bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychological assessment of children and adolescents with systemic lupus erythematosus
Authors: Wyckoff P.M. , Miller L.C. , Tucker L.B. , Schaller J.G.
Published: November 2007

Neuropsychological assessments of adults with SLE have shown cognitive impairment, sequential processing deficits, memory loss, increased incidence of left handedness, learning disabilities and emotional distress compared with healthy individuals or subjects with other medical conditions. Neuropsychological testing regarding these variables in children and adolescents with SLE has been infrequently reported. For this study, eight children with SLE (age 9-17 years at diagnosis) were assessed with neuropsychological testing at a median of 10.5 months (range 1 week to 30 months) after diagnosis. Tests included Wechsler Intelligence Scale for Children-Revised or Wechsler Adult Intelligence Scale-Revised, Wide Range Achievement Test-Revised, Standard Binet Intelligence Scale Fourth Edition Memory Subtests or Wechsler Memory Scale (all mean = 100 ± 15) and Gates MacInitie Reading Comprehension Test, Achenbach Child Behavior Checklist and Achenbach Youth Self Report. Mean intellectual scores were in the low average range (Wechsler Full Scale mean = 85.0 ± 11.9, Verbal Scale mean 85.2 ± 13.9, Performance Scale mean = 88.0 ± 13.9). Academic achievement was globally depressed (reading recognition mean = 79.5 ± 22.0, spelling mean = 78.9 ± 23.5), especially in arithmetic (mean = 70.5 ± 14.9). Children with SLE averaged 5 years behind grade placement in reading comprehension. Visual memory was also depressed in patients with SLE. Behavior ratings failed to demonstrate any significant aberrations in the test subjects.
Acute reversible hypoxemia in systemic lupus erythematosus: a new syndrome or an index of disease activity?
Authors: Martinez-Taboada V.M. , Blanco R. , Armona J. , Fernandez-Sueiro J.L. , Rodriguez-Valverde V.
Published: November 2007

In 1991, Abramson et al reported a new syndrome of acute reversible hypoxemia (ARH) in patients with severe SLE (systemic lupus erythematosus). This syndrome was characterized by an unexplained abnormal value of arterial blood gases (ABG) without obvious parenchymal lung disease, and a good response to high-dose corticosteroid therapy. After we became aware of this entity, four of 16 patients admitted to our unit because of a SLE flare presented respiratory symptoms and abnormal ABG consistent with ARH. In none of our patients were the pulmonary manifestations a prominent clinical feature of the disease. Furthermore, in two of them, treatment with high-dose aspirin and moderate to low doses of corticosteroids was sufficient to improve the pulmonary manifestations, but not to control the systemic activity of the disease. Therefore, we believe that this new pulmonary finding more than a clinically independent syndrome represents an index of disease activity in patients with SLE.
Thyroid peroxidase autoantibodies and their effects on enzyme activity in patients with systemic lupus erythematosus
Authors: Tsai R.-T. , Chang T.-C. , Wang C.-R. , Lee S.-L. , Wang C.-J. , Tsay G.J.
Published: November 2007

Thyroid microsomal antibodies (Ms-Ab) are recently proved to be directed to thyroid peroxidase (TPO). The aim of this study was to investigate whether the sera of patients with systemic lupus erythematosus (SLE) contain anti-TPO antibodies (TPO-Ab) and whether these antibodies influence enzyme activity. Sera from patient with Hashimoto's thyroiditis was also studied. Serum samples were obtained from 37 patients with SLE, 20 patients with Hashimoto's thyroiditis and 20 healthy subjects. TPO-Ab were detected by immunoprecipitation using crude microsomal preparations or enzyme-linked immunoabsorbent assay (ELISA) with recombinant TPO. Positive TPO-Ab by ELISA were found in 11 (61%) of 18 patients with lupus whose serum contained Ms-Ab. Low levels of TPO-Ab also were found in three (16%) of 19 lupus sera that did not contain Ms-Ab. All patients with Hashimoto's thyroiditis had high levels of TPO-Ab in serum. When measured by ELISA, TPO-Ab were highly correlated with the results of a TPO immunoprecipitation assay and with the titers of Ms-Ab in patients with lupus (r = 0.83, n = 18, P < 0.01; r = 0.63, n = 18, P < 0.01) and in Hashimoto's thyroiditis (r = 0.89, n = 20, P < 0.01; r = 0.75, n = 20, P < 0.01). When evaluating the direct influence of TPO-Ab on the activity of TPO, we found no significant inhibition of enzymatic activity in both guaiacol and iodide assays by lupus sera in contrast with sera from Hashimoto's thyroiditis. Our findings raise the possibility that the specificities of TPO-Ab in SLE are distinct from those in patients with Hashimoto's thyroiditis.
Benign intracranial hypertension: a non-thrombotic complication of the primary antiphospholipid syndrome?
Authors: Orefice Giuseppe , De Joanna Gabriella , Coppola Maria , Brancaccio Vincenzo , Ames Paul R.J.
Published: November 2007

Benign intracranial hypertension is a rare complication of systemic lupus erythematosus often attributed to cerebral sinus thrombosis which impairs venous drainage and cerebrospinal fluid outflow. We report the case of a woman with a primary antiphospholipid syndrome who developed benign intracranial hypertension with no actual evidence of venous cerebral thrombosis and with no other possible cause for this clinical manifestation than high titres of anticardiolipin antibodies and a lupus anticoagulant.
Enhancement of renal disease in BXSB lupus prone mice after prior exposure to bacterial lipopolysaccharide
Authors: Granholm NA , Cavallo T.
Published: November 2007

