bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Overnight Creatinine Clearance Compared with 51 Cr‐EDTA Clearance during the Menstrual Cycle
Authors: PAABY PER , BRØCHNER‐MORTENSEN JENS , FJELDBORG PAUL , RAFFN WELD , LARSEN CARSTEN E. , MØLLER‐PETERSEN JENS
Published: August 2010

ABSTRACT Fourteen healthy women aged 21–41 years, who did not take oral contraceptives and who all had ovdatory cycles, were examined once in the follicular phase and once in the luteal phase of a single menstrual cycle. The glomerular filtration rate (51Cr‐EDTA clearance) increased from the follicular to the luteal phase by a median of 7.0% (95% confidence interval: 0.7–10.3%). Endogenous overnight (22.00–08.00 hours) creatinine clearance increased by a median of 7.3% (95% confidence interval: 1.0–14.6%). The urinary creatinine excretion rate also increased with a median of 7.3% (95% confidence interval: 1.511.9%) whereas the serum concentrations of creatinine and β2‐microglobulin, urine flow and urinary excretion rate of urea did not change. The results confirm previous observations of an increase in creatinine clearance in the luteal phase of the menstrual cycle and indicate that the increase in overnight creatinine clearance reflects a true change in glomerular filtration rate.
The Anatomy of the Head of the New Zealand Frog, Leiopelma
Authors: Stephenson Elsie M.
Published: August 2010

An attempt has been made to present a full account of the anatomy of the head (exclusive of the inner ear) of Leiopelma. Material from two species, Leiopelma archeyi and Leiopelma hochstetteri, has been studied and the head of the latter is here described for the first time.

As far as possible, comparison has been made with the head of Ascaphus, the only other genus included in the same primitive anuran family.

Specific differences between Leiopelma archeyi and Leiopelma hochstetteri are described and listed.

A possible homology is suggested between the processus lingularis of Anura and Seydel's palatal process of Urodela.

Particular emphasis is placed on the controversial topic of the basal connection between the quadrate and the neurocranium. An historical account of previous ideas on this subject is included, followed by a discussion based on the view that the ‘basal’ or ‘pseudobasal’ process of Leiopelma, together with the ledge of cartilage forming the floor of the hyomandibular canal, are of hyoid origin.
The growth‐stages of the pouch‐young of the Native Cat (Dasyurus viverrinus) together with observations on the anatomy of the new‐born young.*
Authors: Hill J. P. , Hill W. C. Osman
Published: August 2010

Summary.

The biology of the pouch‐young (mammary foetus) is considered in a graded series of stages of Dasyurus commencing with the new‐born, still unattached young and ending with the fully developed animal at the time it leaves the maternal pouch (at the age of 4 to 4 months) and capable of fending for itself. The series has been divided for convenience into seventeen stages, labelled A‐P, and the growth, external appearances and eruption of teeth has been fully considered.

The problem of the migration of new‐born young to the pouch, their attachment to the nipples, and the mode of lactation and its duration have been considered, together with some comment of the supposed mammary compressor action of the cremaster muscles.

The internal structure of the new‐born Dasyurus has been described in detail, special emphasis being laid on the precocious development of certain structures which are considered necessary adaptational machinery for the insurance of survival of the young in its unusual environment and more particularly those features required for the sole purpose of ensuring its safe arrival in the pouch, its becoming attached to a nipple and the certitude of its receipt of milk without hindrance to its respiration.

Notable at birth are (i) the relatively advanced state of the fore‐limbs, (ii) the presence of deciduous claws upon the manual digits and their later replacement by definitive claws, (iii) the presence of the oral shield as a specialization upon the muzzle, (iv) the unique cervical swelling, (v) special features of the tongue and larynx, with the intranasal epiglottis (vi) the reptilian state of the lungs, (vii) the advanced condition of the stomach and duodenum compared with the rest of the gut, (viii) the state of development of brain and sense organs, the olfactory parts being especially forward in development, together with those parts of the nervous system necessary for controlling the movements of the fore‐limb, sucking and respiratory movements, (ix) the indifferent state of the gonads.

Throughout comparison has been made with the new‐born of other marsupials, so far as these are known, and features common to them all or peculiar to Dasyurus have been pointed out.
The larger arthrodiran fishes from the area of the Burrinjuck Dam, N.S.W.
Authors: WHITE ERROL I.
Published: August 2010

In this paper are described the seven larger arthrodiran fishes from the Lower Devonian strata of the Burrinjuck area in New South Wales. The first is an interesting new palae‐acanthaspid, but the six other fishes are euarthrodires remarkable not only for individual peculiarities but for a mixture of characters usually attributed to two or more of the main lines of arthrodiran evolution. They may be considered as early essays in the development of arthrodires, but they also suggest that the main groups were not descended one from another, as for instance the brachythoracids are often said to have evolved from the arcto‐lepids, but from a more distant common ancestor.

