bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Peritoneal Macrophages in Cytomegalovirus‐induced Acceleration of Autoimmune Diabetes in BB‐rats
Authors: Hillebrands Jan-Luuk , van der Werf Nienke , Klatter Flip A. , Bruggeman Cathrien A. , Rozing Jan 
Published: December 2003

Background: As one of the natural perturbants, infection with cytomegalovirus (CMV) is believed to play a role in the development of Type I diabetes. Using the DP‐BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(at)CMV‐induced accelerated onset of diabetes.Methods: Rats were i.p. infected with 2 × 106 plaque forming units (pfu) RCMV and followed for diabetes development. Presence of RCMV antigens and DNA was analyzed by immunohistochemistry and PCR on pancreatic tissue and isolated islets. The effect of viral infection on peritoneal macrophages (pMΦ) and diabetes development was studied by analyzing numbers of pMΦ, virus permissiveness and by depletion of this subset by peritoneal lavage.Results: RCMV accelerated onset of diabetes without infecting pancreatic islets. Immunohistochemistry and PCR on pancreas and isolated islets indicated that islets are non‐permissive for RCMV. Infection results in an influx of pMΦ 1 day p.i. of which ~0.05% showed signs of reproductive infection. Depletion of pMΦ on days 1‐3 p.i. completely counteracted the accelerating effect of RCMV.Interpretation: RCMV accelerates onset of diabetes without infecting pancreatic islets. pMΦ might function as an carriage to disseminate virus to the pancreas where they enhance activation of autoreactive T cells resulting in accelerated onset of diabetes.
Lack of Association between Anti‐Phospholipid Antibodies (APLA) and Attention Deficit/Hyperactivity Disorder (ADHD) in Children
Authors: Bujanover Shay , Levy Yair , Katz Miriam , Leitner Yael , Vinograd Isaac , Shoenfeld Yehuda 
Published: December 2003

Numerous studies have shown the pathological influence anti‐phospholipid antibodies (APLA) have on the physiology of the single neuron as well as the function of the entire human nervous system. The influence is well demonstrated in the antiphospholipid syndrome (APS). This syndrome is characterized by a triad of arterial or venous thrombotic events, recurrent fetal loss and thrombocytopenic purpura. The syndrome exhibits different neurological pathologies such as: chorea, seizures, transverse myelopathy, migraine, cerebral ataxia, hemiballismus and transient global amnesia, which are not fully explained by the procoagulopathic trait of APLA. A study on mice induced with APS demonstrated hyperactive behavior when compared to the control group. The information gathered from these different studies raised the question whether APLA has any part in the etiology of Attention Deficit/Hyperactive Disorder (ADHD) in children.We compared 41 children diagnosed with ADHD to a control of 28 healthy children. Blood drawn from the two groups was screened using ELISA for the presence of anti‐cardiolipin antibodies, antiβ2GP antibodies, anti‐phosphatidyleserine antibodies and anti‐ethanolamine antibodies. The results show no significant difference in the level of antiphospholipid antibodies (APLA) measured between the children diagnosed with ADHD and the control group.
Pseudo Alopecia Areata Caused by Skull‐caps with Metal Pin Fasteners used by Orthodox Jews in Israel
Authors: Yosefy Chaim , Ronnen Meir , Edelstein Dennis 
Published: December 2003

Background: Alopecia Areata (AA) is a disease characterized by hair loss that is widely believed to be autoimmune in origin. Thus treatment is generally aimed in this direction using immune inhibitors such as steroids and PUVA.Objective: To describe a variant of AA, Pseudo Alopecia Areata, caused by a particular cupola pin holder (tic‐tac) and to offer a non‐pharmacological treatment option (NPT).Methods: A prospective open label study in 37 Jewish religious patients (34 males, 3 females, mean 35 ± 2 years), previously diagnosed and treated for scalp AA were randomly referred to one of the three NPT intervention methods: small cupola held by two pins, large cupola held by one pin and similar cupola held by a different pin.Results: Three of the ten patients (33.3%) from the first group developed secondary AA from the additional pin. No changes were seen in the second group. Ten of the seventeen patients (58.8%) from the third group achieved immediate improvement subsequent to replacing the original pin with a new one on a larger cupola.Conclusions: Conservative pharmacological treatment failed to repair the lesions. The addition of a second pin caused an additional lesion. In contrast, replacing the cupola with a larger one and the original pin‐fastener with a different type, successfully reduced the lesions.
Treatment of Epithelioid Sarcoma at the Royal Marsden Hospital
Authors: Livi L. , Shah N. , Paiar F. , Fisher C. , Judson I. , Moskovic E. , Thomas M. , Harmer C. 
Published: December 2003

