Synthesis and biological evaluation of 17-[131I]iodo-9-telluraheptadecanoic acid, a potential imaging agent.
A method has been developed for the preparation of terminal halogenated tellurium fatty acids (X-R-Te-R'-COOH). The synthesis and physical properties of 17-bromo- and 17-iodo-9-telluraheptadecanoic acid (17-iodo-9-THDA) are described. The radiohalogenated agents are of interest as a result of their expected pronounced and prolonged heart uptake and potential use for evaluation of regional myocardial fatty acid metabolism. Evaluation in rats indicates that the myocardial uptake of 17-[131I]iodo-9-telluraheptadecanoic acid (17-[131I]iodo-9-THDA) is accompanied by significant in vivo deiodination. A comparison of the heart uptake and deiodination of 17-[131I]iodo-9-THDA and 16-[131I]iodopalmitic acid has demonstrated a close similarity in blood levels of radioactivity and thyroid uptake of radioiodide after administration of these agents to rats. These data suggest that the mechanism of deiodination of terminal radioiodinated alkanoic acids primarily results from direct cleavage of the carbon-iodine bond and not from loss of radioiodine from the final catabolite.


Crystal Structures of the C-Terminally Truncated Endoglucanase Cel9Q from Clostridium thermocellum Complexed with Cellodextrins and Tris.
Endoglucanase CtCel9Q is one of the enzyme components of the cellulosome, which is an active cellulase system in the thermophile Clostridium thermocellum. The precursor form of CtCel9Q comprises a signal peptide, a glycoside hydrolase family 9 catalytic domain, a type 3c carbohydrate-binding module (CBM), and a type I dockerin domain. Here, we report the crystal structures of C-terminally truncated CtCel9Q (CtCel9QΔc) complexed with Tris, Tris+cellobiose, cellobiose+cellotriose, cellotriose, and cellotetraose at resolutions of 1.50, 1.70, 2.05, 2.05 and 1.75 Å, respectively. CtCel9QΔc forms a V-shaped homodimer through residues Lys529-Glu542 on the type 3c CBM, which pairs two β-strands (β4 and β5 of the CBM). In addition, a disulfide bond was formed between the two Cys535 residues of the protein monomers in the asymmetric unit. The structures allow the identification of four minus (-) subsites and two plus (+) subsites; this is important for further understanding the structural basis of cellulose binding and hydrolysis. In the oligosaccharide-free and cellobiose-bound CtCel9QΔc structures, a Tris molecule was found to be bound to three catalytic residues of CtCel9Q and occupied subsite -1 of the CtCel9Q active-site cleft. Moreover, the enzyme activity assay in the presence of 100 mm Tris showed that the Tris almost completely suppressed CtCel9Q hydrolase activity.


A tunable erbium-doped fiber ring laser with power-equalized output.
We propose and demonstrate a tunable erbium-based fiber ring laser with power-equalized output. When a mode-restricting intracavity fiber Fabry-Perot tunable filter (FFP-TF) is combined, the proposed resonator can guarantee a tunable laser oscillation. This proposed laser can obtain the flatter lasing wavelength in an effectively operating range of 1533.3 to 1574.6 nm without any other operating mechanism. Moreover, the performances of the output power, wavelength tuning range, and side-mode suppression ratio (SMSR) were studied.


Paraoxonase-1 in female infertility: a possible role against oxidative stress-induced inflammation.
In this observational, case-control study in infertile women, we observed elevated serum oxidative stress that was significantly correlated with an increase in serum paraoxonase-1 activity and without any evidence of a proinflammatory reaction. These results suggest a protective role of paraoxonase-1 against inflammation in this clinical setting.


Relationship between the five-factor model of personality and Axis I disorders in a nonclinical sample.
The relationship between the five-factor model (FFM) of personality and Axis I disorders was evaluated in a nonclinical sample of 468 young adults. In general, scores on the 5 personality dimensions of neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness (assessed via the NEO Five-Factor Inventory) distinguished subjects with and without a variety of Axis I diagnoses from the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders. In several instances, results indicate that scores on these dimensions were differentially sensitive to diagnosis. Furthermore, scores on these 5 personality dimensions accounted for unique variance in several Axis I diagnoses above and beyond that accounted for by a general measure of current psychopathological symptoms. These results support the utility of the FFM of personality in Axis I diagnostic assessment.


[Metoclopramide-induced respiratory dyskinesia].
This case report describes a patient, who presented with extrapyramidal side effects to the treatment with metoclopramide, which is used as an antiemetic, for gastroparesis and reflux. However, beyond its desired effect, serious neurological adverse reactions can be seen, which is why the European Medicines Agency and the Danish Medicines Agency have changed the recommendations for its use. If the extrapyramidal side effects include the respiratory muscles, the patient's ability to breathe can be affected. If a patient receiving metoclopramide or anti-psychotic drugs shows signs of tachypnoea or acute respiratory distress, the possibility of respiratory dyskinesia should always be considered.


An immunocytochemical mapping of methionine-enkephalin-Arg6-Gly7-Leu8 in the cat brainstem.
The distribution of methionine-enkephalin-Arg6-Gly7-Leu8-immunoreactive cell bodies and fibres was studied in the brainstem of the cat using an indirect immunoperoxidase technique. In the mesencephalon, immunoreactive cell bodies were observed in the periaqueductal grey, the dorsal raphe nucleus, the central and pericentral nuclei of the inferior colliculus and the pericentral division of the dorsal tegmental nucleus. In the pons, immunoreactive cell bodies were observed in the dorsolateral division of the pontine nucleus; below the central division of the dorsal tegmental nucleus; above the dorsolateral division of the pontine nucleus, and close to the superior cerebellar peduncle. In the medulla oblongata, immunoreactive cell bodies were observed in the laminar spinal trigeminal nucleus and in the lateral tegmental field; the dorsal motor nucleus of the vagus; the prepositus hypoglossal nucleus; the medial nucleus of the solitary tract; the rostral division of the cuneate nucleus, and close to the parvocellular division of the alaminar spinal trigeminal nucleus. The highest (moderate) density of immunoreactive fibres was observed in the periaqueductal grey; the parvocellular and magnocellular divisions of the alaminar spinal trigeminal nucleus; the laminar spinal trigeminal nucleus; the rostral division of the cuneate nucleus; the dorsal motor nucleus of the vagus; the lateral nucleus of the solitary tract, and in the midline between the central divisions of the reticulotegmental pontine nucleus. The widespread distribution of methionine-enkephalin-Arg6-Gly7-Leu8 in the cat brainstem indicates that the peptide might be involved in several physiological functions.


Renal arteriovenous fistula induced by extracorporeal shock wave lithotripsy treated by retroperitoneoscopic nephrectomy.
Renal arteriovenous fistula (AVF) is a rare but potentially severe and life-threatening entity. It can occur after various invasive renal interventions, including resection of a localized renal tumor, renal biopsy, percutaneous renal surgery, and even blunt injury of the kidney. The time of clinical presentation of a renal AVF is variable and may occur decades after the injury originally occurred. Here, we report a case of renal AVF induced by extracorporeal shock wave lithotripsy 11 years earlier in an asymptomatic 72-year-old woman. Given the patient's pre-existing hemodialysis dependence, retroperitoneoscopic nephrectomy was performed. On the basis of patient's clinical history, the location of the renal AVF, and the pathological diagnosis, we suggested that renal AVF was a late consequence of the injury to the intrarenal vessels induced by extracorporeal shock wave lithotripsy.


Monostotic Vertebral Paget's Disease of the Lumbar Spine.
Paget's disease in the Far East is quite rare. Age at diagnosis is usually greater than 50 years, and the disease typically affects the spine. Most patients are usually diagnosed with Paget's disease following radiographic examination for other purposes. It usually occurs at multiple vertebral levels, with only 10-25% of vertebral Paget's disease being monostotic. The disease rarely causes neurologic complications resulting from compression of intraspinal nerve tissue. Here, we present 2 cases of monostotic vertebral Paget's disease of the third lumbar vertebra. The first patient, who may be the first documented case of Paget's disease in the lumbar spine with progressive neurologic deficiency in an Asian population, received decompressive laminectomy due to marked spinal stenosis with neurologic deficits. The symptoms were greatly relieved following surgery, and ambulatory ability was restored. The second patient was diagnosed with Paget's disease following surgical biopsy. He remained asymptomatic at the most recent follow-up.


[CT diagnosis of glomus-jugulare tumours].
Glomus-jugulare tumours (chemodectomas, non-chromaffin paragangliomas) are semi-malignant tumours arising from the glomus structures of the jugular bulb. They are soft tissue tumours which usually expand the jugular foramen and destroy its bony margins. Conventional methods of examination are therefore very effective. However, they only demonstrate the bone destruction and are therefore an indirect method for showing the tumour. The actual size and extent of the tumour, which are important for the surgeon or radiotherapist, cannot be demonstrated by simple x-rays. Computer tomography is very effective in the diagnosis of soft tissue lesions in the skull. CT is therefore of great importance in the diagnosis of glomus-jugulare tumours.


Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families.
Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.


Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons.
It was suggested that neuronal degeneration in Parkinson's Disease (PD) is linked to dopamine (DA) toxicity. Dopamine has been shown to induce programmed cell death in both neuronal and non-neuronal cell types. We examined the molecular changes associated with dopamine-triggered apoptosis in sympathetic neurons using the differential display approach, and isolated 14 different DA responsive genes whose expression is altered during the early stages of the apoptotic process. Nine of these genes are upregulated and five are downregulated in response to DA exposure. Two of the upregulated genes were identified as cyclin B2 and a chicken homologue of chaperonin, a member of the heat shock protein family. Total increase in mRNA expression of both genes after 12 hours of exposure to DA was 40%. These two genes participate in cell cycle control and are specifically involved in determining entry of dividing cells into mitosis. Upregulation of mitosis-related genes in postmitotic sympathetic neurons undergoing apoptosis, may be indicative of an abortive attempt of these neurons to re-enter the cell cycle prior to their death. Possible implications to neuronal degeneration in PD are discussed.


Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002).
The case records of 80 dogs in which idiopathic inflammatory bowel disease (IBD) had been diagnosed were reviewed, and owners were contacted for follow-up information using a telephone questionnaire. The types of IBD encountered were lymphocytic (n=6), lymphocytic-plasmacytic (n=38), eosinophilic (n=6) and mixed inflammation (n=30). Prednisolone, sulphasalazine, metronidazole and tylosin were the most frequently prescribed medications. At follow-up, 21 dogs (26 per cent) were classified as being in remission (for a median of 14 months), 40 dogs (50 per cent) had intermittent clinical signs (for a median of 17 months) and three dogs (4 per cent) had uncontrolled disease (for a median of 19 months). Ten dogs (13 per cent) had been euthanased due to refractory IBD and four of these had entered remission for a median of 21 months prior to developing severe relapse and refractoriness to further treatment. Six dogs (8 per cent) had been euthanased or had died for reasons unrelated to IBD. Hypoalbuminaemia at the time of diagnosis was significantly associated with a negative outcome (P=0.0007). No association was found between the site (P=0.75), type (P=0.44) and severity (P=0.75) of disease. Dietary change to single protein and carbohydrate commercial diets had no association with outcome (P=0.12). Owner assessment of quality of life at follow-up was significantly associated with outcome (P=0.006).


Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation.
To evaluate use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in detection of mediastinal lymph node metastases from non-small cell lung cancer. A prospective trial to compare FDG PET and computed tomography (CT) of the thorax was performed in 23 patients with newly diagnosed or suspected non-small cell lung cancer. Blinded interpretations of CT alone, PET alone, CT and PET together, and fusion images were performed, and the results were compared with pathologic results. Nineteen of 23 patients had non-small cell lung cancer. Prevalence of mediastinal involvement was 41%. In staging disease in the mediastinum, CT alone was 64% sensitive, 44% specific, and 52% accurate, whereas PET alone and fusion images were 82% sensitive, 81% specific, and 81% accurate (P < .05). FDG PET was more accurate than CT in staging disease in the mediastinum in patients with lung cancer and appears to be the preferred imaging method in this clinical setting.


Ezetimibe and atorvastatin both immunoregulate CD4+ T cells from cardiac transplant recipients invitro.
Statins are LDL lowering agents that reduce cardiac allograft vasculopathy (CAV) incidence after cardiac transplantation. Furthermore, 'pleiotropic effects' including immunomodulation have been demonstrated by statins following transplantation. It has also been previously suggested that ezetimibe may exert specific effects on the innate immune system in vitro. We compared the effects of ezetimibe and atorvastatin on T lymphocytes in vitro on the justification that these cells are implicated in the pathogenesis of atherosclerosis, allograft rejection and CAV. Peripheral blood mononuclear cells (PBMCs) were isolated from 30 cardiac transplant recipients and co-cultured with the study drug (or placebo) over 48 h. In total, 150 cultures were performed (5 per patient). Drug concentrations were calculated to simulate 10 mg or 100 mg daily in a 70 kg adult. Flow cytometry was performed to analyse T lymphocyte counts and functional characteristics. Ezetimibe reduced the standard CD3+CD4+ T cell count and CD3+CD4+CD45ro T memory count by dose linear effect (p < 0.001). Atorvastatin also reduced the CD3+CD4+ T cell count and CD3+CD4+CD45ro T memory count by dose linear effect (p = 0.005). Neither drug affected CD3+CD8+ cytotoxic T cells. Both atorvastatin and ezetimibe may have selective immunomodulatory properties independent of their mechanisms of LDL lowering, given that both drugs affect CD4 T helper cells but have no effect on CD8 cytotoxic lymphocytes in vitro. Although speculative, both of these agents could potentially offer benefits to the transplant patient by modulating important components of the adaptive immune system. CD4+ cells in particular are implicated in both CAV and rejection processes.


Suicide risk and choice of antidepressant.
There is presently concern that patients treated for depression with venlafaxine have a higher suicide rate than those treated with other antidepressants, based on results from observational studies. The aim of this study was to determine whether higher suicide risk, defined as previous suicide attempt or suicidal ideation, influenced the choice of antidepressant prescribed in an outpatient mental health unit, the Bedford East Community Mental Health Team. A database held by a the Community Mental Health Team was used to identify patients with Depression who have been treated with Venlafaxine, Citalopram, and patients diagnosed with bipolar II affective disorder. The data was analysed in terms of presence of suicide risk, gender, and whether bipolar II patients on venlafaxine were treated with mood stabilisers. The results showed that a risk of suicide did not prevent the prescription of venlafaxine, that less venlafaxine was prescribed to male patients than females, and that bipolar II patients were indeed treated with mood stabilisers. It appears that in this Community Mental Health Team, the possibility of suicide risk with venlafaxine therapy is considered and appropriately managed. Early diagnosis and appropriate treatment of bipolar disorder is likely to be the most effective step that we can take to reduce the risk of suicide in patients with bipolar disorder .Appropriate care regarding the judicious use of Venlafaxine as a first line treatment in Unipolar Depression is secondary to this.


An auditory vigilance task for mental fatigue detection.
An Auditory Vigilance Task (AVT) as a validation criterion for monitoring mental fatigue was proposed in this study. The biological basis of this task design is on the understanding that mental fatigue is a cortical deactivation. This AVT is simple to perform, free of learning curve and independent on acquired skills (aptitude, knowledge). The validity and sensitivity of this task was verified by a scientifically controlled 25-hour fatigue experiment recorded by Electroencephalogram (EEG). Results showed that this AVT is highly sensitive to changes during fatigue process. The effectiveness of this AVT was compared to one subjective rating scale (FSS). The 5-level fatigue EEG datasets (labeled by AVT and FSS respectively) were fed into Support Vector Machines (SVM). SVM test accuracy indicated that AVT is more effective than subject's own estimation. The results demonstrate conclusively that this AVT is suitable for fatigue detection study as a reliable validation criterion.


The underlying mechanism of calcium peroxide pretreatment enhancing methane production from anaerobic digestion of waste activated sludge.
Recent investigations verified that calcium peroxide (CaO2) could be used to pretreat waste activated sludge to promote methane yield from anaerobic digestion. However, the underlying mechanism of how CaO2 pretreatment promotes methane production is unclear. This work therefore aims to provide insights into such systems. Experimental results showed that with an increase of CaO2 dosage from 0 to 0.14 g/g VSS (volatile suspended solids) the methane yield increased linearly from 146.3 to 215.9 mL/g VSS. Further increases of CaO2 resulted in decreases in methane yield. CaO2 pretreatment promoted the disintegration of sludge and the degradation of sludge recalcitrant organics (especially humus and lignocellulose), thereby providing more substrates for subsequent methane production. Ultraviolet absorption spectroscopy indicated that CaO2 enhanced the cleavage of unsaturated conjugated bonds and reduced the aromaticity of humus and lignocellulose. Fourier transform infrared spectroscopy showed that CaO2 changed the structures and functional groups of humus and lignocellulose, making them transform to be biodegradable. GC/MS analyses exhibited that the degradation products of humus and lignocellulose included several types of small molecular organics such as ester-like, acid-like, and alcohol-like substances. Further investigation demonstrated that substantial methane could be produced from these degradation products. It was also found that the presence of recalcitrant organics was detrimental to anaerobes relevant to anaerobic digestion, and the degradation of such recalcitrant organics mitigated their inhibitions to the anaerobes. Model-based analysis suggested that CaO2 pretreatment increased the maximum methane yield and methane production rate, which were consistent with the analysis above.


Growth hormone (GH) and estradiol regulation of membrane-associated GH binding protein and GH receptors in GH releasing hormone transgenic mice.
Growth hormone (GH) releasing hormone (GHRH) transgenic mice were used to examine the influence of GH on GH receptor (GHR) and membrane-associated GH binding protein (MA-GHBP) levels by means of specific radioimmunoassays and Western blot analysis, since MA-GHBP was described as the major constituent of somatogenic binding to liver membranes in mice. In transgenic animals, a 10-fold increment over normal values was found for hepatic somatogenic binding that could be accounted for by a 3--4-fold increase in GHR and a 9-fold augmentation of MA-GHBP levels. The apparent molecular weight of MA-GHBP was smaller than that of serum GHBP, a difference that was partially abolished by endoglycosidase F digestion. In vivo treatment of female mice with 17 beta-estradiol led to an unexpected down-regulation of MA-GHBP and GHR by 60--75% only in transgenic animals. MA-GHBP and GHR levels are strongly up-regulated by GH, although MA-GHBP up-regulation is much more important than that of GHR.


Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial.
The study was designed to compare pharmacologic and exercise stress during thallium-201 single-photon tomography in a multicenter prospective crossover trial. Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients. The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thallium tomographic tests performed 30 days apart, one during intravenous administration of adenosine (140 micrograms/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics. Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p less than 0.0001) and 11.1 (p less than 0.00001), respectively. The agreement by computer quantification was 86% with kappa and Z statistics of 0.709 (p less than 0.0001) and 12.2 (p less than 0.00001), respectively. Agreement on localization of the perfusion defect to a specific coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p less than 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p less than 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued. Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine.


Tropomyosin Structure, Function, and Interactions: A Dynamic Regulator.
Tropomyosin is the archetypal-coiled coil, yet studies of its structure and function have proven it to be a dynamic regulator of actin filament function in muscle and non-muscle cells. Here we review aspects of its structure that deviate from canonical leucine zipper coiled coils that allow tropomyosin to bind to actin, regulate myosin, and interact directly and indirectly with actin-binding proteins. Four genes encode tropomyosins in vertebrates, with additional diversity that results from alternate promoters and alternatively spliced exons. At the same time that periodic motifs for binding actin and regulating myosin are conserved, isoform-specific domains allow for specific interaction with myosins and actin filament regulatory proteins, including troponin. Tropomyosin can be viewed as a universal regulator of the actin cytoskeleton that specifies actin filaments for cellular and intracellular functions.


