bluuebunny/crossref_metadata_2025 huggingface dataset:
Folding of an MHC class II-restricted tumor antigen controls its antigenicity via MHC-guided processing
Authors: Mimura Yusuke , Mimura-Kimura Yuka , Doores Katie , Golgher Denise , Davis Benjamin G. , Dwek Raymond A. , Rudd Pauline M. , Elliott Tim
Published: March 2007

CD4+and CD8+T cell responses to endogenous retroviral envelope glycoprotein gp90 generate protective immunity to murine colon carcinoma CT26. A panel of I-Ad-restricted T cell hybridomas recognize gp90 synthesized by CT26 cells but not by other gp90-expressing tumors. Here we report that antigenicity resides in an incompletely folded form of gp90 that is unique to CT26. In contrast to more compact forms of gp90 that are present in other tumors, this open conformer is captured by recycling I-Adon antigen-presenting cells and is processed intracellularly. Thus, gp90 acquires immunodominance via MHC-guided processing, and the generation of an MHC class II-restricted response can be controlled by the intracellular folding environment of antigen-expressing cells.
The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation
Authors: Toogun Oyetunji A. , Zeiger Will , Freeman Brian C.
Published: March 2007

Telomeres are the composite of short DNA element tandem arrays and heterotypic protein components that protect and maintain chromosomal termini. As proper telomere maintenance requires a multitude of DNA extension events, it is important to understand the factors that modulate telomerase DNA association. Here, we show that the endogenous levels of the yeast p23 molecular chaperone Sba1p are required for telomere length maintenance and that Sba1p can modulate telomerase DNA binding and extension activities
in vitro
. Notably, telomere occupancy by telomerase and the extension rate of a shortened telomere fluctuated with changing Sba1 protein levels
in vivo
. In addition, we found that Sba1p displayed a cell cycle-dependent telomere interaction that paralleled telomerase binding; telomere association by Sba1p depended on its inherent chaperone activity. Taken together, our results support a model in which Sba1p modulates telomerase DNA binding activity for optimal function
in vitro
and
in vivo
.
Recurrent DNA inversion rearrangements in the human genome
Authors: Flores Margarita , Morales Lucía , Gonzaga-Jauregui Claudia , Domínguez-Vidaña Rocío , Zepeda Cinthya , Yañez Omar , Gutiérrez María , Lemus Tzitziki , Valle David , Avila Ma. Carmen , Blanco Daniel , Medina-Ruiz Sofía , Meza Karla , Ayala Erandi , García Delfino , Bustos Patricia , González Víctor , Girard Lourdes , Tusie-Luna Teresa , Dávila Guillermo , Palacios Rafael
Published: March 2007

Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on chromosomes 3, 15, and 19, were analyzed. The relative proportion of wild-type to rearranged structures was determined in DNA samples from blood obtained from different, unrelated individuals. The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth. The relevance of our results in regard to human genomic variation is discussed.
NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs
Authors: Schleicher Ulrike , Liese Jan , Knippertz Ilka , Kurzmann Claudia , Hesse Andrea , Heit Antje , Fischer Jens A.A. , Weiss Siegfried , Kalinke Ulrich , Kunz Stefanie , Bogdan Christian
Published: March 2007

Natural killer (NK) cells are sentinel components of the innate response to pathogens, but the cell types, pathogen recognition receptors, and cytokines required for their activation in vivo are poorly defined. Here, we investigated the role of plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs), Toll-like receptors (TLRs), and of NK cell stimulatory cytokines for the induction of an NK cell response to the protozoan parasite Leishmania infantum. In vitro, pDCs did not endocytose Leishmania promastigotes but nevertheless released interferon (IFN)-α/β and interleukin (IL)-12 in a TLR9-dependent manner. mDCs rapidly internalized Leishmania and, in the presence of TLR9, produced IL-12, but not IFN-α/β. Depletion of pDCs did not impair the activation of NK cells in L. infantum–infected mice. In contrast, L. infantum–induced NK cell cytotoxicity and IFN-γ production were abolished in mDC-depleted mice. The same phenotype was observed in TLR9−/− mice, which lacked IL-12 expression by mDCs, and in IL-12−/− mice, whereas IFN-α/β receptor−/− mice showed only a minor reduction of NK cell IFN-γ expression. This study provides the first direct evidence that mDCs are essential for eliciting NK cell cytotoxicity and IFN-γ release in vivo and demonstrates that TLR9, mDCs, and IL-12 are functionally linked to the activation of NK cells in visceral leishmaniasis.
Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy
Authors: Spisek Radek , Kukreja Anjli , Chen Lin-Chi , Matthews Phillip , Mazumder Amitabha , Vesole David , Jagannath Sundar , Zebroski Henry A. , Simpson Andrew J.G. , Ritter Gerd , Durie Brian , Crowley John , Shaughnessy John D. , Scanlan Matthew J. , Gure Ali O. , Barlogie Bart , Dhodapkar Madhav V.
Published: March 2007

Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of spontaneous immunity in MGUS differ from MM. MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells. Intranuclear expression of SOX2 marks the clonogenic CD138− compartment in MGUS. SOX2 expression is also detected in a proportion of CD138+ cells in MM patients. However, these patients lack anti-SOX2 immunity. Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro. Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders. Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer.
Enhancing the functional annotation of PDB structures in PDBsum using key figures extracted from the literature
Authors: Laskowski Roman A.
Published: March 2007

Motivation: The Protein Data Bank (PDB) contains over 43 800 experimentally determined 3D models of macromolecular structures and their complexes. Each 3D model reveals something interesting and important about the given molecule's function and biological significance. Usually the best source of this information is the original article describing it, and it is often possible to discern the key aspects of the structure from just one or two of the figures in that article.