The development of the apron is demonstrated and the nature of the periophthalrnic capsules in relation to sclerotic plates is discussed.
Mechanisms of resistance to anti‐human epidermal growth factor receptor 2 agents in breast cancer
Authors: Mukohara Toru
Published: August 2010

Approximately 20% of breast cancers are characterized by overexpression of human epidermal growth factor receptor 2 (HER2) protein and associated gene amplification, and the receptor tyrosine kinase is believed to play a critical role in the pathogenesis of these tumors. The development and implementation of trastuzumab, a humanized monoclonal antibody against the extracellular domain of HER2 protein, has significantly improved treatment outcomes in patients with HER2‐overexpressing breast cancer. However, despite this clinical usefulness, unmet needs for better prediction of trastuzumab’s response and overcoming primary and acquired resistance remain. In this review, we discuss several potential mechanisms of resistance to trastuzumab that have been closely studied over the last decade. Briefly, these mechanisms include: impaired access of trastuzumab to HER2 by expression of extracellular domain‐truncated HER2 (p95 HER2) or overexpression of MUC4; alternative signaling from insulin‐like growth factor‐1 receptor, other epidermal growth factor receptor family members, or MET; aberrant downstream signaling caused by loss of phosphatase and tensin homologs deleted from chromosome 10 (PTEN), PIK3CA mutation, or downregulation of p27; or FCGR3A polymorphisms. In addition, we discuss potential strategies for overcoming resistance to trastuzumab. Specifically, the epidermal growth factor receptor/HER2 tyrosine kinase inhibitor lapatinib partially overcame trastuzumab resistance in a clinical setting, so its efficacy results and limited data regarding potential mechanisms of resistance to the drug are also discussed. (Cancer Sci 2011; 102: 1–8)
Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists
Authors: Nithipatikom Kasem , Brody Daniel M. , Tang Alan T. , Manthati Vijaya L. , Falck John R. , Williams Carol L. , Campbell William B.
Published: August 2010

Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA and proteins, were expressed in prostate carcinoma (PC‐3, DU‐145 and LNCaP) cells. 11,12‐Epoxyeicosatrienoic acid (11,12‐EET) was the major arachidonic acid metabolite in these cells. Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N‐methylsulfonyl‐6‐(2‐propargyloxyphenyl)hexanamide [MS‐PPOH]) inhibited tonic (basal) invasion and migration (motility) while exogenously added EET induced cell motility in a concentration‐dependent manner. An epidermal growth factor receptor (EGFR) kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12‐EET‐induced cell migration. Importantly, synthetic EET antagonists (14,15‐epoxyeicosa‐5(Z)‐enoic acid [14,15‐EEZE], 14,15‐epoxyeicosa‐5(Z)‐enoic acid 2‐[2‐(3‐hydroxy‐propoxy)‐ethoxy]‐ethyl ester [14,15‐EEZE‐PEG] and 14,15‐epoxyeicosa‐5(Z)‐enoic‐methylsulfonylimide [14,15‐EEZE‐mSI]) inhibited EET‐induced cell invasion and migration. 11,12‐EET induced cell stretching and myosin‐actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473), while 14,15‐EEZE inhibited these effects. These results suggest that EET induce and EET antagonists inhibit cell motility, possibly by putative EET receptor‐mediated EGFR and PI3K/Akt pathways, and suggest that EET antagonists are potential therapeutic agents for prostate cancer. (Cancer Sci 2010; 101: 2629–2636)
Trends in weights, heights, BMI and comparison of their differences in urban and rural areas for Iranian children and adolescents 2–18‐year‐old between 1990–1991 and 1999
Authors: Hosseini M. , Taslimi SH. , Dinarvand P. , Jones M. E. , Mohammad K.
Published: August 2010

Background  Secular trends in height and weight are interesting because in middle‐ and low‐income countries they are a marker for changes in population health. The present study aims to evaluate the secular trend in height and weight and body mass index (BMI) of Iranian children and adolescents aged 2–18 years old between 1990–1991 and 1999 and compare the magnitude of urban–rural differences during this period for the first time in an Asian country.

Methods  Data from two national health surveys in 1990–1991 and 1999, of 22 349 and 25 196 weight and height measures of Iranian children and adolescents were used to study the trend and compare its difference in urban and rural children. Logarithmic transformation of weight, height and BMI was modelled as a polynomial in age for urban and rural boys and girls in each survey separately. The trend in urban and rural growth indexes (weight, height and BMI) and also the comparisons of urban–rural differences between two national surveys were tested in logarithmic scale using a weighted form of Z statistic for comparison of two means adjusted for age groups.