Integrated wireless sensor network for monitoring pregnant women.
The paper presents an integrated monitoring system for pregnant women in the third trimester using a mobile cardiotocograph and body sensors. The medical staff has a useful tool to detect abnormalities and prevent unfortunate events in time. The mobile cardiotocograph sends data in real time to a Smartphone that communicates the information in a cloud. The physician accesses the data using the hospital ObgGyn application. The advantage of using this system is that the pregnant woman can follow her pregnancy status evolution from home, and the physician receives alarms from the system if the data is not in normal range and has available information about the health status at any time and location.


Identification of a novel HLA-A*24:02:55 allele by sequence-based typing.
HLA-A*24:02:55 differs from A*24:02:01:01 by a single nucleotide substitution at position 295, in exon 2.


Prostaglandins and hypertension.
Generalized arteriolar vasoconstriction is the dominant element in essential hypertension. Although the proximate cause of this process remains elusive, several lines of evidence suggest that abnormalities in prostaglandin and thromboxane metabolism may contribute to the pathophysiology of hypertension. Diminished endogenous synthesis of vasodilator prostaglandins and enhanced formation of the vasoconstrictor thromboxane may participate in this process, particularly in the kidney. The use of nonsteroidal anti-inflammatory drugs, which inhibit prostaglandin synthesis, may aggravate blood pressure control, especially when used with certain diuretics and other antihypertensive medications. Attempts to enhance endogenous synthesis of prostaglandin metabolites expressing potent vasodilator properties by supplementation of the diet with polyunsaturated fatty acids may provide a new strategy to control blood pressure.


Meprin β, a novel mediator of vascular remodelling underlying pulmonary hypertension.
Vascular remodelling is a hallmark of pulmonary hypertension (PH) and is characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Accumulating evidence indicates a crucial role of transcription factors in the vascular remodelling processes. Here, we characterize the involvement of meprin β, a novel activator protein-1 (AP-1) effector molecule, in PH. Fra-2 transgenic (TG) mice exhibited increased right ventricular systolic pressure (RVSP), accompanied by vascular remodelling and activation of the pro-proliferative and pro-fibrotic AKT pathway. Microarray studies revealed the collagen-processing metalloprotease meprin β as the most up-regulated gene in Fra-2 TG mice. Its expression, increased at all investigated time points, preceded the decreased expression of MMPs and increased TGFβ, followed by collagen deposition. Correspondingly, remodelled pulmonary arteries from explanted idiopathic pulmonary arterial hypertension (IPAH) patients' lungs exhibited pronounced expression of meprin β. Fra-2 and meprin β expression in human PASMCs was regulated by PDGF-BB and TGFβ in a complementary fashion. Importantly, PDGF-BB-dependent proliferation was attenuated by silencing AP-1 expression or by meprin β inhibition. This study delineates a novel molecular mechanism underlying PASMCs proliferation and extracellular matrix (ECM) deposition by identifying meprin β as an important mediator in regulating vascular remodelling processes. Thus, meprin β may represent a new molecule that can be targeted in pulmonary hypertension.


Role of Inflammation in Depression and Treatment Implications.
Approximately one third of depressed patients fail to respond to currently available antidepressant therapies. Therefore, new conceptual frameworks are needed to identify pathophysiologic pathways and neurobiological targets for the development of novel treatment strategies. In this regard, recent evidence suggests that inflammation may contribute to symptoms relevant to a number of psychiatric disorders and particularly depression. Numerous studies (including meta-analyses) have found elevated peripheral and central inflammatory cytokines and acute phase proteins in depression. Chronic exposure to increased inflammation is thought to drive changes in neurotransmitters and neurocircuits that lead to depressive symptoms and that may also interfere with or circumvent the efficacy of antidepressants. Indeed, patients with high inflammation have been shown to exhibit poor response to conventional antidepressant therapies. Recent developments in our ability to understand and measure the effects of inflammation on the brain in patients have opened new doors for the testing of novel treatment strategies that target the immune system or its consequences on neurotransmitter systems. Such recent developments in the field of behavioral immunology and their translational implications for the treatment of depression are discussed herein.


Service life of counter-current chromatography coils.
A multilayer coil of PTFE tubing, which failed after being used each workday for about 3 years in a type J centrifuge, was examined. Two types of defects were found. One, called crazes, occurs throughout the coil and does not leak initially, but may eventually lead to a short, axially oriented slit. Another, called indentations, is seen primarily in the innermost and other nearby layers. They are elongated, about 5 mm, indentations, usually on the central side of the tubing. These eventually crack and leak. PTFE tubing is permeable to air and hexane and expands by more than 1% when immersed in hexane, heptane or chloroform for a few days. It is suggested that the crazes result from exposure of the somewhat flexible tubing to the undulating centripetal force field in the coil-planet centrifuge, especially when further softened by solvent absorption. The indentations may result from carriage of the excess tubing length, created by solvent absorption, from the coil periphery to the coil center by the centripetal force field, which continuously travels from the peripheral tail to the central head of the coil. A 1% increase in coil length creates 74 cm of excess tubing in the 160-ml coils examined in this study. It is suggested that fluorinated ethylene propylene (FEP) tubing, especially when etched on the outside, may provide more stable CCC coils, since its expansion when exposed to organic solvents is 0.1 or less than that of PTFE.


Nutrition, inflammation and cancer.
Quantitative and qualitative aspects of nutrition have a profound effect on leukocytes and thereby affect proinflammatory carcinogenic effects or anticancer immune responses. As a result, nutrition affects the incidence, natural progression and therapeutic response of malignant diseases, both in humans and in preclinical animal models. Here we discuss the molecular mechanisms through which alimentary cues modulate metabolic, microbial and neuroendocrine circuitries and thus affect the probability of developing premalignant lesions that progress to clinically manifested disease and the response to therapeutic intervention. We examine each of the connections that compose the triangle of nutrition, immunological and inflammatory reactions and cancer while focusing on the mechanistic aspects of these relationships.


Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer.
The epithelial-mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer. The expression of LCN2 protein was immunohistochemically assessed in two well-characterised annotated cohorts of breast cancer (discovery cohort, n = 612; validation cohort, n = 1363). The relationship of LCN2 expression and subcellular location with the clinicopathological factors and outcomes of patients was analysed. Absent or reduced nuclear LCN2 expression was associated with features of aggressive behaviour, including high histological grade, high Nottingham Prognostic Index, high Ki67 labelling index, hormone receptor negativity and human epidermal growth factor receptor 2 positivity. The high cytoplasmic expression of LCN2 was correlated with lymph node positivity. The nuclear downregulation of LCN2 was correlated with the overexpression of EMT associated proteins (N-cadherin and Twist-related protein 2) and basal biomarkers (cytokeratin 5/6 and epidermal growth factor receptor). Unlike the cytoplasmic expression of LCN2, the loss of nuclear expression was a significant predictor of poor outcome. The combinatorial expression tumours with high cytoplasmic and low nuclear expression were associated with the worst prognosis. Tumour cell expression of LCN2 plays a role in breast cancer progression with loss of its nuclear expression which is associated with aggressive features and poor outcome. Further functional analysis is warranted to confirm the relationship between the subcellular localisation LCN2 and behaviour of breast cancer.


Effectiveness and efficiency of guideline dissemination and implementation strategies.
To undertake a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies. To estimate the resource implications of these strategies. To develop a framework for deciding when it is efficient to develop and introduce clinical guidelines. MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE, SIGLE and the specialised register of the Cochrane Effective Practice and Organisation of Care (EPOC) group. Single estimates of dichotomous process variables were derived for each study comparison based upon the primary end-point or the median measure across several reported end-points. Separate analyses were undertaken for comparisons of different types of intervention. The study also explored whether the effects of multifaceted interventions increased with the number of intervention components. Studies reporting economic data were also critically appraised. A survey to estimate the feasibility and likely resource requirements of guideline dissemination and implementation strategies in UK settings was carried out with key informants from primary and secondary care. In total, 235 studies reporting 309 comparisons met the inclusion criteria; of these 73% of comparisons evaluated multifaceted interventions, although the maximum number of replications of a specific multifaceted intervention was 11 comparisons. Overall, the majority of comparisons reporting dichotomous process data observed improvements in care; however, there was considerable variation in the observed effects both within and across interventions. Commonly evaluated single interventions were reminders, dissemination of educational materials, and audit and feedback. There were 23 comparisons of multifaceted interventions involving educational outreach. The majority of interventions observed modest to moderate improvements in care. No relationship was found between the number of component interventions and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. The majority of studies only reported costs of treatment; only 25 studies reported data on the costs of guideline development or guideline dissemination and implementation. The majority of studies used process measures for their primary end-point, despite the fact that only three guidelines were explicitly evidence based (and may not have been efficient). Respondents to the key informant survey rarely identified existing budgets to support guideline dissemination and implementation strategies. In general, the respondents thought that only dissemination of educational materials and short (lunchtime) educational meetings were generally feasible within current resources. There is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgement about how best to use the limited resources they have for clinical governance and related activities to maximise population benefits. They need to consider the potential clinical areas for clinical effectiveness activities, the likely benefits and costs required to introduce guidelines and the likely benefits and costs as a result of any changes in provider behaviour. Further research is required to: develop and validate a coherent theoretical framework of health professional and organisational behaviour and behaviour change to inform better the choice of interventions in research and service settings, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.