Results: Here we describe how, with the permission of the journals and their publishers, we have endeavoured to make these key figures publicly available to enhance the functional information relating to each PDB entry in our PDBsum database.

Availability:  http://www.ebi.ac.uk/pdbsum

Contact:  roman@ebi.ac.uk
On water waves with a corner at the crest
Authors: Gandzha Ivan S , Lukomsky Vasyl P
Published: March 2007

A highly accurate technique for calculating the parameters of the Stokes 120° gravity wave on deep water is proposed. Tanaka's nonlinear transformation of the inverse plane is used to stretch the region near the wave crest for accelerating the convergence of the classical Michell series. Several families of new irregular self-intersecting profiles with a 120° angle at the crest are presented as well. They all degenerate into the Stokes 120° profile as numerical accuracy increases. These solutions seem to represent some kind of the so-called parasitic (or ghost) solutions, which emerge due to discretization of the original continuous problem. Probable physical relevance of such irregular solutions is discussed. The validity of the Stokes theorem about a 120° angle is tested numerically. No solutions with crest angles different from 120° were found. Hence, the Stokes 120° wave seems to be the unique gravity wave with a corner at the crest.
Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain
Authors: Forst Thomas , Smith Terry , Schütte Klemens , Marcus Paul , Pfützner Andreas ,   for the CNS 5161 Study Group
Published: March 2007

What is already known about this subject

• Despite encouraging effects of N‐methyl‐D‐aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side‐effects.

• In a recent study in healthy volunteers, CNS 5161, a novel noncompetetive NMDA receptor antagonist, was well tolerated up to a dosage of 2000 µg without psychotropic side‐effects.

• This is the first study to evaluate the maximal tolerated dosage of CNS 5161 and to gain experience about the analgesic effect of CNS 5161 in patients with different pain syndromes.

What this study adds

• In patients with neuropathic pain CNS 5161 is well tolerated up to a dosage of 500 µg with the most common side‐effect of increasing blood pressure, mild visual disturbances and headaches.

• While no therapeutic effect can be observed in a dosage up to 250 µg, treatment with 500 µg CNS 5161 provides some indications of analgesic activity.

• It appears that this effect occurs predominantly in patients with diabetic neuropathy.

Aims The purpose of the current study was to establish the safety and maximal tolerated dose of CNS 5161 HCl.

Methods Forty patients with chronic neuropathic pain (23 male, 17 female) were treated with escalating dosages of CNS 5161. All adverse events to study drug, blood pressure, heart rate, ECG, drug level and clinical laboratory values were monitored. Actual pain was measured on a 100‐mm visual analogue scale (VAS) and ordinal verbal pain scores.

Results The most commonly occurring nervous system disorder was headache, which was found more often during placebo than during CNS 5161 HCl treatment. Visual disturbances were experienced by 16.7% of patients receiving 250 µg and by 33.3% receiving 500 µg CNS 5161 HCl, but not during placebo treatment. An increase in blood pressure was observed in 8.3% of patients receiving 250 µg and in 50% of patients receiving 500 µg CNS 5161 HCl, compared with 15.4% during placebo treatment. The study was abandoned after two patients entered the 750 µg cohort due to a sustained systolic blood pressure response. Although this study was underpowered for the confirmation of efficacy, some indications of greater pain relief after 500 µg CNS 5161 compared with placebo could be observed (change in VAS between baseline and 12 h 10 ± 22 mm vs. 2 ± 19 mm; P = 0.11).

Conclusions CNS 5161 HCl was reasonably well tolerated up to 500 µg. The most common adverse events were hypertension, headache and mild visual disorders.
CYP2B6983T>C polymorphism is prevalent in West Africa but absent in Papua New Guinea: implications for HIV/AIDS treatment
Authors: Mehlotra Rajeev K. , Bockarie Moses J. , Zimmerman Peter A.
Published: March 2007

What is already known about this subject

• The novelCYP2B6functional polymorphism 983T>C (either alone asCYP2B6*18or linked with 785A>G as theCYP2B6*16allele) was found in Africans and African‐Americans but not in Caucasians and Asians.

• The polymorphism by itself and together with 516G>T (the key polymorphism in the most frequent variant alleleCYP2B6*6) was associated with significantly higher mean plasma efavirenz concentrations in the African HIV patients.