The mechanism, or mechanisms, responsible for enhancement of renal disease after episodes of infection are poorly understood. We used the BXSB mouse as a lupus model of autoimmune disease and we used bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism by which infections promote enhancement of autoimmune disease to chronicity. BXSB mice were exposed to LPS for 5 weeks, LPS was withdrawn and various tests and measurements were performed 6 weeks thereafter. Matched BXSB mice exposed to vehicle injections for 5 weeks served as controls. We verified that previous exposure to LPS enhances polyclonal B cell activation, impairs carrier function of blood cells for immune complexes, increases deposition of immune complexes in the microcirculation and promotes glomerular inflammation and sclerosis. These changes occurred at 6 weeks after withdrawal of LPS in the presence of unimpaired function of mononuclear phagocytes. Some of the effects of LPS are reversible, others are partially so and others are irreversible. Altered immune functions elicited by prior exposure to LPS can result in enhanced involvement of various renal compartments and can result in renal insufficiency.
Erythrocyte aplasia and systemic lupus erythematosus
Authors: Kiely Pdw , McGuckin CP , Collins DA , Bevan DH , Marsh Jcw
Published: November 2007

Pure erythrocyte aplasia is a recognised feature of systemic lupus erythematosus (SLE); here we report two cases, one predating the onset of SLE, the other following a long period of disease quiescence. One case demonstrates the typical features of this disorder and was successfully treated with prednisolone. The second case is unusual in being resistant to immunosuppressive treatment. Bone marrow culture from the second patient revealed an inhibition of BFU-E colony formation in the presence of the patient's serum, indicating that a serum inhibitor of haemopoiesis was present. Furthermore, following T cell depletion of this patient's marrow, there was an increase in BFU-E, CFU-G and CFU-GM colony growth implicating, in addition, a possible T cell-mediated inhibition of marrow haemopoiesis. This is a novel observation and may explain the resistance shown by this patient to standard treatment.
Pneumonitis in a lupus twin pregnancy: a case report
Authors: Comer M. , D'Cruz D. , Thompson I. , Erskine K. , Dacre J.
Published: November 2007

We describe a patient with systemic lupus erythematosus (SLE), whose pregnancy was com plicated by fulminant lupus pneumonitis and pericarditis. Maternal disease responded to therapy and twin girls were delivered, both with thrombocytopenia, one of whom died of an intraventricular haemorrhage. Pneumonitis is a rare complication of lupus in pregnancy which may be fatal. We suggest patients with previous severe pneumonitis should have lung function tests at the onset of pregnancy, and treatment be modified to suppress flare if there is any indication of severe pneumonitis in early pregnancy.
Review : Variable regions of two murine antibodies that bind the SLE associated 16/6 idiotype
Authors: Waisman A. , Ruiz P.J. , Mozes E.
Published: November 2007

Experimental systemic lupus erythematosus can be induced in naive mice of different strains using a human monoclonal antibody bearing the 16/6 idiotype and a murine anti-16/6 Id monoclonal antibody designated 1A3-2. Herein we report the isolation of a second anti-16/6 Id antibody, 3F7-8, from BALB/c mice afflicted with experimental SLE. In contrast to the previously reported (1A3-2) anti-16/6 Id monoclonal antibody, mAb 3F7-8 does not induce experimental SLE upon immunization. The variable heavy and light chains of both anti bodies were cloned and their sequences were determined. The VH of mAb 1A3-2 was found to express a germ line gene from the Q52 family, with a high homology to an anti-lysozyme antibody. The VH of monoclonal antibody 3F7-8 was found to express a 7183 germ line gene, showing over 95% homology with the VH of 12 anti-Sm antibodies isolated from MRL-1pr mice. Based on sequence homology to other known antibodies, we further demon strated that monoclonal antibodies 1A3-2 and 3F7-8 bind lysozyme and the Sm ribonu cleoproteins, respectively, in addition to their binding to the 16/6 Id.
Review : Transverse myelopathy in SLE: clinical features and functional outcomes
Authors: Chan K-F. , Boey M-L.
Published: November 2007

The objective of the study was to examine the clinical features of lupus patients who present with transverse myelopathy (TM) and ascertain functional outcomes when treated early with high dose corticosteroids and/or cyclophosphamide. Case records of nine patients who developed a total of 14 episodes of TM were retrospectively studied. All the patients were female and their ages ranged from 21 to 59 years. Nine episodes of paraperesis, three of tetraperesis, one of numbness and one of neurogenic bladder were reported early in the diagnosis of SLE (median of two years). Neurogenic bowel and bladder and presence of ANA and ds-DNA were invariable. Urodynamics assessment in six patients showed abnor mal detrusor behavior in all. CT scans and myelograms were uninformative and CSF studies were normal. ESR and complement levels were insensitive as markers of disease activity. The treatment regimens included pulses of methylprednisolone and/or cyclophos phamide followed by prednisolone and high dose prednisolone from onset. The functional outcomes were uniformly good - with independent ambulation in all except three (who needed assistive devices) and improvement of motor scores. Acute hospital stays were short (range of three to 45 days) whilst only two were referred for inpatient rehabilitation. Bladder abnormalities persisted despite motor recovery and would require long-term review.
Factor V:Q506 mutation and anticardiolipin antibodies in systemic lupus erythematosus
Authors: Bengtsson A. , Zöller B. , de Frutos PG , Dahlbäck B. , Sturfelt G.
Published: November 2007

