Role of balloon dilation in the management of adult idiopathic subglottic stenosis.
We evaluated the efficacy of balloon dilation for adjunctive and symptomatic management of isolated idiopathic subglottic stenosis in adults. Adults with airway obstruction symptoms classified as idiopathic subglottic stenosis based on history and findings of a single discrete stenotic area on microlaryngoscopy and bronchoscopy were included in this series. Patients who met these criteria underwent dilation with a 10- to 14-mm balloon in a single procedure or in 2 consecutive dilations within 7 days. The patients were followed for up to 30 months after dilation. Six patients met the criteria. One of the 6 had prior laser treatments and a cricotracheal resection. One patient had a previous scar band lysis procedure. The remaining 4 patients had no prior procedures. The airway sizes prior to dilation ranged from a 2.5 endotracheal tube to a 5.0 endotracheal tube. In all cases the airway was dilated to 2.0 to 3.5 endotracheal tube sizes larger than the initial size. To date, 4 patients have been followed for 10 to 30 months without symptoms of recurrent airway stenosis. One patient was symptom-free for 22 months, then presented with progressive airway difficulty following an upper respiratory tract infection, and has undergone a repeat dilation. No patients had adverse effects or complications from the procedure. Balloon dilation of idiopathic subglottic stenosis in adults is a relatively safe and effective method to manage this disease entity for cases of isolated and discrete lesions. Patients who underwent a single procedure have remained symptom-free for up to 30 months after balloon dilation.


LiSiCA: A Software for Ligand-Based Virtual Screening and Its Application for the Discovery of Butyrylcholinesterase Inhibitors.
We developed LiSiCA (ligand similarity using clique algorithm)--ligand-based virtual screening software that uses a fast maximum clique algorithm to find two- and three-dimensional similarities between pairs of molecules and applied it to the discovery of novel potent butyrylcholinesterase inhibitors. LiSiCA, which runs in parallel on multiple processor cores, was successfully tested on the Database of Useful Decoys-Enhanced, to evaluate its ability to discriminate active molecules from decoys. We then applied LiSiCA for the discovery of novel inhibitors of human butyrylcholinesterase, a promising anti-Alzheimer target, using a known inhibitor as the reference compound. We demonstrated that LiSiCA is capable of finding potent nanomolar inhibitors, whose scaffolds differed from the reference compound, thus proving its ability for scaffold hopping and usefulness in drug discovery.


Small bowel and mesenteric injury following traditional treatment and self-inflicted trauma to inguinal hernia.
Inguinal hernia is a common indication for emergency surgery in our environment after intestinal obstruction. Occasionally other rare indications may be seen. Recently, two patients with such unusual presentation were managed in this institution. One had his hernia incised, by a traditional barber with evisceration and the other incised his hernia himself with evisceration and laceration of the small bowel. Both patients were successfully managed. The menace of traditional barbers and medical ignorance in tropical Africa are reported.


A probable submandibular gland defect in a prehistoric mandible.
The mandible of a prehistoric male Indian, 35 to 40 years old at death, displays a probable bilateral submandibular gland defect. This defect is described, its incidence in prehistoric and modern populations is reviewed, and a possible genetic etiology is proposed.


Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells.
Gain/loss of function studies were utilized to assess the potential role of the endogenous vanilloid receptor TRPV4 as a sensor of flow and osmolality in M-1 collecting duct cells (CCD). TRPV4 mRNA and protein were detectable in M-1 cells and stably transfected HEK-293 cells, where the protein occurred as a glycosylated doublet on Western blots. Immunofluorescence imaging demonstrated expression of TRPV4 at the cell membranes of TRPV4-transfected HEK and M-1 cells and at the luminal membrane of mouse kidney CCD. By using intracellular calcium imaging techniques, calcium influx was monitored in cells grown on coverslips. Application of known activators of TRPV4, including 4alpha-PDD and hypotonic medium, induced strong calcium influx in M-1 cells and TRPV4-transfected HEK-293 cells but not in nontransfected cells. Applying increased flow/shear stress in a parallel plate chamber induced calcium influx in both M-1 and TRPV4-transfected HEK cells but not in nontransfected HEK cells. Furthermore, in loss-of-function studies employing small interference (si)RNA knockdown techniques, transfection of both M-1 and TRPV4-transfected HEK cells with siRNA specific for TRPV4, but not an inappropriate siRNA, led to a time-dependent decrease in TRPV4 expression that was accompanied by a loss of stimuli-induced calcium influx to flow and hypotonicity. It is concluded that TRPV4 displays a mechanosensitive nature with activation properties consistent with a molecular sensor of both fluid flow (or shear stress) and osmolality, or a component of a sensor complex, in flow-sensitive renal CCD.


Antimicrobial Susceptibility Test with Plasmonic Imaging and Tracking of Single Bacterial Motions on Nanometer Scale.
Antimicrobial susceptibility tests (ASTs) are important for confirming susceptibility to empirical antibiotics and detecting resistance in bacterial isolates. Currently, most ASTs performed in clinical microbiology laboratories are based on bacterial culturing, which take days to complete for slowly growing microorganisms. A faster AST will reduce morbidity and mortality rates and help healthcare providers administer narrow spectrum antibiotics at the earliest possible treatment stage. We report the development of a nonculture-based AST using a plasmonic imaging and tracking (PIT) technology. We track the motion of individual bacterial cells tethered to a surface with nanometer (nm) precision and correlate the phenotypic motion with bacterial metabolism and antibiotic action. We show that antibiotic action significantly slows down bacterial motion, which can be quantified for development of a rapid phenotypic-based AST.


[Participation of the primary motor cortex in programming of muscle activity during catching of falling object].
Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.


Contrast alternatives for iodinated contrast allergy and renal dysfunction: options and limitations.
Diagnostic angiography and vascular interventions make routine use of iodinated contrast material (ICM). Patients with renal disease or contrast allergy pose limitations on the use of ICM. In such cases, alternative contrast media may be used to carry out the procedure. Current alternatives include carbon dioxide, gadolinium, and dilute ICM. Each of these alternatives has its own unique features and limitations. In the present review article, the current alternatives to ICM are explored, with a focus on the applications and restrictions of each.


Study Design and Cohort Description of DEFIB-WOMEN: A National Danish Study in Patients with an ICD.
Little systematic evidence is available on potential gender differences in patients with an implantable cardioverter defibrillator (ICD) from a real-world cohort. We designed the DEFIB-WOMEN (The Utilization of Implantable Cardioverter DEFIBrillator Therapy in the Treatment of Heart Disease: Clinical and Psychological outcomes in WOMEN) study to examine gender differences on (1) patient-reported outcomes (PROs), (2) procedure- and device-related complications, and (3) ventricular tachyarrhythmia and mortality. This presents the study design and baseline characteristics of the cohort. DEFIB-WOMEN is a national, multicenter, prospective, observational study. First-time implanted patients are asked to complete PROs at several time points. Information on baseline and follow-up characteristics are captured from patients' medical records, purpose-designed questions, and the Danish national registers. The DEFIB-WOMEN cohort is composed of 1,790 (19% women; 343/1,790) patients implanted between June 2010 and April 2013. Women and men differed on several demographic and clinical baseline characteristics, including on the prescription of β-blockers, statins, angiotensin-converting enzyme inhibitors, and psychotropic agents. Although women generally had a healthier clinical profile, they reported significantly more symptoms of anxiety and depression and ICD concerns (fear of shock) as compared to men. These differences were not only statistically significant but also clinically relevant, with the magnitude of the differences in anxiety and ICD concerns being 0.44 and 0.42, respectively, as indicated by Cohen's effect size index. These preliminary results indicate that women with an ICD experience particularly more anxiety and ICD concerns as compared to men at the time of implant. Future results of DEFIB-WOMEN will show whether these gender differences persist and whether there are also gender differences in complications and survival.


Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain.
Transferrin (Tf)-conjugated solid lipid nanoparticles (SLNs) were investigated for their ability to deliver quinine dihydrochloride to the brain, for the management of cerebral malaria. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidyl choline (HSPC), triolein, cholesterol and distearylphosphatidylethanolamine (DSPE). Coupling of SLNs with Tf was achieved by incubation of Tf with quinine-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride in phosphate buffered saline (pH 7.4) as a cross-linker. SLNs were characterized for shape, particle size, polydispersity and percentage drug entrapment. The SLNs were 108-126 nm in size, and maximum drug entrapment was 38.4-42.7%. Average size increased on coupling with Tf but percentage drug entrapment was reduced. The in-vitro release profile was determined using a dialysis technique; non-conjugated SLNs released comparatively more drug than Tf-SLNs. Fluorescence studies revealed enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs. In in-vivo performance studies, quinine plasma level and tissue distribution after intravenous administration of drug-loaded Tf-SLNs and unconjugated SLNs was compared with that of free drug. Intravenous administration of quinine dihydrochloride solution resulted in much higher concentrations of drug in the serum than with SLNs. Conjugation of SLNs with Tf significantly enhanced the brain uptake of quinine which was shown by the recovery of a higher percentage of the dose from the brain following administration of Tf-coupled SLNs compared with unconjugated SLNs or drug solution.


Cases of parasitic pneumonia in Scottish cattle.
Parasitic pneumonia in cattleNutritional osteodystrophy in cattleWhite liver disease in lambsErysipelas in pigsLead poisoning and atherosclerosis in an eagle These are among matters discussed in the disease surveillance report for October 2015 from SAC Consulting: Veterinary Services (SAC C VS).