• In Papua New Guinea, the HIV/AIDS epidemic is escalating,CYP2B6*6is highly prevalent, and the prevalence of 983T>C is not known.

What this study adds

• CYP2B6983T>C is absent in the Papua New Guinea population.

• The outcome of treatment with efavirenz may prove different in Papua New Guineans ([CYP2B6*6 +][983T>C –]) compared with Africans or African‐Americans ([CYP2B6*6 +][983T>C +]).

AimsTo determine the prevalence of the novelCYP2B6functional polymorphism 983T>C in Papua New Guinea where HIV/AIDS poses a significant health problem.

MethodWe genotyped Papua New Guineans (PNG,n = 174), West Africans (WA,n = 170), and North Americans (NA,n = 361).

ResultsThe polymorphism was absent in PNG, while its overall frequency was 4.7% in WA. Among NA, the polymorphism was present in African‐Americans (7.5%) and Hispanic‐Americans (1.1%) but not in Caucasian‐Americans and Asian‐Americans. Haplotype analysis indicated that 983T>C was present alone as theCYP2B6*18allele in WA and African‐Americans.

ConclusionsSignificant interethnic differences occur at theCYP2B6locus, which may influence treatment outcomes with efavirenz.
Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five‐category classification of different cytological diagnoses
Authors: Garbar C. , Mascaux C. , Wespes E.
Published: March 2007

Background:  The aim of this study was to estimate the efficiency of a recent five‐category urinary cytological classification.

Methods:  A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto‐centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five‐category cytological classification was used: negative, suspicious of low (S‐Lg) or high (S‐Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia.

Results:  For cytological diagnoses of S‐Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low‐grade non‐invasive urothelial papillary tumour (Lg‐UPT), which included papillary urothelial neoplasm of low malignant potential and low‐grade urothelial carcinoma. For cytological diagnosis of S‐Hg and Hg, sensitivity was 44% for high‐grade non‐invasive urothelial papillary carcinoma (Hg‐UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S‐Hg or Hg was not found for Lg‐UPT (0/59) and no cytological diagnosis of S‐Lg or Lg was found for invasive carcinoma, but was seen for Hg‐UPC in 10% (3/28) and for CIS in 6% (3/50) of cases.

Conclusion:  Despite the absence of international consensus, the recent five‐category cytological classification for urine is accurate for current urological practice.
Referral compliance, outcome and predictors of CIN after repeated borderline cervical smears in the Netherlands
Authors: Siebers A. G. , Massuger L. F. A. G. , Bulten J.
Published: March 2007

Background:  Borderline cytological abnormalities are diagnosed very frequently but have limited predictive value for high‐grade cervical lesions, resulting in high costs, patient anxiety and over treatment. A conservative management strategy for the Dutch diagnostic equivalent of borderline nuclear changes (BNC) was introduced in the Netherlands in 1996, with repeat cytology at 6 and 18 months and referral for colposcopy if BNC is persistent.

Objective:  To analyse compliance with the current guidelines for referral, as well as the outcome after repeated BNC. Concurrently we investigated whether other variables are predictive of high‐grade lesions.

Methods:  We retrieved 1898 eligible cases of repeated BNC with 4 years follow‐up from the national pathology database (PALGA) and performed a nationwide survey.

Results:  The management strategy for women with repeated BNC in the Netherlands has been accepted and supported. Seventy‐seven per cent (77%) of the patients had visited a gynaecologist within 1 year and only 4.3% were lost to follow‐up. We found that 25.2% of the patients had a low‐grade lesion or worse (CIN 1+) and 10.2% had a high‐grade lesion or worse (CIN 2+), among which were four malignancies. The only variable associated with CIN or worse was age. Women under 40 years were found to be at a higher risk.

Conclusion:  This finding may be used for prioritizing women for colposcopy on the basis of their age. More stringent use of the diagnosis of BNC, higher thresholds for colposcopically directed biopsy and introduction of HPV triage, combined with more specific new techniques or combination of techniques such as molecular markers for P16, MIB‐1 and L1 may reduce the unnecessary high referral rate and over treatment of healthy women.
Pain relief after knee replacement in patients with a bleeding disorder
Authors: VANARASE M. Y. , PANDIT H. , KIMSTRA Y. W. M. , DODD C. A. F. , POPAT M. T.
Published: March 2007

Summary.  Peripheral nerve blocks can be safely used on patients with bleeding disorder, to achieve peri‐operative amalgesia.
Monocytoid/marginal zone B‐cell differentiation in follicle centre cell lymphoma
Authors: SCHMID U. , COGLIATTI S.B. , DISS T.C. , ISSACSON P.G.
Published: March 2007