Inherited resistance to activated protein C (APC resistance) is an important risk factor of venous thrombosis. It is caused by a point mutation in the gene coding for coagulation factor V, called FV:Q506. Arterio-venous thrombosis is a common and serious medical problem in patients with systemic lupus erythematosus (SLE). We studied the prevalence of the factor V mutation associated with APC resistance and IgG anticardiolipin antibodies (aCLs) in an epidemiological cohort of 78 Swedish SLE patients, to determine their roles as risk factors for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these patients was performed. Totally, 19 (24%) of the 78 SLE patients had thrombosis, 11 (14%) had venous thrombosis and 8 (10%) had a cerebral infarction caused by occlusion of cerebral vessels. Twenty-six (33%) SLE patients were aCL positive and 8 (10%) were heterozygous for the factor V mutation. Only one of the patients with venous thrombosis and one of the patients with cerebral thrombosis had the FV:Q506 mutation, whereas 3 patients with venous thrombosis and 5 patients with cerebral infarction were aCL positive. Eleven of 19 patients with heart valve disease were aCL positive, a statistically significant association ( P = 0.01). In conclusion, we found no statistically significant association between venous thrombosis and FV:Q506 mutation or venous thrombosis and aCL positivity. There was, however, an association between heart valve disease and aCL positivity.
Disease activity, cumulative damage and quality of life in systematic lupus erythematosus: results of a cross-sectional study
Authors: Hanly J.G.
Published: November 2007

The relationship between disease activity, cumulative damage and self-reported quality of life was examined in 96 patients with Systematic Lupus Erythematosus (SLE).

Disease activity was measured by the SLE Disease Activity Index (SLEDAI) and cumulative damage by the Systematic Lupus International Cooperating Clinics/ACR damage index (DI). Quality of life was assessed by the Medical Outcomes Survey Short Form 20 (SF-20) self-report questionnaire which consists of six subscales.

The study population was predominantly Caucasian (91 %) and female (90%). The mean (± s.d.) age was 42.0 ± 11.0 years and disease duration was 7.5 ± 5.5 years. SLEDAI scores varied from 0-28, with a mean (± s.d.) of 4.8 ± 5.2. The mean (± s.d.) DI score was 0.74 ± 1.06, with a range of 0-5. Subscales of the SF-20 varied from 0-100 and the range of mean (± s.d.) scores varied from 35.0 ± 42.2 to 70.5 ± 28.7. There was no correlation between SLEDAI and DI scores or between SLEDAI scores and any of the six subscales of the SF-20. Likewise there was no correlation between DI scores and SF-20 subscales with the exception of Health perception ( r = 0.34, P = 0.02).

These results indicate that there are at least three independent dimensions of health status in SLE, namely disease activity, cumulative damage and quality of life. Furthermore, the extent of inflammatory disease activity and irreversible target organ damage are not the sole determinants for quality of life in SLE patients.
Side-effects of intravenous cyclophosphamide pulse therapy
Authors: Martin F. , Lauwerys B. , Lefèbvre C. , Devogelaer J.-P. , Houssiau F.A.
Published: November 2007

We reviewed the side-effects of intravenous (IV) cyclophosphamide (CPM) pulse therapy in a group of 75 patients suffering from various autoimmune disorders (mostly systemic lupus erythematosus and vasculitis) who received a total of 451 IV CPM pulses, given on a monthly basis (mean ± s.d. CPM dose per pulse: 764 ± 217 mg; mean ± s.d. follow-up period: 26.7 ± 22.1 mon). Infection was the most common side-effect (30 episodes in 21 patients; 28% of the patients) but rarely required in-patient treatment (8 episodes in 7 patients; 9% of the patients). No relationship could be found between the occurrence of infection and the dose of CPM or of glucocorticoids. Other side-effects were rare. Only one patient suffered from neutropenia. Haemorragic cystitis was never observed nor did premature ovarian failure in the 25 female patients at risk. Four patients developed neoplasia and three died suddenly a few days after receiving a CPM pulse but the causal relationship between CPM therapy and these poor outcomes is speculative. Taken together, our data confirm in a large group of patients that IV CPM pulse therapy is relatively safe. In particular, the rate of severe infection requiring in-patient treatment is rare (1.8% of 451 pulses).
Churg-Strauss syndrome presented as multiple intracerebral hemorrhage
Authors: Liou H.-H. , Liu H.-M. , Chiang I.-P. , Yeh T.-S. , Chen R.-C.
Published: November 2007

Intracerebral hemorrhage is an uncommon sequel of Churg-Strauss syndrome. We describe a 27 y old Taiwanese male patient who was clinicopathologically diagnosed as Churg-Strauss syndrome. The patient experienced a sudden onset of blurring of vision and slowness of motion and speech. Magnetic resonance imaging of the brain revealed lobar hemorrhage on right parieto-occipital and left parietal areas. The cause of cerebral hemorrhage was probably due to poorly controlled high blood pressure and vasculitis. He received pulse therapy of methylprednisolone and cyclophosphamide followed by oral prednisolone. His neurological symptoms responded well to such a regimen. Cerebral hemorrhage is a major cause of morbidity and death in patients with Churg-Strauss syndrome. Uncontrolled high blood pressure may cause cerebral hemorrhage. Careful monitor of blood pressure is critical for the management of Churg-Strauss syndrome patients.
Immunologically restricted and inhibitory anti-Ro/SSA in monozygotic twins
Authors: Scofield RH , Kurien BT , Reichlin M.
Published: November 2007

