTP, when applied 40 min before tetanic stimulation. 4) The D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. 5) Activation of protein kinase A by spinal application of 8-Br-cAMP also induced spinal LTP, and the action occluded the potentiation induced by the D1/D5 receptor agonist. These results suggest that the spinal D1/D5 receptors participate in the protein synthesis–dependent late-phase LTP of C-fiber–evoked field potentials in spinal dorsal horn through the cAMP signaling pathway.
Molecular characterization of rat gastric mucosal response to potent acid inhibition
Authors: Nørsett Kristin G. , Lægreid Astrid , Langaas Mette , Wörlund Sara , Fossmark Reidar , Waldum Helge L. , Sandvik Arne K.
Published: April 2005

Potent acid inhibition with proton pump inhibitors (PPIs) is widely used in clinical medicine, especially for gastroesophageal reflux disease. PPIs cause profound changes in the intragastric environment with near-neutral pH and increase serum concentration of the gastric secretagogue hormone gastrin. Long-term hypergastrinemia increases mucosal thickness and enterochromaffin-like cell density in gastric corpus mucosa and results in development of gastric carcinoids in experimental animals. Our aim was to study responses to potent acid inhibition by characterizing genome-wide gene expression changes in gastric corpus mucosa in rats dosed with the PPI omeprazole. Nine rats received 400 μmol/kg omeprazole daily for 10 wk. Seven rats received vehicle only. Analysis of gastric corpus with microarrays representing 11,848 genes identified 134 genes with changed gene expression levels in omeprazole-dosed rats. Several of the identified genes were previously known to be affected by potent acid inhibition. Of the 62 genes with known functions that changed gene expression levels after PPI dosing, 27 are known to be involved in proliferation and apoptosis and immune, inflammatory, and stress responses. Our study indicates that microarray analysis can detect relevant gene expression changes in the complex gastric tissue, and that cellular processes involved in cell growth and defense responses are strongly affected by PPI dosing. Many genes are identified that were not previously known to be affected by inhibition of gastric acid secretion or that have unknown biological functions. Characterization of the roles of these genes may give new insight into molecular responses to treatment with PPIs.
Von Willebrand gene tracking by single-tube automated fluorescent analysis of four short tandem repeat polymorphisms
Authors: Vidal Francisco , Julià Antoni , Altisent Carme , Puig Lluís , Gallardo Dominique
Published: April 2005

Molecular diagnosis of von Willebrand disease (VWD) has been hampered by the large size and complex genomic characteristics of the gene involved. For this reason, indirect methods using in-tragenic polymorphic markers described along the von Wille-brand factor (VWF) gene are valuable tools for gene monitoring and linkage analysis. Several studies have demonstrated the four commonly utilized short tandem repeats (STRs), three located in intron 40 and one in the promoter region of the VWF gene, to be highly informative for this task. Our objective was to develop a rapid, automated method to simultaneously analyze these four STRs for VWF gene tracking. Amplification of the four loci is achieved in a single multiplex fluorescent PCR which is then analyzed in the same run by capillary electrophoresis. Data processing with Gene Scan and Genotyper software has simplified management and tabulation of the resulting haplotypes. Analysis of the VWF gene in DNA from 102 individuals (204 chromosomes) revealed that the three STRs within intron 40 showed significant linkage disequilibrium against each other but not against the VWP locus. Moreover, the combination of the four markers offers a high heterozygosity rate (>99%) that improves tracing VWF gene inheritance. In conclusion, the automated fluorescent capillary electrophoresis method presented here is an extremely rapid, simple and highly informative technique for association studies between VWD and the VWF gene in addition to genetic counseling and prenatal diagnosis by precise linkage analysis in VWD-affected families.