A proteomic approach to identify differentially expressed plasma proteins between the fed and prolonged fasted states.
Prolonged fasting is characterized by consecutive phases, a short period of adaptation (phase 1), phase 2 (P2) characterized by fat oxidation, and phase 3 (P3) during which energy requirements are mostly derived from increased protein utilization. At this latter stage, food seeking behavior is induced. Very few circulating biomolecules have been identified that are involved in the response to prolonged fasting. To this end, rat plasma samples were compared by a proteomic approach, using 2-DE. The results revealed a selective variation of the levels of apolipoprotein A-IV, A-I, and E, haptoglobin, transthyretin, plasma retinol binding-protein, and vitamin D binding-protein in P2 and P3. The variations in protein levels were confirmed by ELISA. Changes in mRNA levels encoding these proteins did not systematically correlate well with protein concentrations, and tissue-specific regulation of mRNA expression was observed, underlining the complex metabolic regulation in response to food deprivation. In late fasting, the marked reduction of apolipoprotein A-IV levels could contribute to the alarm signal that triggers refeeding. The variations of the other differentially expressed proteins are more likely related to lipid metabolism and insulin signaling alterations.


Carcinoma of the lip--a case presentation.
An unusually advanced case of squamous cell carcinoma of the lip is presented. Case management involved the use of a radiosensitizing agent, radiotherapy, surgical resection, and reconstruction. Two years later the patient is free of disease.


Enhancing effect of ubenimex (bestatin) on proliferation and differentiation of hematopoietic progenitor cells, and the suppressive effect on proliferation of leukemic cell lines via peptidase regulation.
Ubenimex (Bestatin) significantly enhanced the G- and GM-CSF-induced colony formation of human bone marrow cells at concentrations of 0.001, 0.01, 0.1 and 1.0 microgram/ml (21-61% enhancement), but not at 10 micrograms/ml. Ubenimex did not influence the EPO-induced erythroid colony and burst formation between 0.0001-100 micrograms/ml. Against human and mouse leukemic cell lines, the growth-inhibitory activities of ubenimex were dose-dependently observed. Aminopeptidase activities on U937 and TF-1 cells were almost inhibited with 10 and 100 micrograms/ml of ubenimex, respectively. Cross-linking studies of 125I-GM-CSF binding to TF-1 cells demonstrated that the 150-kDa band of 2 major bands was enhanced after incubation with 0.01 microgram/ml ubenimex but decreased after that with 100 micrograms/ml, and that the 95-kDa band was not changed at any concentration of ubenimex. Change in density of the 150-kDa band on ubenimex-treated TF-1 cells was correlated with that in expression of CD10 (neutral endopeptidase) on them, whereas that in expression of CD13 (aminopeptidase N) was not changed at any concentration. These results suggest that one possible mechanism of ubenimex action in hematopoietic progenitor cells is the up-regulation of the high affinity receptor for GM-CSF and that in leukemic cell lines is suppression of amino acid incorporation via peptidase regulation.


Cysticercosis in laboratory rabbits.
There are no data on the current incidence of Taenia pisiformis in laboratory rabbits. Two cases of cysticercosis most likely due to T. pisiformis in laboratory rabbits (intermediate host) are presented. Both rabbits had no contact with dogs (final host); their caretakers did not work with dogs, and these caretakers changed into facility scrubs and wore gloves when working with the rabbits. Rabbit 1 may have been infected after being fed hay at our facility. In light of the life cycle of the parasite and the history of rabbit 2, it potentially could have been infected prior to arrival at our facility. There have been only three cases of tapeworm cysts in rabbits in our facility (average daily census, 250) during the last 10 years (incidence, < 1%). This report indicates that although cysticercosis is rare in laboratory rabbits, one should always be aware of such incidental findings. Although it may not produce overt illness in the rabbit, hepatic migration could adversely affect the outcome of some experimental procedures


Brentuximab vedotin: an anti-CD30 antibody-drug conjugate.
The pharmacology, pharmacokinetics, clinical efficacy, and safety and tolerability of brentuximab vedotin are reviewed. Brentuximab vedotin is a potent antibody-drug conjugate composed of the monoclonal antibody cAC10, which targets the CD30 antigen on Hodgkin lymphoma and systemic anaplastic large-cell lymphoma (sALCL) cells; a highly stable valine-citrulline linker; and a potent chemotherapeutic agent monomethyl auristatin E, which inhibits microtubule polymerization. Brentuximab is indicated for patients with relapsed Hodgkin lymphoma after autologous stem-cell transplantation (ASCT), for patients who are not candidates for ASCT who have not responded to at least two multiagent chemotherapy regimens, and for patients with ALCL who have not responded to at least one multiagent chemotherapy regimen. In a Phase II, single-group, multicenter study, brentuximab produced an overall response rate of 75% in relapsed or refractory Hodgkin lymphoma. In another Phase II study, brentuximab demonstrated clinical benefit in sALCL, with 86% of patients achieving a response and 57% of patients achieving complete remission. Adverse events most commonly reported included nausea, fatigue, diarrhea, neutropenia, and peripheral sensory neuropathy. A Phase III study is currently ongoing in patients at high risk for residual Hodgkin lymphoma after ASCT. Brentuximab vedotin, a novel antibody-drug conjugate combining a cytotoxic agent with a selective monoclonal antibody, is a therapeutic option for patients with relapsed or refractory Hodgkin lymphoma and sALCL. Phase I and II studies have shown brentuximab to have a manageable toxicity profile.


Destruction of human tear proteins by ozone.
By an in vitro system human tears from healthy donors were exposed in a sealed vessel to a single dose of ozone. A marked destruction of tear proteins by ozone was observed as indicated by the disappearance of the protein pattern in polyacrylamide gel electrophoresis compared with the control. Lysozyme, a significant protein in tears, was demonstrated to be susceptible to degradation by O3. The destruction of tear proteins by ozone can be determined quantitatively by radial immunodiffusion as shown for human tear albumin. Variations of ozone concentrations and reaction time showed that destruction of tear proteins by ozone depended on the ozone concentration and occurred within a few minutes of exposure of tears to ozone.


[Partial synthesis of adenosylcorrinoids and of 1,N6-etheno-adenosylcobalamin with a fluorescent nucleoside (author's transl].
Adenosylcobalamin and several analogs of this corrinoid are prepared by an improved method and separated by an one-step-chromatography on columns of carboxymethylcellulose. Pure water is the eluting agent. The same method is suitable for the preparation of 1,N6-ethenoadenosylcobalamin, a corrinoid with fluorescent nucleoside.


Endoscopic transiliac approach to L5-S1 disc and foramen. A cadaver study.
The toros of fresh cadavers were used to create endoscopic channels through the iliac wings to gain access to the L5-S1 disc and foramen. The spine and pelvis then were dissected out en bloc, and the anatomic relationships were studied. To determine the feasibility of a transiliac approach to the L5-S1 disc and foramen and to assess the safety of this approach by studying the anatomic relationships of the transiliac track. Because of its location deep in the pelvis, the L5-S1 disc and foramen are not easily accessible via a supra-iliac portal. A laparoscopic approach violates the abdominal cavity, and makes major vessels and viscera at risk for injury. A core drill was inserted over a guide wire into the iliac wing under fluoroscopy to obtain a core of bone, which then was removed to create a transiliac channel. An arthroscope was inserted through the channel to perform discoscopy or foraminoscopy. The spine was dissected out en bloc to study the relationships of the track. It was possible to use a transiliac approach to L5-S1 in all the experiments. There was no damage of neural structures in any of the experiments. The results of this study suggest that it is possible to access the L5-S1 disc and foramen through the ilium without injuring important structures. It would be necessary to conduct a study based on an animal model and to evaluate the results before using this procedure in a clinical situation.


Attenuation of low-frequency sound in freshwater.
Lake Superior was chosen as an experimental site to compare sound absorption of freshwater with the results of absorption measurements in seawater. The relaxation-like absorption at 1 kilohertz occurring in seawater is also present in freshwater. A relaxation related to the structural characteristics rather than to the salt content of water may be responsible for the anomalous absorption.


Heart Failure Patients' Perceptions of Received and Wanted Information: A Cross-Sectional Study.
This study aimed to investigate heart failure patients' perceptions of received and wanted information and to identify differences regarding received and wanted information in relation to sociodemographic variables. A cross-sectional descriptive design was used. Patients with heart failure ( n = 192) were recruited from six primary health care centers in Sweden. Data were collected by a postal questionnaire. A majority of the respondents had received information about the condition and the medication. Within primary health care, most respondents had been informed about medication. The respondents wanted more information about continued care and treatment, medication, and the condition. There were significant differences between sociodemographic groups concerning what information they wanted. Clinical nurses can support patients with heart failure by using evidence-based methods that strengthen the patients' self-efficacy and by individualized information that increases patients' knowledge and improves their self-care behaviors. Future studies are needed to identify informational needs of particular fragile groups of patients.


Interaction of resveratrol with membrane glycerophospholipids in model system in vitro.
Resveratrol is a polyphenol that among other sources occurs in grapes and for this reason, red wines also contain considerable amounts of this compound. Interactions of resveratrol with pure molecular species of phosphatidylcholine (PC), phosphatidylethanoloamine (PE) and phosphatidylserine (PS) were studied with the Langmuir technique on monolayers and with differential scanning calorimetry on unilamellar liposomes. Resveratrol caused a modest increase in the mean molecular area (MMA) of dipalmitoyl-PC (DPCC) and PE (DPPE) monolayers, but profoundly increased the MMA of dipalmitoyl-PS (DPPS). The resveratrol-induced increase in MMA was enlarged in PS species containing stearolyl and oleoyl acyls suggesting that increase in the acyl chain length and unsaturation enhanced the resveratrol-phospholipid interaction. In liposomes resveratrol lowered T(m) (main transition temperature) and increased T(C1/2) (transition interval) in DPPE, DPPS and 1-palmitoyl-2-oleoyl-PS (POPS), suggesting that resveratrol causes an increase in the anisotropy of these liposomes. In DPPE and POPS liposomes resveratrol caused a lowering of ΔH, further substantiating a pure enhancement of anisotropy for these molecular species. However, resveratrol caused a marked increase of ΔH in DPPS liposomes, indicating that, in addition to increase anisotropy, DPPS and resveratrol attracted each other specifically. This study has clearly shown interactions between resveratrol and glycerophospholipids on a molecular level and that these interactions are influenced by the acyl chain length, degree of unsaturation and head group of the lipids.