A pair of monozygotic twins with Sjögren's syndrome are described who both have large amounts of anti-Ro/SSA in their sera by ELISA, but no precipitin in double immunodiffusion. Unique among previously encountered specimens, sera from the twins inhibit the formation of Ro/SSA precipitins in double immunodiffusion by known anti-Ro/SSA positive SLE patients. The twins have near identical, clonally restricted anti-Ro/SSA autoantibodies as evaluated by isoelectric focusing and bind the same 60 kD Ro/SSA peptides. Thus, this pair of monozygotic twins has an identical fine specificity in their immune response to 60 kD Ro/SSA, despite potential differences in their immune response generated by random processes in the formation of immunoglobulin molecules and T cell receptors. These data imply that the anti-Ro/SSA found in these sera binds less than three epitopes such that soluble antigen/antibody complexes are formed instead of an insoluble complex that precipitates.
Review : Clinical relevance of calreticulin in systemic lupus erythematosus
Authors: Eggleton P. , Reid Kbm , Kishore U. , Sontheimer RD
Published: November 2007

Calreticulin is an abundant intracellular protein which is proposed to have numerous biological functions. However, there is increasing evidence to suggest that calreticulin plays a multifunctional role as an autoantigen present in patients with systemic lupus erythematosus. In this review we detail some of the recent evidence which indicate that calreticulin may play a supportive role in the formation of the autoantigen complex - Ro/SS-A. In addition, several proposed mechanisms of release and surface expression of calreticulin are described in relation to SLE mediated responses to the autoantigen. In particular, the generation of autoantibodies to specific regions of the protein and the ability of calreticulin to interfere with complement mediated inflammatory processes.
Review : Grand Rounds from International Lupus Centres Accelerated atherosclerosis and coronary disease in SLE
Authors: Farhey Y. , Hess E.V.
Published: November 2007

Atherosclerosis may represent a significant cause of death and morbidity in patients with systemic lupus erythematosus. Coronary involvement is more premature in lupus patients. We present the case of a young woman diagnosed with SLE at the age of 20 years who had a myocardial infarction at age 29 years. We review the mechanisms of atherosclerosis, the interrelations between atherosclerosis and autoimmunity, and between atherosclerosis and SLE. We also review the risk factors, influence of disease and treatment and the guidelines for management of accelerated atherosclerosis in lupus patients.
Review : Abnormalities in the protein C anticoagulant pathway detected by a novel assay using human thrombomodulin
Authors: Mohri M. , Sata M. , Gomi K. , Maruyama Y. , Osame M. , Maruyama I.
Published: November 2007

We developed a novel assay using human thrombomodulin (TM), which detected overall abnormalities in the protein C anticoagulant pathway (PC pathway). This assay indicates the degree of inhibition of prothrombinase by TM, which is represented as the percentage of prothrombinase inhibition by 25 ng/ml of TM, termed PIP 25 (Prothrombinase Inhibition Percentage). We examined PIP25 in plasma samples from patients with systemic lupus erythematosus (SLE) with or without lupus anticoagulant (LA), patients with Behret's disease (BD), and patients with miscellaneous thrombotic vasculitis and compared these with the PIP25 of plasma samples from healthy volunteers in Japan. The PIP25s were significantly lower in SLE alone (35.5 ± 12.8%, P = 0.036) and SLE with LA (33.0 ± 13.3%, P = 0.030) and BD (33.3 ± 13.4%, P = 0.010) than those in healthy volunteers (43.5 ± 10.7%). There was no significance between healthy PIP25 and those with miscellaneous thrombotic vasculitis (44.2±8.4%, P = 0.823). These results suggest that the abnormalities of the protein C anticoagulant pathway were present in patients with SLE(LA) and BD.
Systemic lupus erythematosus associated with transverse myelitis and Parkinsonian symptoms
Authors: Osawa H. , Yamabe H. , Kaizuka M. , Tamura N. , Tsunoda S. , Shirato KI , Okumura K.
Published: November 2007

A 31-year old woman developed transverse myelitis after 10 years remission since she was first diagnosed as systemic lupus erythematosus. Although pulse methyl prednisolone resolved her myelitis, Parkinson-like symptoms developed subsequently after reduction of steroid. Treatments including apheresis did not improve her Parkinson-like symptoms such as rigidity, akinesia, impairment of speech and mask-like facial expression. Levodopa was effective as a symptomatic therapy. Orally administered cyclophosphamide eventually led her to remission and withdrawal from levodopa. Her clinical course and the absence of other possible causes prompted us to conclude that Parkinsonian symptoms as well as transverse myelitis may have developed as manifestations of central nervous system lupus.
Ethical Dilemmas in the Lived Experience of Nursing Practice
Authors: Gold Carrol , Chambers Jewell , McQuaid Dvorak Eileen
Published: November 2007