Results  Urban and rural boys and girls became taller and heavier (P≤ 0.02) with no change of BMI (P > 0.05) during the period. There was not any significant difference between the magnitudes of urban–rural difference between two surveys (P≥ 0.61).

Conclusion  Although generally positive weight and height trend was observed among urban and rural residents, the magnitude of their differences was not changed.
Elevation of heat shock protein synthesis and hsp gene transcription during monocyte to macrophage differentiation of U937 cells
Authors: TWOMEY B M , McCALLUM S , ISENBERG D A , LATCHMAN D S
Published: August 2010

During the phorbol myristale acetate (PMA)-induccd differentiation of U937 cells to a macrophage-like phenotype, the levels of the heat shock proteins hsp90, hsp72 and hsp65 increased dramatically to a peak level following 24 h of treatment, and then declined. In contrast, no significant increase was observed in the level of the constitutive hsp73 protein in this process. The observed increases in hsp levels were preceded by an increase in the transcription of each of the genes encoding these hsps, including both of the two genes which encode hsp90. The mechanism of this effect and the possible role of the hsps in the function of differentiated macrophages and in the differentiation process are discussed.
CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57− subset and its progressive replacement by CD8+CD57+ T cells
Authors: LABALETTE M , SALEZ F , PRUVOT F R , NOEL C , DESSAINT J P
Published: August 2010

Allograft recipients undergoing eytomegalovirus infection present increased proportions of circulating CD8+ lymphocytes. A longitudinal study of 11 kidney and five liver allograft recipients with primary CMV infection but no other etiological factor of graft dysfunction revealed selective imbalances of peripheral blood CDS+ T cell subsets. Initially, CMV viraemia is associated with elevated CDS+ bright T cell numbers and T cell activation. Activation markers fall to normal when viral cultures become negative (before the end of the first month). During the second to sixth month, most (12/16) patients keep up high CD8+ T cell counts (1050-2900 CD8+ cells/mm3), comprising an uncommon CD8+ T cell subset, as 45-73% of CD8+bright lymphocytes were CD3+ and TCRαβ+, but were not stained by anti-CD28, CDIIb, CD16. CD56. and CD57 antibody. Unexpectedly, CD8+CD57+ T cells, a hallmark of CMV infection, do not appear until the second to sixth month of primary CMV infection, and their numbers increase progressively thereafter. They become the predominant CD8+ T cell subset after 6 months of infection and their persistence for several (up to 4) years is strongly correlated (r = 0-87) with expansion of CD8+ cells. By analysis with MoAbs, there was no bias towards the use of particular TCR-Vβ gene families al any time of primary CMV infection. Persistence of CD8 lymphocytosis is thus directly related to the rate of expansion of an uncommon CD8+ CD57- subset and its progressive replacement by CD8+ CD57+ T cells that are chronically elicited by CMV.
Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: characterization and clinical correlates
Authors: MULDER A H L , BROEKROELOFS J , HORST G , LIMBURG P C , NELIS G F , KALLENBERG C G M
Published: August 2010

ANCA were detected by indirect immunofluorescence in 34 out of 67 patients with ulcerative colitis (UC, 51%) and in 14 out of 35 patients with Crobn's disease (CD, 40%). All but one ANCA-positive sera produced a perinuclear pattern of fluorescence (P-ANCA) on ethanol-fixed neutrophils. On paraformaldehyde-fixed neutrophils 76% of P-ANCA-positive sera in UC and 50% of P-ANCA-positive sera in CD produced cytoplasmic fluorescenec, indicating that, indeed, cytoplasmie antigens are recognized by a considerable number of these sera. By Western blot analysis using whole neutrophil extract as a substrate 46% of sera from patients with UC and 32%, of sera from patients with CD showed reactivity with either lactolerrin, polypeptides occurring as a doublet of 66/67 kD mol. wt, or polypeptides occurring as a doublet of 63/54 kD mol. wt, respectively. Identical patterns of reactivity have been observed among P-ANCA-positive sera from patients with autoimmune liver disease and rheumatoid arthritis. These data suggest that ANCA of restricted specificities are not specific for inflammatory bowel disease (IBD), but are present in diverse conditions characterized by chronic idiopathie inflammation.
In vitrotreatment of monocytes with 8-methoxypsolaren and ultraviolet A light induces dendritic cells with a tolerogenic phenotype
Authors: Legitimo A , Consolini R , Failli A , Fabiano S , Bencivelli W , Scatena F , Mosca F
Published: August 2010