Vitamin A deficiency and wheezing.
Vitamin A deficiency may increase the responsiveness of the respiratory tract and increase the risk of respiratory tract infection, resulting in airway obstruction and wheezing. This study aimed to investigate the relation between vitamin A deficiency and infant wheezing. Three ml venous blood samples were collected from 331 hospitalized children who suffered from wheezing to determine the serum vitamin A concentration and the relationship between vitamin A and some causative factors of wheezing. The severity of vitamin A deficiency was related to the course of wheezing. In the persistent wheezing group, 14 patients (34.1%) were diagnosed as having severe vitamin A deficiency and 16 patients (39%) having moderate vitamin A deficiency; among the acute wheezing group, 18 patients (16.4%) were diagnosed as having severe vitamin A deficiency and 32 patients (29%) having moderate vitamin A deficiency. Comparison of the two groups revealed that there was a significantly higher rate of moderate and severe vitamin A deficiency in the persistent wheezing group than in the acute wheezing group (P<0.01). The severity of vitamin A deficiency was related to the infants' wheezing severity. Severe vitamin A deficiency was found in 24 patients (47%) in the severe wheezing group and 8 (8%) in the mild and moderate wheezing groups. The rate of severe vitamin A deficiency was significantly higher in patients with severe wheezing than in those with mild and moderate wheezing (P<0.01). Serum vitamin A deficiency could be commonly found in infants with wheezing. The severity of vitamin A deficiency might be related to the course of wheezing and the infants' wheezing severity.


Metabolic profile of FYX-051 (4-(5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile) in the rat, dog, monkey, and human: identification of N-glucuronides and N-glucosides.
FYX-051, 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile, is a novel xanthine oxidoreductase inhibitor that can be used for the treatment of gout and hyperuricemia. We examined the metabolism of FYX-051 in rats, dogs, monkeys, and human volunteers after the p.o. administration of this inhibitor. The main metabolites in urine were pyridine N-oxide in rats, triazole N-glucoside in dogs, and triazole N-glucuronide in monkeys and humans, respectively. Furthermore, N-glucuronidation and N-glucosidation were characterized by two types of conjugation: triazole N(1)- and N(2)-glucuronidation and N(1)- and N(2)-glucosidation, respectively. N(1)- and N(2)-glucuronidation was observed in each species, whereas N(1)- and N(2)-glucosidation was mainly observed in dogs. With regard to the position of conjugation, N(1)-conjugation was predominant; this resulted in a considerably higher amount of N(1)-conjugate in each species than N(2)-conjugate. The present results indicate that the conjugation reaction observed in FYX-051 metabolism is unique, i.e., N-glucuronidation and N-glucosidation occur at the same position of the triazole ring, resulting in the generation of four different conjugates in mammals. In addition, a urinary profile of FYX-051 metabolites in monkeys and humans was relatively similar; triazole N-glucuronides were mainly excreted in urine.


Flavin binding site differences between lipoamide dehydrogenase and glutathione reductase as revealed by static and time-resolved flavin fluorescence.
Subnanosecond-resolved fluorescence measurements of the FAD bound in glutathione reductase and lipoamide dehydrogenase revealed characteristic differences in dynamic properties of both enzymes, which are considered to have common structural features. The flavin fluorescence in glutathione reductase is quenched mainly via a dynamic mechanism, in agreement with enhanced flexibility of the flavin as inferred from rapid depolarization of the fluorescence.


Negative ion transport inside collisional presheaths.
Modeling of negative ion sources proposed for spallation sources or neutral beam injectors must include several ion production mechanisms, in particular, for wall production, the initially backward ion motion must be reversed in the presheath to obtain extraction. An adequate analytic simplification of the full Vlasov-Boltzmann equations to a one space dimension model for the investigation of the transport effects of the presheath voltage is described here. Integrodifferential collision dominated transport equations are written and solved for typical profiles of the presheath voltage. The results for space charge density improve previous estimates. A transverse magnetic field can be included in the formalism to treat electron transport: principles of its solution are summarized and numerical examples are given; plasma quasineutrality is approximately verified.


Thymic but not splenic CD8⁺ DCs can efficiently cross-prime T cells in the absence of licensing factors.
Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for cross-presentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady-state thymic CD8(+) DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic CD8(+) DCs was dependent on licensing factors such as GM-CSF. In the absence of GM-CSF, antigen-MHC-class-I complexes were detected on thymic but not on splenic CD8(+) DCs, indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences between thymic and splenic CD8(+) DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall impairment of antigen presentation, as peptide-loaded splenic CD8(+) DCs were able to induce CD8(+) T-cell proliferation. The observation that thymic CD8(+) DCs are more efficient than splenic CD8(+) DCs in T-cell cross-priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells.


Failure of high-dose steroid therapy to influence intracranial pressure in patients with severe head injury.
While corticosteroids in standard neurosurgical dosage do not appear to influence recovery from severe head injury or elevated intracranial pressure (ICP), some reports claim that a much higher dose is effective. A resultant hypothesis is that an abrupt increase in corticosteroid dosage in patients with severe head injury should cause a detectable reduction in ICP and in cerebral elastance within 48 hours. To test this hypothesis 20 consecutive patients with severe head injury, 12 of whom had had surgical decompression of mass lesions, were studied. All patients were artificially ventilated, and had continuous monitoring of ICP and intermittent testing of elastance by measurement of the volume-pressure response (VPR). For the first 12 hours after admission, patients received methylprednisolone, 40 mg every 6 hours. The dose was then increased abruptly by giving a single dose of 2 gm and 500 mg every 6 hours for the next 24 hours, then tapering rapidly. No significant change in ICP or VPR could be detected after 24 or 48 hours of high-dose steroid therapy. Of the 20 patients, 50% had good recovery or were moderately disabled, 15% were severely disabled or vegetative, and 35% had died. The course of ICP and the outcomes in these patients were not significantly different from those observed in a previous group of 262 patients managed in the same way for the high-dose regimen. There was, however, high incidence of gastric hemorrhage (50%) and of hyperglycemia with glucosuria (85%) in these 20 patients. These negative results in patients with head injury stand in marked contrast to our experience of the benefit of methylprednisolone in patients with brain tumors.


Effect of continuous LDL apheresis with dextran-sulfate cellulose column system on a child with homozygous familial hypercholesterolemia.
A new system for selective low density lipoprotein apheresis with an automated regenerating column using dextran-sulfate (DS) as ligand was evaluated for six months in a 13-year-old boy homozygous for familial hypercholesterolemia. Two columns each containing 150 ml of DS cellulose were alternately used after rinsing with a regenerating solution. The patient could well tolerate the volume in the system. The values of plasma total cholesterol decreased by 79.4 +/- 4.9% of the pretreatment levels after a total of 5l plasma apheresis, while those of high density lipoprotein cholesterol did not change. Although the values of CH50 decreased, no adverse reaction was seen during the period of treatment. It was concluded that the present apheresis system was highly efficacious and safe for children homozygous for the mutant LDL receptor gene.


Influence of aromatic compounds on biodegradation of [14C]-labeled xylan and mannan by the white-rot fungus Phlebia radiata.
Radiolabeled [14C]arabinoxylan from wheat meal and [14C]galactoglucomannan from red clover meal were prepared by using 14CO2 as a precursor. Twice as much mannan was mineralized than xylan after 14 days of incubation with Phlebia radiata. Low-molecular-weight phenolic compounds structurally related to lignin increased during mineralization of both hemicellulose fractions. Veratryl alcohol increased degradation of arabinoxylan by approximately 28.5%, whereas veratric acid increased it by only 9.0%. Vanillic acid and ferulic acid also stimulated degradation by 16.6% and 34.7%, respectively. Veratryl alcohol and ferulic acid increased degradation of galactoglucomannan by approximately 75%. Veratraldehyde in both cases repressed the degradation process (23.6% arabinoxylan, 43.8% galactoglucomannan). These results indicate that the degradation of hemicelluloses, e.g., xylan and mannan, by P. radiata is enhanced by addition of aromatic compounds.


Immunosuppressive activity of class I antigens in the absence of antigen-presenting cells that are MHC-compatible with the host.
Pretransplant transfusions of heat-treated spleen and lymph node cells were shown to prolong the survival of DA strain heart grafts in 3 allogeneic host strains: BS, HS, and AS2. To examine whether MHC incompatibility was necessary for immunosuppression mediated by heat-treated cells, AS strain skin-graft recipients were pretreated with fresh or heated inocula from either MHC compatible or incompatible congenic donor strains, AS2.1L(AS) and AS.1F(AS2) prior to transplanting donor strain skin. Prolonged survival was observed only in the MHC-incompatible strain combination, and in this MHC-incompatible strain combination, and in this instance heated cells were conspicuously more immunosuppressive than fresh cells. To determine the effect of intra-MHC differences between donor and host on graft survival, cells from a recombinant donor strain (r22), which shared class II antigens with the graft donor strain and class I antigens with the host, were transfused prior to heart transplantation. Neither fresh nor heated r22 cells prolonged graft survival. Our data accord with the suggestion that in the absence of MHC-compatible antigen-presenting cells, foreign class I antigen is immunosuppressive.


Longitudinal course of body-focused repetitive behaviors in obsessive-compulsive disorder.
The course of body-focused repetitive behaviors (BFRBs) (eg, trichotillomania, skin picking, and nail biting) has received scant research attention. We sought to understand the longitudinal course of BFRBs over an 8-year period and whether the co-occurrence of a BFRB with obsessive-compulsive disorder (OCD) affects the course of OCD. Three hundred ninety-five participants with OCD completed annual interviews using the Longitudinal Interval Follow-up Evaluation to estimate BFRB and OCD symptom severity during each week of follow-up. Of the 395 participants, 83 (21%) had a co-occurring BFRB. In almost one-half of the participants, BFRB onset occurred before OCD. Participants with OCD and BFRB spent the majority of the rating period experiencing full BFRB symptoms. Having a BFRB was associated with spending less time in remission from OCD. Although BFRBs have long been known to be common in individuals with OCD, these data demonstrate that most individuals who have a co-occurring BFRB with OCD do not experience BFRB remission and that having a BFRB predicts a worse course for OCD.


