bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of the inducible costimulator molecule for the induction of allergic immune responses and its decreased expression on T helper cells after venom immunotherapy
Authors: Bellinghausen Iris , Klostermann Bettina , Böttcher Ingo , Knop Jürgen , Saloga Joachim
Published: April 2004

The inducible costimulator (ICOS), a newly identified member of the CD28 receptor family that is induced after T‐cell activation, and its ligand (ICOSL), being expressed on activated monocytes and dendritic cells play a key role in T‐cell‐mediated immune responses. As ICOS costimulation also seems to regulate T helper 2 effector cells, the aim of this study was to analyse the function of this molecule in allergic immune responses and their specific therapy, mainly venom immunotherapy (VIT). CD4+ T cells from grass pollen‐, or bee or wasp venom‐allergic donors were stimulated in the presence of autologous mature dendritic cells, which were pulsed with different allergen doses. In this system, costimulation of ICOS strongly enhanced the production of the T helper 2 cytokines interleukin (IL)‐4, IL‐5 and IL‐10 and, to a lesser extent, secretion of the T helper 1 cytokine, interferon‐γ. Expression of ICOS on CD4+ T cells was induced, in a dose‐dependent manner, after a few days of stimulation with allergen‐pulsed dendritic cells, reaching a peak on day 6. The upregulation of ICOS after stimulation with venom allergens was significantly reduced after VIT. Addition of exogenous IL‐10 (which is induced during VIT) to the co‐cultures before VIT also led to an inhibition of ICOS expression, while blocking of IL‐10 in co‐cultures after VIT partially restored the expression of ICOS. These data indicate that the inhibition of T cells after immunotherapy also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL‐10, also associated with the inhibited status of T cells after VIT. This makes the ICOS–ICOSL pathway a potential target for therapeutic intervention in T helper 2‐mediated diseases, such as allergic diseases.
Murine CD8 lymphocyte expansion in vitro by artificial antigen‐presenting cells expressing CD137L (4‐1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour‐reactive effector cells in vivo
Authors: Yan Xiaocai , Johnson Bryon D. , Orentas Rimas J.
Published: April 2004

The ability to expand tumour‐infiltrating lymphocytes in vitro has been greatly enhanced by the use of antigen‐independent mechanisms of immune cell costimulation. We have produced human, using the K562 cell line, and murine, using YAC‐1 cells, artificial antigen presenting cells (aAPC) and demonstrate that these cell types stimulate murine lymphocyte populations in distinct ways. Using aAPC that have been transfected with CD137L (4‐1BBL) and CD32 (FcRγII), as a means to bind anti‐CD3 and anti‐CD28 antibody, we found that CD4 cells preferentially expanded in vitro with K562 aAPC, while CD8 cells expanded with both K562 and YAC‐1 aAPC. Co‐stimulation mediated by CD137L on aAPC was superior to that mediated by anti‐CD28 antibody. This was seen in both long and short‐term expansion assays, and by the rapid induction of a CD8+ DX5+ population. DX5 serves, under these in vitro conditions, as a general marker for lymphocyte activation. In vivo, the superiority of CD137L was demonstrated by the induction of T helper 1 effectors seen in freshly isolated splenocytes from mice immunized with CD137L‐expressing neuroblastoma tumour vaccines. The ability to stimulate a strong CD8 CTL response in vivo correlated with the induction of a DX5+ cell population in splenocytes with a memory‐effector phenotype. The presence of this unique DX5+ cell population, phenotypically distinct with regards to CD69 and CD62L expression from DX5+ cells induced by aAPC in vitro, may be associated with the ability of CD137L to induce strong anti‐tumour immunity.
Response of lung γδ T cells to experimental sepsis in mice
Authors: Hirsh Mark , Dyugovskaya Larissa , Kaplan Viktoria , Krausz Michael M.
Published: April 2004

γδ T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung γδ T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of γδ T cells progressively increased in lungs during sepsis, and reached a seven‐fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P = 0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P < 0·05 versus sham), low interferon‐γ (IFN‐γ; 8·5 ± 2·5%; P < 0·05 versus control) and interleukin‐10 (IL‐10) expression, and high tumour necrosis factor‐α expression (19·5 ± 1·7%; P < 0·05 versus control). The restoration of cytotoxicity, and increase in IFN‐γ and IL‐10 expression was observed at day 7 of CLP‐induced sepsis. In summary, our results demonstrate significant progressive accumulation of γδ T cells in lungs during CLP‐induced ALI. The temporary functional suppression of lung γδ T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage.
Type‐A CpG oligonucleotides activate exclusively porcine natural interferon‐producing cells to secrete interferon‐α, tumour necrosis factor‐α and interleukin‐12
Authors: Guzylack‐Piriou Laurence , Balmelli Carole , McCullough Kenneth C. , Summerfield Artur
Published: April 2004