Extracorporeal photopheresis (ECP) has been considered an efficient dendritic cell (DC) therapy, used for treating both T cell malignancy, as well as T cell-mediated diseases. During the ECP procedure leucocytes are exposed to photoactivable agent 8-methoxypsolaren (8-MOP) and ultraviolet (UV) A radiation (PUVA) prior to reinfusion. Despite its clinical efficacy the mechanism of action remains elusive. As it has been reported that ECP might promote the differentiation of monocytes into immature DCs, we investigated the effects of UVA light (2 J/cm2) and 8-MOP (100 ng/ml) on in vitro monocyte-to-DC differentiation from normal donors. DCs were generated from human purified CD14+ cells. Because monocytes are killed by PUVA and taking into account that only 5–10% of circulating mononuclear cells are exposed to PUVA during the ECP procedure, we developed an assay in which 10% of PUVA-treated monocytes were co-cultured with untreated monocytes. We first demonstrate that the presence of 10% apoptotic cells and monocyte activation were not enough to induce monocyte differentiation into DCs. Adding cytokines to our culture system, we obtained immature DCs characterized by significantly higher phagocytic activity and human leucocyte antigen D-related (HLA-DR) expression. These DCs preserved the capacity to be activated by lipopolysaccharide, but showed a reduced capacity to induce allogeneic T cell proliferation when first co-cultured with 10% of PUVA-treated cells. Our experimental design provides a novel insight into the real action of 8-MOP and UVA light on dendritic cell biology, suggesting an additional mechanism by which 8-MOP and UVA light exposure may influence immune responses.
Clonotypic analysis of T cell reconstitution after haematopoietic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency
Authors: Okamoto H , Arii C , Shibata F , Toma T , Wada T , Inoue M , Tone Y , Kasahara Y , Koizumi S , Kamachi Y , Ishida Y , Inagaki J , Kato M , Morio T , Yachie A
Published: August 2010

Haematopoietic stem cell transplantation (HSCT) is performed for treatment of a broad spectrum of illnesses. Reconstitution of an intact immune system is crucial after transplantation to avoid infectious complications, and above all, the establishment of T cell receptor (TCR) diversity is the most important goal in the procedure. Until recently, little has been known of the mechanism of T cell reconstitution in the very early period after HSCT. In this study, we analysed TCR repertoires sequentially in four patients with severe combined immunodeficiency (SCID) before and after HSCT. In all patients, the TCR repertoires were extremely abnormal before HSCT, whereas after transplantation there was progressive improvement in TCR diversity, based on analysis of the TCR Vβ repertoire and CDR3 size distributions. Somewhat unexpectedly, there was a significant but transient expansion of TCR diversity 1 month after transplantation in all cases. Clonotypic analysis of TCRs performed in one case showed that many T cell clones shared identical CDR3 sequences at 1 month and that the shared fraction decreased progressively. These results indicate that early expansion of TCR diversity may reflect transient expansion of pre-existing mature T cells from the donor blood, independent of de novo T cell maturation through the thymus.
Epithelial overexpression of interleukin-32α in inflammatory bowel disease
Authors: Shioya M , Nishida A , Yagi Y , Ogawa A , Tsujikawa T , Kim-Mitsuyama S , Takayanagi A , Shimizu N , Fujiyama Y , Andoh A
Published: August 2010

Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by induction of nuclear factor (NF)-κB activation. We studied IL-32α expression in the inflamed mucosa of inflammatory bowel disease (IBD). We also investigated mechanisms regulating IL-32α expression. Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n = 10), Crohn's disease (CD) (n = 10), ischaemic colitis (n = 4) and normal colorectal tissues (n = 10). IL-32α expression was evaluated by standard immunohistochemical procedure. IL-32 mRNA expression was analysed by Northern blot. IL-32α was expressed weakly by colonic epithelial cells from normal individuals and subjects with ischaemic colitis. In the inflamed mucosa of IBD patients, epithelial IL-32α expression was increased markedly. In UC and CD patients, IL-32α expression was enhanced in affected mucosa compared to non-affected mucosa. In intestinal epithelial cell lines, expression of IL-32α mRNA and protein was enhanced by IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. A combination of TNF-α plus IFN-γ exerted synergistic effects. IL-32α induction by IL-1β and/or TNF-α was mediated by NF-κB activation. Epithelial IL-32α expression was increased in IBD patients, and in CD patients in particular. IL-32α might be involved in the pathophysiology of IBD as a proinflammatory cytokine and a mediator of innate immune response.
Impairment of circulating myeloid dendritic cells in immunosuppressed liver transplant recipients
Authors: Bosma B M , Metselaar H J , Tra W M W , Mancham S , Kuipers E J , Tilanus H W , Kwekkeboom J
Published: August 2010