We report on two cases of low grade follicle centre cell lymphoma with a pronounced parafollicular monocytoid/marginal zone B‐cell component. One patient had a history of preceeding follicular high grade B‐cell lymphoma of centroblastic type showing the same light chain restriction and identical immunoglobulin heavy chain gene rearrangement as the low grade lymphoma diagnosed 15 months later. Morphologically, in both cases the two constituents of the low grade tumours were clearly distinguishable. Immunohistochemically, the follicular component strongly expressed bcl‐2 protein in contrast to a weak staining of the marginal zone B‐cell component. Performing PCR, a rearrangement of the major breakpoint region of bcl‐2 was not found. Identical light chain restriction of the follicular and the monocytoid B‐cell/marginal zone components strongly indicates a clonal relationship between them. A monocytoid/marginal zone B‐cell component in follicular lymphoma probably results from differentiation of the follicle centre cells and does not indicate a composite lymphoma.
Massive arterial haemorrhage from the lower gastrointestinal tract
Authors: BATEMAN A.C. , BEER T.W. , BASS P.S. , ODURNY A. , GALLAGHER P.J.
Published: March 2007

We have studied the clinical, radiological and pathological features of three patients with recurrent massive lower gastrointestinal arterial haemorrhage. Case 1 was an example of Dieulafoy's vascular malformation within the proximal ascending colon in a 46‐year‐old woman. Cases 2 and 3 were men aged 81 and 83 years with arterial erosions contained within small mucosal diverticula in the hepatic flexure and descending colon, respectively. All three patients presented with recurrent acute episodes of massive lower gastrointestinal haemorrhage. Selective mesenteric angiography was performed in cases 1 and 3 to localize the bleeding point in both patients. The features were very different to those of angiodysplasia, lacking the tuft of abnormal vessels and the early venous filling phase commonly seen in the latter condition. The patients were all successfully treated by partial colectomy. The aetiology of Dieulafoy's vascular malformation remains unclear. The ruptured arteries in cases 2 and 3 shared many histological features with the Dieulafoy lesion in case 1. The lesions in cases 1 and 2 were associated with recent oral non‐steroidal anti‐inflammatory therapy, suggesting coincidental mucosal ulceration as a contributory factor.
Neural variant of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome
Authors: HARDISSON D. , JIMENEZ‐HEFFERNAN J.A. , NISTAL M. , PICAZO M.L. , TOVAR J.A. , CONTRERAS F.
Published: March 2007

A 15‐year‐old boy with the characteristic features of the naevoid basal cell carcinoma syndrome presented with a retroperitoneal mass. The tumour showed morphological features of a still ill‐defined variant of fetal rhabdomyoma, characterized by well‐differentiated nerve fibres admixed with immature striated muscle cells, similar to neuromuscular choristoma. Four cases of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome have been previously reported. The behaviour of this tumour has been benign, although a complete excision was impossible due to its close relation with abdominal vascular trunks.
Fusocellular gonadal stromal tumour of the testis with epithelial and myoid differentiation
Authors: NISTAL M. , PURAS A. , PERNA C. , GUARCH R. , PANIAGUA R.
Published: March 2007

We describe an unusual fusocellular gonadal stromal tumour with a benign behaviour in the left testis from a 16‐year‐old man. The neoplasm consisted of a non‐encapsulated proliferation of irregularly arranged, fusiform cell bundles in fibrous connective tissue. The tumour cells contained a slightly infolded nucleus, some dilated rough endoplasmic reticulum cisternae, abundant filament bundles which connected to subplasmalemmal electron‐dense bodies, pinocytotic vesicles and a discontinuous basal lamina. The intercellular spaces were narrow and the tumour cells were joined by desmosomes. These cells were immunoreactive for muscle actin, α‐actinin and vimentin. Focal immunostaining for collagen type IV was observed around the cells. No immunoreactivity for keratins, desmin S‐100 protein or XIIIa factor was found. The findings suggest that the tumour arose from the peritubular myoid cells.
Foamy cell aggregation in duodenal diverticula
Authors: MATSUKUMA S. , SUDA K.
Published: March 2007

We have investigated 44 cases of duodenal diverticulum to delineate the pathological features. Foamy cell aggregations were observed in 24 (54.5%) of the cases. The foamy cells were located within the submucosa in all 24 cases and were found around the deepest portion of the diverticula in 14. There were no statistically significant differences between the depth of the diverticulum and the presence or degree of foamy cell aggregation. Lymphoid aggregates, focal thickening of the muscularis mucosae, submucosal fibrosis, intimal thickening of submucosal vessels and submucosal haemorrhage were also detected, but statistical analysis showed no significant associations between these pathological findings and the presence of foamy cell aggregates. We conclude that the foamy cell aggregates are a non‐specific but frequent pathological finding in duodenal diverticula and which have not been described in previous studies.
Epstein‐Barr virus in tumours
Authors: ANAGNOSTOPOULOS I. , HUMMEL M.
Published: March 2007