Natural interferon‐producing cells (NIPC), also referred to as immature plasmacytoid dendritic cells (PDC), constitute a small population of leucocytes secreting high levels of type I interferons in response to certain danger signals. Amongst these signals are those from DNA containing unmethylated CpG motifs. The present work demonstrated that the CpG oligonucleotides (CpG‐ODN) 2216, D32 and D19 induce high amounts of interferon‐α (IFN‐α), tumour‐necrosis factor‐α (TNF‐α) and interleukin (IL)‐12 in porcine peripheral blood mononuclear cells (PBMCs). Swine workshop cluster 3 (SWC3)1ow CD4high cells, with high IL‐3‐binding activity, representing NIPC, were the exclusive cytokine‐producing cells responding to the CpG‐ODN. These cells did not express CD6, CD8 or CD45RA. Importantly, monocyte‐derived DC did not respond to CpG‐ODN by secretion of IFN‐α or TNF‐α or by the up‐regulation of costimulatory molecule expression. CpG‐ODN up‐regulated MHC class II and CD80\86 expression on the NIPC, but were unable to promote NIPC survival. Interestingly, certain CpG‐ODN, incapable of inducing NIPC to secrete IFN‐α or up‐regulate MHC class II and CD80\86, did promote NIPC viability. Taken together, the influence of CpG‐ODN on porcine NIPC, monocytes and myeloid DCs relates to that observed with their human equivalents. These results represent an important basis for the application of CpG‐ODN as adjuvants for the formulation of novel vaccines and demonstrate the importance of the pig as an alternative animal model for this approach.
Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs
Authors: Maehara S. , Ono K. , Ito N. , Tsuzuki K. , Seno T. , Yokoyama T. , Yamashita K. , Izumisawa Y. , Kotani T.
Published: April 2004

Nipradilol is an α1, β‐blocker with milder side effects than other β‐blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C‐value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C‐value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing β‐adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.
Indium‐111 labeled vitamin B12 imaging of a ciliary adenoma with concurrent grade 2 soft tissue sarcoma of the leg in a Labrador Retriever
Authors: Whittemore Jacqueline C. , Gionfriddo Juliet R. , Steyn Phillip F. , Ehrhart E. J.
Published: April 2004

An 11‐year‐old, male castrated, Labrador Retriever was evaluated for the presence of rapidly growing concurrent leg and intraocular masses. Metastasis was noted in the chest at time of initial presentation. Indium‐111 labeled vitamin B12 imaging was performed, and there was significant uptake by both primary tumors and the lung metastases. Enucleation and amputation were performed for palliative relief. The leg mass was a grade 2 soft tissue sarcoma and the ocular mass a ciliary adenoma. The dog remained symptom‐free for approximately 10 weeks before developing signs of respiratory distress. He was euthanized 12 weeks after initial presentation, and there was diffuse infiltration of the lungs with metastatic sarcoma. Indium‐111 labeled vitamin B12 imaging identified a ciliary adenoma in this case and may provide a useful differentiation technique for evaluation of intraocular and retrobulbar masses if it can be demonstrated that there is differential uptake between inflammatory or infectious conditions and neoplasia.
Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs
Authors: Grahn Bruce H. , Storey Eric S. , McMillan Catherine
Published: April 2004

The objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test‐bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro‐ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test‐bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.
Mycotic endophthalmitis in a dog caused byCandida albicans
Authors: Linek Jens
Published: April 2004

A case of mycotic endophthalmitis in the dog caused byCandida albicansis presented. The 3‐year‐old dog had a history of bloody diarrhea 3 months previously. The dog presented with acute signs of unilateral panuveitis. Aqueocentesis, vitreocentesis, and routine blood tests were performed but did not contribute to the diagnosis. The posterior segment could not be visualized because of flare and fibrin. On day 7 ultrasonography showed retinal separation which progressed to vitreous compartmentalization and abscessation by day 14. Three weeks after onset, glaucoma developed and enucleation was performed. Histology revealed the yeastCandidato be the causative agent. Post‐enucleation serumCandidaantibody titer was 1 : 640 (human threshold 1 : 120), as determined by agglutination test. A relapse of enteric signs 3 months later led to the diagnosis of chronic lymphocytic enteritis. An hematogenous route of infection is suspected.
Normalization of lens protein kinase Cγ in galactosemic dogs by a novel aldose reductase inhibitor
Authors: Takemoto Dolores J. , Harris Richard , Brightman Al , McGill John , Hua Duy , Davidson Harriet , Fenwick Brad , Wagner Lynn M.
Published: April 2004