The aim of the present study was to elucidate the impact of liver transplantation (LTX) on myeloid dendritic cell (MDC) homeostasis. We observed a threefold reduction of circulating CD1c+ MDC immediately after LTX (n = 16; P < 0·01), and normalization between 3 and 12 months after LTX. This decline was not due to recruitment of MDC into the liver graft, as numbers of MDC in post-LTX liver graft biopsies were not increased compared to pre-LTX biopsies (n = 7). Moreover, no change in chemokine receptor expression on circulating MDC was observed, suggesting that their homing properties were not altered. Normalization of circulating MDC was associated with withdrawal of corticosteroid therapy, and not with changes in calcineurin inhibitor intake, indicating that corticosteroids are responsible for the observed changes in numbers of circulating MDC. During high-dose corticosteroid treatment early after LTX, circulating MDC showed a lowered maturation status with decreased expression of human leucocyte antigen D-related (HLA-DR) and CD86 compared to pre-LTX values (P < 0·01). However, when MDC from blood of LTX recipients were matured ex vivo, they up-regulated HLA-DR and co-stimulatory molecules to a comparable extent as MDC from healthy individuals. In addition, ex vivo matured MDC from both groups had equal allogeneic T cell stimulatory capacity. In conclusion, during the first months after LTX numbers and maturational status of circulating MDC are impaired significantly, probably due to a suppressive effect of corticosteroids on MDC. However, corticosteroid therapy does not imprint MDC with an intrinsic resistance to maturation stimuli.
Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)
Authors: Talor M V , Stone J H , Stebbing J , Barin J , Rose N R , Burek C L
Published: August 2010

In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg–Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (–) sera (P < 0·01). Patients with IF+ PR3-MPO- sera showed the most varied reactivity to the minor antigens. Among the IF+ groups, the IF+ PR3+/MPO- sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.
Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiency
Authors: Bacchelli C , Buckridge S , Thrasher A J , Gaspar H B
Published: August 2010

Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10–15% of all cases of CVID and it is highly likely that further genetic defects will be identified.
A murine model of appendicitis and the impact of inflammation on appendiceal lymphocyte constituents
Authors: Watson Ng W S , Hampartzoumian T , Lloyd A R , Grimm M C
Published: August 2010

Data indicate that appendicectomy for intra-abdominal inflammation protects against inflammatory bowel disease (IBD). This suggests an important role for the appendix in mucosal immunity. There is no established model of appendicitis. We therefore developed a murine model of appendicitis and examined the effect of inflammation on appendiceal lymphocyte constituents. The caecal patch of specific pathogen-free (SPF)-Balb/c mice was transformed into an obstructed ‘appendiceal pouch’ by standardized suction and band ligation. Mice were killed and ‘pouches’ removed for histology and phenotypic analysis of leucocytes by flow cytometry. Serum C-reactive protein (CRP) was determined by enzyme-linked immunosorbent assay. All ‘pouches’ developed features resembling human appendicitis – mucosal ulceration, transmural inflammation with neutrophils, lymphocytes and occasional eosinophils, and serositis. These changes were most evident between days 7 and 10. There was significant elevation of serum CRP (8·0 ± 0·3 ng/ml to 40·0 ± 3·1 ng/ml; P < 0·01), indicating systemic inflammation. Following the initial neutrophil-predominant response, there was an increase in CD4+ (15·3% ± 1·2% to 31·0 ± 2·0%; P < 0·01) and CD8+ T lymphocytes (3·7% ± 0·6% to 9·2 ± 0·8%; P < 0·01). CD25+ forkhead box P3 (FoxP3)+ regulatory T lymphocytes were increased by 66% (P < 0·01). Furthermore, significant increases in CD8+ FoxP3+ regulatory T lymphocytes were restricted to younger mice (age < 10 weeks, P < 0·003). This is the first description of a murine model of appendicitis. Inflammation resulted in T lymphocyte accumulation associated with an increase in regulatory T lymphocytes, which might explain the age-dependent protective phenomenon. Further exploration will provide insights into the mechanisms of intestinal immune homeostasis and the immunopathogenesis of IBD.
Anti-tumour necrosis factor-α therapy for severe enteropathy in patients with common variable immunodeficiency (CVID)
Authors: Chua I , Standish R , Lear S , Harbord M , Eren E , Raeiszadeh M , Workman S , Webster D
Published: August 2010

We present three common variable immunodeficiency (CVID) patients with severe inflammatory bowel disease of unknown aetiology, resistant to steroid treatment, treated with infliximab. After exclusion of any infection, infliximab was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed by every 4–8 weeks depending on clinical response. Two of these patients had predominantly small bowel disease; they both showed clinical response to infliximab with weight gain and improvement of quality of life scores. The third patient had large bowel involvement with profuse watery diarrhea; this patient improved dramatically within 48 hours of having infliximab treatment. All three patients have been maintained on infliximab treatment for between 5 and 53 months (mean 37 months) with no evidence of increased susceptibility to infections in the patients with small bowel disease, although the third patient developed two urinary tract infections and a herpes zoster infection following therapy. This is the first small case series to show that infliximab is a useful addition to current therapy in this rare group of patients with potentially life threatening enteritis.
Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing coeliac disease
Authors: Ankelo M , Kleimola V , Simell S , Simell O , Knip M , Jokisalo E , Tarkia M , Westerlund A , He Q , Viander M , Ilonen J , Hinkkanen A E
Published: August 2010