Room-Temperature Aqueous Suzuki-Miyaura Cross-Coupling Reactions Catalyzed via a Recyclable Palladium@Halloysite Nanocomposite.
A reliable method for encapsulation of palladium nanoparticles (6-8 nm particles) in halloysite (Pd@Hal) has been developed. The Pd@Hal was found to be a highly efficient room-temperature catalyst for Suzuki-Miyaura cross-coupling reactions that gave high yields of a diverse array of coupling products in 5:2 n-PrOH/H2O within 1 h. The catalytic system was remarkably effective with a broad substrate scope. In addition, the catalyst was easily recovered and recycled without a significant loss of catalytic activity.


Low dose intra-arterial streptokinase and acylated plasminogen-streptokinase activator complex: a retrospective review of two thrombolytic regimes in recent peripheral arterial ischaemia.
Thrombolytic therapy was used for 57 patients with acute and sub-acute lower limb arterial ischaemia. In the first 34 patients a new thrombolytic agent, acylated plasminogen-streptokinase complex (BRL 26921) was assessed. Following this, 23 patients received low dose intra-arterial streptokinase. The two thrombolytic regimes have been analysed retrospectively. There were differences observed between the two groups in the type of patients treated and in the severity of limb ischaemia. Of the patients receiving BRL 26921, five (15%) had complete, and three (9%) partial lysis of the occluding thrombus. Serious bleeding occurred in six (18%) and minor bleeding in ten (29%) patients. After 30 days, twelve patients (35%) had limb salvage and eleven (32%) had died. Fifteen patients (65%) receiving intra-arterial streptokinase had lysis of the occluding thrombus. Minor bleeding was observed in three patients (13%). After 30 days, 15 (65%) had limb salvage and three (13%) had died. Patients receiving BRL 26921 had a significantly greater reduction in plasma fibrinogen and plasminogen concentrations during treatment which may have accounted for the bleeding complications. At the dose used, BRL 26921 had no demonstrable fibrinogen sparing effect. Improved lysis rates with fewer bleeding complications might be achieved by reducing the dose of BRL 26921. Low dose intra-arterial streptokinase has been confirmed as a safe, effective method of thrombolysis in recent peripheral arterial ischaemia.


Induction of constitutive heat shock protein 73 mRNA in the dentate gyrus by seizures.
We examined the effects of generalized seizures on heat shock protein (hsp) mRNA induction in the rat brain using in situ hybridization. Seizures induced by electroconvulsive shock, electrical or cocaine kindling caused a selective induction of the constitutive hsp 73 gene in the dentate gyrus. In these seizure paradigms, not thought to induce widespread tissue damage, neither the heat-inducible hsp 72 gene nor a member of the hsp 90 family (hsp 84) were induced. Hsp 73 may play a role in the adaptation and/or in the maintenance of dentate granule cell integrity following seizures.


Elevated recombination rates in transcriptionally active DNA.
We have examined the effect of RNA polymerase II-dependent transcription on recombination between directly repeated sequences of the GAL10 gene in S. cerevisiae. Direct repeat recombination leading either to plasmid loss or conversion was examined in isogenic strains containing null mutations in the positive activator, GAL4, or the repressor, GAL80. A 15-fold increase in the rate of plasmid loss is observed in cells constitutively expressing the construct compared with cells that are not. Conversion events that retain the integrated plasmid are not stimulated by expression of the repeats. Northern analysis of strains containing plasmid inserts with various promoter mutations suggests that the stimulation in recombination is mediated by events initiating within the integrated plasmid sequences.


The association between BMI and health-related quality of life in the US population: sex, age and ethnicity matters.
Obesity is a major public health problem. Detailed knowledge about the relationship between body mass index (BMI) and health-related quality of life (HRQL) is important for deriving effective and cost-effective prevention and weight management strategies. This study aims to describe the sex-, age- and ethnicity-specific association between BMI and HRQL in the US adult population. Analyses are based on pooled cross-sectional data from 41 459 participants of the Medical Expenditure Panel Survey (MEPS) Household Component (HC) for the years 2000-2003. BMI was calculated using self-reported height and weight, and HRQL was assessed with the EuroQol five-dimensional questionnaire. Generalized additive models were fitted with a smooth function for BMI and a smooth-factor interaction for BMI with sex adjusted for age, ethnicity, poverty, smoking and physical activity. Models were further stratified by age and ethnicity. The association between BMI and HRQL is inverse U-shaped with a HRQL high point at a BMI of 22 kg m-2 in women and a HRQL high plateau at BMI values of 22-30 kg m-2 in men. Men aged 50 years and older with a BMI of 29 kg m-2 reported on average five-point higher visual analog scale (VAS) scores than peers with a BMI of 20 kg m-2. The inverse U-shaped association is more pronounced in older people, and the BMI-HRQL relationship differs between ethnicities. In Hispanics, the BMI associated with the highest HRQL is higher than in white people and, in black women, the BMI-HRQL association has an almost linear negative slope. The results show that a more differentiated use of BMI cutoffs in scientific discussions and daily practice is indicated. The findings should be considered in the design of future weight loss and weight management programs.


Acute Toxic Effects of the Herbicide Formulation Focus(®) Ultra on Embryos and Larvae of the Moroccan Painted Frog, Discoglossus scovazzi.
For regulatory and scientific purposes, there is a need to understand the sensitivity of a wider variety of wild species of amphibians and the sensitivities within their life stages to chemicals of widespread use such as herbicides. We investigated the acute toxic effects of the herbicide formulation Focus Ultra [with the active ingredient (a.i.) cycloxydim plus solvent naphtha and sodium dioctylsulphosuccinate as added substances] on embryos and early stage larvae of the Moroccan painted frog (Discoglossus scovazzi). Different clinical signs (twitching, convulsion, and narcosis) occurred at 40 and 80 mg/L in embryos (4 and 8 mg a.i./L) and narcotic effects (total immobilization or irregular escape responses) at 10, 15, and 20 mg/L in larvae (1, 1.5, and 2 mg a.i./L). Growth inhibition (total length), starting at 20 mg/L in embryos and 2.5 mg/L in larvae (2 and 0.25 mg a.i./L, respectively) was understood as sign of toxicity (retardation) and not as sign of teratogenicity. However, the connection to teratogenesis remained unclear though total length reduction occurred at concentrations <20 % of the 96-h LC50 value and at a minimum concentration that inhibits growth of only 17 % of the 96-h LC50 value. Starting at 20 mg/L, mortality in embryos significantly increased and at 15 mg/L in early larvae (2 and 1.5 mg a.i./L, respectively). Mortality of larvae was enhanced during the first 24 h of exposure to 15 and 20 mg/L (1.5 and 2 mg a.i./L). Morphology of the embryos remained unobtrusive. In contrary, axial malformations significantly increased in the early larvae starting at 10 mg/L (1 mg a.i./L), a concentration free of lethal effects. In all considered end points, larvae were significantly more sensitive than embryos, probably because of developmental and physiological properties or different exposure and bioavailability of the compound. Focus Ultra induced comparable lethal and immobilization effects in D. scovazzi as it does to standard test organisms in pesticide approval. However, to validate the apparent safety in the field, which is based on calculated surface water concentrations of the a.i., more data on real contamination levels is necessary (e.g., peak concentrations, concentrations of added substances). Furthermore, sufficient buffer strips between the farmland and amphibian ponds must be considered, and the effects of the substance on terrestrial life stages have not been assessed yet.


MyD88 or TRAM knockdown regulates interleukin (IL)-6, IL-8, and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts.
In a previous report, it was shown that Toll-like receptor (TLR) 2 knockdown modulates interleukin (IL)-6 and IL-8 but not the chemokine CXCL12, an important mediator with inflammatory and proangiogenic effects, in human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPDLF). This study investigates whether knocking down two important TLR adaptor molecules, such as myeloid differentiation protein 88 (MyD88) and TRIF-related adaptor molecule (TRAM), could affect mRNA expression of IL-6, IL-8, and CXCL12 in HGF and HPDLF. After small interfering (si) RNA-mediated silencing of MyD88 or TRAM, HGF and HPDLF were stimulated with Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) or two synthetic ligands of TLR2 (Pam2CSK4 and Pam3CSK4) for 6 hours. IL-6, IL-8, and CXCL12 mRNAs were evaluated by quantitative polymerase chain reaction. Knockdown of MyD88 or TRAM partially impaired the IL-8 mRNA upregulation in both fibroblast subpopulations. Similarly, IL-6 upregulation was partially prevented by siMyD88 or siTRAM in HGF stimulated with Pg LPS, as well as in both fibroblast subtypes challenged with Pam2CSK4. Conversely, constitutive CXCL12 mRNA levels were upregulated by MyD88 or TRAM knockdown in non-stimulated cells. These results suggest that TLR adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8 mRNA and increase CXCL12 mRNA expression in HGF and HPDLF. This can be an important step for better understanding the mechanisms that control the inflammatory cytokine and chemokine expression, which in turn contributes to periodontal pathogenesis.


Hepatocolonic vagrancy: wandering liver with colonic abnormalities.
Abnormalities of hepatic fixation resulting in excessive mobility in a transverse plane are uncommonly encountered. The unusual incidental finding of a freely mobile liver and spleen in a patient presenting with sigmoid volvulus is reported. At laparotomy, the inferior aspect of the right hemidiaphragm was smoothly peritonealized, without evidence of coronary or triangular ligaments. It is postulated that this abnormal hepatic mobility reflects persistence of the primitive ventral mesogastrium. To the authors' knowledge, this unusual condition has not previously been recognized. The literature relating to wandering liver is reviewed and four other cases are presented. An invariable association of persisting ventral mesogastrium with abnormalities in colonic anatomy (hepatocolonic vagrancy) is described.


Unclassifiable interstitial lung disease: A review.
Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.