Optic surface changes in Intraocular lens scaffold: An ex vivo study.
We aimed to assess the micro injuries on the intraocular lens (IOL) optic in the IOL scaffold technique by ex vivo study. This study was conducted at the Tahira Research Laboratory, Dr Agarwal's Eye Hospital and Eye Research Centre, Chennai. This was an experimental study. IOL scaffold technique was simulated in 12 caprine eyes with moderate lens changes using 12 IOLs (six acrylic hydrophilic and six polymethyl methacrylate IOL) in experimental set up. IOLs (6 mm optic diameter) were explanted from the caprine eyes immediately after the surgery and examined under light microscopy and phase contrast microscopy for anterior and posterior optic changes, and again after 24 hours. Scanning electron microscopy (SEM) was performed in IOLs with abnormalities. Two IOLs placed in caprine eyes that did not undergo scaffold procedure acted as controls. A trocar anterior chamber maintainer was used in four eyes. Four out of 12 IOLs showed mark defects on the surface in mid periphery. Linear mark defects measured IOL 1 (190 μm), IOL 6 (18 μm), IOL 2 (2.33 μm, 2.3 μm, 14 μm, 14 μm) and IOL 5 (12 μm). The marks do not change after 24 hours. There were no mark defects (micro abrasions or scratches) seen on any of the IOL's in the central 4 mm of the optic anterior surface. The control IOLs showed no surface changes. The pre-experiment mark defects (n = 0) in study IOLs changed to post-experiment (n = 7), with no statistical significance obtained (p = 0.059). IOL scaffold technique can cause microscopic optic surface changes seen as linear marks defects in the mid periphery and intraoperative fluid maintenance can reduce its incidence.


Computed tomography for diagnosis of Morton's neuroma.
Fifteen patients suspected to have Morton's neuroma were examined by computed tomography, which revealed the neuroma in seven cases. All seven underwent surgery and had the diagnosis confirmed. If there is doubt about the diagnosis, it is possible to use computed tomography as shown here.


Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole.
Central nervous system involvement in infection with Blastomyces dermatitidis is uncommon, except in immunocompromised patients. We report a case of central nervous system blastomycosis occurring 18 months after treatment of pulmonary blastomycosis in an immunocompetent child. Our patient was successfully treated sequentially with liposomal amphotericin B followed by oral voriconazole without need for surgical resection.


Purification and characterization of a new alcohol dehydrogenase from human stomach.
Starch gel electrophoresis of homogenates from human stomach mucosa resolves three alcohol dehydrogenase (ADH) forms: the anodic chi-ADH (class III), the cathodic gamma-ADH (class I), and a new form of slow cathodic mobility that has not been previously characterized. In this work, we describe the purification in three chromatographic steps and the physical and kinetic characterization of this new human alcohol dehydrogenase, which we have named sigma-ADH. The enzyme exhibits the general physicochemical features (Mr, zinc content, subunit Mr, cofactor preference) of all mammalian alcohol dehydrogenases. The kinetic studies show a high Km value (41 mM) and a high kcat value (280 min-1) for ethanol at pH 7.5. The Km decreases as the alcohol increases its chain length. The aldehydes are better substrates than the corresponding alcohols, with m-nitrobenzaldehyde being the best substrate examined. sigma-ADH is strongly inhibited by 4-methylpyrazole, but with a Ki (10 microM) still higher than that for a class I isoenzyme. These properties suggest that sigma-ADH is a class II isoenzyme, different from pi-ADH and similar to that previously described by us in rat stomach. At the high ethanol concentrations in stomach after drinking, sigma-ADH is probably the ADH form with the largest contribution to human gastric ethanol metabolism.


Toward a high-throughput approach to quantitative proteomic analysis: expression-dependent protein identification by mass spectrometry.
The isotope-coded affinity tag (ICAT) technology enables the concurrent identification and comparative quantitative analysis of proteins present in biological samples such as cell and tissue extracts and biological fluids by mass spectrometry. The initial implementation of this technology was based on microcapillary chromatography coupled on-line with electrospray ionization tandem mass spectrometry. This implementation lacked the ability to select proteins for identification based on their relative abundance and therefore to focus on differentially expressed proteins. In order to improve the sample throughput of this technology, we have developed a two-step approach that is focused on those proteins for which the abundance changes between samples: First, a new software program for the automated quantification of ICAT reagent labeled peptides analyzed by microcapillary electrospray ionization time-of-flight mass spectrometry determines those peptides that differ in their abundance and second, these peptides are identified by tandem mass spectrometry using an electrospray quadrupole time-of flight mass spectrometer and sequence database searching. Results from the application of this approach to the analysis of differentially expressed proteins secreted from nontumorigenic human prostate epithelial cells and metastatic cancerous human prostate epithelial cells are shown.


Low predictive value of positive transplant perfusion fluid cultures for diagnosing postoperative infections in kidney and kidney-pancreas transplantation.
Infection following transplantation is a cause of morbidity and mortality. Perfusion fluid (PF) used to preserve organs between recovery and transplantation represents a medium suitable for the growth of microbes. We evaluated the relevance of positive growth from PF sampled before the implantation of kidney or kidney-pancreas (KP) allografts. Between January 2007 and January 2011, 548 kidney/KP transplants were performed in our centre. A retrospective review of patient records with culture-positive PF was performed. PF was received from 483 (88%) patients, of which 35 (7%, 95% CI 5.3% to 9.9%) were positive for bacteria (31/483, 6.4%, 95% CI 4.6% to 9.8%) and fungi (4/483, 0.8%, 95% CI 0.3% to 2.1%). Thirty-two of the 35 culture-positive PF (91.4%, 95% CI 77.6% to 97%) were considered insignificant. The remaining three patients developed sepsis postoperatively, which was considered to be possibly related to growth in PF; Escherichia coli in one and Klebsiella pneumoniae in two. Of the non-skin flora bacteria cultured from PF, six were resistant to the prophylactic antibiotic given intraoperatively, but only one developed infection postoperatively (E coli, resistant to the co-amoxiclav). Significant attributable morbidity associated with PF-positive culture results was relatively rare. Culture of organisms other than Enterobacteriaceae or fungi are likely to represent contamination.


[Noninstrumental immunoanalysis based on dyed polyacrolein latexes. Determination of a group-specific polysaccharide from Streptococcus pyogenes].
Non-instrumental immunoassays based on immunofiltration and microtiter particle agglutination (MPA) techniques have been developed using coloured polyacrolein latex. These methods have been applied to the quantification of the group-specific polysaccharide (PS) of S. pyogenes (group A streptococcus) and compared with standard ELISA tests. The most efficient method was MPA; as little as 0.05 ng A-PS/ml could be detected in 1.5 h. In comparison with ELISA test, the sensitivity of MPA was 10 times higher and the procedure was much simpler. The sensitivity of immunofiltration assay using both enzyme and latex conjugates was shown to be the same (50 ng/ml A-PS) and the duration of the assay 3-5 min. No cross-reactions of latex conjugates with non A streptococcus cell lysates have been observed. The developed methods are rapid, robust, easy to perform, don't need any sophisticated equipment and specially trained staff.


Comparability and reproducibility of the results of water loss measurements: a study of 4 evaporimeters.
A study was made of the comparability and reproducibility of the results of measurements of water loss, both in vitro and in vivo, using 4 ServoMed Evaporimeters (3 single-probe and 1 double-probe instrument). The optimum time for recording transepidermal water loss (TEWL) after the initial application of the probe to the skin (in vivo), and the best technique for optimizing the accuracy of measuring TEWL were determined. An evaporation device with a constant level of water loss was constructed for in vitro studies. The volar aspect of the right forearm skin of one subject was used in vivo. Both in vitro and in vivo measurements showed that there were some differences between the results of 4 of the 5 probes. The other probe was distinctly out of range. For all probes, the reproducibility of results of successive measurements was high. Stabilization of TEWL values was reached for all probes from 30-45 s after their initial application to the skin. It is recommended that TEWL be recorded for a further 30-s period, after the initial stabilization (45 s), and that this be taken as the true value. The manufacturer's recommended calibration procedure is based only on adjustments for the standard specified humidities and zero water loss. The importance of incorporating an additional calibration procedure which includes adjustments for an actual standard constant water loss is thus strongly stressed.


Footrot vaccines and vaccination.
Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of acquired immunity.


High efficiency Agrobacterium rhizogenes-mediated transformation of Saponaria vaccaria L. (Caryophyllaceae) using fluorescence selection.
A highly efficient and convenient method for the Agrobacterium rhizogenes-dependent production of transformed roots of Saponaria vaccaria L. (Caryophyllaceae) is described. The parameters tested and optimized include S. vaccaria cultivar, explant type, Agrobacterium rhizogenes strain and culture conditions. For cotransformation using additional recombinant T-DNA-containing A. rhizogenes strains, use of neomycin phosphotransferase and enhanced green fluorescent protein genes as selectable markers were tested alone and in combination. Optimal results, yielding a minimum of one transformed root per explant, were obtained using the cultivar Pink Beauty, the A. rhizogenes strain LBA9402 and internode explants precultured on a phytohormone mixture. Selection of cotransformed roots by observation of enhanced green fluorescent protein fluorescence alone was highly effective and convenient.