Coeliac disease (CD) is an enteropathy induced in genetically susceptible individuals by gluten components, gliadin, hordein and secalin, polypeptides present in cereals such as wheat, barley and rye, respectively. Although the disease starts as intolerance to gliadins, antibodies to tissue transglutaminase (tTG) in the gut epithelium are characteristic of the disease. Whereas serum autoantibodies against tTG (tTGA) are highly specific for CD, antibodies to gliadin are less informative as they can also be detected in other enteropathies, and even in healthy individuals. However, it was shown recently that antibodies to certain gliadin peptides occur with high specificity in CD patient sera. We developed a solid phase lanthanide-based immunofluorometric assay for simultaneous detection of serum IgA and IgG antibodies to a synthetic peptide derived from gamma gliadin of wheat comprising amino acids 86–103. Three glutamine residues of this native 18-mer peptide were replaced by glutamic acids and the peptide was biotinylated. Sera from 87 individuals who had undergone duodenal biopsy and were diagnosed with CD and from 81 healthy individuals were analysed for the presence of both IgA and IgG anti-gliadin peptide antibodies. The performance of the peptide AGA assay was excellent, showing a specificity and sensitivity of 90% and 92% for IgA, and 98% and 75% for IgG, respectively. The corresponding values for conventional anti-gliadin antibody (AGA) enzyme-linked immunosorbent assay (ELISA) tests were 72% specificity and 87% sensitivity for IgA, and 64% specificity and 78% sensitivity for IgG. In a prospective study, almost all the tTGA-positive sera drawn from children who later developed CD were also positive for gliadin peptide antibodies.
The immunodominant T helper 2 (Th2) response elicited in BALB/c mice by theLeishmaniaLiP2a and LiP2b acidic ribosomal proteins cannot be reverted by strong Th1 inducers
Authors: Iborra S , Abánades D R , Parody N , Carrión J , Risueño R M , Pineda M A , Bonay P , Alonso C , Soto M
Published: August 2010

The search for disease-associated T helper 2 (Th2) Leishmania antigens and the induction of a Th1 immune response to them using defined vaccination protocols is a potential strategy to induce protection against Leishmania infection. Leishmania infantum LiP2a and LiP2b acidic ribosomal protein (P proteins) have been described as prominent antigens during human and canine visceral leishmaniasis. In this study we demonstrate that BALB/c mice infected with Leishmania major develop a Th2-like humoral response against Leishmania LiP2a and LiP2b proteins and that the same response is induced in BALB/c mice when the parasite P proteins are immunized as recombinant molecules without adjuvant. The genetic immunization of BALB/c mice with eukaryotic expression plasmids coding for these proteins was unable to redirect the Th2-like response induced by these antigens, and only the co-administration of the recombinant P proteins with CpG oligodeoxynucleotides (CpG ODN) promoted a mixed Th1/Th2 immune response. According to the preponderance of a Th2 or mixed Th1/Th2 responses elicited by the different regimens of immunization tested, no evidence of protection was observed in mice after challenge with L. major. Although alterations of the clinical outcome were not detected in mice presensitized with the P proteins, the enhanced IgG1 and interleukin (IL)-4 response against total Leishmania antigens in these mice may indicate an exacerbation of the disease.
High thyrotrophin levels at end term increase the risk of breech presentation
Authors: Kooistra L. , Kuppens S. M. I. , Hasaart T. H. M. , Vader H. L. , Wijnen H. A. , Oei S. G. , Pop Victor J.
Published: August 2010

Objective  To study the relationship between maternal thyrotrophin (TSH) and breech presentation at term.

Design  Combined data sets of two prospective studies to obtain adequate epidemiological power.

Patients   One thousand and fifty‐eight healthy pregnant women (58 breech, 1000 cephalic) and 131 women who presented in breech at an obstetrical outpatient clinic.

Measurements  Maternal thyroid parameters [TSH, free thyroid hormone (FT4), thyroid peroxidase antibody (TPO‐Ab)] and foetal presentation were assessed in both groups between 35 and 38 weeks gestation. Power calculations suggested that at least 148 breech cases were required.