The Epstein‐Barr virus (EBV) is the best characterized human virus known to infect most people all over the world. In most cases, primary infection with EBV is asymptomatic and the virus persists life‐long without causing any disease. The availability of sensitive detection methods, however, has led to the identification of a wide array of EBV‐associated disease entities. Although nearly 9000 publications have been written since the first description of this virus in 1964, many questions concerning its function and infection patterns remain unanswered. The direct involvement of EBV in the pathogenesis of a disease has only been established for infectious mononucleosis and lymphoproliferative disorders in the setting of congenital or acquired immunodeficiency. Extensive investigations on the role of EBV infection in the pathogenesis of all other EBV‐associated lymphoid and epithelial proliferations have led to the conclusion that EBV is not the primary causative agent but it can promote tumour development. Since the early steps in neoplastic development are difficult to assess, further studies are required to clarify the precise role of EBV infection. Furthermore, the clinical significance of the presence of EBV in neoplasia is largely unknown.
Expression of adhesion molecules in endemic and epidemic Kaposi's sarcoma
Authors: KAAYA E.E. , CASTAÑOS‐VELEZ E. , AMIR H. , LEMA L. , LUANDE J. , KITINYA J. , PATARROYO M. , BIBERFELD P.
Published: March 2007

Spindle cells and vascular endothelium in nodular lesions of AIDS associated (epidemic) and endemic Kaposi's sarcoma showed similar immunohistochemical patterns of expression for cell adhesion molecules and extracellular matrix proteins. Spindle cells as well as endothelium also expressed both α5 and αV integrin subunits and ICAM‐1 suggesting a possible role for inflammatory cytokines in spindle cell formation. The spindle cell compartment was rich in collagen, laminin, fibronectin and tenascin suggesting an important reactive component in the evolution of Kaposi's sarcoma. The lack of thrombospondin expression in the spindle cells favours the contention that they could be transitional, proliferating cells of endothelial origin. Specific expression of tat protein was not seen suggesting minimal if any HIV replication in these lesions. Our findings suggest similar histopathogenetic mechanisms for endemic and epidemic Kaposi's sarcoma. The clinically more malignant features of most AIDS related cases may reflect an important effect of systemic and focal cytokines in HIV patients and possibly other cofactor(s), i. e. tat protein in the induction and growth of the lesions.
Bronchogenic squamous cell carcinomas with invasion along alveolar walls
Authors: NAKANISHI K. , KAWAI T. , SUZUKI M. , TORIKATA C.
Published: March 2007

In bronchogenic squamous cell carcinoma, a growth pattern along the alveolar walls of the peripheral lung parenchyma is unusual. In order better to understand the way tumour cells invade the peripheral lung parenchyma, we studied two cases of squamous cell carcinoma with invasion along the alveolar walls (in 30% to 40% of the area surrounding the tumour). We used immunohistochemical staining with antibodies against pulmonary surfactant, apoproteins (PE‐10) and collagen type IV, and electron microscopy. Tumour cells invading the peripheral lung tissue were located between one layer of type II alveolar epithelial cells and the basement membrane of the alveolar walls. These results suggest that the cells of a squamous carcinoma (unlike an adenocarcinoma) have the ability to spread along the basement membrane of the alveolar walls without destroying pre‐existing normal peripheral lung parenchyma.
Endometrial stromal sarcoma with sex cord‐like areas and focal rhabdoid differentiation
Authors: McCLUGGAGE W.G. , DATE A. , BHARUCHA H. , TONER P.G.
Published: March 2007

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern, with areas of typical low‐grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord‐like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions. Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2. but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord‐like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity. A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.
Comparison of ventilator‐dependent child reports of health‐related quality of life with parent reports and normative populations
Authors: Noyes Jane
Published: March 2007

Title. Comparison of ventilator‐dependent child reports of health‐related quality of life with parent reports and normative populations

Aims.  This paper is a report of the first study of ventilator‐dependent child and parent ratings of health‐related quality of life using a validated instrument, which was undertaken as part of a case study of costs and consequences.

Background.  Advances in medical care and technologies such as the ventilator have extended childhood illness trajectories beyond our current range of knowledge and experience. These advances and their effects reinforce the need for further research to determine health‐related quality of life as an outcome of ventilator‐dependency in childhood.

Methods.  The KINDL was administered to ventilator‐dependent children aged 4–18 years and parents as part of an in‐depth case study. Twenty‐seven parents and 17 children (including 17 child‐parent pairs) completed questionnaires. Data were collected between 2001 and 2004. Findings were compared with normative values derived from a representative sample of children of a similar age in the general population.

Results.  Ventilator‐dependent children reported significantly lower overall health‐related quality of life, and significantly lower scores on all domains except about their friends, compared with school children, and chronically ill children in respect of their disease. Parents and children rated children's overall health‐related quality of life the same but parents reported significantly lower scores for their child's disease and relationships with friends. There was a positive correlation between children and parents in all areas apart from self‐esteem and school.

Conclusions.  Both child and parent perspectives are needed to understand the impact of ventilator‐dependency and associated co‐morbidity on the child. As new interventions and models of service delivery emerge it will be important for nurses to understand the impact on the child by evaluating physical, emotional and social consequences.
The effect of nurses’ use of the principles of learning organization on organizational effectiveness
Authors: Jeong Seok Hee , Lee Taewha , Kim In Sook , Lee Myung Ha , Kim Mi Ja
Published: March 2007

Title. The effect of nurses’ use of the principles of learning organization on organizational effectiveness

Aim.  This paper is a report of a study to describe the effect on organizational effectiveness of nurses’ use of the principles of learning organization.