Through a series of semistructured interviews with 12 nurses delivering direct patient care in acute, long-term and home care settings, information was sought regarding the ethical concerns of practicing nurses. Although these nurses frequently did not specifically identify the areas of expressed concern as ethical in nature, thematic analysis of the transcribed interviews uncovered four major ethical areas of concern common to these 12 nurses. These areas are: (1) Withholding of information and truth-telling; (2) Unequal access or inequalities in care; (3) Differences between business and professional values; (4) Breaking and reporting broken rules. Several reasons are offered to explain the failure of nurses accurately to identify specific practice dilemmas as ethical in nature and the sequelae of these failures. Possibilities involving ongoing education and mentored experiences in practice areas are reported.
Robust Three-impulse Sequence Input Shaper Design
Authors: Gürleyük S.S. , Cinal Ş.
Published: November 2007

This article presents an unsophisticated method for tuning the amplitudes and time locations of a three-impulse sequence input shaper. The method helps to solve the insufficient constraint equations directly. A wide range of shapers can be obtained using the proposed method, including Zero Vibration (ZV), Zero Vibration Derivative (ZVD) and Extra Insensitive (EI) or Specified Insensitive (SI) shapers. The impulse amplitudes can be produced without additional derivative constraints or an initial penalty of residual vibration. It is also shown that a more robust input shaper can be obtained using the new algorithm. Experimental results from a step motor are used to support the numerical solutions.
Interaction between mercaptopurine and milk
Authors: de Lemos Mário L. , Hamata Linda , Jennings Sarah , Leduc Tanya
Published: November 2007

Mercaptopurine is a purine analog used for acute lymphoblatic leukemia and chronic myelogenous leukemias. Since it is inactivated by xanthine oxidase (XO), concurrent intake of substances containing XO may potentially reduce bioavailability of mercaptopurine. Cow's milk is known to contain a high level of XO. In vitro and in vivo data suggest that concurrent intake of cow's milk may reduce the bioavailability of mercaptopurine. This interaction may be clinically significant. Therefore most patients should try to separate the timing of taking mercaptopurine and drinking milk. J Oncol Pharm Practice (2007) 13: 237—240.
Fungitoxic Activity Against Phytopathogenic Fungi and the Chemical Composition of Thymus zygis Essential Oils
Authors: Pérez-Sánchez R. , Infante F. , Gálvez C. , Ubera J.L.
Published: November 2007

The yield, chemical composition, and antifungal properties of essential oils from six populations of Thymus zygis Loefl. ex L. were studied. Phytopathogenic fungi Pythium irregulare, Rhizoctonia solani, Colletotrichum acutatum, Fusarium oxysporum, and Sclerotinia sclerotiorum showed a clear inhibition in the poisoned food test. Inhibition is tested by EC50. This activity indicator ranges from 86 ppm in the most active oils to 577 ppm. Among the identified components of the oils, 3-octanol and α-terpinene had the highest correlation with the antifungal activity. Yield, antifungal activity, and plant morphology, led to the selection of the population T. zygis ssp. gracilis harvested at flowering stage as most suitable for potential agronomical use.
Comparative analysis of cyanobacterial superoxide dismutases to discriminate canonical forms
Authors: Priya Balakrishnan , Premanandh Jagadeesan , Dhanalakshmi Raman T , Seethalakshmi Thangaraj , Uma Lakshmanan , Prabaharan Dharmar , Subramanian Gopalakrishnan
Published: November 2007

Background

Superoxide dismutases (SOD) are ubiquitous metalloenzymes that catalyze the disproportion of superoxide to peroxide and molecular oxygen through alternate oxidation and reduction of their metal ions. In general, SODs are classified into four forms by their catalytic metals namely; FeSOD, MnSOD, Cu/ZnSOD and NiSOD. In addition, a cambialistic form that uses Fe/Mn in its active site also exists. Cyanobacteria, the oxygen evolving photosynthetic prokaryotes, produce reactive oxygen species that can damage cellular components leading to cell death. Thus, the co-evolution of an antioxidant system was necessary for the survival of photosynthetic organisms with SOD as the initial enzyme evolved to alleviate the toxic effect. Cyanobacteria represent the first oxygenic photoautotrophs and their SOD sequences available in the databases lack clear annotation. Hence, the present study focuses on structure and sequence pattern of subsets of cyanobacterial superoxide dismutases.

Result

The sequence conservation and structural analysis of Fe (Thermosynechococcus elongatus BP1) and MnSOD (Anabaena sp. PCC7120) reveal the sharing of N and C terminal domains. At the C terminal domain, the metal binding motif in cyanoprokaryotes is DVWEHAYY while it is D-X-[WF]-E-H-[STA]-[FY]-[FY] in other pro- and eukaryotes. The cyanobacterial FeSOD differs from MnSOD at least in three ways viz. (i) FeSOD has a metal specific signature F184X3A188Q189.......T280......F/Y303 while, in Mn it is R184X3G188G189......G280......W303, (ii) aspartate ligand forms a hydrogen bond from the active site with the outer sphere residue of W243 in Fe where as it is Q262 in MnSOD; and (iii) two unique lysine residues at positions 201 and 255 with a photosynthetic role, found only in FeSOD. Further, most of the cyanobacterial Mn metalloforms have a specific transmembrane hydrophobic pocket that distinguishes FeSOD from Mn isoform. Cyanobacterial Cu/ZnSOD has a copper domain and two different signatures G-F-H-[ILV]-H-x-[NGT]-[GPDA]-[SQK]-C and G-[GA]-G-G-[AEG]-R-[FIL]-[AG]-C-G, while Ni isoform has an nickel containing SOD domain containing a Ni-hook HCDGPCVYDPA.

