bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing a putative dantrolene-binding site on the cardiac ryanodine receptor
Authors: PAUL-PLETZER Kalanethee , YAMAMOTO Takeshi , IKEMOTO Noriaki , JIMENEZ Leslie S. , MORIMOTO Hiromi , WILLIAMS Philip G. , MA Jianjie , PARNESS Jerome 
Published: April 2005

Dantrolene is an inhibitor of intracellular Ca2+ release from skeletal muscle SR (sarcoplasmic reticulum). Direct photoaffinity labelling experiments using [3H]azidodantrolene and synthetic domain peptides have demonstrated that this drug targets amino acids 590–609 [termed DP1 (domain peptide 1)] of RyR1 (ryanodine receptor 1), the skeletal muscle RyR isoform. Although the identical sequence exists in the cardiac isoform, RyR2 (residues 601–620), specific labelling of RyR2 by dantrolene has not been demonstrated, even though some functional studies show protective effects of dantrolene on heart function. Here we test whether dantrolene-active domains exist within RyR2 and if so, whether this domain can be modulated. We show that elongated DP1 sequences from RyR1 (DP1-2s; residues 590–628) and RyR2 (DP1-2c; residues 601–639) can be specifically photolabelled by [3H]azidodantrolene. Monoclonal anti-RyR1 antibody, whose epitope is the DP1 region, can recognize RyR1 but not RyR2 in Western blot and immunoprecipitation assays, yet it recognizes both DP1-2c and DP1-2s. This suggests that although the RyR2 sequence has an intrinsic capacity to bind dantrolene in vitro, this site may be poorly accessible in the native channel protein. To examine whether it is possible to modulate this site, we measured binding of [3H]dantrolene to cardiac SR as a function of free Ca2+. We found that ≥10 mM EGTA increased [3H]dantrolene binding to RyR2 by ∼2-fold. The data suggest that the dantrolene-binding site on RyR2 is conformationally sensitive. This site may be a potential therapeutic target in cardiovascular diseases sensitive to dysfunctional intracellular Ca2+ release.
Generation and function of astroglial lipoproteins from Niemann–Pick type C1-deficient mice
Authors: KARTEN Barbara , HAYASHI Hideki , FRANCIS Gordon A. , CAMPENOT Robert B. , VANCE Dennis E. , VANCE Jean E. 
Published: April 2005

NPC (Niemann–Pick type C) disease is a progressive neurological disorder characterized by defects in intracellular cholesterol trafficking, accumulation of cholesterol in the endosomal system and impaired cholesterol homoeostasis. Although these alterations appear to occur in all NPC1-deficient cell types, the consequences are most profound in the nervous system. Since glial cells are important mediators of brain cholesterol homoeostasis, we proposed that defective generation and/or function of lipoproteins released by glia might contribute to the neurological abnormalities associated with NPC disease. We found that, as in other cell types, Npc1−/− glia accumulate cholesterol intracellularly. We hypothesized that this sequestration of cholesterol in glia might restrict the availability of cholesterol for lipoprotein production. Cerebellar astroglia were cultured from a murine model of NPC disease to compare the lipoproteins generated by these cells and wild-type glia. The experiments demonstrate that the amount of cholesterol in glia-conditioned medium is not reduced by NPC1 deficiency. Similarly, cholesterol efflux to apo (apolipoprotein) A1 or glial expression of the transporter ATP-binding-cassette transporter A1 was not decreased by NPC1 deficiency. In addition, the ratio of apo E:cholesterol and the density distribution of lipoproteins in Npc1−/− and Npc1+/+ glia-conditioned medium are indistinguishable. Importantly, in a functional assay, apo E-containing lipoproteins generated by Npc1−/− and Npc1+/+ glia each stimulate axonal elongation of neurons by approx. 35%. On the basis of these observations, we speculate that the neuropathology characteristic of NPC disease can quite probably be ascribed to impaired processes within neurons in the brain rather than defective lipoprotein production by astroglia.
Recombinant FVIIa in the management of intracerebral haemorrhage in severe thrombocytopenia unresponsive to platelet‐enhancing treatment
Authors: Barnes C. , Blanchette V. , Canning P. , Carcao M. 
Published: April 2005

summary.  Intracranial haemorrhage (ICH) is a dramatic and potentially life‐threatening presentation of children with thrombocytopenia. Management is limited to supportive care. Recent evidence suggests that ongoing bleeding following the initial ICH may result in greater neurological morbidity and mortality. Haemostatic agents, including recombinant factor VIIa (rFVIIa), a product licensed for use in patients with haemophilia and inhibitors, may be helpful in reducing bleeding in children with refractory thrombocytopenia.We present the case of a 16‐year‐old girl with severe refractory immune thrombocytopenia, who presented with a major ICH and responded to treatment that included rFVIIa and platelet transfusions. The dose of rFVIIa was empirically chosen and based on reported cases in the literature. The case highlights a number of issues regarding off‐label use of rFVIIa and demonstrates the need to prospectively collect accurate information on the off‐label use of this new potentially useful medication.
About the role of boundary conditions on compositional imaging with a scanning electron microscope
Authors: MERLI P. G. , MORANDI V. , CORTICELLI F. 
Published: April 2005