The purpose of this study was to determine the effects of a novel aldose reductase inhibitor on lens protein kinase Cγ (PKCγ) levels in galactosemic dogs. Six‐month old Beagles (12 total; 6 male and 6 female) were made galactosemic by feeding a diet of 40% galactose for 6 weeks. Three dogs per group were fed either control, normal diet, 40% galactose diet, 40% galactose diet with aldose reductase inhibitor at 100 mg/kg body weight per day given orally, or a control diet with aldose reductase inhibitor alone (1‐H,7‐H‐5α,6,8,9‐tetrahydro‐1‐oxopyran[4,3‐β]1 benzopyran, referred to herein as HAR‐1). Lenses were removed and analyzed for toxicity by pathological examination. Lens polyol concentrations were determined by GC/MS. PKCγ levels were determined by Western blot and by reverse transcriptase‐polymerase chain reaction (RT‐PCR). No toxicity was observed from the aldose reductase inhibitor when given at 100 mg/kg body weight per day for 6 weeks. Galactosemic dogs showed deterioration of lens cells. Deterioration included vacuole formation in the lens, cell lysis, and loss of cell nuclei. Galactosemic dogs given the HAR‐1 appeared identical to control dogs. Polyol concentrations in the lenses were reduced by 50% in dogs fed the 40% galactose diet with the aldose reductase inhibitor, HAR‐1. PKCγ protein levels were reduced in the galactosemic dog lenses, but synthesis of PKCγ was not affected, as measured by RT‐PCR. The PKCγ protein levels were similar to controls in dogs given the aldose reductase inhibitor, HAR‐1, even when polyol concentrations remained 50% elevated above control levels. HAR‐1, when given to control dogs, caused a reduction in the synthesis of PKCγ mRNA but not in total PKCγ protein levels. This study demonstrates the use of a novel aldose reductase inhibitor to control changes in PKCγ in dog lens, a PKC that is known to control gap junction activity.
Ocular histopathologic observations in Norwegian Elkhounds with primary open‐angle, closed‐cleft glaucoma
Authors: Oshima Yoshie , Bjerkas Ellen , Peiffer Robert L.
Published: April 2004

A retrospective histopathologic study of primary glaucoma in the Norwegian Elkhound was undertaken with the study of 9 clinically normal eyes and 22 glaucomatous eyes. All glaucomatous eyes showed goniodysgenesis as manifested by pectinate ligament dysplasia and/or trabecular meshwork dysplasia. Cystic degeneration of the iridociliary epithelial and/or peripheral retina was present in a high percentage of both normotensive and glaucomatous eyes. Utilizing the scheme proposed by Smithet al. (Veterinary and Comparative Ophthalmology1993;3: 16–28) the morphology of this disease in the Norwegian Elkhound would be classified as an open‐angle, closed‐cleft glaucoma, with histopathologic alterations of the outflow pathway similar to that described in other breeds with primary glaucoma.
A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic‐based cohort of patients with diabetes onset over 50 years
Authors: Monge L. , Bruno G. , Pinach S. , Grassi G. , Maghenzani G. , Dani F. , Pagano G.
Published: April 2004

Aims  To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50.

Methods  From a clinic‐based cohort of 3327 patients with Type 2 DM diagnosed over age 50 we recruited those with at least one feature suggestive of insulin deficiency: (i) fasting blood glucose ≥ 15 mmol/l and/or HbA1c ≥ 10% in spite of adequate compliance to diet and treatment; (ii) decreasing body weight ≥ 10% in the previous 3 months in spite of constant diet; (iii) BMI < 25 mg/kg2. A control group of 240 patients not presenting any of the previous criteria was randomly selected from the out‐patient clinic.

Results  We identified 220 (6.6%) patients, of whom 70 were positive for glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA), giving a prevalence of LADA of 31.8% (95% CI 25.7–38.4). In contrast, no patient randomly selected from the remaining cohort had marker positivities. With respect to patients negative for both ICA and GADA, those who were positive had lower C‐peptide values (0.53 ± 0.51 vs. 0.88 ± 0.42 nmol/l, P < 0.001); the lowest levels were found in patients in whom both antibodies were positive. In linear regression analysis, variables independently associated with fasting C‐peptide were GADA (β = −0.25, P < 0.001), ICA (β = −0.15, P = 0.04), BMI (β = 0.03, P < 0.001) and duration of diabetes (β = −0.02, P < 0.001).

Conclusion  This study shows that: (i) a clinically orientated approach increases the efficiency of a screening programme for LADA, so that one in three screened patients are classified correctly; (ii) ICA and GADA positivity were negatively associated with residual β‐cell function, independent of BMI and duration of the disease; (iii) positivity for both ICA and GADA identifies patients with the lowest residual β‐cell function.
What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?
Authors: Hillman N. , Herranz L. , Grande C. , Vaquero P. M. , Pallardo L. F.
Published: April 2004

Aims  To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes.

Methods  Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA1c measured at the end of each record period was analysed.

Results  Significant linear correlations were found between HbA1c and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA1c (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post‐breakfast glycaemia correlated significantly and independently with HbA1c. The model accounted for 47.8% of the variance in HbA1c.

Conclusions  Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA1c in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.

Diabet. Med. (2004)
Albuminuria in Afro‐Caribbeans with Type 2 diabetes mellitus: is the sickle cell trait a risk factor?
Authors: Oli J. M. , Watkins P. J. , Wild B. , Adegoke O. J.
Published: April 2004

Aims  To determine the prevalence of albuminuria [raised albumin–creatinine ratio (ACR)] in an out‐patient population of Afro‐Caribbeans with Type 2 diabetes mellitus (DM) and to determine if the possession of the sickle cell trait (SCT) is a risk factor.