Conclusion

The present analysis unravels the ambiguity among cyanobacterial SOD isoforms. NiSOD is the only SOD found in lower forms; whereas, Fe and Mn occupy the higher orders of cyanobacteria. In conclusion, cyanobacteria harbor either Ni alone or a combination of Fe and Ni or Fe and Mn as their catalytic active metal while Cu/Zn is rare.
Improved protocols for functional analysis in the pathogenic fungus Aspergillus flavus
Authors: He Zhu-Mei , Price Michael S , OBrian Gregory R , Georgianna D Ryan , Payne Gary A
Published: November 2007

Background

An available whole genome sequence for Aspergillus flavus provides the opportunity to characterize factors involved in pathogenicity and to elucidate the regulatory networks involved in aflatoxin biosynthesis. Functional analysis of genes within the genome is greatly facilitated by the ability to disrupt or mis-express target genes and then evaluate their result on the phenotype of the fungus. Large-scale functional analysis requires an efficient genetic transformation system and the ability to readily select transformants with altered expression, and usually requires generation of double (or multi) gene deletion strains or the use of prototrophic strains. However, dominant selectable markers, an efficient transformation system and an efficient screening system for transformants in A. flavus are absent.

Results

The efficiency of the genetic transformation system for A. flavus based on uracil auxotrophy was improved. In addition, A. flavus was shown to be sensitive to the antibiotic, phleomycin. Transformation of A. flavus with the ble gene for resistance to phleomycin resulted in stable transformants when selected on 100 μg/ml phleomycin. We also compared the phleomycin system with one based on complementation for uracil auxotrophy which was confirmed by uracil and 5-fluoroorotic acid selection and via transformation with the pyr4 gene from Neurospora crassa and pyrG gene from A. nidulans in A. flavus NRRL 3357. A transformation protocol using pyr4 as a selectable marker resulted in site specific disruption of a target gene. A rapid and convenient colony PCR method for screening genetically altered transformants was also developed in this study.

Conclusion

We employed phleomycin resistance as a new positive selectable marker for genetic transformation of A. flavus. The experiments outlined herein constitute the first report of the use of the antibiotic phleomycin for transformation of A. flavus. Further, we demonstrated that this transformation protocol could be used for directed gene disruption in A. flavus. The significance of this is twofold. First, it allows strains to be transformed without having to generate an auxotrophic mutation, which is time consuming and may result in undesirable mutations. Second, this protocol allows for double gene knockouts when used in conjunction with existing strains with auxotrophic mutations.

To further facilitate functional analysis in this strain we developed a colony PCR-based method that is a rapid and convenient method for screening genetically altered transformants. This work will be of interest to those working on molecular biology of aflatoxin metabolism in A. flavus, especially for functional analysis using gene deletion and gene expression.
Cross-sectional analysis of adverse outcomes in 1,029 pregnancies of Afro-Caribbean women in Trinidad with and without systemic lupus erythematosus
Authors: Molokhia Mariam , Maconochie Noreen , Patrick Alan Leslie , Doyle Pat
Published: November 2007

The objective of the study was to examine pregnancy outcomes in women with systemic lupus erythematosus (SLE) and population controls in Trinidad. We performed a cross-sectional analysis of adverse outcomes in pregnancies of Afro-Caribbean women with SLE and without SLE. One hundred and twenty-two female adult cases of SLE and 203 neighbourhood age-matched women without SLE were interviewed concerning details of their reproductive history, and the anticardiolipin antibody (ACL) status was established for women with SLE. A total of 1,029 pregnancies were reported (356 by women with SLE, 673 by women without SLE). In women with ≥ 1 pregnancy the total number of pregnancies was similar in women with a diagnosis of SLE and women without; however, a lower proportion of women with SLE had ever been pregnant compared with women without SLE (80% versus 91%, P = 0.002). In multivariate logistic regression analyses adjusted for maternal age, district of residence, pregnancy order and smoking, SLE pregnancies were more than twice as likely to end in foetal death than non-SLE pregnancies (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2–4.7). This effect was driven by a large increase in the odds of stillbirth (OR, 8.5; 95% CI, 2.5–28.8). The odds of early miscarriage (OR, 1.4; 95% CI, 0.6–3.1) and of mid-trimester miscarriage (OR, 1.9; 95% CI, 0.4–9.5) were higher, but were not statistically significantly different, in SLE pregnancies than in non-SLE pregnancies. The odds of ectopic pregnancy (OR, 7.5; 95% CI, 0.9–62.5) and of preterm birth (OR, 3.4; 95% CI, 1.2–10.0) were higher in SLE pregnancies conceived after diagnosis than in non-SLE pregnancies. There was no evidence of raised levels of IgG or IgM ACL among the majority (93/97 women, 96%) of SLE cases who reported sporadic mid-trimester miscarriage or stillbirth, although there was evidence of high levels of IgM and IgG ACL among women reporting three or more miscarriages and three consecutive miscarriages, and of raised IgG ACL among those experiencing ectopic pregnancy. In conclusion, we found evidence for a large increase in risk of stillbirth in the pregnancies of Afro-Caribbean Trinidadian women with SLE (not accounted for by high ACL status). There was some evidence of an increased risk of preterm delivery and ectopic pregnancy in pregnancies conceived after a diagnosis of maternal SLE.
Cancer Risk Management Practices of Noncarriers WithinBRCA1/2Mutation–Positive Families in the Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer
Authors: Dawson Sarah-Jane , Price Melanie A. , Jenkins Mark A. , McKinley Joanne M. , Butow Phyllis N. , McLachlan Sue-Anne , Lindeman Geoffrey J. , Weideman Prue , Friedlander Michael L. , Hopper John L. , Phillips Kelly-Anne
Published: November 2007

Purpose

Women from BRCA mutation–positive families who do not carry the family-specific mutation are generally at average cancer risk and therefore do not require intensive risk management.