SummaryWe consider the effects of different boundaries on the visibility of a specimen detail providing a compositional contrast in scanning electron microscopy, operating with backscattered electrons or secondary electrons. An object characterized by a gradual variation in composition, an As‐doped region in Si, is investigated. The different boundaries in the cross‐sectioned specimen correspond to the absence or presence of a poly‐Si layer on top of the implanted region, deposited after the annealing treatment. It is shown that the interpretation model used for image formation is of paramount relevance for understanding the experimental results, indicating that the boundaries of the doped region are important in hindering or enhancing its visibility. The relevance of experimental parameters such as electron energy and probe dimension is also reported.
An optical differential scanning calorimeter cryomicroscope
Authors: YUAN S. , DILLER K. R. 
Published: April 2005

SummaryAn optical‐DSC system was designed, built, tested, calibrated and verified to incorporate into a single device the capability for simultaneous optical cryomicroscopy and differential scanning calorimetry (DSC). This instrument can be used to obtain both visual and thermal data for an individual specimen subjected to a defined freezing and thawing protocol with very little compromise in quality or range of data available in comparison with dedicated single instruments. Temperature and caloric calibrations were performed based on phase transition states in water, n‐dodecane and n‐decane. The instrument has proven effective for process analysis in living cells and in foodstuffs.
Anthropometric measurements for neonates, 23 to 29 weeks gestation, in the 1990s
Authors: Karna Padmani , Brooks Kevin , Muttineni Jyotsna , Karmaus Wilfried 
Published: April 2005

SummaryReference data describing weight, length, and head circumference (anthropometric measurements) at birth were published by Lubchenco and Usher before 1970. Few attempts have been made to investigate whether these data are appropriate for today's cohort of preterm neonates. We analysed anthropometric data for neonates born between 23 and 29 weeks’ gestation. Reference charts were developed from the measurements obtained from neonatal records, and gestational age, obtained from maternal charts, on 975 neonates delivered at four neonatal centres in Michigan during 1992 and 1997. The analysis was confined to children with gestational age that was consistent or within 7 days by last menstrual period, obstetric examination, ultrasound and neonatal determinations. At 23 to 29 weeks’ gestation, ethnicity and multiple births did not have any significant impact on birthweight but girls were lighter. We compared our anthropometric charts with those presently being used at many neonatal centres. In our study, physical measurements at birth of preterm neonates born between 1992 and 1997 were significantly different from those currently used to assess growth status. Furthermore data derived from published studies that utilised birth certificates with gestational age based on last menstrual period seem to overestimate birthweight. For preterm infants, our findings are concordant with recently published values from 18 states of the US.Because of improved survival, gestational age assessment and perinatal care of preterm neonates, development of new reference anthropometric measurements for neonates is overdue. Our Michigan data of 23–29 weeks preterm provides new national reference values, which we recommend for use in US neonatal centres for extremely preterm neonates.
Colorectal intervention as part of surgery for patients with gynaecological malignancy
Authors: Bedirli A. , Mentes B. B. , Onan A. , Kerem M. , Pala M. I. , Sakrak O. , Oguz M. 
Published: April 2005