Patients and methods  The ACR in a morning urine sample was determined in each of 181 Afro‐Caribbeans with Type 2 DM attending the out‐patient clinic at King's Diabetes Centre of King's College Hospital, London. The subjects were genotyped for the SCT, Haemoglobin AS (HbAS).

Results  Although a raised ACR was demonstrated more frequently in those with the SCT than in those without, with an odds ratio of 1.19, this was not statistically significant (P = 0.68).

Conclusions  In this study the possession of the SCT does not appear to play a significant role in the development of albuminuria. However, a larger study is needed to clarify its role as a risk factor for development of albuminuria in Afro‐Caribbeans with Type 2 DM.
Power, Innovation and Problem‐Solving: The Personnel Managers’ Three Steps to Heaven?
Authors: Guest David , King Zella
Published: April 2004

ABSTRACT  Legge's seminal book on personnel managers (Legge, 1978) identified ambiguities in their role, vicious circles that limited their power and possible strategies to improve their effectiveness. This paper explores how far the advent of human resource management has altered the circumstances in which they find themselves and how far it offers a new basis for power and influence. Analysis of interviews with 48 senior executives indicates that although there have been changes in features of the ambiguities and vicious circles, personnel managers have failed to overcome many of the problems identified by Legge 25 years earlier or to seize the opportunities outlined by Ulrich (1997) to become human resource champions.
HRM and Critical Social Science Analysis
Authors: Watson Tony J.
Published: April 2004

ABSTRACT  In her early work on personnel management, Karen Legge showed the way forward for a non‐prescriptive and critical analysis of employment management practices. Legge has developed this concern in subsequent work and given it a wider focus by setting her analysis of HRM in its broad socio‐political context. A great deal of the academic HRM literature has tended not to follow this lead, however, and often remains prescriptive, functionalist and uncritical. Even when HRM analysis does set out to be critical, it can be seen as out of touch with important developments in social science thinking. A scheme for undertaking critical social scientific analysis is developed to overcome some of these difficulties and this is applied to a narrative of HRM strategy‐making in Moddens Foods.
Symmetrical Absence/Symmetrical Absurdity: Critical Notes on the Production of Actor‐Network Accounts
Authors: McLean Chris , Hassard John
Published: April 2004

ABSTRACT An enduring concern within management and organization studies (MOS) is how to conduct research from perspectives deemed ‘alternatives’ to those of functionalism and positivism. Our aim is to address this concern with regard to an approach employed by Karen Legge in research on knowledge workers, namely that of actor‐network theory (ANT) (or the ‘sociology of translation’). Following an introduction to ANT, the views of some its key proponents, and Legge's own use of the approach, the paper presents critical notes on five issues related to the production of ANT accounts – the inclusion and exclusion of actors; the treatment of humans and non‐humans; the nature of privileging and status; the handling of agency and structure; and the nature of politics and power in ‘heterogeneous engineering’. We discuss the relationships between these issues and the key ANT goal of achieving a sense of ‘general symmetry’ in the accounting process. In so doing we note how ANT authors are frequently chastised for either failing to take sufficient account of, or promoting too strong a sense of, analytical symmetry in their writing. It is argued that the primary challenge facing ANT researchers is to produce accounts that are robust enough to negate the twin charges of symmetrical absence and symmetrical absurdity.
Seasonal Episodic Paroxysmal Hemicrania Responding to Cyclooxygenase-2 Inhibitors
Authors: Siow HC
Published: April 2004

Chronic paroxysmal hemicrania (CPH) was first described by Sjaastad who also described a remitting form of this condition (1, 2). This new entity was named episodic paroxysmal hemicrania (EPH) in 1987 by Kudrow (3). It is characterized by brief, frequent attacks of unilateral orbital or temporal pain with associated autonomic symptoms. Most cases respond to indomethacin. A seasonal variant of EPH has been described (4), but never a response to treatment with cyclooxygenase (COX)-2 inhibitors.
The Prevalence of Migraine and Tension-Type Headaches Among Adolescents in Norway. The Nord-Trøndelag Health Study (Head-Hunt-Youth), A Large Population-Based Epidemiological Study
Authors: Zwart J-A , Dyb G , Holmen TL , Stovner LJ , Sand T
Published: April 2004