Results  The characteristics of the women in breech in both samples were similar. Women in breech (n = 58 + 131) had significantly higher TSH (but not FT4) than those (n = 1000) with cephalic presentation (Mann–Whitney U‐test, P = 0·003). Different cut‐offs were used to define high TSH in the 916 TPO‐Ab‐negative women with cephalic presentation: the 90th, 95th and 97·5th percentiles were 2·4 mIU/l (n = 149), 2·7 mIU/l (n = 77) and 3·2 mIU/l (n = 37). The prevalence rates of breech presentation in these women were all higher compared to the prevalence of breech in women below these cut‐offs (df = 1, P < 0·01). The relative risk of the 149 women with a TSH >90th percentile (>2·4 mIU/l) to present in breech was 1·82 (95% CI: 1·30–2·56).

Conclusions  Women with high TSH at end term are at risk for breech presentation. Substantial evidence for a relation between breech presentation and neurodevelopmental delay exists. As high TSH during gestation has also been linked to poor neurodevelopment, the relation between breech presentation and poor neurodevelopment might be thyroid‐related.
Characterization of a novel loss‐of‐function mutation of PAX8 associated with congenital hypothyroidism
Authors: Di Palma Tina , Zampella Emilia , Filippone Maria Grazia , Macchia Paolo Emidio , Ris‐Stalpers Carrie , De Vroede Monique , Zannini Mariastella
Published: August 2010

Background  Congenital hypothyroidism (CH) is a common endocrine disease that occurs in about 1:3000 newborns. In 80–85% of the cases, CH is presumably secondary to thyroid dysgenesis (TD), a defect in the organogenesis of the gland leading to an ectopic (30–45%), absent (agenesis, 35–40%) or hypoplastic (5%) thyroid gland. The pathogenesis of TD is still largely unknown. Most cases of TD are sporadic, although familial occurrences have occasionally been described. Recently, mutations in the PAX8 transcription factor have been identified in patients with TD.

Objective  Our aim was to identify and functionally characterize novel PAX8 mutations with autosomal dominant transmission responsible for TD.

Design  The PAX8 gene was sequenced in a mother and child both suffering from congenital hypothyroidism (CH) because of thyroid hypoplasia. Subsequently, expression vectors encoding the mutated PAX8 were generated, and the effects of the mutation on both the DNA‐binding capability and the transcriptional activity were evaluated.

Results  PAX8 gene sequencing revealed a heterozygous mutation that consists of the substitution of a histidine residue with a glutamine at position 55 of the PAX8 protein (H55Q). When tested in cotransfection experiments with a thyroglobulin promoter reporter construct, the mutant protein turned out to be still able to bind DNA in Electrophoretic Mobility Shift Assay assays but transcriptionally inactive.

Conclusions  Our findings confirm the important role of PAX8 in normal thyroid development and support the evidence that in humans haploinsufficiency of PAX8 is associated with TD.
AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED
Authors: Cervato Sara , Morlin Luca , Albergoni Maria Paola , Masiero Stefano , Greggio Nella , Meossi Cristiano , Chen Shu , Del Pilar Larosa Maria , Furmaniak Jadwiga , Rees Smith Bernard , Alimohammadi Mohammad , Kämpe Olle , Valenzise Mariella , Betterle Corrado
Published: August 2010

Objective  To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ‐ or non‐organ‐specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison’s disease (AD) or chronic candidiasis (CC).

Design, Patients and Measurements  Twenty‐four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first‐degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine‐rich‐repeat protein‐5 (NALP5) and interferon omega (IFNω) were tested in all 24 patients.

Results  AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher (P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune‐Poly‐Endocrinopathy‐Candidiasis‐Ectodermal‐Dystrophy and all three were also positive for IFNω‐autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine–rich‐repeat protein 5 and IFNω autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first‐degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls.

Conclusions  Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases.
Patient‐centred evaluation and rehabilitative care
Authors: Grenville James , Lyne Patricia
Published: August 2010

The evaluation of health care outcomes is becoming increasingly important in today's health service The wide range of measures used to evaluate these outcomes often makes clinical audit difficult and the comparison of research papers almost impossible In this paper we will discuss some of the issues surrounding outcome measurement in rehabilitative care, examine one of the most commonly used outcome measures from this area (the Barthel Index) and consider Goal Attainment Scaling, a technique which offers both clinicians and researchers the opportunity to evaluate health care outcomes on the basis of patient‐centred practice We have identified certain methodological problems that need to be addressed if Goal Attainment Scaling is to become an acceptable measure in the area of physical rehabilitative care
Partnership nursing: influences on involvement of informal carers
Authors: Casey Anne
Published: August 2010