AbstractObjective  This study was conducted to determine the indications for and outcome of colorectal intervention in patients with advanced gynaecological malignancy.Methods  Between January 1999 and June 2004, 27 gynaecological cancer patients underwent 36 colorectal intervention performed by general surgeons. The 36 operations were associated with 14 (39%) primary surgical procedures, 9 (25%) second‐look laparotomies, and 13 (36%) procedures for recurrence or palliation.Results  The mean age was 56 years (range 32–83 years). The majority of operations were performed in patients with ovarian (67%), endometrial (18%) and cervical (15%) malignancy. The primary indications for colorectal resection was tumour cytoreduction in 56% of the 36 operations. Other indications included repair of iatrogenic bowel injuries (n = 9, 25%), resection for multiple iatrogenic enterotomies (n = 4, 11%), and bowel obstruction (n = 3, 8%). The most frequently performed bowel operation was rectosigmoid resection with end‐to‐end anastomosis (n = 19, 53%). Colostomy was performed in 14% of the rectosigmoid resections at primary surgery. Small‐bowel resection was required in 31% of the 36 operations. Postoperative complications included wound complications (14%), pulmonary infections (8%), cardiac complications (6%) and intra‐abdominal abscess (6%). There was a single surgical mortality (3%).Conclusion  Colorectal intervention is frequently indicated during operations for advanced gynaecological malignancy, and they are associated with a significant rate of postoperative complications. Specialists operating on gynaecological malignancy should have the technical skills necessary to perform these procedures.
MRI assessment of the bony pelvis may help predict resectability of rectal cancer
Authors: Boyle K. M. , Petty D. , Chalmers A. G. , Quirke P. , Cairns A. , Finan P. J. , Sagar P. M. , Burke D. 
Published: April 2005

AbstractObjective  The outcome after surgical treatment of rectal cancer may be influenced by the technical difficulty of the operation, which is thought to be affected by pelvic size. The aim of this study was to examine the association between bony pelvic dimensions and CRM involvement.Patients and methods  All patients with primary rectal cancer between December 1999 and January 2002 were studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were measured from the MR images on a workstation. Pathology reports were obtained for all patients and the mesorectal specimen was examined. Technical difficulty was assessed by circumferential resection margin (CRM) involvement.Results  Of 126 patients with primary rectal cancer, 88 had staging MRI and rectal excision; there were significant differences between the sexes in all 9 pelvic dimensions (P < 0.05). In females, the interspinous diameter was significantly shorter in patients with CRM involvement compared with patients with a negative CRM. In female patients predicted to have a negative CRM, the anteroposterior diameter of the inlet, the anteroposterior diameter of the midplane and the transverse diameter of the midplane (interspinous distance) were significantly shorter in patients who actually had a positive CRM compared with those in whom the CRM was negative. In male patients, there was no correlation between pelvic dimensions and CRM status.Conclusions  In certain patients with rectal cancer, CRM positivity may be predicted from pre‐operative MRI pelvic measurements. This may influence the choice of adjuvant therapy.
The mbuna cichlids of Lake Malawi: a model for rapid speciation and adaptive radiation
Authors: Genner Martin J. , Turner George F. 
Published: April 2005

AbstractMbuna, the dominant fishes on the rocky shores of Lake Malawi, have become a major ‘model system’ for the study of rapid speciation and adaptive radiation. At least 295 putative species are known, of which more than 200 remain undescribed. There is no good evidence for monophyly in the mbuna, rather mitochondrial DNA phylogenies indicate that they are polyphlyetic with respect to benthic feeding cichlids of the generaAulonocara,Alticorpusand some species ofLethrinops. Male mbuna hold territories for 18 months or more and breed year‐round. All species are maternal mouthbrooders, but females do not guard free‐swimming young. Mbuna are polygamous (both sexes). There is sexual dimorphism in size, colour and fin length, and many species show within‐population colour polymorphism. Mbuna genera are largely differentiated on the basis of head, jaw and tooth morphology, but congeneric species are generally distinguished by male colour. Many morphologically specialized forms have broad diets and often feed on common easily obtainable resources. While it is likely that dietary and habitat niche partitioning contributes to species coexistence, this has never clearly been demonstrated under experimental conditions. Populations on spatially separated habitat patches are often genetically differentiated, probably because most species are specialized for life on rocky shores, and lack a dispersal phase in their life histories. Males seem to disperse more than females, but are able to home several kilometres back to their territories. Some closely related ecologically equivalent allopatric populations are differentiated in male colour. Those tested have been shown to mate at least partially assortatively. Sexual selection acting on male colour seems the most plausible mechanism for initial species divergence. The same colour forms seem to have arisen several times, suggesting frequent parallel evolution. The main conservation threat to mbuna at present seems to be translocation of species within the lake as a result of the aquarium trade. However, deleterious effects on indigenous populations are not documented. In the long run, sedimentation, pollution, introduction of alien species and the development of targeted food fisheries could be more serious threats.
Perianal ulceration: a case of tuberculosis cutis orificialis
Authors: Leon‐Mateos A , Sánchez‐Aguilar D , Lado F , Toribio J 
Published: April 2005