Health care expenditure and life expectancy in Australia: how well do we perform?
The Australian health care system consists of mixed public and private financing underpinned by Medicare, a universal government-run insurance scheme paid through taxation (and levy) on income. Australia has improved its ranking for life expectancy (at birth) since 1960, and in 1990 ranked ninth and seventh of 24 countries for females and males respectively; this is ahead of the United States and United Kingdom, and approximately equal to Canada. Australian hospital bed supply and utilisation are average, after deletion of day-only cases. The proportion of gross domestic product (GDP) spent on health, in relation to GDP per capita (adjusted for purchasing power), in Australia in 1990 was average, and the prices for health care from 1975 to 1990 did not increase when adjusted for inflation. Although 68 per cent of health expenditure emanates from public sources in Australia, this is lower than in the majority of European countries and Canada. Some countries are doing poorly (such as the United States, with lower than average life expectancy and higher than predicted health expenditure) and some countries are doing well (with higher than average life expectancy and lower than predicted health expenditure; for example, Japan). Australia has higher than average life expectancy and only slightly higher than predicted health expenditure per capita. Although the Australian system could be improved, there are no indications that radical changes are required. The relatively high life expectancy in Australia can be attributed to favourable social and economic conditions, successful public health programs, and the availability of universal quality health care.


[Expression of survivin in different stages of carcinogenesis and progression of breast cancer].
Survivin is one of the newly identified apoptosis inhibitor; it can block the cell apoptosis by inhibiting the function of the enzyme caspase-3 and caspase-7. Present studies indicate that survivin is overexpressed in malignant tumor. This current study was designed to investigate the effects of survivin in tumorigenesis and progression of breast carcinoma through observing the expression of survivin in the tissue of normal mammary, cystic hyperplasia mammary, atypical hyperplasia mammary and breast carcinoma. The expression of survivin in the tissue of normal mammary (96 cases), cystic hyperplasia mammary (56 cases), atypical hyperplasia mammary (12 cases), and breast carcinoma (119 cases) were evaluated by SP immunohistochemistry. The relationship between survivin expression and the pathologically biological features of breast cancer was assessed. The positive rates of survivin were 4.2%(4/96),5.4% (3/56),42.7% (5/12), and 72.3%(86/119)in the tissue of normal mammary, cystic hyperplasia mammary, atypical hyperplasia mammary, and breast carcinoma, respectively. The positive rates in the last two groups were higher than those in the former two groups (P< 0.005). Survivin was more expressed in the infiltrative nonspecial breast carcinoma (82.0%, 73/89) than in the special and early stage infiltrative breast carcinoma (37.5%,3/8)(P< 0.05). Expression of survivin was correlated with lymph node metastasis although the difference is not significant (P >0.05). Overexpression of survivin is common in tumorigenesis and progression of breast carcinoma. Altered expression of survivin may contribute to tumorigenesis and progression of breast carcinoma by inhibiting cell apoptosis, its overexpression indicates worse prognosis.


[Atopic eczema: psychophysiological reactivity with standardized stressors].
In 18 atopic eczema patients with active symptomatology and 15 control subjects a comparison of reactivity to psychological stressors was made. The physiological measures were heart rate, peripheral vasomotor response, skin resistance level, spontaneous fluctuations of the skin resistance, and forearm skin temperature. In addition, self-ratings of subjective state, situational anxiety, and social anxiety were assessed. Mental arithmetic performed undisturbed and in distracting conditions, and anticipation of the latter and of having to speak in public served as stressors. The results show higher reaction values of the eczema patients for heart rate, peripheral vasomotor response, fluctuations of skin resistance and subjective tension. A subgroup of patients with extreme skin irritation (itching) reacted with an elevation of skin temperature, in contrast to control subjects and patients with less marked itching, in whom skin temperature dropped slightly. The results suggest that atopic eczema may have a psychophysiological component.


Serum DKK1 is correlated with γ peak of serum electrophoresis in multiple myeloma: a multicenter biomarker study.
Aim: DKK1 is reported to be produced at high levels by myeloma cells. Therefore, the applicability of DKK1 as a tumor marker for multiple myeloma (MM) diagnosis was examined. Methods: Serum samples were collected and analyzed by DKK1 concentration kit and capillary zone electrophoresis. Then, the obtained results were statically analyzed. Results: It has been determined that the 10 ng/ml of DKK1 is the optimal level for MM diagnosis. Moreover, there was an ascending linear correlation between the DKK1 concentration and γ peak. Discussion: The observed correlation could be rooted in the positive feedback loop between MM cells and the mesenchymal stem cells. In view of these results, DKK1 could be deemed as diagnostic marker for MM.


Green kiwifruit modulates the colonic microbiota in growing pigs.
To investigate whether green kiwifruit modulates the composition of colonic microbiota in growing pigs. Thirty-two pigs were fed the control diet or one of the three test diets containing either cellulose, freeze-dried kiwifruit or kiwifruit fibre as the sole fibre source for 14-day study. A Ward's dendrogram of similarity cluster analysis on PCR-DGGE gels revealed that inclusion of freeze-dried kiwifruit and kiwifruit fibre into diets altered the bacterial community, indicating the presence of two distinct clusters. Quantification of different bacterial groups by qPCR demonstrated that pigs fed the freeze-dried kiwifruit or kiwifruit fibre diets had a significantly higher number (P < 0·05) of total bacteria and Bacteroides group and a lower number of Enterobacteria and Escherichia coli group, as well as a greater ratio of Lactobacillus to Enterobacteria when compared to pigs fed the control or cellulose diets. Green kiwifruit, mainly because of fibre, modulated the colonic microbiota, leading to an improved intestinal environment in growing pigs. This is the first report regarding the effect of green kiwifruit on gut microbiota using the in vivo pig model. These results provide the first evidence of interaction between green kiwifruit and colonic microbiota.


A set of biogenetically interesting polyhalogenated acetogenins from Ptilonia magellanica.
Ptilonines A-F, pyranosylmagellanicus D-E and magellenediol are previously undescribed acetogenins isolated from the red alga Ptilonia magellanica. Their structures were determined from spectroscopic evidence. The absolute configuration of the known pyranosylmagellanicus A, was established by derivatization with (R)- and (S)-α-methoxy -α-phenylacetic acids (MPA). Ptilonines exhibit an unusual halogenation pattern, that may confer evolutionary advantages to Ptilonia magellanica, for which a biogenetic origin is proposed. The antimicrobial effect of some of these compounds was evaluated.


Nonuniversal Transverse Electron Mean Free Path through Few-layer Graphene.
In contrast to the in-plane transport electron mean-free path in graphene, the transverse mean-free path has received little attention and is often assumed to follow the "universal" mean-free path (MFP) curve broadly adopted in surface and interface science. Here we directly measure transverse electron scattering through graphene from 0 to 25 eV above the vacuum level both in reflection using low energy electron microscopy and in transmission using electronvolt transmission electron microscopy. From these data, we obtain quantitative MFPs for both elastic and inelastic scattering. Even at the lowest energies, the total MFP is just a few graphene layers and the elastic MFP oscillates with graphene layer number, both refuting the universal curve. A full theoretical calculation taking the graphene band structure into consideration agrees well with experiment, while the key experimental results are reproduced even by a simple optical toy model.


Treatment of venous thrombo-embolism.
Clinically suspected deep vein thrombosis (DVT) or pulmonary thromboembolism (PE) should be initially treated with heparin, and an objective diagnosis obtained. In pregnancy, heparin is usually continued until delivery, following which warfarin is substituted. In the absence of pregnancy, warfarin is substituted and usually continued for 3 months after a first thrombo-embolic event. Low molecular weight heparins are increasingly preferred to unfractionated heparin in non-pregnant patients with acute DVT, because of efficacy when given by daily subcutaneous injection without routine monitoring of coagulation assays, greater efficacy, and lower risks of major bleeding and of mortality. Unfractionated heparin requires monitoring by the APTT (target ratio 1.5-2.5), and warfarin requires monitoring by the International Normalized Ratio (INR) of the prothrombin time (target ratio 2.0-3.0). Graduated elastic compression stockings reduce post-thrombotic leg symptoms after DVT. Secondary prevention is important in future high risk situations.


[Increased expression of endothelin-1 and its mitogen receptor ET(A) in thyroid papillary cancer in humans].
Since its discovery in 1988, endothelin has initiated intense research activities, showing that it was not only a vasoconstrictor and mitogenic peptide produced by the vascular endothelium but also a ubiquitous molecule with various functions. A production of ET-1 has been evidenced in the thyroid and ET-1 receptors have been detected on thyroid cells. Produced by the vessels and the thyrocytes, ET-1 could exert paracrine and/or autocrine effects on vascular tone in the thyroid and on some functions of thyrocytes. Because of proliferative effects, its role in thyroid diseases could involve goitrogenesis and carcinogenesis. Using thyroid samples obtained at the time of surgery, we demonstrated increased expressions of ET-1 and its mitogenic receptor ET(A) in papillary carcinoma of the thyroid. Immunohistochemical studies and real-time quantitative polymerase chain reaction (RTQ-PCR) were used for this purpose. As demonstrated in other cancers, activation of endothelin axis, particularly through ET(A) receptor could contribute to cell proliferation, cell survival, angiogenesis and the development of bone metastases. ET-1 is also a proinflammatory mediator and we demonstrated an overexpression of ET-1 and of its receptor ET(A) in Hashimoto's thyroiditis. This suggests a role of ET-1 as a cytokine. In nodular goitre, ET-1 is also overexpressed but to a lesser extent than in papillary thyroid carcinoma and in Hashimoto's thyroiditis. Finally, antagonists of ET-1 receptors are currently under development and could be used in man. They could open new therapeutic perspectives in the treatment of metastatic thyroid carcinoma.