The efficacy of chelation therapy and factors influencing mortality in lead intoxicated petrol sniffers.
The use of chelating agents to treat patients with petrol sniffing encephalopathy has been controversial, since alkyllead additives in petrol are not chelatable. A high mortality has also been reported in hospitalised petrol sniffers. (i) Evaluate the efficacy of chelating agents in mobilising lead for excretion and lowering blood lead; (ii) Review factors contributing to mortality in hospitalised petrol sniffers. All males chelated between 1992-1993 were studied (n = 20). Blood and urinary lead were measured daily before and during chelation then twice weekly until discharge. Parenteral calcium disodium edetate (EDTA) and dimercaprol (BAL) were administered together, every six hours for five days, seven patients subsequently received oral D-penicillamine until discharge. Clinical details were reviewed for eight patients with petrol sniffing encephalopathy who died between 1990-1994. Urinary lead excretion substantially increased during parenteral chelation (median excretion = 113 microM/5 days, compared with pre-chelation excretion = 1.1 microM/day). Median blood lead concentration fell from 4.83 microM/L (pre-chelation) to 1.91 microM/L (post-chelation). D-Penicillamine did not appear to increase urinary lead excretion appreciably. All eight deaths followed sepsis; five from complications of aspiration pneumonia. Airway maintenance and management are crucial for survival in these patients. In the short-term, parenteral chelation was effective in mobilising lead for excretion and reducing blood lead in encephalopathic petrol sniffers and was comparable to cases of inorganic lead intoxication. However, as in the treatment of inorganic lead intoxication, the long-term efficacy of chelation for petrol sniffers remains controversial. Prevention strategies against petrol sniffing at a community level are recommended.


Controlling the electrophoretic mobility of single-walled carbon nanotubes: a comparison of theory and experiment.
The electrophoretic mobilities of single-walled carbon nanotubes (SWNTs) in agarose gels subjected to negatively charged covalent functionalization and noncovalent anionic surfactant adsorption are compared using a simplified hydrodynamic model. Net charges are calculated on the basis of estimated friction coefficients for cylindrical rodlike particles. The effects of functionalization with negatively charged 4-hydroxybenzene diazonium and anionic sodium cholate are quantified and compared with model predictions. The adsorption of Na+ counterions into the nonionic surfactant layer adsorbed on SWNTs (Triton-X-405) is shown to induce a positive charge and reverse the mobility under select conditions. This effect has not been identified or quantified for nanoparticle systems and may be important in the processing of these systems.


Summation of arousal in partial fetishism.
A summation model of classical conditioning was used to describe the deviant sexual arousal pattern of a male psychiatric patient. Penile assessment showed a response to a compound stimulus (radio static plus a picture of a woman) that was approximately equal to the sum of the responses to each component alone. The subject's self-report of sexual arousal followed a similar pattern. A distinction was made between total and partial fetishism. It was suggested that what may be particularly troublesome in partial fetishism is the potential for high levels of summated arousal.


Reflection from bound microbubbles at high ultrasound frequencies.
Targeted contrast agents and ultrasound imaging are now used in combination for the assessment and tracking of biomarkers in animal models in vivo. These applications have triggered interest in the understanding and prediction of the ultrasound echoes from contrast agents attached to cells. This study describes the reflection enhancement due to microbubbles bound on a gelatin surface. The reflection enhancement was measured using ultrasound pulses at high frequency (40 MHz) and low pressure (38 kPa peak-negativepressure) allowing a linear approximation to be applied. The observed reflection coefficient increased with the number of microbubbles, until reaching saturation at 0.9 when the surface coverage fraction was 35%. A multiple scattering model assuming that the targeted microbubbles are confined within an infinitesimally thin layer appeared suitable in predicting the reflection coefficient even at very high surface densities. These results could permit the optimization of the sensitivity of highfrequency ultrasound to targeted contrast agents.


Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications.
At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss, and central regulation. Whereas some changes are related to the aging process per se, others appear to be secondary to other factors, for which the risk increases with aging, notably a decreased level of fitness and physical activity. Moreover, functional implications of the body temperature rhythm are discussed. For example, the relation between circadian rhythm and thermoregulation has hardly been investigated, while evidence showed that sleep quality is dependent on both aspects. It is proposed that the circadian rhythm in temperature in homeotherms should not be regarded as a leftover of ectothermy in early evolution, but appears to be of functional significance for physiology from the level of molecules to cognition. A new view on the functional significance of the circadian rhythm in peripheral vasodilation and the consequent out-of-phase rhythms in skin and core temperature is presented. It is unlikely that the strong, daily occurring, peripheral vasodilation primarily represents heat loss in response to a lowering of set point, since behavioral measures are simultaneously taken in order to prevent heat loss. Several indications rather point towards a supportive role in immunological host defense mechanisms. Given the functional significance of the temperature rhythm, research should focus on the feasibility and effectiveness of methods that can in principle be applied in order to enhance the weakened circadian temperature rhythm in the elderly.


In vivo dilatation of the ductus arteriosus by Rho kinase inhibition in the rat.
Fasudil hydrochloride, a Rho kinase inhibitor, was reported to dilate the constricted ductus arteriosus in vitro, and was suggested as a neonatal bridge to heart surgery. To clarify the in vivo effectiveness of fasudil to dilate the neonatal ductus arteriosus, and its usefulness as a bridge to heart surgery. We studied the dose and timing of administration of fasudil in the neonatal rat. Postnatal ductal closure was studied on the 21st gestational day following cesarean section and incubation for 30-480 min in room air at 33 degrees C, with a rapid whole-body freezing method. In control rats, the ductus closed rapidly after birth, and the ductal diameter was 0.80 and 0.12 mm at 0 and 30 min after birth. Fasudil was injected peritoneally into the neonate, and the ductus was studied 30 min after injection and 60 min after birth. Fasudil, 10 mg/kg, injected within 5 min after birth, dilated the ductus completely to 0.8 mm, and the dose used clinically, 1 mg/kg, dilated the ductus to 0.4 mm. The ductus-dilating effect of fasudil decreased rapidly as the neonatal ductus constricted. Fasudil, 100 mg/kg, dilated the ductus completely, but induced severe respiratory depression and frequent death in 1-hour-old rats. Fasudil dilates the neonatal ductus arteriosus dose-dependently in the rat. Fasudil in large doses dilates the neonatal ductus completely, but is associated with fatal side effects, including respiratory depression.


Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator.
We report cancer cell death initiated by the intracellular molecular self-assembly of a peptide lipid, which was derived from a gelator precursor. The gelator precursor was designed to form nanofibers via molecular self-assembly, after cleavage by a cancer-related enzyme (matrix metalloproteinase-7, MMP-7), leading to hydrogelation. The gelator precursor exhibited remarkable cytotoxicity to five different cancer cell lines, while the precursor exhibited low cytotoxicity to normal cells. Cancer cells secrete excessive amounts of MMP-7, which converted the precursor into a supramolecular gelator prior to its uptake by the cells. Once inside the cells, the supramolecular gelator formed a gel via molecular self-assembly, exerting vital stress on the cancer cells. The present study thus describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity.


[Mortality and morbidity of newborn infants in intensive care (birth weight less than 1,501 grams)].
A comparative analysis of the mortality and morbidity of premature infants with a birthweight below 1.501 g, born in the years 1974, 1978 and 1981, is given. The mortality rate has remained unchanged in the years 1974 (when a neonatal intensive care unit was installed at the University Children's Hospital Graz) and 1981 with 33% and 32% respectively. The total number of admissions rose from 36 (1974) to 67 (1978) and 91 (1981). Simultaneously the number of patients, who needed neonatal intensive care increased. Whilst in 1974 only 2 of 24 surviving infants needed artificial ventilation, in 1978 19 of 38 patients had respirator therapy. Despite the increasing severity of neonatal affections the number of severe handicaps caused by perinatal complications remained constantly low with altogether 5 cases in the years 1978 and 1981. Two children had a spastic tetraplegia, two others had a posthaemorrhagic hydrocephalus and one child was blind due to bilateral septic abscesses of the vitreous body. Only two of these children had long time artificial ventilation. Approximately 80% of the surviving children exhibited normal psychomotor development and showed no neurological sequelae. This rate was unchanged in the investigated periods.


Combined rigid and flexible ureteropyeloscopy.
The development of rigid and flexible ureteropyeloscopes has provided the means for direct visualization of the upper urinary collecting system. Each instrument has its own advantages and disadvantages. The combined use of these instruments extends the range of endoscopy throughout the intrarenal collecting system, permits irrigation and provides a working channel.


Molecular identification of bloodmeals from biting midges (Diptera: Ceratopogonidae: Culicoides Latreille) in Denmark.
Culicoides vectors are critical to the survival and transmission of bluetongue virus as infection only occurs in areas or regions where competent vectors are present. The success of Culicoides biting midges as vectors is mainly related to their vast population sizes and to their means of dispersal. Their choice of host for blood feeding is sparsely described. The aim of the present study was to establish methods for the identification of bloodmeal hosts and determine the identity and diversity of bloodmeals of vertebrate hosts from wild-caught biting midges near livestock farms. The study includes some of the most common and abundant species of biting midges in Denmark: Culicoides obsoletus, Culicoides scoticus, Culicoides pulicaris and Culicoides punctatus. We collected 8,378 biting midges including nine species of Culicoides of which blood-fed specimens were found from six species. We identified 251 blood engorged biting midges, and hosts were identified in 115 of 125 analysed specimens (90%). Cow, roe deer, horse, mallard and wood pigeon were identified as hosts. The most abundant host species was cow, which constituted 73.9% of the total identified bloodmeals, but the common wood pigeon was found with a frequency as high as 18.3%. In conclusion, the molecular methods applied were proven useful in identifying bloodmeal hosts from different Culicoides species. The results indicate that Culicoides species are opportunistic in their choice of bloodmeal host with a preference for cattle when present, which is important to have in mind for epidemiologist when making predictive models. Accordingly, the results of this study will add useful parameters for modelling bluetongue virus transmission and in the development of veterinary contingency plans.