Methods

Participants were female noncarriers from BRCA mutation–positive families who had responded to 3 yearly follow-up questionnaires and had chosen to either receive or not receive their genetic test result. In the former group, undertaking mammography younger than age 40 years or more than once every 2 years, clinical breast examination (CBE) more than yearly, breast self-examination (BSE) more than monthly, or any transvaginal ultrasound (TVU) or CA-125 was considered overscreening. Screening behaviors of women who did and did not know their genetic test result were compared. Logistic regression and nonparametric analyses were performed to identify demographic and psychosocial factors (respectively) associated with overscreening.

Results

Of 325 eligible women, 116 knew their mutation status and 209 did not. For the first group, proportions overscreening were mammography, 53%; CBE, 10%; BSE, 11%; TVU, 7%; and CA-125, 10%. There were no significant differences in screening behaviors between the groups. In those aware of their mutation status, parous women were more likely to overuse mammography (odds ratio [OR] = 4.4; 95% CI, 1.1 to 17; P = .03) and women with one or more first-degree relative with ovarian cancer (OC) were more likely to overuse OC screening (TVU: OR = 6.00; 95% CI, 1.0 to 35.1; P = .047, and CA-125: OR = 6.50; 95% CI, 1.49 to 28.4; P = .013).

Conclusion

The reasons for overuse of screening (particularly mammography) by mutation noncarriers require additional elucidation given the potential for harm.
Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile
Authors: DeBoer Mark D. , Zhu Xinxia , Levasseur Peter R. , Inui Akio , Hu Zhaoyong , Han Guofeng , Mitch William E. , Taylor John E. , Halem Heather A. , Dong Jesse Z. , Datta Rakesh , Culler Michael D. , Marks Daniel L.
Published: November 2007

Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide α-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.
Sustaining Effect of Gold Colloids on the Amorphous Titanium Dioxide Particles
Authors: Takayanagi Mariko , Imai Yoko , Tajima Kazuo
Published: November 2007

We have reported that TiO2 particles prepared in reverse micelles showed high photocatalytic activity in an amorphous rather than anatase state and that the amorphous state changes easily into the anatase state just by irradiating visible light. So we prepared Au/TiO2 complex particles which included Au colloids in TiO2 by the reverse micelle method. We found that Au colloids exhibited the sustaining effect of amorphous TiO2 particles. Moreover, Au/TiO2 complex particles showed higher photocatalytic activity than single TiO2 particles and also could be used repeatedly.
Three essential and conserved regions of the group II intron are proximal to the 5′-splice site
Authors: de Lencastre Alexandre , Pyle Anna Marie
Published: November 2007

Despite the central role of group II introns in eukaryotic gene expression and their importance as biophysical and evolutionary model systems, group II intron tertiary structure is not well understood. In order to characterize the architectural organization of intron ai5γ, we incorporated the photoreactive nucleotides s4U and s6dG at specific locations within the intron core and monitored the formation of cross-links in folded complexes. The resulting data reveal the locations for many of the most conserved, catalytically important regions of the intron (i.e., the J2/3 linker region, the IC1(i-ii) bulge in domain 1, the bulge of D5, and the 5′-splice site), showing that all of these elements are closely colocalized. In addition, we show by nucleotide analog interference mapping (NAIM) that a specific functional group in J2/3 plays a role in first-step catalysis, which is consistent with its apparent proximity to other first-step components. These results extend our understanding of active-site architecture during the first step of group II intron self-splicing and they provide a structural basis for spliceosomal comparison.
Seven Steps Towards an Instrumentation Theory for Environmental Policy
Authors: Glasbergen Pieter
Published: November 2007

This article focuses on the questions of the effectiveness of the instruments of environmental policy. After an inspection of the tool kit, a discussion of advantages and disadvantages of various control models is started. The legal, the economic, the communication and the spatial control model are distinguished. On the basis of this discussion elements of a practical instrumentation theory for environmental policy are introduced. The lessons learned provide the principles on which strategies to deal with complex environmental problems may be based.
Immunohistochemical Localization of Collagen Type XI α1 and α2 Chains in Human Colon Tissue
Authors: Bowen Kara B. , Reimers Aaron P. , Luman Sarah , Kronz Joseph D. , Fyffe William E. , Oxford Julia Thom
Published: November 2007

In previous studies, collagen XI mRNA has been detected in colon cancer, but its location in human colon tissue has not been determined. The heterotrimeric collagen XI consists of three a chains. While it is known that collagen XI plays a regulatory role in collagen fibril formation, its function in the colon is unknown. The characterization of normal human colon tissue will allow a better understanding of the variance of collagen XI in abnormal tissues. Grossly normal and malignant human colon tissue was obtained from pathology archives. Immunohistochemical staining with a 58K Golgi marker and α1(XI) and α2(XI) antisera was used to specifically locate their presence in normal colon tissue. A comparative bright field microscopic analysis showed the presence of collagen XI in human colon. The juxtanuclear, dot-like collagen XI staining in the Golgi apparatus of goblet cells in normal tissue paralleled the staining of the 58K Golgi marker. Ultra light microscopy verified these results. Staining was also confirmed in malignant colon tissue. This study is the first to show that collagen XI is present in the Golgi apparatus of normal human colon goblet cells and localizes collagen XI in both normal and malignant tissue. Although the function of collagen XI in the colon is unknown, our immunohistochemical characterization provides the foundation for future immunohistopathology studies of the colon.
Rapid sperm acrosome reaction in the absence of acrosomal CD46 expression in promiscuous field mice (Apodemus)
Authors: Johnson Peter M , Clift Leanne E , Andrlikova Petra , Jursova Michaela , Flanagan Brian F , Cummerson Joanne A , Stopka Pavel , Dvorakova-Hortova Katerina
Published: November 2007