Factors influencing family involvement in the care of children in hospital were explored in a survey of 243 inpatients in two hospitals Eighty‐five per cent of the children were receiving some or all of their care from a family member, usually the mother Significant influences on the amount and type of involvement included acuity, type of illness, length of stay and the language spoken by the family Other social factors, such as distance from the hospital, number of dependent siblings, social class and ethnicity were not significant influencing factors in this population The influence of language on involvement, and conclusions from related literature, suggest that characteristics of the interaction such as communication and nursing style are more significant than social structural factors A typology of nursing approaches to informal carers is proposed which could apply beyond the paediatric context Further work is needed to test the hypothesis that such approaches are characterized by nurses excluding the carer, or permitting, making assumptions about, or negotiating carer involvement
Using video and conversational analysis to train staff working with people with learning disabilities
Authors: Couchman Wendy
Published: August 2010

Through analysis of video data of interaction between staff and clients with learning disabilities and limited vocal skills, it was possible to demonstrate that clients used gaze and body orientation to display a readiness that was often not responded to by staff Yet staff could recognize that readiness from the videos Video analysis was therefore developed as a medium for education and training where staff were helped to become more aware of strategies for non‐vocal communication, which could help them achieve their policies of supporting clients more successfully The study also allowed development of methodology in the field of services for people with learning disabilities
Linguistic entrapment: medico‐nursing biographies as fictions
Authors: Crawford Paul , Nolan Peter , Brown Brian
Published: August 2010

This paper argues that in their trainings health professionals are encouraged to use language naively as if it were a transparent medium of scientific communication We contend that language use, particularly in the field of mental health care, should be studied in terms of its social functions and attention should be paid to the inevitably constructive nature of language in patients’records, in order that a‘fictional distance’opens up between patients and their records Recent developments in literary theory and narrative analysis can be deployed as theoretical frameworks to understand this process, and we suggest that more attention to the use of language should be included in the educational programmes for health care professionals to counteract the risk of‘linguistic entrapment’or‘incarceration’
Organizational commitment as a predictor variable in nursing turnover research: literature review
Authors: Wagner Cheryl M.
Published: August 2010

Title.  Organizational commitment as a predictor variable in nursing turnover research: literature review

Aim.  This paper is a report of a literature review to (1) demonstrate the predictability of organizational commitment as a variable, (2) compare organizational commitment and job satisfaction as predictor variables and (3) determine the usefulness of organizational commitment in nursing turnover research.

Background.  Organizational commitment is not routinely selected as a predictor variable in nursing studies, although the evidence suggests that it is a reliable predictor. Findings from turnover studies can help determine the previous performance of organizational commitment, and be compared to those of studies using the more conventional variable of job satisfaction.

Methods.  Published research studies in English were accessed for the period 1960–2006 using the CINAHL, EBSCOHealthsource Nursing, ERIC, PROQUEST, Journals@OVID, PubMed, PsychINFO, Health and Psychosocial Instruments (HAPI) and COCHRANE library databases and Business Source Premier. The search terms included nursing turnover, organizational commitment or job satisfaction. Only studies reporting mean comparisons, R2 or beta values related to organizational commitment and turnover or turnover antecedents were included in the review.

Results.  There were 25 studies in the final data set, with a subset of 23 studies generated to compare the variables of organizational commitment and job satisfaction. Results indicated robust indirect predictability of organizational commitment overall, with greater predictability by organizational commitment vs job satisfaction.

Conclusion.  Organizational commitment is a useful predictor of turnover in nursing research, and effective as a variable with the most direct impact on antecedents of turnover such as intent to stay. The organizational commitment variable should be routinely employed in nursing turnover research studies.
Grounded theory research: literature reviewing and reflexivity
Authors: McGhee Gerry , Marland Glenn R. , Atkinson Jacqueline
Published: August 2010

Title.  Grounded theory research: literature reviewing and reflexivity

Aim.  This paper is a report of a discussion of the arguments surrounding the role of the initial literature review in grounded theory.

Background.  Researchers new to grounded theory may find themselves confused about the literature review, something we ourselves experienced, pointing to the need for clarity about use of the literature in grounded theory to help guide others about to embark on similar research journeys.

Discussion.  The arguments for and against the use of a substantial topic‐related initial literature review in a grounded theory study are discussed, giving examples from our own studies. The use of theoretically sampled literature and the necessity for reflexivity are also discussed. Reflexivity is viewed as the explicit quest to limit researcher effects on the data by awareness of self, something seen as integral both to the process of data collection and the constant comparison method essential to grounded theory.

Conclusion.  A researcher who is close to the field may already be theoretically sensitized and familiar with the literature on the study topic. Use of literature or any other preknowledge should not prevent a grounded theory arising from the inductive–deductive interplay which is at the heart of this method. Reflexivity is needed to prevent prior knowledge distorting the researcher’s perceptions of the data.