Overexpression and molecular characterization of Aga50D from Saccharophagus degradans 2-40: an exo-type beta-agarase producing neoagarobiose.
beta-Agarases are mostly categorized into three glycoside hydrolase (GH) families 16, 50, and 86. Recent genomic analysis of Saccharophagus degradans 2-40 revealed the presence of five agarase genes belonging to these GH families. Among the five agarases, Aga50D (a member of GH50) had neither been functionally characterized nor overexpressed. In this report, we present soluble overexpression and molecular characterization of Aga50D. Aga50D was expressed in an active form resulting in a single major product from agarose without intermediates. While known GH50 agarases have both endo-lytic and exo-lytic activities, which produce neoagarobiose as a final product through the intermediate, neoagaro-oligosaccharides, identification and analysis of the reaction product by mass spectrometry and 13C NMR showed that Aga50D had unique exo-lytic activity and was able to produce neoagarobiose directly from agarose. The optimum pH and temperature for the activity were 7.0 and 30 degrees C, respectively. The K (m) and V (max) for agarose were 41.9 mg/ml (4.2 mM) and 17.9 U/mg, respectively.


GABA immunoreactive neurons in rat visual cortex.
An antiserum to gamma-aminobutyric acid (GABA) was used in a light and electron microscopic immunocytochemical study to determine the morphology and distribution of GABA-containing neurons in the rat visual cortex and to ascertain whether all classes of nonpyramidal neurons in this cortex are GABAergic. The visual cortex used for light microscopy was prepared in such a way that the antibody penetrated completely through tissue sections, and in these sections large numbers of GABA immunoreactive neurons were apparent. The labeled neurons could be identified as being either multipolar, bitufted, bipolar, or horizontal neurons. In layers II through VIa, GABA immunostained cells were distributed uniformly and accounted for approximately 15% of all neurons, but in layer I all neurons appeared to be immunostained. Electron microscopy of GABA immunostained visual cortex prepared to ensure good fine structural preservation confirmed the presence in layers II through VIa of numerous immunoreactive bipolar neurons, both small and large varieties, as well as multipolar and bitufted neurons. Additionally, electron microscopy reveals that astrocytes are frequently GABA immunoreactive. From a correlated light and electron microscopic evaluation of neurons in GABA immunostained visual cortex, it was possible to confirm which kinds of neurons are GABAergic and what proportion of the neuronal population they represent. Thus, from an analysis of some 950 neurons, it was found that pyramidal neurons were never immunoreactive and that except for 20% of the bipolar cell population, all examples of other types of nonpyramidal neurons encountered in this material were GABA immunoreactive.


Regression of atherosclerotic lesions and control of plasma lipids and lipoprotein cholesterol by Anna Pavala Sindhooram therapy.
Plasma and lipoprotein distribution of cholesterol and triglycerides were measured in experimentally induced hypercholesterolemia associated with moderate hypothyroidism and after Anna Pavala Sindhooram (APSm) therapy in rat models. Feeding atherogenic diet increased all the three lipoprotein classes (HDL, LDL and VLDL). When APSm was administered for 90 days at a dose of 30 mg/rat/day, orally with and without atherogenic diet, it brought down the already raised levels of cholesterol and triglycerides in LDL and VLDL. Histological studies on the aorta revealed that APSm therapy produces regression of the atherosclerotic lesions.


Dermatoglyphics and acute lymphocytic leukemia in children.
Cellular features of acute lymphocytic leukemia (ALL) in children suggest that it originates in abnormal embryogenesis. Because palmar flexion creases develop in the embryo at the same time as the blood-forming cells, and because both arise from mesodermal tissue, insults to the embryo that may lead to leukemic changes in the blood-forming cells may also result in aberrant palmar crease patterns. This study investigated the relationship between aberrant palmar creases and ALL in children who developed leukemia at age 6 years or younger. Odds ratios and chi squares demonstrated significant differences in bilateral aberrant palmar creases between ALL children and relatives (P less than .025). Differences were not explained by familial clustering of aberrant creases. These results support the theory that the insult occurred during pregnancy, probably in the first trimester. There were no significant differences in either bilateral or unilateral aberrant palmar creases between ALL children and their siblings. All children with bilateral aberrant creases had a higher incidence of central nervous system involvement (50%) than those without bilateral aberrant creases (6%). This may reflect a preleukemic change in utero before the time the blood-brain barrier has been established.


Infection of Cranberry Flowers by Monilinia oxycocci and Evaluation of Cultivars for Resistance to Cottonball.
ABSTRACT Infection of cranberry flowers by conidia of Monilinia oxycocci, the cottonball pathogen, was investigated using a squash-mount histological method. Conidia germinated on anthers, nectaries, petals, and stigmata, but not styles. The stigma was the only flower part penetrated by the fungus, but no specialized infection structures were noted. Both fungal and pollen germ tubes grew through the stylar canal and made contact with ovules and nucellar tissue by 72 h after inoculation and pollination. Cottonball incidence was greatest when stigmata were inoculated; the low level of cottonball that resulted from inoculation of other flower parts and in noninoculated flowers was attributed to contamination of stigmata. In greenhouse tests, cottonball incidence was 25, 28, 31, and 38% for cvs. Searles, Pilgrim, Ben Lear, and Stevens, respectively, and was greater for M. oxycocci isolate 593 than isolate 591. We conclude that the stigma is the sole floral infection court for conidia of M. oxycocci and that the most popular cranberry cultivars in Wisconsin do not differ in inherent resistance to cottonball. The relevance of these findings to the long-term management of cottonball is discussed.


Deconvolution of x-ray phase contrast images as a way to retrieve phase information lost due to insufficient resolution.
When free-space propagation x-ray phase contrast imaging is implemented outside synchrotron radiation facilities, the combined effect of detector resolution and source size swamps the fine phase contrast fringes, often making them almost undetectable. In an attempt to mitigate this effect, a simple deconvolution procedure based on division in the Fourier space plus multiplication by an appropriate filter was applied to experimental x-ray phase contrast images of a simple geometric phantom. The filter parameter was varied in order to assess its impact on the level of retrieved phase signal. The deconvolved images were compared to simulated ones obtained under different resolution conditions, showing that this simple procedure provided signals equivalent to those that would be obtained with a detector with three times better resolution. By accepting an increase in the overall image noise, the method also appears to bring up secondary phase contrast fringes, which are not visible in the unprocessed signal.


Cognitive Behavioural Therapy for anorexia nervosa: a systematic review.
Evidence for the effectiveness of psychological therapies for anorexia nervosa (AN) is inconsistent. There have been no systematic reviews solely on the effectiveness for Cognitive Behavioural Therapy (CBT) for AN. This review aimed to synthesise and appraise the recent evidence for CBT as a treatment for AN. Using specific search criteria, 16 relevant articles were identified which evaluated CBT alone or as part of a broader randomised/non-randomised trial. Various formats of CBT were utilised in the reviewed papers. Studies were evaluated using established quality criteria. The evidence reviewed suggested that CBT demonstrated effectiveness as a means of improving treatment adherence and minimising dropout amongst patients with AN. While CBT appeared to demonstrate some improvements in key outcomes (body mass index, eating-disorder symptoms, broader psychopathology), it was not consistently superior to other treatments (including dietary counselling, non-specific supportive management, interpersonal therapy, behavioural family therapy). Numerous methodological limitations apply to the available evidence. Further research and ongoing review is needed to evaluate the settings, patient groups and formats in which CBT may be effective as a treatment for AN.


Efficacy of chlorhexidine mouthrinses with and without alcohol: a clinical study.
Plaque control is the main method for preventing periodontal diseases. Chlorhexidine digluconate mouthrinse is widely recognized as helping to maintain plaque control. Most of these mouthrinses contain alcohol, making them impractical for many patients, including those with oral mucosal hypersensitivity. Mouthrinses without alcohol might cause fewer side effects, but also be less efficient. In this study, we evaluated the efficacy of a 0.12% chlorhexidine mouthrinse without alcohol against one with 11% ethanol and a placebo. This a double-blind, parallel group study with 96 patients who tested 3 mouthrinses containing 1) chlorhexidine digluconate 0.12% sodium fluoride 0.05%, and ethanol 11% (group 1; CHX-A); 2) the same solution without alcohol (group 2; CHX-NA); and a placebo (group 3; P). Plaque and bleeding indexes were recorded in all patients prior to treatment and at 14 and 28 days. There were significant differences in plaque, gingivitis, and papilla bleeding indexes in both chlorhexidine rinses compared to placebo, but no differences between the 2 CHX products. In this study, the alcohol-free rinse was as effective as one containing alcohol in controlling plaque and reducing gingival inflammation. Therefore, it would seem that its use can be recommended in all patients, but especially in patients for whom the use of alcohol is contraindicated.


Preparative synthesis of GDP-beta-L-fucose by recombinant enzymes from enterobacterial sources.
The 6-deoxyhexose L-fucose is an important and characteristic element in glycoconjugates of bacteria (e.g., lipopolysaccharides), plants (e.g., xyloglucans) and animals (e.g., glycolipids, glycoproteins, and oligosaccharides). The biosynthetic pathway of GDP-L-fucose starts with a dehydration of GDP-D-mannose catalyzed by GDP-D-mannose 4,6-dehydratase (Gmd) creating GDP-4-keto-6-deoxymannose which is subsequently converted by the GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase-4-reductase (WcaG; GDP-beta-L-fucose synthetase) to GDP-beta-L-fucose. Both biosynthetic genes gmd and wcaG were cloned from Escherichia coli K12 and the enzymes overexpressed under control of the T7 promoter in the expression vectors pET11a and pET16b, yielding both native and N-terminal His-tag fusion proteins, respectively. The activities of the Gmd and WcaG were analyzed. The enzymatic conversion from GDP-D-mannose to GDP-beta-L-fucose was optimized and the final product was purified. The formation of GDP-beta-L-fucose by the recombinant enzymes was verified by HPLC and NMR analyses. The His-tag fusion variants of the Gmd and WcaG proteins were purified to near homogeneity. The His-tag Gmd recombinant enzyme was inactive, whereas His-tag WcaG showed very similar enzymatic properties relative to the native GDP-beta-L-fucose synthetase. With the purified His-tag WcaG Km and Vmax values, respectively, of 40 microM and 23 nkat/mg protein for the substrate GDP-4-keto-6-deoxy-D-mannose and of 21 microM and 10 nkat/mg protein for the cosubstrate NADPH were obtained; a pH optimum of 7.5 was determined and the enzyme was stimulated to equal extend by the divalent cations Mg2+ and Ca2+. The Gmd enzyme showed a strong feedback inhibition by GDP-beta-L-fucose.