There is pronounced promiscuity and sperm competition in long-tailed field mice (Apodemus sylvaticus). These mice have evolved unusual sperm behaviour favouring rapid fertilisation, including dynamic formation of sperm trains and their subsequent dissociation. The cell surface complement regulatory (CReg) protein CD46 is broadly expressed in eutherian mammals other than rodents, in which it is expressed solely on the spermatozoal acrosomal membrane. Ablation of the CD46 gene has been associated with a faster acrosome reaction (AR) rate in inbred laboratory mice. Here, we demonstrate that wild-caught field mice of three species, A. sylvaticus, A. flavicollis and A. microps, exhibit a more rapid AR than wild-caught house mice Mus musculus or inbred laboratory BALB/c mice. We also demonstrate that wild-caught field mice of these three species, unlike house mice, produce alternatively spliced transcripts of testicular CD46 mRNA lacking exons 5–7 or 6–7, together with an extended 3′ - and often truncated 5′-utr, leading to failure to express any sperm CD46 protein in both the testis and epididymis. Male field mice may therefore have traded expression of this CReg protein for acrosomal instability, providing a novel genus-specific strategy to favour rapid fertilisation and competitive advantage in the promiscuous reproductive behaviour of wild field mice.
Key Articles and Guidelines in the Management of Acute Coronary Syndromes and in Percutaneous Coronary Intervention: 2007 Update
Authors: Dobesh Paul P. , Brouse Sara D. , Dager William E. , Spinler Sarah A. , Stacy Zachary , Wiggins Barbara S.
Published: November 2007

Clinical evidence in the management of acute coronary syndromes (ACS) and in percutaneous coronary intervention (PCI) continues to evolve at a rapid pace. For clinicians to provide optimal care for these patients, it is important to keep up with new information as it becomes available. With the existence of numerous pharmacologic agents, abundance of major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence‐based decisions on the care of patients with ACS or those undergoing PCI can be difficult for clinicians. Therefore, we provide an update to the first compiled bibliography of key articles and guidelines relative to patients with ACS published in Pharmacotherapy in 2004. A number of guidelines and practice‐changing literature have been published since the initial 2004 document. We hope that this compilation will serve as a resource for pharmacists, physicians, nurses, residents, and students responsible for the care of patients with coronary heart disease.
Nebulized Milrinone Use in a Pulmonary Hypertensive Crisis
Authors: Buckley Mitchell S. , Feldman Jeremy P.
Published: November 2007

Significant advances have been achieved over the past few decades regarding comprehension of the pathogenesis of pulmonary arterial hypertension (PAH). The development of new agents and use of existing drug therapies have targeted the underlying abnormalities and pathways leading to progression of PAH. Milrinone, a phosphodiesterase inhibitor, remains a therapeutic option. Unfortunately, intravenous administration of the drug in patients with PAH may be limited by systemic hypotension, especially in those already receiving prostanoid treatment. We describe a 42‐year‐old woman with acute decompensated idiopathic PAH who was given nebulized milrinone as a novel adjunctive therapy. She was acutely treated with intravenous treprostinil 2 ng/kg/minute and inhaled nitric oxide 20 ppm. However, increasing the treprostinil infusion rate or adding other therapies such as intravenous milrinone for acute symptomatic relief was limited by her hemodynamic instability, which required treatment with dobutamine, vasopressin, and epinephrine. Nebulized milrinone was added as salvage therapy for her acute PAH crisis. After 8 days of therapy, the patient's PAH symptoms improved without compromising her mean arterial pressure and heart rate. Nebulized milrinone in addition to inhaled nitric oxide and low‐dose intravenous treprostinil may have played a major role in the acute management of her PAH crisis. Further studies are needed to assess the role of nebulized milrinone in patients with PAH.
Microstructure development during thermomechanical treatment of Al-Mg-Si alloy
Authors: Martinova Z. , Zlateva G.
Published: November 2007

The effect of natural aging and 95% cold deformation on the microstructure evolution and aging characteristics in commercial Al - 1 mass % Mg2Si alloy subjected to thermomechanical treatment (TMT) was examined. Transmission electron microscopy observations, tensile tests and electrical conductivity measurements were carried out in order to correlate microstructural features to properties on each TMT step. It was established that pre-aging at room temperature affected the morphology of dislocation structure induced by next cold deformation. The observed transition from cellular to homogenous dislocation distribution was explained by the different stability of zones produced by pre-aging of different duration. Natural aging suppressed recovery processes during post-deformation artificial aging, especially after prolonged storage after quenching and at lower aging temperature. It influenced the morphology of precipitates produced by post deformation artificial aging also. The overall effect of TMT involving prior-deformation natural aging in the scheme, on hardness, tensile properties and electrical conductivity is discussed based on experimental microstruture observations.