Background.  Since Senge proposed the learning organization model in 1990, the principles of learning organization have been considered as a new organizational vision. However, there is little empirical evidence that shows how nurses’ use of the principles of learning organization affects organizational effectiveness in healthcare settings.

Method.  A cross‐sectional survey was used and the data were collected in 2003. Participants were 629 professional nurses who had worked full‐time for more than 1 year in the general units of nine tertiary medical hospitals in South Korea. A questionnaire was distributed to nurse managers of nine hospitals, who distributed it to 665 nurses, 635 of whom responded (response rate 95·5%). Six returns were discarded due to incomplete responses, leaving 629 for data analysis.

Results.  There was a statistically significant positive relationship between nurses’ use of the principles of learning organization and organizational effectiveness. Hierarchical multiple regression analysis revealed that the concept explained an additional 24·9% of organizational commitment and a further 22·6% of job satisfaction. The learning organization principles of shared vision and team learning were statistically significant predictors for organizational effectiveness.

Conclusion.  Individual nurses can use the principles of learning organization to enhance organizational effectiveness. Intervention programmes that integrate and strengthen shared vision and team learning may be useful to enhance organizational effectiveness. Further research is required to identify other factors related to the principles of learning organization.
Euthanasia and physician‐assisted suicide in the Dutch homecare sector: the role of the district nurse
Authors: Van Bruchem‐van de Scheur G.G. , Van Der Arend Arie J.G. , Spreeuwenberg Cor , Huijer Abu‐Saad Huda , Ter Meulen Ruud H.J.
Published: March 2007

Title. Euthanasia and physician‐assisted suicide in the Dutch homecare sector: the role of the district nurse

Aim.  This paper is a report of the findings of a study into the role of district nurses in euthanasia and physician‐assisted suicide in homecare organizations, conducted as part of a study into the role of nurses in medical end‐of‐life decisions.

Background.  Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician‐assisted suicide gave the Minister for Health reason to commission a study into the role of nurses in medical end‐of‐life decisions in hospitals, nursing homes and homecare organizations. This is the first quantitative study from the perspective of nurses. Previous quantitative studies were conducted under physicians and information on the role of nurses was obtained indirectly.

Method.  A questionnaire was sent in 2003 to 500 district nurses employed in 55 homecare organizations. The absolute response rate was 86·0% and 81·6% (408) could be used for analysis.

Results.  In 22·3% of 278 cases, the district nurse was the first with whom patients discussed their request for euthanasia or physician‐assisted suicide. In about half (49·8%) of 267 cases nurses were not involved in the general practitioner's decision‐making process, and in only 13·3% of 264 cases, did they attend the administration of the lethal drugs. District nurses had provided some degree of aftercare to the surviving relatives in 80·3% of 264 cases.

Conclusion.  Collaboration between general practitioners and district nurses needs improvement, particularly in relation to decision‐making. Our Dutch data could help nurses in other countries to define their (future) role in euthanasia and physician‐assisted suicide.
Using Nominal Group Technique to investigate the views of people with intellectual disabilities on end‐of‐life care provision
Authors: Tuffrey‐Wijne Irene , Bernal Jane , Butler Gary , Hollins Sheila , Curfs Leopold
Published: March 2007

Title. Using Nominal Group Technique to investigate the views of people with intellectual disabilities on end‐of‐life care provision

Aim.  This paper is a report of a study using the Nominal Group Technique as a method to elicit the views of people with intellectual disabilities on sensitive issues, in this example end‐of‐life care provision.

Background.  Establishing consumer views is essential in providing appropriate end‐of‐life care, yet people with intellectual disabilities have historically been excluded from giving their opinion and participating in research.

Methods.  Nominal Group Technique was used in three groups, with a total of 14 participants who had mild and moderate intellectual disabilities. This technique involves four steps: (1) silent generation of ideas, (2) round robin recording of ideas; (3) clarification of ideas and (4) ranking of ideas (voting). Participants were presented with an image of a terminally ill woman (Veronica), and were asked: ‘What do you think people could do to help Veronica?’

Findings.  Participants generated a mean of nine individual responses. The highest rankings were given to issues around involvement in one's own care, presence of family and friends, offering activities to the ill person, and physical comfort measures.

Conclusion.  People with mild and moderate intellectual disabilities are capable of expressing their views on end‐of‐life care provision, and should be asked to do so. The Nominal Group Technique presents an effective and acceptable methodology in enabling people with intellectual disabilities to generate their views.
Grounded theory: a methodological spiral from positivism to postmodernism
Authors: Mills Jane , Chapman Ysanne , Bonner Ann , Francis Karen
Published: March 2007

Title. Grounded theory: a methodological spiral from positivism to postmodernism

Aim.  Our aim in this paper is to explain a methodological/methods package devised to incorporate situational and social world mapping with frame analysis, based on a grounded theory study of Australian rural nurses’ experiences of mentoring.