Purpose: The aim of this study was to assess treatment and outcome with respect to clinical and pathological features.Patients and methods: Thirty‐nine patients were identified (range 7–66 years, mean 23). Initial treatment comprised local
excision in 11 patients and wide excision in 14. Post‐operative external beam radiotherapy was prescribed in 22 patients
with a total dose of 60 Gy, delivered in two phases.Results: The cause‐specific survival for the entire group was 79, 63, 56 and 45% at 1, 3, 5 and 10 years, respectively. A distal
limb location was associated with a better prognosis than proximal limb location (P = 0.04).Conclusions: Our data favour treatment with wide functional excision followed by radical dose radiotherapy in attempt to
minimize risk of local recurrence, especially when primary tumours are bigger than 3 cm. Our data also suggest the same
treatment for local recurrence, when technically possible, to avoid amputation.
Low Dose Methotrexate and Vinblastine, Given Weekly to PatientsWith Desmoid Tumours, is Associated With Major Toxicity
Authors: van der Hul René L. , Seynaeve Caroline , van Geel Bert N. , Verweij Jaap 
Published: December 2003

Purpose: To evaluate the tolerance of a low dose chemotherapy regimen for desmoid tumours.Patients and methods: Patients with desmoids for whom radical resection was impossible or related to extensive mutilation
were treated with chemotherapy. Treatment consisted of intravenous methotrexate at a dose of 50mg and vinblastine at a
dose of 10mg weekly, scheduled to be given for a total period of 1 year. Doses were reduced and/or delayed on an individual
basis, depending on the observed type of toxicity.Results: Ten patients (six males; four females), median age 43 years (range17–75), median WHO performance score 1
(range 0–1), were treated. None of them was able to complete the treatment as scheduled, due to observed side effects,
while in two patients treatment was also discontinued because of progressive disease. In six patients, less than 50% of the
projected administrations and dose could be given. Severe organ toxicity was noted in three patients (one interstitial
pneumonitis, two toxic hepatitis), which, however, was reversible in all cases.Discussion: Methotrexate and vinblastine given at this dose and schedule lead to an unacceptable level of toxicity for a
long‐term treatment, and cannot be recommended for standard use.
Factors Influencing Prognosis After Initial Inadequate Excision(IIE) for Soft Tissue Sarcoma
Authors: Van Geel Albert N. , Eggermont Alexander M. M. , Hanssens Patrick E. J. , Schmitz Paul I. M. 
Published: December 2003

Purpose. The influence of initial inadequate excision (IIE) of soft tissue sarcoma (STS) on local control and overall survival
is not well established. It is generally believed that an IIE may have a negative impact on both, despite subsequent treatment
by radical surgery and radiotherapy. However, data on local recurrence‐free survival/overall survival are conflicting and there
are no data on the effect of IIE on overall survival.Patients and methods. A retrospective analysis was made of 86 patients with soft tissue sarcoma of the extremities and trunk
after an IIE had been performed due to inappropriate work‐up. The minimal follow‐up was 7 years. Specimens of the
subsequent radical resection were evaluated for residual tumor, grade of tumor and complications of IIE. Endpoints were
recurrence‐free survival and overall survival.Results. Specimens of the subsequent radical resection showed residual tumor in 66 patients (77%). The most common
complication after IIE was hematoma. In both univariate and multivariate analyses, grade II/III tumors and complications
after IIE are significant negative prognostic factors for local recurrence‐free survival (P = 0.008 and P = 0.002, respectively,
in the Cox model). For this survival, three prognostic groups could be formed based on grade, or presence or absence of
complications. Adjuvant radiotherapy did not change the rate of local recurrence‐free survival. For overall survival, only
tumor grade is a significant factor (log‐rank test).Conclusion. This retrospective study shows that complications associated with an IIE have a significant negative effect on
local control, but not on overall survival, because IIE is often the result of inappropriate work‐up before surgery. For better
diagnosis and therapy STS should be treated in specialized centers.
NO Production by Pseudomonas aeruginosa cd1 Nitrite Reductase
Authors: Cutruzzolà Francesca , Rinaldo Serena , Centola Fabio , Brunori Maurizio 
Published: December 2003