ABSTRACTBackground  Tuberculosis cutis orificialis is an extremely rare variant of cutaneous tuberculosis. Perianal location is a possible site of presentation.Methods  We describe the management of a young male with a painless non‐specific perianal ulcer, who presented an asymptomatic disseminate pulmonary and intestinal tuberculosis. He had a history of pulmonary sarcoidosis and long‐term corticosteroid therapy.Results  Healing of the ulcer was achieved after three‐drug antituberculous therapy, with an improvement of the radiographic pulmonary alterations.Conclusions  Tuberculous origin should be considered in persistent perianal ulcers to avoid delays in the treatment of this rare form of tuberculosis.
Mucosal vulval lichen planus: outcome, clinical and laboratory features
Authors: Kirtschig G , Wakelin SH , Wojnarowska F 
Published: April 2005

ABSTRACTBackground  Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas.Objective  To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features.Subjects and methods  Forty‐four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected.Results  Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC.Conclusions  Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long‐term follow‐up, and that all non‐healing ulcerative and papular lesions should be biopsied.
Clinico‐pathological analysis of the cutaneous lesions of a patient with type I pseudohypoaldosteronism
Authors: Martín JM , Calduch L , Monteagudo C , Alonso V , García L , Jordá E 
Published: April 2005

ABSTRACTThe autosomal recessive form of type I pseudohypoaldosteronism (PHA‐I) is an unusual disorder characterized by aldosterone resistance at the target organs, which leads to an excessive loss of sodium chloride through urine, sweat and saliva, among other secretions. Such a high concentration of salt in the sweat during the depletive crises directly causes inflammation and damage in the eccrine structures, with cutaneous lesions similar to those appearing in miliaria rubra. We report an autosomal recessive PHA‐I in a 4‐year‐old girl, with cutaneous lesions mimicking miliaria rubra, that improved after treatment with astringent solutions and avoidance of profuse sweating.
Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin
Authors: Brown MB , Jones SA 
Published: April 2005

ABSTRACTHyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N‐acetyl‐d‐glucosamine and β‐glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock‐absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non‐immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze®, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost‐effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5‐fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.
Kaposi sarcoma associated with lipoedema
Authors: Ekmekci TR , Ayabakan O , Sakiz D , Koslu A 
Published: April 2005

ABSTRACTLipoedema is a form of lipodistrophy, which consists of abnormal accumulation of fat in subcutaneous tissue of the lower limbs. It does not cause any disease and it has not been reported association with malignity. We describe a 63‐year‐old woman occuring of Kaposi sarcoma on the lipoedema base.
Case–control study to identify melanoma risk factors in the Belgian population: the significance of clinical examination
Authors: Nijsten T , Leys C , Verbruggen K , Verlinden V , Drieghe J , Stas M , Lambert J , DeGreef H , Garmyn M 
Published: April 2005

ABSTRACTBackground  Although numerous studies have evaluated risk factors associated with cutaneous malignant melanoma (CMM), no such study has been carried out in Belgium.Objectives  To identify individuals who are at high risk of developing malignant melanoma in Belgium, which could enhance the efficacy of screening interventions and avoid unnecessary skin inspections.Study design/setting/subjects  We prospectively included patients who were diagnosed with invasive malignant melanoma between 1998 and 2001 at the Department of Dermatology in a case–control study. Controls were selected from the outpatient dermatology clinic. Participants were interviewed and clinically examined by a dermatologist. We asked questions concerning most known risk factors associated with malignant melanoma such as phenotypical and skin characteristics, and environmental and lifestyle exposures. To adjust for confounding variables and to estimate odds ratios (ORs) and 95% confidence intervals (CIs), a multivariate model was used.Results  Although sunburn in childhood and substantial occupational solar exposure were modestly, but significantly, associated with malignant melanoma risk, clinical examination yielded several stronger risk factors. In a multivariate model, which adjusted for age, gender and skin phototype, phenotypical characteristics such as skin, hair and eye colour were significantly associated with the development of malignant melanoma. In the multivariate model, people with three or more atypical naevi were at more than 10‐fold risk of developing a malignant melanoma (≥ 3 atypical naevi; adjusted OR = 11.40, 95% CI = 4.79–17.53) compared to those without an atypical naevus. The presence of one or more palpable naevi on the upper extremities or having solar lentigines increased the odds of developing malignant melanoma at least twofold.Conclusions  In Belgium, risk factors associated with malignant melanoma appear to be in accordance with previous studies. To assess peoples’ risk profile, clinical skin examination is likely to yield the most important sporadic malignant melanoma risk factors. Therefore, focusing screening campaigns on individuals with predefined findings on skin self‐examination may increase its efficacy.