The aim of this study was to examine the prevalence of headache and primary headache disorders like migraine and tension-type headaches among adolescents, and to explore the differences in headache prevalence and frequency by gender and age. This cross-sectional study was conducted in Nord-Trøndelag county, Norway, during the years 1995-97. In total, 8984 (88%) out of 10 202 invited adolescents aged 12-19 years participated in the youth part of the Nord-Trøndelag Health Study [Helseundersøkelsen i Nord-Trøndelag (HUNT)]. The total study population in this study consisted of 8255 individuals after exclusion of invalid questionnaires and students outside the target range of 13-18 years of age. The students completed a comprehensive questionnaire, and one of the questions was whether the students had experienced any headaches during the last 12 months. In addition, 5847 of these students were also subject to an interview in which they were asked whether they had experienced recurring headaches during the last year and, if so, were they classified as migraine (MI), tension-type headache (TTH) or non-classifiable headache. In the total questionnaire-based population, 76.8% reported having had headaches during the last 12 months (69.4% boys and 84.2% girls). Among those who also were interviewed, 29.1% reported having recurrent headaches (21.0% boys and 36.5% girls). The overall 1-year prevalence of migraine was 7%, of tension-type headache 18%, and of non-classifiable headache 4.8%. Higher prevalence rates were found for girls in all age groups and for all headache categories. The overall frequency of recurrent headaches did not vary significantly with age, but girls had significantly more frequent headaches than boys. We concluded that headache in general, and recurrent primary headache disorders like migraine and tension-type headaches, are common somatic complaints among Norwegian adolescents, especially among girls.
Extracephalic Yawning Pain
Authors: Jacome DE
Published: April 2004

The aim of this study was to report on two patients with recurrent, paroxysmal, extracephalic pain triggered by yawning. Pain with yawning may occur in several conditions (secondary yawning pain) or develop in the absence of precipitating lesions (primary yawning pain). Primary yawning pain is normally of cephalic location. Methods used were clinical neurological examinations, magnetic resonance imaging of the brain, computerized head tomography, electroencephalogram, blink reflex studies and Panorex X-ray views of the skull. The first patient had intense right shoulder pain and brief apnea for 2 years triggered by yawning. The second patient had yawning pain referred to an area of the neck where a thyroid tumour (Hürthle cell carcinoma) was later found. Neither of the two patients could precipitate their pain with imitation of yawning and neither had evidence of Eagle syndrome. Only the second patient had a history of migraine. Yawning pain may have an extratrigeminal and extracephalic distribution. It rarely serves to identify a lesion underlying the area where the pain is perceived.
Policymaking in the Parallelogram of Forces: Common Agency and Human Service Provision
Authors: Bertelli Anthony , Lynn Laurence E.
Published: April 2004

The “congressional dominance” literature in political science provides valuable insights into the legislative control of administrative agencies. However, this literature tends to be conceptualized with respect to regulatory agencies, and it is not especially helpful in understanding the dynamics of policymaking in the provision of human services. After distinguishing the tasks of regulation and human services provision, we present an alternative: a common agency model of human service policy as the outcome of interest group bargaining. We illustrate its implications with an analytic narrative of service provision for the seriously mentally ill.
Regulation of a
Bacteroides
Operon That Controls Excision and Transfer of the Conjugative Transposon CTnDOT
Authors: Wang Yanping , Shoemaker Nadja B. , Salyers Abigail A.
Published: April 2004

CTnDOT is a conjugative transposon (CTn) that is found in many
Bacteroides
strains. Transfer of CTnDOT is stimulated 100- to 1,000-fold if the cells are first exposed to tetracycline (TET). Both excision and transfer of CTnDOT are stimulated by TET. An operon that contains a TET resistance gene,
tetQ
, and two regulatory genes,
rteA
and
rteB
, is essential for control of excision and transfer functions. At first, it appeared that RteA and RteB, which are members of a two-component regulatory system, might be directly responsible for the TET effect. We show here, however, that neither RteA nor RteB affected expression of the operon. TetQ, a ribosome protection type of TET resistance protein, actually reduced operon expression, possibly by interacting with ribosomes that are translating the
tetQ
message. Fusions of
tetQ
with a reporter gene,
uidA
, were only expressed at a high level when the fusion was cloned in frame with the first six codons of
tetQ
. However, out of frame fusions or fusions ending at the other five codons of
tetQ
showed much lower expression of the
uidA
gene. Moreover, reverse transcription-PCR amplification of
tetQ
mRNA revealed that despite the fact that the
uidA
gene product, β-glucuronidase (GUS), was produced only when the cells were exposed to TET,
tetQ
mRNA was produced in both the presence and absence of TET. Computer analysis of the region upstream of the
tetQ
start codon predicted that the mRNA in this region could form a complex RNA hairpin structure that would prevent access of ribosomes to the ribosome binding site. Mutations that abolished base pairing in the stem that formed the base of this putative hairpin structure made GUS production as high in the absence of TET as in TET-stimulated cells. Compensatory mutations that restored the hairpin structure led to a return of regulated production of GUS. Thus, the
tetQ
-
rteA
-
rteB
operon appears to be regulated by a translational attenuation mechanism.
HybF, a Zinc-Containing Protein Involved in NiFe Hydrogenase Maturation
Authors: Blokesch Melanie , Rohrmoser Michaela , Rode Sabine , Böck August
Published: April 2004

HypA and HypB are maturation proteins required for incorporation of nickel into the hydrogenase large subunit. To examine the functions of these proteins in nickel insertion, the
hybF
gene, which is a homolog of
hypA
essential for maturation of hydrogenases 1 and 2 from
Escherichia coli
, was overexpressed, and the product was purified. This protein behaves like a monomer in gel filtration and contains stoichiometric amounts of zinc but insignificant or undetectable amounts of nickel and iron. In filter binding assays radioactively labeled nickel binds to HybF with a