A rapid high-performance thin-layer chromatographic urine screen for laxative abuse.
Laxative abuse, if unrecognized, can lead to unnecessary and costly investigations. The stimulants and cathartics are the most commonly abused laxatives and have the potential for causing the most long-term damage. We have optimized a solid-phase extraction coupled with high-performance thin-layer chromatography (HPTLC) to provide rapid, simple, and sensitive detection of phenolphthalein, danthron, rhein, aloin, and bisacodyl and its metabolites in urine. Positive screens have revealed laxative abuse in 3 of 42 samples from patients presenting with diarrhea of unknown origin.


Hypoglycemic episodes are associated with an increased risk of incident frailty among new onset diabetic patients.
Patients with diabetes mellitus (DM) are at risk for developing frailty due to the complex interplay between different cardiometabolic factors. We examined whether hypoglycemia could independently increase frailty risk besides these factors. From the Longitudinal Cohort of Diabetic Patients, 210,254 patients with new onset DM between 2004 and 2011 were identified, among whom 2119 non-frail patients had at least 1 hypoglycemic episode within 3 years of DM diagnosis. They were propensity score-matched to 8432 non-frail ones without hypoglycemia throughout the study period. Both groups were followed up longitudinally for incident physical frailty according to a modified FRAIL scale (Fatigue, Resistance, Ambulation, Illness, and Loss of weight). We analyzed the risk of frailty (primary) and mortality (secondary outcome) introduced by hypoglycemia, adjusted for known risk factors of frailty. The mean age of patients (46.2% male) was 65.9 ± 14 years; diabetic patients with hypoglycemia had significantly higher comorbidity burden than those without. After 2.68 years, 172 (1.6%) patients with hypoglycemia developed incident frailty, representing a 60% higher risk (hazard ratio [HR] 1.599, 95% confidence interval [CI] 1.14-2.42). After adjusting for other risk factors, those with hypoglycemia had a significantly higher risk of frailty than those without (HR 1.443, 95% CI 1.01-2.05). Additionally, the mortality of those with hypoglycemia was 2-fold higher than those without, and the risk persisted despite confounder adjustment (HR 1.462, 95% CI 1.3-1.65). In this population-based cohort, hypoglycemic episodes among diabetic patients increased the risk of incident frailty and mortality.


Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study.
The main objective of this study was to evaluate the clinical differences and the pattern and extent of organ damage in late-onset systemic lupus erythematosus (SLE). A nested case-control study was performed from patients with SLE followed in the Rheumatology Unit of the State University of Campinas between 1974 and 2005. Patients who developed SLE after the age of 49 were considered late-onset SLE. SLE patients with age <49 years, matched for sex, ethnicity, disease duration and organ damage at study entry were randomly chosen to compose the control group. Baseline and cumulative clinical manifestations, laboratory data, SLE disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-damage index (SDI) and mortality were compared between groups. At diagnosis and follow-up, late-onset group had lower SLEDAI scores when compared with younger age onset. Clinically, they presented less frequently arthritis (P = 0.0002) and malar rash (P = 0.02) and more frequently Raynaud's phenomenon (P = 0.002) and arterial hypertension (P = 0.02) when compared with young onset at diagnosis. Late-onset SLE received lower total corticosteroid dose (P < 0.001) and less frequently cyclophosphamide (P = 0.01). During the study period, late-onset SLE had always lower SLEDAI scores (P = 0.001). At study endpoint, late-onset SLE patients had significantly higher SDI scores (P = 0.001) and a higher mortality rate when compared with younger onset group (P < 0.01). In conclusion, late-onset SLE is milder on presentation and during course of disease, but patients have more organ damage and a higher rate of mortality than young onset SLE. Patients with late onset should be followed with close monitoring and early identification of complications is mandatory in this subgroup of patients with SLE.


Acute coronary occlusion during radiofrequency catheter ablation of typical atrial flutter.
We report the first case of acute right coronary artery occlusion in an adult patient during radiofrequency catheter ablation of typical atrial flutter. ST segment elevation rapidly resolved with antithrombotic therapy. This complication was thought to be due to the short distance between the endocardium and the right coronary artery at the ablation site, the high-wattage output from the radiofrequency generator, and the lack of sufficient cooling effect related to a severe upstream coronary stenosis. In patients with known right coronary artery stenosis who are suffering from typical atrial flutter, evaluation of the significance of the stenosis would be reasonable.


The 12-month prevalence and risk factors for major depressive episode in Finland: representative sample of 5993 adults.
This study reports the 12-month prevalence of major depressive episode and its risk factors in a representative nationwide sample. A random sample of non-institutionalized Finnish individuals aged 15-75 years (N = 5993) was interviewed in 1996. Major depressive episode during the last 12 months was assessed using the Short Form of the University of Michigan version of the Composite International Diagnostic Interview (the UM-CIDI Short Form). The population prevalence of major depressive episode was 9.3% [95% CI 8.5,10.0], and the age-adjusted prevalences for females and males were 10.9% [95% CI 9.7,12.0] and 7.2 [95% CI 6.2,8.2], respectively. In logistic regression analyses the factors associated with major depressive episode after adjustment for age were urban residency, smoking, alcohol intoxication and chronic medical conditions. In addition, being single and obese were found to be risk factors for males. The female to male risk ratio for major depressive episode was smaller than in many previous studies. The sex-specific risk factor associations warrant further investigation into sex differences in depression.


Vibration-compensated interferometry system using phase-modulating interference fringe subdivision technology.
An innovative vibration-compensation method, with phase-modulating interference fringe subdivision technology, is described. It simulates fringe movement by the phase difference of signals and can detect the fringe movement with an accuracy of 1/400 fringe spacing using this subdivision technology. A closed-loop vibration-compensation system is built, and the measurement of an interference fringe movement and a vibration-compensation test are successfully demonstrated. Because of this new method and a new feedback algorithm that was introduced, interference fringes can be stabilized at any preset phase position in real time. Compared with known methods, this method is simple and inexpensive, as well as effective.


Quantitative application of transverse friction massage and its neurological effects on flexor carpi radialis.
The purpose of the study was to determine the effects of transverse friction massage (TFM) on flexor carpi radialis (FCR) motoneuron (MN) pool excitability. Twenty-eight healthy subjects were randomly assigned into massage and control groups. Pre- vs post-TFM H-reflex data were collected. Controls received a rest period instead of massage. Massage dose was standardized by a novel electronic method which recorded the massage rate, momentary pressure and total cumulative pressure (energy). Two-way ANOVA of H/M ratios derived from maximal amplitudes of Hoffman reflexes (Hmax) and motor responses (Mmax) was used to analyze neurological effects and group differences. Analysis of pressure/time curve data showed: mean massage rate was 0.501+/-0.005 Hz; mean duration of massage sessions was 184.6+/-26.4s; mean peak pressure was 4.990+/-1.006 psi. Hmax/Mmax ratios declined from 14.3% to 10.3% for massage (P<0.01) but showed no change for controls (P>0.05). In conclusion a novel quantitative approach to the study of massage has been demonstrated while testing the effects of TFM on FCR MN pool excitability. TFM appears to reduce MN pool excitability. The novel method of quantifying massage permits more rigorous testing of client-centered massage in future research.


Identification of atypical glandular cells in pap smears: is it a hit and miss scenario?.
Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign. A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background. This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%. A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.


Effects of garlic oil and its organosulfur compounds on the activities of hepatic drug-metabolizing and antioxidant enzymes in rats fed high- and low-fat diets.
We examined the effects of garlic oil (GO) and two of its organosulfur compounds, diallyl sulfide (DAS) and diallyl disulfide (DADS), on the drug-metabolizing and antioxidant systems in rats and sought to determine whether these effects are associated with dietary fat. Rats were fed a high-fat diet and received GO or DADS (200 mg/kg body wt) or DAS (100 mg/kg) orally three times a week for seven weeks. Control animals received corn oil alone. Another group of rats was fed a low-fat diet, with or without GO. GO and DADS significantly reduced the body weight gain of rats (p < 0.05). GO, however, dramatically increased the spleen weight and spleen weight-to-body weight ratio (p < 0.05). DAS increased glutathione S-transferase (GST) and 7-pentoxyresorufin O-dealkylase activities, whereas DADS increased only GST activity (p < 0.05). Immunoblot assay showed GO-, DAS-, and DADS-enhanced expression of the placental form of GST and cytochrome P-450 IIBI but suppressed cytochrome P-450 IIEI expression. Hepatic antioxidant enzyme activities were also modulated by these garlic components. GO and DADS inhibited glutathione peroxidase activity (p < 0.05), and DADS and DAS enhanced glutathione reductase activity (p < 0.05). Only GO enhanced the superoxide dismutase activity (p < 0.05). All these garlic components increased glutathione levels in red blood cells (p < 0.05) but did not influence hepatic glutathione levels. Although the amount of fat in the diet modulated drug-metabolizing and antioxidant functions, no interactions between GO and dietary fat were observed. These results indicate that GO and its allyl sulfide components, as well as dietary lipid, modulate drug-metabolizing and antioxidant enzyme activities. The action of GO appears to be independent of dietary lipid content.