Background.  Situational analysis, as conceived by Adele Clarke, shifts the research methodology of grounded theory from being located within a postpositivist paradigm to a postmodern paradigm. Clarke uses three types of maps during this process: situational, social world and positional, in combination with discourse analysis.

Method.  During our grounded theory study, the process of concurrent interview data generation and analysis incorporated situational and social world mapping techniques. An outcome of this was our increased awareness of how outside actors influenced participants in their constructions of mentoring.

In our attempts to use Clarke's methodological package, however, it became apparent that our constructivist beliefs about human agency could not be reconciled with the postmodern project of discourse analysis. We then turned to the literature on symbolic interactionism and adopted frame analysis as a method to examine the literature on rural nursing and mentoring as secondary form of data.

Findings.  While we found situational and social world mapping very useful, we were less successful in using positional maps. In retrospect, we would argue that collective action framing provides an alternative to analysing such positions in the literature. This is particularly so for researchers who locate themselves within a constructivist paradigm, and who are therefore unwilling to reject the notion of human agency and the ability of individuals to shape their world in some way.

Conclusion.  Our example of using this package of situational and social worlds mapping with frame analysis is intended to assist other researchers to locate participants more transparently in the social worlds that they negotiate in their everyday practice.
Emergence of pathogenic betanodaviruses belonging to the SJNNV genogroup in farmed fish species from the Iberian Peninsula
Authors: Cutrín J M , Dopazo C P , Thiéry R , Leao P , Olveira J G , Barja J L , Bandín I
Published: March 2007

Betanodaviruses are the causative agents of viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER) in cultured marine fish. Based on the RNA2 gene fish nodaviruses have been traditionally classified into four different genotypes and recently a fifth genotype has been proposed. This study presents sequencing data of 24 new nodaviruses obtained from three different fish species: sea bass, Dicentrarchux labrax (L.), sea bream, Sparus aurata L., and Senegalese sole, Solea senegalensis Kaup, cultured in the Iberian Peninsula (Spain and Portugal). Sequence analysis was performed on the T4 region (388 nt) of the coat protein gene. In addition, phylogenetic analysis, according to maximum parsimony and neighbour‐joining methods, was performed using these sequences and other nucleotide sequences available in the databases or in the literature. Results obtained indicate that all these new nodaviruses should be classified into the striped jack nervous necrosis virus (SJNNV) genotype. This finding suggests that SJNNV genotype is emerging in the Iberian Peninsula and could easily spread throughout the Mediterranean, representing a serious threat to the fish farming industry.
Evaluation of the link between gyrodactylosis and streptococcosis of Nile tilapia,Oreochromis niloticus(L.)
Authors: Xu D‐H , Shoemaker C A , Klesius P H
Published: March 2007

Streptococcus iniaeandGyrodactylus niloticusare two common pathogens of cultured Nile tilapia,Oreochromis niloticus. We studied concurrent infection of tilapia byG. niloticusandS. iniaeand evaluated whether parasitism in tilapia withGyrodactylusincreased susceptibility and mortality following immersion infection withS. iniae. Results showed that death mainly occurred in fish withG. niloticusand challenged withS. iniae(G–S group). The accumulative mortality (42.2%) was significantly higher in the G–S group than in fish not infected by the parasite (6.7%), but exposed toS. iniae. Bacteriological examination revealedS. iniaefrom ≥92% of dead or moribund fish challenged withS. iniae.Gyrodactylusnot only damaged fish epithelium and provided entry for invasive bacteria but also was found to harbour viable cells ofS. iniaefor 24 and 72 h.Streptococcus iniaewas isolated from 60% and 40% ofG. niloticuscollected from fish infected by intraperitoneal injection or immersion, respectively, at 24 h post‐challenge. The present study confirms that parasitism of tilapia byG. niloticusincreased host mortality following exposure to the bacterial pathogenS. iniae.
Phylogeography of the fire‐bellied toadsBombina: independent Pleistocene histories inferred from mitochondrial genomes
Authors: HOFMAN SEBASTIAN , SPOLSKY CHRISTINA , UZZELL THOMAS , COGĂLNICEANU DAN , BABIK WIESŁAW , SZYMURA JACEK M.
Published: March 2007