A comparative morphological and ultrastructural study of endometrial gland and fallopian tube epithelia at different stages of the menstrual cycle and the menopause.
Cyclical ultrastructural changes in the endometrium and Fallopian tube have been reported previously but in different subjects. The aim of this study is to compare cyclical changes in endometrial gland and tubal (isthmic, mid-tube, ampulla, and fimbria) epithelia in the same subjects with a view to identifying any similarities or differences which may have clinical implications for assisted reproduction treatment. Endometrial and Fallopian tube samples were obtained from women undergoing hysterectomy and salpingectomy. We report similar epithelial surface changes taking place in the endometrial glandular and endosalpingeal epithelia with the exception of the fimbriae. Secretions within endometrial gland lumen and the isthmus increase throughout the late follicular phase and before ovulation, then dissipate in these two regions simultaneously in the early/mid luteal phase. Similarly, in the late follicular and pre-ovulatory phases, the process of granule secretion is similar in the glandular epithelium, isthmus and ampulla. In the fimbriae, no comparable activity is noted during these phases of the menstrual cycle. The differences reflect the functional differentiation between these regions. Equally, the observed similarities highlight the need for further comparative studies to determine the role of these secretions in early embryonic development and their clinical relevance.


Single-clone and mixed-clone infections versus host environment in Crithidia bombi infecting bumblebees.
Current theories assume that adaptive parasite evolution explains variation in the level of virulence and parasite success. In particular, mixed-genotype infections by parasites should generally be more virulent, and faster multiplying strains more successful, either because fixed strategies have evolved or because parasites facultatively alter virulence in response to co-infecting competitors. We compared several measures of parasite success and virulence between single-clone and mixed-clone infections of 2 strains of the trypanosome Crithidia bombi in its bumblebee host, Bombus terrestris. Contrary to expectation, we could not find differences between single-clone and mixed-clone infections in parasite prevalence, infection success, duration and clearance rate. However, a clearly significant effect of colony on infection intensity was present, and the colony effect emerged in virtually all other measures. We thus conclude that host environment as defined by the family (colony) genotype and thus host heterogeneity are more important in determining parasite virulence than the parasite characteristics. This does not invalidate modern theories of parasite evolution but suggests that variation in both hosts and parasites must be taken into account in more detail.


Patients' profile, clinical presentations and histopathological features of colo-rectal cancer in Al Hassa region, Saudi Arabia.
Patients' demographics, presenting clinical and histopathological features for colo-rectal cancer (CRC) are important factors for patients' outcome and disease prognosis. This study aimed to describe the pattern of CRC in terms of patients' demographics, main presenting symptoms and histopathological features in Al Hassa region of Saudi Arabia. A retrospective hospital records-based study which included reviewing of patients' records diagnosed with CRC at three general hospitals in Al Hassa region, Saudi Arabia. A compilation form was designed to collect information regarding socio-demographics, age at diagnosis; referral sites and the main presentations at CRC diagnosis. sites and the main presentations at CRC diagnosis. Histopathological reports were reviewed to delineate the main cytopathologic features, prominent cytological characteristics, the presence of predisposing pathology, and disease stage. Of the 142 cases with CRC, 15.5% and 33.1% were affected before 40 and 50 years of age respectively. Emergency rooms were main referral sites for CRC cases (31.0%). Right colon was affected in 16.9% while left colonic lesions accounted for 62.7%. Intestinal obstruction was the main presentations (41.5%), and 26.1% presented with symptoms indicating distant metastatic lesions. Adenocarcinoma was the predominant pathological lesions (86.6%). Metastatic CRC was diagnosed in 62.7%. Duke's staging showed that 22.5% and 40.1% of lesions were classified into C and D categories respectively. Saudi patients with CRC present late with distant metastasis, and advanced disease stage. A sizeable proportion of patients developed the lesions at relatively young age. Screening recommendations should be enacted and revised in response to current change with younger age of affection.


Isolation and characterization of a novel class of plant antimicrobial peptides form Mirabilis jalapa L. seeds.
We have isolated from seeds of Mirabilis jalapa L. two antimicrobial peptides, designated Mj-AMP1 and Mj-AMP2, respectively. These peptides are highly basic and consist of 37 and 36 residues for Mj-AMP1 and Mj-AMP2, respectively. Both peptides contain three disulfide bridges and differ from one another only by 4 amino acids. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the reduced and unreduced peptides suggests that the peptides associate into dimers in their native form. The Mj-AMPs exhibit a broad spectrum of antifungal activity since they are active against all 13 tested plant pathogenic fungi. Concentrations required for 50% inhibition of fungal growth vary from 6 to 300 micrograms/ml for Mj-AMP1 and from 0.5 to 20 micrograms/ml for Mj-AMP2. These peptides were also active on two tested Gram-positive bacteria but were apparently nontoxic for Gram-negative bacteria and cultured human cells. Although the Mj-AMPs show sequence similarity to mu-agatoxins, a class of insecticidal neurotoxic peptides isolated from the venom of spiders, they do not affect pulse transmission in insect nerves.


Prognostic significance of endothelial Per-Arnt-sim domain protein 1/hypoxia-inducible factor-2alpha expression in a subset of tumor associated macrophages in invasive bladder cancer.
Endothelial Per-Arnt-Sim domain protein 1 (EPAS1) is induced under hypoxia and it transactivates a series of genes involved in angiogenesis and energy metabolism. Recent studies showed that EPAS1 is expressed in tumor associated macrophages (TAMs), which have multifaceted roles in tumor progression. We hypothesized that EPAS1 expressed in TAMs may contribute to bladder cancer progression. Clinicopathological and followup data on 69 patients undergoing radical cystectomy for T1-4N0-2M0 high grade bladder urothelial carcinoma were reviewed. Quantitative immunohistochemical analysis of TAMs and EPAS1 was performed separately in invasive front and in other superficial parts of carcinoma tissues. TAM counts and EPAS1 positive cell counts were compared with pathological variables and cancer specific survival (CSS). The 5-year CSS rate in the 69 patients was 69% at a median followup of 58 months (range 2 to 196). EPAS1 expression was restricted to a small subset of TAMs. Although TAM counts were not associated with T stage or lymph node metastasis, EPAS1 expressing TAM counts were significantly associated with higher T stage. On univariate and multivariate analyses higher EPAS1 expressing TAM counts in invasive front along with higher T stage and positive lymph node metastasis were significantly associated with shorter CSS, while total TAM counts or EPAS1 expressing TAM counts in other superficial parts did not. Despite limited prognostic effects of total TAMs EPAS1 expressing TAMs were associated with a poor prognosis of invasive bladder cancer, suggesting that EPAS1 expressed in a subset of TAMs mediates bladder cancer progression.


Alleviating effects of active fraction of Euonymus alatus abundant in flavonoids on diabetic mice.
Euonymus alatus (E. alatus) has been used as a folk medicine for diabetes in China for more than one thousand years. In order to identify major active components, effects of different fractions of E. alatus on the plasma glucose levels were investigated in normal mice and alloxan-induced diabetic mice. Our results show that ethyl acetate fraction (EtOAc Fr.) displayed significant effects on reducing plasma glucose. In oral glucose tolerance, EtOAc Fr. at 17.2 mg/kg could significantly decrease the blood glucose of both normal mice and diabetic mice. After 4 weeks administration of the EtOAc Fr, when compared with the diabetic control, there were significant difference in biochemical parameters, such as glycosylated serum protein, superoxide dismutase and malondial dehyde, triglyceride, and total cholesterol, between alloxan-induced diabetic mice and the control group. Additional histopathological studies of pancreatic islets also showed EtOAc Fr. has beneficial effects on diabetic mice. Chemical analysis with three-dimensional HPLC demonstrated that the major components from EtOAc Fr were flavonoids and phenolic acids, which had anti-oxidative effects on scavenging DPPH-radical in vitro. All these experimental results suggest that EtOAc Fr. is an active fraction of E. alatus and can prevent the progress of diabetes. The mechanism of E. alatus for glucose control may be by stimulating insulin release, improving glucose uptake and improving oxidative-stress.


Effects of angiotensin II and aldosterone on diastolic function in vivo in normal man.
1. Doppler echocardiographic indices of diastolic function and systemic haemodynamics were studied in response to infusions of angiotensin II (1, 2, 5 and 10 ng min-1 kg-1), D-aldosterone (2, 4, 10 and 20 ng min-1 kg-1) and placebo [0.9% (w/v) NaCl] in ten normal male subjects. 2. Dose-related increases in systolic and diastolic blood pressure were observed with angiotensin II infusion at rates of 2 ng min-1 kg-1 and above, whereas no changes in blood pressure occurred with D-aldosterone. No changes in aortic stroke distance or heart rate were seen with either angiotensin II or aldosterone infusion. 3. Compared with placebo, angiotensin II infusion produced a dose-related prolongation of the isovolumic relaxation time [mean and 95% confidence intervals 12.0 (8.2-15.8) ms, P < 0.001] at 10 ng min-1 kg-1, and a significant reduction in the ratio between early and late transmitral flow velocity integrals at 2 ng min-1 kg-1, [-0.84 (-1.63 to -0.05), P < 0.05] and 5 ng min-1 kg-1 [-0.76 (-1.47 to -0.05), P < 0.05]. No changes in Doppler echocardiographic indices of diastolic function were observed with D-aldosterone infusion. 4. These data suggest that angiotensin II, even at a sub-pressor concentration, produces an impairment of left ventricular diastolic filling, which occurs independently of its effect on aldosterone release.


Optimizing the technique of embryo transfer.
To review currently available literature on various technical aspects of the ET procedure. Publications related to ET technique were identified using PubMed and Medline. Numerous technical aspects of the ET procedure have been studied to determine their effect on pregnancy outcome. Although much of the published data that evaluates these factors is conflicting or confounded, good and consistent evidence does appear to support the following: optimizing the "ease" of the transfer, ultrasound guidance, and soft catheters. Limited evidence also supports trial transfers, removal of cervical mucus, deposition of embryos in the midportion of the uterus, avoiding negative pressure from the catheter, and completion of the procedure in a timely manner. Although there is no consensus on the optimal technique of ET, there is evidence that certain methods in the ET are associated with improved outcomes after IVF.