K
D

of 1.87 μM and in a stoichiometric ratio. To identify amino acid residues of HybF involved in nickel and/or zinc binding, variants in which conserved residues were replaced were studied. An H2Q replacement eliminated both in vivo activity and in vitro binding of nickel. The purified protein, however, contained zinc at the level characteristic of the wild-type protein. When E3 was replaced by Q, activity was retained, but an E3L exchange was detrimental. Replacement of each of the four conserved cysteine residues of a zinc finger motif reduced the cellular amount of HybF protein without a loss of in vivo activity, indicating that these residues play a purely structural role. A triple mutant deficient in the synthesis or activity of HypA, HybF, and HypB was constructed, and it exhibited the same responsiveness for phenotypic complementation by high nickel as mutants with a single lesion in one of the genes exhibited. The results are interpreted in terms of a concerted action of HypB and HybF in nickel insertion in which HybF (as well as its homolog, HypA) functions as a metallochaperone and HypB functions as a regulator that controls the interaction of HybF with the target protein.
Evolution of the Leucine Gene Cluster in
Buchnera aphidicola
: Insights from Chromosomal Versions of the Cluster
Authors: Sabater-Muñoz Beatriz , van Ham Roeland C. H. J. , Moya Andrés , Silva Francisco J. , Latorre Amparo
Published: April 2004

In
Buchnera aphidicola
strains associated with the aphid subfamilies Thelaxinae, Lachninae, Pterocommatinae, and Aphidinae, the four leucine genes (
leuA
, -
B
, -
C
, and -
D
) are located on a plasmid. However, these genes are located on the main chromosome in
B. aphidicola
strains associated with the subfamilies Pemphiginae and Chaitophorinae. The sequence of the chromosomal fragment containing the leucine cluster and flanking genes has different positions in the chromosome in
B. aphidicola
strains associated with three tribes of the subfamily Pemphiginae and one tribe of the subfamily Chaitophorinae. Due to the extreme gene order conservation of the
B. aphidicola
genomes, the variability in the position of the leucine cluster in the chromosome may be interpreted as resulting from independent insertions from an ancestral plasmid-borne leucine gene. These findings do not support a chromosomal origin for the leucine genes in the ancestral
B. aphidicola
and do support a back transfer evolutionary scenario from a plasmid to the main chromosome.
Modulation of DNA Repair and Recombination by the Bacteriophage λ Orf Function inEscherichia coliK-12
Authors: Poteete Anthony R.
Published: April 2004

Theorfgene of bacteriophage λ, fused to a promoter, was placed in thegalKlocus ofEscherichia coliK-12. Orf was found to suppress the recombination deficiency and sensitivity to UV radiation of mutants, in a Δ(recC ptr recB recD)::Ptacgam bet exo pae cIΔrecGbackground, lackingrecF,recO,recR,ruvAB, andruvCfunctions. It also suppressed defects of these mutants in establishing replication of a pSC101-related plasmid. Compared toorf, therecA803allele had only small effects onrecF,recO, andrecRmutant phenotypes and no effect on aruvABmutant. In a fully wild-type background with respect to known recombination and repair functions,orfpartially suppressed the UV sensitivity ofruvABandruvCmutants.
Isolation of a Minireplicon of the Virulence Plasmid pXO2 of
Bacillus anthracis
and Characterization of the Plasmid-Encoded RepS Replication Protein
Authors: Tinsley Eowyn , Naqvi Asma , Bourgogne Agathe , Koehler Theresa M. , Khan Saleem A.
Published: April 2004

A minireplicon of plasmid pXO2 of
Bacillus anthracis
was isolated by molecular cloning in
Escherichia coli
and shown to replicate in
B. anthracis
,
Bacillus cereus
, and
Bacillus subtilis
. The pXO2 replicon included (i) an open reading frame encoding the putative RepS replication initiation protein and (ii) the putative origin of replication. The RepS protein was expressed as a fusion with the maltose binding protein (MBP) at its amino-terminal end and purified by affinity chromatography. Electrophoretic mobility shift assays showed that the purified MBP-RepS protein bound specifically to a 60-bp region corresponding to the putative origin of replication of pXO2 located immediately downstream of the RepS open reading frame. Competition DNA binding experiments showed that the 5′ and central regions of the putative origin were important for RepS binding. MBP-RepS also bound nonspecifically to single-stranded DNA with a lower affinity.
A Novel Tetrahydrofolate-Dependent
O
-Demethylase Gene Is Essential for Growth of
Sphingomonas paucimobilis
SYK-6 with Syringate
Authors: Masai Eiji , Sasaki Miyuki , Minakawa Yasunori , Abe Tomokuni , Sonoki Tomonori , Miyauchi Keisuke , Katayama Yoshihiro , Fukuda Masao
Published: April 2004