AbstractThe structural and catalytic properties of Pseudomonas aeruginosa cd1 nitrite reductase, a key enzyme in bacterial denitrification, are reviewed in this paper. The mechanism of reduction of nitrite to NO is discussed in detail with special attention to the structural interpretation of function. The ability to stabilize negatively charged molecules, such as the substrate (nitrite) and other ligands (hydroxide and cyanide), is a key feature of catalysis in cd1NIRs. The positive potential in the active site is largely due to the presence of the two conserved distal histidines, which are involved in both substrate binding and product release. IUBMB Life, 55: 617‐621, 2003
Interplay of Cu,Zn Superoxide Dismutase and Nitric Oxide Synthase in Neurodegenerative Processes
Authors: Rotilio Giuseppe , Aquilano Karia , Ciriolo Maria Rosa 
Published: December 2003

AbstractReactive oxygen and nitrogen species (ROS and RNS) have been extensively recognized as important signaling molecules implicated in physiological processes such as gene expression, cell differentiation and immune activation. Nevertheless, continuous production of these species may produce oxidative and/or nitrosative stress resulting in cell damage and ultimately leading to cell death. Due to the high oxygen consumption and relative poor antioxidant defense, the central nervous system is highly susceptible to ROS‐ and RNS‐mediated toxicity. Actually, the oxidative and nitrosative stress have been implicated in the pathogenesis of neurodegeneration of a large variety of neurological disorders. This review will cover some aspects of the involvement of ROS‐ and RNS‐mediated apoptotic processes occurring in cellular models of familial amyotrophic lateral sclerosis (FALS), in particular the cases associated with mutations in SOD1, the gene encoding Cu,Zn superoxide dismutase (Cu,Zn SOD). A possible role for proteasome in the inhibition of neurodegenerative process by balancing ROS and RNS species is envisaged on the basis of evidence provided by results obtained from studies on this experimental model. IUBMB Life, 55: 629‐634, 2003
Nitric Oxide and Mitochondrial Complex IV
Authors: Sarti Paolo , Arese Marzia , Bacchi Antonella , Barone Maria Cecilia , Forte Elena , Mastronicola Daniela , Brunori Maurizio , Giuffrè Alessandro 
Published: December 2003

AbstractMicromolar nitric oxide (NO) rapidly (ms) inhibits cytochrome c oxidase in turnover with physiological substrates. Two reaction mechanisms have been identified leading, respectively, to formation of a nitrosyl‐ [a32+‐NO] or a nitrite‐ [a33+‐NO2‐] derivative of the enzyme. In the presence of O2, the nitrosyl adduct recovers activity slowly, following NO displacement at k'≈0.01 s‐1 (37°C); the recovery of the nitrite adduct is much faster. Relevant to patho‐physiology, the enzyme does not degrade NO by following the first mechanism, whereas by following the second one it promotes NO oxidation and disposal as nitrite/nitrate. The reaction between NO and cytochrome c oxidase has been investigated at different integration levels of the enzyme, including the in situ state, such as in mouse liver mitochondria or cultured human SY5Y neuroblastoma cells. The respiratory chain is inhibited by NO, either supplied exogenously or produced endogenously via the NO synthase activation. Inhibition of respiration is reversible, although it remains to be clarified whether reversibility is always full and how it depends on concentration of and time of exposure to NO. Oxygraphic measurements show that cultured cells or isolated state 4 mitochondria exposed to micromolar (or less) NO recover from NO inhibition rapidly, as if the nitrite reaction was predominant. Mitochondria in state 3 display a slightly more persistent inhibition than in state 4, possibly due to a higher accumulation of the nitrosyl adduct. Among a number of parameters that appear to control the switch over between the two mechanisms, the concentration of reductants (reduced cytochrome c) at the cytochrome c oxidase site has been proved to be the most relevant one. IUBMB Life, 55: 605‐611, 2003
SMC Proteins at the Crossroads of Diverse Chromosomal Processes
Authors: Jessberger Rolf 
Published: December 2003