The fire‐bellied toadsBombina bombinaandBombina variegata,interbreed in a long, narrow zone maintained by a balance between selection and dispersal. Hybridization takes place between local, genetically differentiated groups. To quantify divergence between these groups and reconstruct their history and demography, we analysed nucleotide variation at the mitochondrial cytochromebgene (1096 bp) in 364 individuals from 156 sites representing the entire range of both species. Three distinct clades with high sequence divergence (K2P = 8–11%) were distinguished. One clade groupedB. bombinahaplotypes; the two other clades groupedB. variegatahaplotypes. OneB. variegataclade included only Carpathian individuals; the other representedB. variegatafrom the southwestern parts of its distribution: Southern and Western Europe (Balkano–Western lineage), Apennines, and the Rhodope Mountains. Differentiation between the Carpathian and Balkano–Western lineages,K2P ∼8%, approached interspecific divergence. Deep divergence among EuropeanBombinalineages suggests their preglacial origin, and implies long and largely independent evolutionary histories of the species. Multiple glacial refugia were identified in the lowlands adjoining the Black Sea, in the Carpathians, in the Balkans, and in the Apennines. The results of the nested clade and demographic analyses suggest drastic reductions of population sizes during the last glacial period, and significant demographic growth related to postglacial colonization. Inferred history, supported by fossil evidence, demonstrates thatBombinaranges underwent repeated contractions and expansions. Geographical concordance between morphology, allozymes, and mtDNA shows that previous episodes of interspecific hybridization have left no detectable mtDNA introgression. Either the admixed populations went extinct, or selection against hybrids hindered mtDNA gene flow in ancient hybrid zones.
Influence of different dietary calcium levels on the digestibility of Ca, Mg and P in Hermann's tortoises (Testudo hermanni)
Authors: Liesegang A. , Hatt J.‐M. , Wanner M.
Published: March 2007

Calcium and phosphorus are very important minerals in reptile nutrition, but many diets are still not balanced. To achieve optimal growth, including a healthy skeleton and a strong shell, a well‐balanced supply with these minerals is prerequisite. The purpose of this study was to evaluate the apparent digestibility in Hermann's tortoises of diets with different calcium levels with special emphasis on the digestibility of minerals. Eight adult Hermann's tortoises of the veterinary faculty in Zurich were used. The animals were housed indoors at a mean temperature between 23 °C and 26 °C. The animals were fed a diet, which consisted of vegetables, herbs and different supplementation of calcium carbonate. Daily faecal samples of all tortoises were collected from day 8 to day 12. A proximate analysis was performed and the HCl‐insoluble ash was used as an indigestible natural indicator (marker) for the determination of the apparent digestibility of minerals. The calcium content of the mixed feedstuffs of diet I was 0.64% on a dry matter basis, and the Ca:P ratio in the food was 3:1. In diet II the Ca content was 1.29% on a dry matter basis, and the Ca:P ratio in the food was 6:1. The digestibility of Ca in diet I was 57%. The other examined minerals, Mg and P, had a digestibility of 46% and 58% respectively. In diet II the digestibility of Ca was 79%, of Mg 52% and of P 52%. The results of this study indicated, that higher Ca concentrations in the diet led to an increased apparent digestibility of Ca and Mg.
Evaluation of diabetes determinants in woolly monkeys (Lagothrix lagotricha)
Authors: Ange‐van Heugten K. D. , Burns R. , Verstegen M. W. A. , Jansen W. L. , Ferket P. R. , Van Heugten E.
Published: March 2007

Woolly monkeys (Lagothrix lagotricha) are a threatened specie in the wild with limited successful management in captivity due to diagnosed hypertension and suspected diabetic conditions. Six woolly monkeys with known hypertension problems were tested to determine if diabetes mellitus and current daily diet are underlying links to health problems for the captive population of this species. Blood and urine were collected and serum was analysed for fructosamine, glucose, glycated haemoglobin, insulin, triacylglycerides, total cholesterol, high‐density lipoprotein cholesterol (HDL‐Chol) and low‐density lipoprotein cholesterol (LDL‐Chol) while urine was tested for glucose concentrations. Diet disappearance was determined for 3 days prior to blood collection and nutrient content was calculated using Zoo Diet Analysis computer program. Serum analyses were within normal ranges (fructosamine (139–242 μmol/l), glucose (2.22–4.78 mmol/l), glycated haemoglobin (3.52–4.73%), insulin (6.2–13.0 μU/ml), triacylglycerides (0.38–3.4 mmol/l), total cholesterol (2.5–5.1 mmol/l), HDL‐Chol (0.4–1.6 mmol/l) and LDL‐Chol (1.8–3.4 mmol/l)). Urine glucose concentrations were below the detection limit. Diets were not limiting in starch and total sugars and were similar in non‐starch polysaccharides. Potential dietary deficiencies were noted for vitamin A, vitamin D, calcium, phosphorus and selenium. When compared with the available primate reference ranges, the results do not indicate problems with diabetes mellitus or with glucose metabolism and therefore they are not causes of the diagnosed hypertension. Further research to ascertain the true cause of health related problems and the role of dietary factors is needed.
Hirudin, heparin and Heinrich Necheles
Authors: GEORGE CRP
Published: March 2007

SUMMARY: The early history of haemodialysis was closely linked to the development of methods of anticoagulation. After John B. Haycroft identified hirudin, several investigators, including J.J. Abel and his colleagues, used it for extra‐corporeal anticoagulation, however it was not until Jay McLean and William Howell developed heparin that a reliable substance became available. Heinrich Necheles appears to have been the first to apply this to dialysis in experiments that he carried out in Peking.