Sphingomonas paucimobilis
SYK-6 degrades syringate to 3-
O
-methylgallate (3MGA), which is finally converted to pyruvate and oxaloacetate via multiple pathways in which protocatechuate 4,5-dioxygenase, 3MGA dioxygenase, and gallate dioxygenase are involved. Here we isolated the syringate
O
-demethylase gene (
desA
), which complemented the growth deficiency on syringate of a Tn
5
mutant of the SYK-6 derivative strain. The
desA
gene is located 929 bp downstream of
ferA
, encoding feruloyl-coenzyme A synthetase, and consists of a 1,386-bp open reading frame encoding a polypeptide with a molecular mass of 50,721 Da. The deduced amino acid sequence of
desA
showed 26% identity in a 325-amino-acid overlap with that of
gcvT
of
Escherichia coli
, which encodes the tetrahydrofolate (H
4
folate)-dependent aminomethyltransferase involved in glycine cleavage. The cell extract of
E. coli
carrying
desA
converted syringate to 3MGA only when H
4
folate was added to the reaction mixture. DesA catalyzes the transfer of the methyl moiety of syringate to H
4
folate, forming 5-methyl-H
4
folate. Vanillate and 3MGA were also used as substrates for DesA; however, the relative activities toward them were 3 and 0.4% of that toward syringate, respectively. Disruption of
desA
in SYK-6 resulted in a growth defect on syringate but did not affect growth on vanillate, indicating that
desA
is essential to syringate degradation. In a previous study the
ligH
gene, which complements the growth deficiency on vanillate and syringate of a chemical-induced mutant of SYK-6, DC-49, was isolated (S. Nishikawa, T. Sonoki, T. Kasahara, T. Obi, S. Kubota, S. Kawai, N. Morohoshi, and Y. Katayama, Appl. Environ. Microbiol. 64:836-842, 1998). Disruption of
ligH
resulted in the same phenotype as DC-49; its cell extract, however, was found to be able to convert vanillate and syringate in the presence of H
4
folate. The possible role of
ligH
is discussed.
Bdellovibrio bacteriovorusStrains Produce a Novel Major Outer Membrane Protein during Predacious Growth in the Periplasm of Prey Bacteria
Authors: Beck Sebastian , Schwudke Dominik , Strauch Eckhard , Appel Bernd , Linscheid Michael
Published: April 2004

Bdellovibrio bacteriovorusis a predatory bacterium that is capable of invading a number of gram-negative bacteria. The life cycle of this predator can be divided into a nonreproductive phase outside the prey bacteria and a multiplication phase in their periplasm. It was suggested that during the reproduction phase,B. bacteriovorusreutilizes unmodified components of the prey's cell wall. We therefore examined the outer membranes ofB. bacteriovorusstrains HD100 (DSM 50701) and HD114 (DSM 50705) by usingEscherichia coli,Yersinia enterocolitica, andPseudomonas putidaas prey organisms. The combined sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analyses revealed novel and innate major outer membrane proteins (OMPs) ofB. bacteriovorusstrains. An incorporation of prey-derived proteins into the cell wall ofB. bacteriovoruswas not observed. The corresponding genes of theB. bacteriovorusstrains were elucidated by a reverse-genetics approach, and a leader peptide was deduced from the gene sequence and confirmed by Edman degradation. The host-independent mutant strainB. bacteriovorusHI100 (DSM 12732) growing in the absence of prey organisms possesses an OMP similar to the major OMPs of the host-dependent strains. The similarity of the primary structure of the OMPs produced by the threeBdellovibriostrains is between 67 and 89%. The leader peptides of all OMPs have a length of 20 amino acids and are highly conserved. The molecular sizes of the mature proteins range from 34.9 to 37.6 kDa. Secondary-structure predictions indicate preferential α-helices and little β-barrel structures.
The θ Subunit ofEscherichia coliDNA Polymerase III: a Role in Stabilizing the ε Proofreading Subunit
Authors: Taft-Benz Sharon A. , Schaaper Roel M.
Published: April 2004

The function of the θ subunit ofEscherichia coliDNA polymerase III holoenzyme is not well established. θ is a tightly bound component of the DNA polymerase III core, which contains the α subunit (polymerase), the ε subunit (3′→5′ exonuclease), and the θ subunit, in the linear order α-ε-θ. Previous studies have shown that the θ subunit is not essential, as strains carrying a deletion of theholEgene (which encodes θ) proved fully viable. No significant phenotypic effects of theholEdeletion could be detected, as the strain displayed normal cell health, morphology, and mutation rates. On the other hand, in vitro experiments have indicated the efficiency of the 3′-exonuclease activity of ε to be modestly enhanced by the presence of θ. Here, we report a series of genetic experiments that suggest that θ has a stabilizing role for the ε proofreading subunit. The observations include (i) defined ΔholEmutator effects in mismatch-repair-defectivemutLbackgrounds, (ii) strong ΔholEmutator effects in certain proofreading-impaireddnaQstrains, and (iii) yeast two- and three-hybrid experiments demonstrating enhancement of α-ε interactions by the presence of θ. θ appears conserved among gram-negative organisms which have an exonuclease subunit that exists as a separate protein (i.e., not part of the polymerase polypeptide), and the presence of θ might be uniquely beneficial in those instances where the proofreading 3′-exonuclease is not part of the polymerase polypeptide.
Molecular Evolution and Mosaicism of Leptospiral Outer Membrane Proteins Involves Horizontal DNA Transfer
Authors: Haake David A. , Suchard Marc A. , Kelley Melissa M. , Dundoo Manjula , Alt David P. , Zuerner Richard L.
Published: April 2004