AbstractHow should a protein be designed to serve in processes as diverse as chromosome condensation, sister chromatid cohesion, DNA recombination, gene dosage regulation, and perhaps even gene silencing or transcriptional regulation ‐ which occur in both mitosis and meiosis? Such a protein or protein complex needs to bear DNA interaction domains, it needs the capacity to use energy to move DNA, it needs to enter into highly specific protein interactions, it needs to be large enough to link two DNA molecules, it needs to be of sufficient flexibility to cope with different types of chromatin structure, yet it also needs to be rigid enough to pull, push or enclose DNA. SMC proteins fulfill these requirements and form the core units of high molecular weight complexes that act in all those processes, and are essential for some of them. SMC stands for 'Structural Maintenance of Chromosomes', although SMC proteins are not static scaffold proteins merely providing support for a particular chromosome structure. SMC proteins are rather highly dynamic actors, that generate and modulate chromosome structures, affecting a plethora of biological processes. IUBMB Life, 55: 643‐652, 2003
Small Heat‐shock Proteins and Clusterin: Intra‐ and Extracellular Molecular Chaperones with a Common Mechanism of Action and Function?
Authors: Carver John A. , Rekas Agata , Thorn David C. , Wilson Mark R. 
Published: December 2003

AbstractSmall heat‐shock proteins (sHsps) and clusterin are molecular chaperones that share many functional similarities despite their lack of significant sequence similarity. These functional similarities, and some differences, are discussed. sHsps are ubiquitous intracellular proteins whereas clusterin is generally found extracellularly. Both chaperones potently prevent the amorphous aggregation and precipitation of target proteins under stress conditions such as elevated temperature, reduction and oxidation. In doing so, they act on the slow, off‐folding protein pathway. The conformational dynamism and aggregated state of both proteins may be crucial for their chaperone function. Subunit exchange is likely to be important in regulating chaperone action; the dissociated form of the protein is probably the chaperone‐active species rather than the aggregated state. They both exert their chaperone action without the need for hydrolysis of ATP and have little ability to refold target proteins. Increased expression of sHsps and clusterin accompanies a range of diseases that arise from protein misfolding and deposition of highly structured protein aggregates known as amyloid fibrils, e.g., Alzheimer's, Creutzfeldt‐Jakob and Parkinson's diseases. The interaction of sHsps and clusterin with fibril‐forming species is discussed along with their ability to prevent fibril formation. IUBMB Life, 55: 661‐668, 2003
The HIV‐1 Tat Transactivator Protein: a Therapeutic Target?
Authors: Fulcher Alex J. , Jans David A. 
Published: December 2003

AbstractThe human immunodeficiency virus‐1 (HIV‐1), the causative agent of autoimmune deficiency syndrome (AIDS) is a major health problem world‐wide. Central to HIV infection is the transactivator protein Tat, that plays a critical role in the nucleus during the HIV infectious cycle, by binding the transactivation‐responsive region (TAR) and thereby enhancing transcriptional elongation. Tat appears to gain nuclear entry through a novel mechanism, independent of the normal cellular importin/Ran‐dependent pathways, and regulated by a cytoplasmic retention mechanism. Since blocking Tat nuclear import is likely to prevent HIV infection, detailed delineation of Tat's nuclear import pathway is critical to assessing its viability as a therapeutic target. Other feasible anti‐HIV therapies include approaches to inhibit Tat‐TAR interaction. IUBMB Life, 55: 669‐680, 2003
Comparative Diagnostic Performances of Auscultation, Chest Radiography, and Lung Ultrasonography in Acute Respiratory Distress Syndrome
Authors: Lichtenstein Daniel , Goldstein Ivan , Mourgeon Eric , Cluzel Philippe , Grenier Philippe , Rouby Jean-Jacques 
Published: December 2003