NHS Improvement U-turn on 'ill-conceived' agency ban.
The RCN is celebrating a 'U-turn' over plans to prevent nurses working for an agency if they already have a substantive contract with the NHS.


Mucous cysts of the nose: a postrhinoplasty complication?: a long-term follow-up.
Mucous cysts are very rare complications following rhinoplasty; less than 20 cases have been reported in literature. We present 2 new cases. The first case presented a cyst located beneath the glabella and above the articulation between the spina nasalis and the os nasale. The lesion first appeared 22 months following elective rhinoplasty. The treatment was complete surgical excision using a direct open approach. In the second case, a cyst was indentified between the right inner canthus and the sidewall of the nose. It appeared 6 months following elective rhinoplasty. The treatment was complete surgical excision through a transcartilaginous approach. Both patients had good postoperative results with no evidence of recurrence after a 7- and 8-year follow-up period, respectively. We believe that it is possible to prevent the appearance of mucous cysts after rhinoplasty, with careful dissection and avoidance of dispersion of mucosal material into a subcutaneous plane.


Childhood problem behaviours as precursors of drinking to intoxication trajectories - from age 1.5 to 19.
We examined behaviour problem precursors (i.e. internalising and externalising) in childhood (ages 1.5 to 8.5) and early adolescence (age 12.5) and consequences (i.e. harmful alcohol use) in emerging adulthood (age 19), of developmental trajectories of drinking to intoxication across adolescence (ages 14.5-19). Data from 921 children and their parents followed for 18 years from the population-based Tracking Opportunities and Problems (TOPP) Study were used to examine adolescent trajectories of drinking to intoxication. Logistic regression was used to examine predictors of trajectory group membership. We identified 3 trajectory classes: low / abstainer (41%), late onset high (31%) and early onset high (28%) using latent class analyses. Logistic regression analyses showed that childhood high externalising characterised early onset of intoxication vs. other classes, while early adolescence externalising discriminated both early and late onset of intoxication. High early childhood internalising characterised those consistently low or abstinent on alcohol intoxication, while early adolescent internalising characterised those having an early onset of intoxication. However, after additional adjustment for co-occurring externalising, there were no evidence for a link between early adolescent internalising and intoxication. The findings suggest that both child and early adolescent-focused prevention efforts may be warranted.


Hyaluronan efflux from canine lung with increased hydrostatic pressure and saline loading.
Although lymphatic washout of hyaluronan during lung hydration has been postulated to deplete lung interstitial hyaluronan content and thereby contribute to the decreased interstitial exclusion of albumin observed under these conditions, this hypothesis has not been directly tested. In anesthetized, ventilated mongrel dogs, a prenodal lung lymphatic was cannulated for measurement of lymph flow and hyaluronan concentration. Following baseline measurements, Pla was increased in four steps of 5 cm H2O in Group 1 or set to one pressure ranging between 6 and 32 cm H2O in Group 2. In Group 3, saline (15% body weight) was infused over 30 min and then Pla increased as in Group 2. Invariably, as lymph flow increased in Groups 1 through 3, lymph hyaluronan concentration and hyaluronan flux increased significantly (p < 0.05). In a separate control group, there were no changes in lymph flow, hyaluronan concentration, or hyaluronan flux. In Group 3, lung hyaluronan content at 5 h (0.76 +/- 0.08 mg/g dry weight) was not significantly less than that during baseline (0.88 +/- 0.05 mg/g dry weight), although total uronic acid content actually increased by 38% over the same time course. In contrast, in the control group, both lung hyaluronan and uronic acid content remained stable over the experimental period. From these data, approximately 2 to 3% of lung hyaluronan is predicted to leave the interstitium via lymphatic flux per day under baseline conditions. The daily turnover of interstitial hyaluronan by this route increased to 15 to 18% of total content when Pla was elevated and to 54% following saline infusion. Thus, lung hyaluronan can be rapidly mobilized with increased lymph flow.(ABSTRACT TRUNCATED AT 250 WORDS)


The diagnostic value of multislice computed tomography in evaluation of coronary artery disease in patients with left bundle branch block.
Noninvasive diagnostic methods do not supply sufficient data for patients with left bundle branch block (LBBB) accompanied with coronary artery diseases (CAD). Therefore, generally coronary angiography is required for these patients. Our aim was to evaluate the diagnostic value of multislice spiral computed tomographic (MSCT) coronary angiography to detect CAD in patients with LBBB. Sixty one patients (31 males, 30 females, mean age: 56+/-13 years) with LBBB who have determined stenosis higher than 50% in quantitative coronary angiography were included in the cross-sectional study. The MSCT coronary angiography was applied to the patients with a 16-detector MSCT scanner that has an electrocardiographic synchronization unit. Each coronary artery was evaluated segmentally in the images acquired from MSCT coronary angiographies and any detected stenosis higher than 50% was recorded. The data of 793 coronary artery segments achieved from MSCT coronary angiographies of 61 patients (13 segments for each patient) were compared with the results of conventional coronary angiographies of the same patients. When all the segments evaluated were included in this comparison, the diagnostic accuracy, sensitivity, specificity, positive and negative predictive values of MSCT coronary angiography to detect stenosis higher than 50% were 91%, 67%, 97%, 85% and 92%, respectively. Also, it was observed that, MSCT coronary angiography has 80% sensitivity and 90% specificity to detect, at least, one segment coronary artery stenosis. The MSCT coronary angiography can be utilized as a noninvasive diagnostic method for patients with LBBB, in order to evaluate coronary artery disease.


Refluxing chimney versus nonrefluxing LeDuc ureteroileal anastomosis for orthotopic ileal neobladder: a comparative analysis for patients with bladder cancer.
Radical cystectomy and various techniques of urinary diversion are gold standard treatments for invasive bladder cancer. However, postoperative hydronephrosis is a common complication in these patients. A special focus was placed on the type of ureteroileal anastomosis used with 2 different techniques performed at 1 institution. Between 1995 and 2003 a total of 106 consecutive patients with bladder cancer underwent cystectomy followed by construction of an ileal neobladder. The nonrefluxing technique of ureter tunneling described by LeDuc and the refluxing chimney technique used for ureter implantation into the ileum-neobladder were compared. Hydronephrosis due to ureteral strictures was studied immediately following surgery and up to 5 years after surgery. A total of 204 RU were included in the study. The LeDuc technique was used in 132 RU (64%) and the chimney technique was used in 72 RU (36%). Hydronephrosis rate of 2% were found in each of the 2 groups after 5 years of followup. Postoperative hydronephrosis due to ureteral strictures is observed at the same rate during long-term followup with the LeDuc and chimney techniques. We favor the chimney technique compared to the LeDuc tunnel due to easier technical preparation and a better chance to identify the ureters endoscopically at a later time. The chimney does give extra length to reach the ureteral stump, especially in cases of distal ureteral carcinoma in situ.


Novel drug-delivery systems for hypertension.
Although novel controlled-release drug-delivery systems have been used in other areas of medicine, their application in the treatment of hypertension has been relatively recent. Biotechnical use of chemical-dispensing systems has been applied to propranolol, clonidine (the transdermal therapeutic system), nifedipine (the gastrointestinal therapeutic system), verapamil (the sodium alginate and spheroidal oral-delivery absorption system), felodipine (the hydrophilic gel principle), metoprolol succinate (the multiple-unit pellet system), and diltiazem (one system comprising sustained-release beads and the other utilizing the patented Geomatrix extended-release system). Oral drug-delivery systems allow antihypertensive agents that previously had to be administered two to four times daily to be administered once each day. Potential disadvantages of the oral controlled-release products include delayed attainment of pharmacodynamic effect, unpredictable or reduced bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosing inflexibility, and increased cost. Potential advantages include reduced dosing frequency, enhanced compliance and convenience, reduced toxicity, stable drug levels, uniform drug effect, and decreased total dose. Although skin reactions are common, the transdermal drug delivery of clonidine provides another innovative approach to supplying transcutaneous, controlled, continuous delivery of drug for 7 days. It is possible that future research will prove that the agents that provide complete 24-hour control may reduce the cardiovascular events associated with the early-morning blood pressure surge. This evolution in antihypertensive therapy to achieve once-daily dosing may prove to be of great value to both physicians and patients in the 1990s.


Profile of Reiter's disease in Saudi Arabia.
We studied the clinical features of cases of Reiter's disease as seen in two tertiary care hospitals in Riyadh, Saudi Arabia, over a period of 9 years. We gathered 34 cases, 29 (85%) males and 5 (15%) females (M:F ratio 5.8:1). The mean age of onset was 29.4 (SD 6.4) years. Gastrointestinal and genitourinary infection were elicited in 24 patients (71%). Fever occurred in 6 patients (18%), fatigue in 13 (38%) and conjunctivitis in 13 (38%). Lower limb large joints were affected at presentation in 23 patients (68%), followed by combined presentation of peripheral joints and axial joints in 10 patients (30%). Sacroilitis was seen in 5 cases (15%). One patient had spondylitis, while enthesopathy was seen in 6 patients (18%). Bone scintigraphy was done in 14 patients, 11 of which were positive at peripheral joints, while 9 showed increased uptake at the sacroiliac joints. HLA B27 status was tested in 15 patients, 4 (27%) of which were positive.