Leptospires belong to a genus of parasitic bacterial spirochetes that have adapted to a broad range of mammalian hosts. Mechanisms of leptospiral molecular evolution were explored by sequence analysis of four genes shared by 38 strains belonging to the core group of pathogenic
Leptospira
species:
L. interrogans
,
L. kirschneri
,
L. noguchii
,
L. borgpetersenii
,
L. santarosai
, and
L. weilii
. The 16S rRNA and
lipL32
genes were highly conserved, and the
lipL41
and
ompL1
genes were significantly more variable. Synonymous substitutions are distributed throughout the
ompL1
gene, whereas nonsynonymous substitutions are clustered in four variable regions encoding surface loops. While phylogenetic trees for the 16S,
lipL32
, and
lipL41
genes were relatively stable, 8 of 38 (20%)
ompL1
sequences had mosaic compositions consistent with horizontal transfer of DNA between related bacterial species. A novel Bayesian multiple change point model was used to identify the most likely sites of recombination and to determine the phylogenetic relatedness of the segments of the mosaic
ompL1
genes. Segments of the mosaic
ompL1
genes encoding two of the surface-exposed loops were likely acquired by horizontal transfer from a peregrine allele of unknown ancestry. Identification of the most likely sites of recombination with the Bayesian multiple change point model, an approach which has not previously been applied to prokaryotic gene sequence analysis, serves as a model for future studies of recombination in molecular evolution of genes.
Origin and Diversity of Alginate Lyases of Families PL-5 and -7 in
Sphingomonas
sp. Strain A1
Authors: Miyake Osamu , Ochiai Akihito , Hashimoto Wataru , Murata Kousaku
Published: April 2004

Sphingomonas
sp. strain A1 has three endotype alginate lyases (A1-I, A1-II [family PL-7], and A1-III [family PL-5]), each of which is encoded by a single gene. In addition to those of these lyases, a gene (the A1-II′ gene) showing significant identity with the A1-II gene was present in the bacterial genome and coded for an alginate lyase with broad substrate specificity. Since no expression of A1-II′ was observed even in bacterial cells grown on alginate, the A1-II′ gene was thought to be a silent gene derived from the A1-II gene, presumably through duplication, modification, and translocation.
Preferential Reduction of Fe(III) over Fumarate by
Geobacter sulfurreducens
Authors: Esteve-Núñez Abraham , Núñez Cinthia , Lovley Derek R.
Published: April 2004

The presence of Fe(III), but not that of Fe(II), resulted in ca. 20-fold-lower levels of mRNA for fumarate reductase, inhibiting fumarate reduction and favoring utilization of fumarate as an electron donor in chemostat cultures of
Geobacter sulfurreducens
, despite the fact that growth yield with fumarate was 3-fold higher than with Fe(III).
Employment retention after moderate-severe traumatic brain injury (TBI) in the British Army 1989–98
Authors: McLeod A , Wills A , Etherington J
Published: April 2004

Aims:To examine retention in employment of subjects with moderate-severe traumatic brain injury (TBI) in the British Army.

Methods:Comparative groups study of retention in Army employment after TBI using 564 TBI, 368 lower limb fracture, and 25 575 healthy subjects. Kaplan-Meier survival analysis was used to examine, stratifying for age, continuation in Army employment for six years after TBI.

Results:Subjects in the younger groups (mean ages 23 years and 27 years respectively) with either TBI or lower limb fracture remained in employment longer than healthy peers (median time for TBI, 3.91 years, lower limb fracture, 4.39 years, and healthy, 1.74 years). This trend changed through age stratification and for older subjects the reverse pattern was seen. In group 4 (mean age 41 years), median retention time for TBI was 3.33 years, for lower limb fracture, 3.75 years, healthy 5.55 years. Older subjects also showed a marked drop out rate at one year after injury; 32.7% of those with TBI in group 3 (mean age 31 years) had left Army employment at the end of year one compared with 19% in age group 1 (mean age 23 years).

Conclusions:Younger soldiers with either TBI or lower limb fracture are retained in Army employment longer than their healthy peers. This may be due to sheltered employment, the availability of ongoing support, or transience of the healthy population. Since these results were drawn from incidence data on moderate and severe TBI it may be that those who serve on after TBI will do so with some degree of disability which affects occupational performance. There may be a significant unmet rehabilitation need for this group which is the focus of ongoing research.