Background
Lung auscultation and bedside chest radiography are routinely used to assess the respiratory condition of ventilated patients with acute respiratory distress syndrome (ARDS). Clinical experience suggests that the diagnostic accuracy of these procedures is poor.

Methods
This prospective study of 32 patients with ARDS and 10 healthy volunteers was performed to compare the diagnostic accuracy of auscultation, bedside chest radiography, and lung ultrasonography with that of thoracic computed tomography. Three pathologic entities were evaluated in 384 lung regions (12 per patient): pleural effusion, alveolar consolidation, and alveolar-interstitial syndrome.

Results
Auscultation had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung ultrasonography, in contrast to auscultation and chest radiography, could quantify the extent of lung injury. Interobserver agreement for the ultrasound findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and 0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and pleural effusion, respectively.

Conclusions
At the bedside, lung ultrasonography is highly sensitive, specific, and reproducible for diagnosing the main lung pathologic entities in patients with ARDS and can be considered an attractive alternative to bedside chest radiography and thoracic computed tomography.
Noninvasive Positive Pressure Ventilation Using a Helmet in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Antonelli Massimo , Pennisi Mariano Alberto , Pelosi Paolo , Gregoretti Cesare , Squadrone Vincenzo , Rocco Monica , Cecchini Luca , Chiumello Davide , Severgnini Paolo , Proietti Rodolfo , Navalesi Paolo , Conti Giorgio 
Published: December 2003

Background
Noninvasive positive pressure ventilation (NPPV) with a facemask (FM) is effective in patients with acute exacerbation of their chronic obstructive pulmonary disease. Whether it is feasible to treat these patients with NPPV delivered by a helmet is not known.

Methods
Over a 4-month period, the authors studied 33 chronic obstructive pulmonary disease patients with acute exacerbation who were admitted to four intensive care units and treated with helmet NPPV. The patients were compared with 33 historical controls treated with FM NPPV, matched for simplified acute physiologic score (SAPS II), age, PaCO2, pH, and PaO2:fractional inspired oxygen tension. The primary endpoints were the feasibility of the technique, improvement of gas exchange, and need for intubation.

Results
The baseline characteristics of the two groups were similar. Ten patients in the helmet group and 14 in the FM group (P = 0.22) were intubated. In the helmet group, no patients were unable to tolerate NPPV, whereas five patients required intubation in the FM group (P = 0.047). After 1 h of treatment, both groups had a significant reduction of PaCO2 with improvement of pH; PaCO2 decreased less in the helmet group (P = 0.01). On discontinuing support, PaCO2 was higher (P = 0.002) and pH lower (P = 0.02) in the helmet group than in the control group. One patient in the helmet group, and 12 in the FM group, developed complications related to NPPV (P < 0.001). Length of intensive care unit stay, intensive care unit, and hospital mortality were similar in both groups.

Conclusions
Helmet NPPV is feasible and can be used to treat chronic obstructive pulmonary disease patients with acute exacerbation, but it does not improve carbon dioxide elimination as efficiently as does FM NPPV.
High Incidence of Myocardial Ischemia during Postpartum Hemorrhage
Authors: Karpati Peter C. J. , Rossignol Mathias , Pirot Marcus , Cholley Bernard , Vicaut Eric , Henry Patrick , Kévorkian Jean-Philippe , Schurando Patrick , Peynet Jacqueline , Jacob Denis , Payen Didier , Mebazaa Alexandre 
Published: December 2003

Background
Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia.

Methods
On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia.

Results
A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels.

Conclusions
These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.