Paenibacillus phoenicis sp. nov., isolated from the Phoenix Lander assembly facility and a subsurface molybdenum mine.
A novel Gram-positive, motile, endospore-forming, aerobic bacterium was isolated from the NASA Phoenix Lander assembly clean room that exhibits 100 % 16S rRNA gene sequence similarity to two strains isolated from a deep subsurface environment. All strains are rod-shaped, endospore-forming bacteria, whose endospores are resistant to UV radiation up to 500 J m(-2). A polyphasic taxonomic study including traditional phenotypic tests, fatty acid analysis, 16S rRNA gene sequencing and DNA-DNA hybridization analysis was performed to characterize these novel strains. The 16S rRNA gene sequencing convincingly grouped these novel strains within the genus Paenibacillus as a separate cluster from previously described species. The similarity of 16S rRNA gene sequences among the novel strains was identical but only 98.1 to 98.5 % with their nearest neighbours Paenibacillus barengoltzii ATCC BAA-1209(T) and Paenibacillus timonensis CIP 108005(T). The menaquinone MK-7 was dominant in these novel strains as shown in other species of the genus Paenibacillus. The DNA-DNA hybridization dissociation value was <45 % with the closest related species. The novel strains had DNA G+C contents of 51.9 to 52.8 mol%. Phenotypically, the novel strains can be readily differentiated from closely related species by the absence of urease and gelatinase and the production of acids from a variety of sugars including l-arabinose. The major fatty acid was anteiso-C(15 : 0) as seen in P. barengoltzii and P. timonensis whereas the proportion of C(16 : 0) was significantly different from the closely related species. Based on phylogenetic and phenotypic results, it was concluded that these strains represent a novel species of the genus Paenibacillus, for which the name Paenibacillus phoenicis sp. nov. is proposed. The type strain is 3PO2SA(T) ( = NRRL B-59348(T) = NBRC 106274(T)).


Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a bicoid-like specificity and is expressed in the developing mouse brain.
The vast majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2. These patients exhibit broad and variable phenotypes that include conotruncal cardiac defects, hypocalcemia, palatal and facial anomalies and developmental delay. Most of these abnormalities are thought to be due to defects in neural crest cell migration or differentiation. We have identified a homeobox-containing gene, Goosecoid-like (GSCL), that is in the region within 22q11 that is deleted most consistently in patients with DGS/VCFS. The GSCL gene is expressed in a limited number of adult tissues as well as in early human development, and is a member of a family of homeobox genes in vertebrates that includes Goosecoid and GSX. In this report, we present functional studies of the GSCL protein and determine the expression pattern of the GSCL gene in mouse embryos. We demonstrate that GSCL exhibits DNA sequence-specific recognition of sites bound by the Drosophila anterior morphogen, Bicoid. Several of these sites (TAATCCC) were found in the 5' upstream region of the GSCL gene itself, and we present evidence suggesting that GSCL might regulate its own transcription. In situ hybridization revealed that the mouse ortholog of GSCL, Gscl, is expressed in the brain starting as early as embryonic day 9.5, and expression continues in adults. This expression pattern is consistent with GSCL having either an indirect role in the development of neural crest-derived structures or a direct role in a subset of the phenotype observed in DGS/VCFS, such as learning disorders or psychiatric disease.


Tumor necrosis factor-α regulates interleukin-33 expression through extracellular signal-regulated kinase, p38, and nuclear factor-κB pathways in airway epithelial cells.
Interleukin (IL)-33 plays an important role in controlling immune responses in barrier tissues, and is a potent mediator of inflammatory diseases such as asthma, rheumatoid disease, and chronic rhinosinusitis. The aims of the present study were 2-fold: (1) to determine the stimulatory effect of tumor necrosis factor-α (TNF-α) on IL-33 production in nasal epithelial and A549 cells; and (2) to identify downstream pathways that activate IL-33 production. Primary nasal epithelial cells (PNECs) from 5 normal patients were isolated and cultured. To identify which cytokines stimulate IL-33 production, we performed reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Three mitogen-activated protein kinases (MAPKs) (p38, extracellular signal-regulated kinase [ERK], and c-Jun N-terminal kinase [JNK]) and nuclear factor κB (NF-κB) were evaluated as downstream signaling molecules by RT-PCR, ELISA, Western blot analysis, and luciferase reporter assay. The IL-33 messenger RNA (mRNA) and protein levels were increased significantly by TNF-α in PNECs and A549 cells. TNF-α stimulated the expression of IL-33 in a dose- and time-dependent manner in A549 cells. PNECs and A549 cells were treated with TNF-α in the presence of specific inhibitors of p38, ERK, JNK, and NF-κB. In both cell types, inhibitors of ERK, p38, and NF-κB reversed TNF-α-induced IL-33 production. In the luciferase reporter assay, NF-κB activity was inhibited not only by an NF-κB inhibitor, but also by ERK and p38 inhibitors. TNF-α stimulated IL-33 expression through ERK, p38, and NFκB pathways in PNECs and A549 cells.


Treatment of thyroid eye disease.
Thyroid eye disease (TED) is an autoimmune disease characterized by varying degrees of proptosis, congestion and inflammation of the extraocular tissues, and eyelid retraction. It is usually seen in the setting of Graves' disease, but the severity of TED does not necessarily correlate with the level of systemic disease in a given patient. It is very important, nonetheless, to try to achieve a euthyroid state to minimize the chances of exacerbation of TED. Treatment of TED is based on the signs and symptoms displayed by the patient; there is no "one size fits all" approach. Generally, it is advisable to start with conservative measures, such as ocular lubrication with artificial tears, to manage symptoms of chronic irritation and redness. It is also imperative that the patient be advised to quit smoking, because there is a clear link between smoking and disease activity. Medical treatment with systemic oral or pulsed intravenous corticosteroids should be reserved for patients with active inflammation resulting in increased orbital pressure, compressive optic neuropathy, severe periorbital edema, or similar presentations. Once there is significant improvement in the acute inflammation, it is useful to treat patients who have residual inflammation with external beam radiation in order to be able to wean the patient off steroids and avoid their well-known complications.If there is significant corneal exposure due to lid retraction, and the lid position has been stable for at least 6 months, eyelid surgery can be considered. If exposure is minimal, this may consist of a lateral tarsorrhaphy. For larger amounts of exposure, recession of the levator muscle, Müller's muscle, or both can be performed. Those patients who have stable diplopia for at least 6 months are candidates for strabismus surgery. Patients who progress to severe proptosis or compressive optic neuropathy may need orbital decompression surgery. Generally, if more than one type of surgical procedure is necessary, orbital decompression is performed first, followed by strabismus surgery; eyelid surgery is performed last.


[Relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis].
To investigate the relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis. Mycobacterium tuberculosis (dormant bacteria) was cultured for 100 days, then diluted into 1 mg/ml concentration with 7H9, and further diluted into 0.5, 0.25, 0.125, 0.0625, and 0.03125 mg/ml. Twelve new tubes added with 5 ml 7H9 and divided into two groups: the first group was added with the resuscitation-promoting factor protein, and the second group as control was added with 7H9. In each group the above diluted solutions were added. The tubes were located at 37 degrees C for culture. Optical density (OD) was detected on day 15, 25, 30, and 35. From each tube 1 microl culture solution was plated on 7H11 medium for colony counting. OD detection showed that bacteria proliferation in each group had positive linear correlation (P < 0.05, P < 0.01), indicating that the resuscitation-promoting factor played a similiar role in solutions with different dilution concentrations. 7H11 results and the OD results show that these two detection methods in each group had linear correlation (P < 0.05, P < 0.01), indicating that these two methods showed consistent test results. The resuscitation-promoting factor has no effect on the resuscitation of dormant Mycobacterium tuberculosis and its initial bacteria amount.


A brave new world.
Whereas up to 1950s the two major activities of academic Pathology-diagnostic and experimental-were both practiced by a single individual, thereafter, scientific, academic and economic factors created the conditions that favored monothematic practitioners. In this white paper, I argue that now, at the beginning of the 21st century, this separation is detrimental to the discipline, and I propose changes that would reunite the two strands.


Surgical treatment of the infected hip implant. Two-stage reimplantation with a one-month interval.
Successful treatment of the infected hip prosthesis demands careful planning for infection control and reimplantation. Inadequate surgical debridement dooms well-executed revision surgery to infection failure. Reimplantation is difficult after resection arthroplasty, and this difficulty is increased with longer intervals between resection and reimplantation. Older patients will rehabilitate better if the interval is shorter. The reported protocol successfully compromises between one-stage exchanges and reported two-stage exchanges.


Possible thyroidal involvement in a case of Fabry disease.
Endocrinological evaluations of a 48-year-old man with Fabry disease revealed low levels of serum thyroid hormones and high levels of serum thyrotropin (TSH), indicating that the patient had primary hypothyroidism. Also, an exaggerated growth hormone (GH) response to hypoglycemic stimuli was observed. Thin layer chromatography of the lipid extract of the thyroid gland obtained by biopsy demonstrated marked accumulation of ceramide trihexoside (CTH) and ceramide dihexoside (CDH). These findings strongly suggest that thyroid hypofunction and hypothalamic dysfunction could be involved in Fabry disease.


[Clinical effectiveness of pefloxacin (abaktal)in the treatment of inflammatory diseases of the kidneys, urinary tracts and genital organs].
Pefloxacin (Abaktal) was used in treatment of 83 patients: 14 patients with acute pyelonephritis, 5 patients with carbuncle of the kidney, 17 patients with postoperative acute pyelonephritis, 3 patients with urosepsis, 7 patients with acute prostatitis, 18 patients with chronic pyelonephritis in the phase of active inflammation, 9 patients with exacerbation of chronic prostatitis, 3 patients with acute cystitis, 2 patients with acute urethritis and 5 patients with epididymo-orchitis. Two dosage forms of pefloxacin were used i.e. tablets of 400 mg and ampoules of 5 ml containing 400 mg of the active substance. The treatment course amounted to 7-14 days. In the patients with inflammatory infectious diseases of the lower urinary tracts (cystitis and urethritis) the treatment course amounted up to 5 days. The results of the treatment with the ampoule solutions were good and satisfactory. With the use of the tablets the results were unsatisfactory in 3 patients (8.1 per cent). Satisfactory bacteriological efficacy of the treatment was stated in 89.5 per cent of the cases. The adverse reactions such as nausea, vomiting, diarrhea and skin eruption were recorded in 5 patients (6 per cent).