Is cytomegalovirus a cause of ureteral stricture in renal transplant recipients?
Cytomegalovirus (CMV) is regarded as a predominant infectious agent in solid organ transplants. CMV disease has highly protean clinical manifestations. Nevertheless, urinary tract involvement seems to be very rare during CMV infection. We report two cases of renal transplant recipients in whom ureteral stricture developed in the course of CMV disease. Histologic data were available for them and were consistent with CMV infection. We discuss previous case reports and propose physiopathologic mechanisms.


Case-controlled study on risk factors for the development of constipation in hospitalized patients.
Constipation is a common problem in hospitalized patients; however, the relative risks of its development with various factors have not been clarified. To clarify the risk factors associated with constipation, we performed a case-controlled study of 165 hospitalized patients who were not laxative users on admission. They were divided into case (n=35) and control (n=130) groups according to laxative administration during hospitalization. Comparison of the patient backgrounds in the two groups revealed significant differences in the activities of daily living, length of fasting, rest level on admission, cerebrovascular disease, and administration of hypnotics. Multiple logistic regression analysis using these five factors as autonomous variables showed that administration of hypnotics (odds ratio, 2.79; 95% confidence interval, 1.10-7.06; p=0.031) was significantly related to laxative use. Therefore, the administration of hypnotics may be the principal cause of constipation development in hospitalized patients and they should be used with caution.


New insights into 4-amino-2-tri-fluoromethyl-phenyl ester inhibition of cell growth and migration in the A549 lung adenocarcinoma cell line.
The present study was designed to investigate the probable mechanisms of synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 human lung carcinoma cells. After the A549 cells were treated with different concentrations of ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration. Immunofluorescence was used to determine the distribution of CAV1 and RXRα, while expression of CAV1, MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting. ATPR could block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreased compared with control group. In addition, ATPR decreased the expression of a migration related proteins, MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. At the same time, CAV1 accumulated at cell membranes, and RXRα relocated to the nucleus after ATPR treatment. Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression and distribution of RXRα may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPR reduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC and P38.


D-type cyclin-binding regions of proliferating cell nuclear antigen.
Proliferating cell nuclear antigen (PCNA) is an auxiliary protein for DNA polymerase delta and is required for both DNA replication and DNA repair. PCNA forms complexes with D-type cyclins, candidate G1 cyclins in mammalian cells. To better understand the functions of the complexes, we examined interactions between PCNA and D-type cyclins, using in vitro-translated mouse PCNA and mouse cyclin D1 or D3 fused to glutathione S-transferase (GST). Analysis of a set of deletion mutants of PCNA revealed that either the N-terminal (residues 2-64) or the C-terminal (residues 197-228) region is necessary for association with D-type cyclins. The cyclin binding of the chimeric protein of the N-terminal (residues 1-68) or the C-terminal (residues 195-261) region of PCNA and rat DNA polymerase beta which does not bind to the cyclins by itself supports this notion. The purified recombinant mouse PCNA expressed in Escherichia coli bound to the D-type cyclin-GST fusion proteins, thereby suggesting that PCNA binds directly to D-type cyclins, without the requirement of other cellular factors. This is apparently the first report on the structure-function relationship of PCNA which may link DNA replication and DNA repair with cell cycle control.


Human extravillous trophoblasts express laeverin, a novel protein that belongs to membrane-bound gluzincin metallopeptidases.
Human extravillous trophoblasts (EVTs) invade the maternal decidua. To identify the molecules involved in EVT invasion, we raised a murine monoclonal antibody (CHL2) that reacts with human EVTs. The molecular mass of CHL2 antigen purified from placental tissues was 160 kDa. Although the N-terminal partial amino acid sequence and one internal sequence are still unreported, the other three internal sequences matched those deduced from the coding region of the estimated sequence tag (1672 bp, AK075131). Based on this information, the full-length of the coding cDNA sequence of CHL2 antigen (2970 bp), which has not been reported elsewhere, was determined by 5' RACE. This novel protein, named laeverin, has a peptidase M1 motif containing a zinc-binding active site. It also has a transmembrane domain near the N-terminus. Its amino acid sequence is homologous with aminopeptidase N. These data indicate that human EVTs express laeverin, a novel protein belonging to gluzincin metallopeptidases.


Computational study of substituent effects on the interaction energies of hydrogen-bonded Watson-Crick cytosine: guanine base pairs.
The substituent effects on interaction energies of hydrogen-bonded DNA Watson-Crick base pairs in the gas phase were captured in a model using ab initio descriptors (at the B3LYP/6-311+G(2d,p) level). While forming a noncovalently bonded complex with unsubstituted guanine (G), cytosine (C) carried 42 possible substituents both at the C6 position (C6X:G) and at the C5 position (C5X:G). We rationalize why complexes possessing a more strongly electron-withdrawing group in CX form less stable base pairs. Multivariate linear regression constructed the quantitative relationships between the interaction energies of the complexes and the descriptors, which were drawn from quantum chemical topology (QCT). For the C6X dataset, the best model yielded r2 = 0.93 and a root-mean-square (rms) energy of 0.53 kJ/mol for the 28 complexes in the training set. This model was evaluated by an external test set (14 complexes), yielding an r2 value of 0.96 and an rms error of 0.42 kJ/mol. For the C5X dataset, the QCT descriptors generated a linear model, with r2 values of 0.92 and 0.97 and rms values of 1.69 and 1.24 kJ/mol for the training set (31 compounds) and the external test set (11 compounds), respectively. The models built here could therefore be useful for the assessment of the interaction energy of C6X:G and C5X:G purely from monomeric data.


Green liquor dregs effect on Kraft mill secondary sludge composting.
Increased Kraft pulp mill production generates increased solid wastes. In response, composting has emerged as an interesting alternative for disposal of these solid wastes. A central composite factor design was used to investigate the influence of incubation conditions (dregs addition and operation time) on chemical and biological parameters, determining the best in-vessel conditions in order to develop a correct composting design. Dregs helped reduce the pH drop that occurs at the beginning of the process. Biological activities presented high values during the active phase, followed by a decrease with stable final values along with N-NH(4)(+) and N-NO(3)(-) trend, which were indicative of mature compost. Dregs addition had not significant effect on the biological activities during composting of Kraft mill sludge. However, moderate amounts of dregs (between 5% and 8%) at operation time of 60-70 days would be the best compromise.


Imaging findings in pancreatic lymphoma: differential aspects.
When the radiologist is faced with a well-circumscribed tumoral mass in the pancreas, knowing when to direct the patient toward nonsurgical biopsy instead of surgical biopsy and staging is critical. Lymphoma does not require surgical staging or a palliative Whipple's procedure before chemotherapy or radiation therapy. A better overall prognosis with nonsurgical treatment is additional impetus to search for secondary signs of primary pancreatic lymphoma. In patients with primary pancreatic lymphoma, no marked pancreatic ductal dilatation is present even with ductal invasion. Adenocarcinoma commonly dilates the more distal pancreatic duct when more proximal ductal invasion has taken place. Lymph node involvement below the level of the renal veins was another finding not seen with adenocarcinoma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, but a bulky homogeneous tumoral mass without alteration of Wirsung's duct or the peripancreatic vessels should suggest the diagnosis. In patients with diffuse infiltration of the pancreatic gland without clinical signs of pancreatitis, the radiologist should be alert to the possibility of pancreatic lymphoma.


[Possible model of interaction between areas of the cat cerebral cortex].
The effect of neuronal activity of one area in the cerebral cortex on the activity of another area was studied on adult alert cats with algorhythm of estimation of dependence and backward connection. On this basis a structural-functional model was developed of interaction between the visual and somatosensory cortical areas in the periods of aftereffect of repeated photic stimulations. This algorhythm permits to determine quantitatively the weight and direction of the mutual influences of these areas as well as to calculate approximately the volumes of the cellular masses which may participate in the formation of connections between these areas. It is assumed that the model may be used as one of the numerous means of studying the complex pattern of brain structures interactions.


Guinea fowl eggshell quantitative proteomics yield new findings related to its unique structural characteristics and superior mechanical properties.
The Guinea fowl eggshell is a bioceramic material with the remarkable mechanical property of being twice as strong as the chicken eggshell. Both eggshells are composed of 95% calcite and 3.5% organic matrix, which control its structural organization. Chicken eggshell is made of columnar calcite crystals arranged vertically. In the Guinea fowl, the same structure is observed in its inner half, followed by a dramatic change in crystal size and orientation in the outer region. Guinea fowl eggshell is thicker than chicken eggshell. Both structure and shell thickness confer a superior resistance to breakage compared to eggshells of other bird species. To understand the underlying mechanisms controlling the structural organization of this highly resistant material, we used quantitative proteomics to analyze the protein composition of the Guinea fowl eggshell organic matrix at key stages of the biomineralization process. We identified 149 proteins, which were compared to other bird eggshell proteomes and analyzed their potential functions. Among the 149 proteins, 9 are unique to Guinea fowl, some are involved in the control of the calcite precipitation (Lysozyme, Ovocleidin-17-like, Ovocleidin-116 and Ovalbumin), 61 are only found in the zone of microstructure shift and 17 are more abundant in this zone. SIGNIFICANCE: The avian eggshell is a critical physical barrier to protect the contents of this autonomous reproductive enclosure from physical and microbial assault. The Guinea fowl (Numida meleagris) eggshell exhibits a unique microstructure (texture), which confers exceptional mechanical properties compared to eggshells of other species. In order to understand the mechanisms that regulate formation of this texture in the Guinea fowl eggshell, we performed comparative quantitative proteomics at key stages of shell mineralization and particularly during the dramatic shift in shell microstructure. We demonstrate that the Guinea fowl eggshell proteome comprises 149 proteins, of which 61 were specifically associated with the change in size and orientation of calcite crystals. Comparative proteomics analysis with eggshell of other bird species leads to new insights into the biomineralization process. Moreover, our data represents a list of organic compounds as potential additives to regulate material design for industrial fabrication of ceramics. This information also provides molecular markers for efficient genomic selection of chicken strains to lay eggs with improved shell mechanical properties for enhanced food safety.