BACKGROUND

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD). The mortality rate for EPS has been high, primarily because of complications related to bowel obstruction. Also, therapeutic guidelines for EPS have not yet been established. In our hospital, favorable postoperative results were obtained in 50 patients whose EPS was treated surgically.

METHODS

All patients had chronic glomerulonephritis as the underlying kidney disease. All had undergone PD for between 29 months and 220 months (average: 113.9 months). During the course of PD, 3 patients developed EPS and were subsequently transferred to hemodialysis (HD). The other 47 patients (94.0%) developed EPS after discontinuation of PD. The reasons for transfer to HD were inadequate ultrafiltration (26 patients), bacterial peritonitis (16 patients), hypoalbuminemia (2 patients), renal transplantation (3 patients), and occurrence of EPS (3 patients).

METHODS

At laparotomy, a definitive diagnosis of EPS was established in all patients by the presence of clumped intestine cocooned with a dense sclerotic membrane. In all cases, the small intestine was completely released by ablation of the capsules, resulting in resolution of the bowel obstruction symptoms. In 5 patients, the large intestine was ablated solely at the region of the sigmoid colon. The operating time varied from 3 hours to 18 hours (average: 6.9 hours). Oral food intake was initiated 5 - 60 days (average: 10.2 days) after surgery.

RESULTS

Perforation of the small intestine was detected postoperatively in 2 patients, who died 26 days and 37 days after surgery. The remaining 48 patients were followed for between 9 months and 107 months (average: 34.6 months). During follow-up, 6 - 12 months after the initial surgery, 4 patients experienced a recurrence of bowel obstruction symptoms that required a second laparotomy with enterolysis. Excluding the 2 patients with fatal outcomes, 46 patients (96%) experienced complete relief from bowel obstruction symptoms. The remaining 2 patients continued to experience mild, sub-acute bowel obstruction symptoms that could be successfully controlled solely by diet.

CONCLUSIONS

Surgical treatment of 50 patients with EPS produced successful outcomes in all but 2 patients (96% success). Encapsulating peritoneal sclerosis should be actively treated by surgeons who genuinely understand this pathologic condition.

OBJECTIVE

To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons.

METHODS

Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores.

RESULTS

Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups.

CONCLUSIONS

Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire.

On the heels of clozapine, we now have a number of newer agents (risperidone, olanzapine, quetiapine, sertindole, and ziprasidone). Are they all the same? What are the differences? How do we best understand them? In this article we review current clinical evidence to compare these issues on four measures of atypicality: EPS, prolactin elevation, superior efficacy in refractory/positive symptoms and efficacy against negative symptoms. All the newer agents are superior on EPS and, with the exception of risperidone, avoid prolactin elevation. Clozapine shows the most convincing efficacy in refractory schizophrenia, although comparative data concerning risperidone's benefit in this respect are also emerging. It is unclear, however, whether any of the agents produce a greater effect than conventional antipsychotics against positive symptoms in responsive patients. Both clozapine and olanzapine have demonstrated superior efficacy against negative symptoms, although it remains controversial whether this is an effect on primary or secondary symptoms. The precise pharmacologic mechanisms underlying "atypicality" remain unclear, but several conceptual frameworks are highlighted that characterize, and perhaps differentiate, these newer agents.

Tannerella forsythia is a Gram-negative oral anaerobe implicated in the development of periodontitis, a chronic inflammatory disease induced by bacterial infections which leads to tooth loss if untreated. Since biofilms formed by periodontal bacteria are considered important in disease progression and pose difficulties in treatment, we sought to investigate the underlying mechanisms of T. forsythia biofilm formation. This was carried out by screening random insertion mutants of T. forsythia for alterations in biofilm development. This approach lead to the identification of an operon involved in exopolysaccharide (EPS) synthesis. An isogenic mutant of one of the genes, wecC, contained within the operon was constructed. The isogenic wecC mutant showed increased ability to form biofilms as compared to the parent strain. The wecC mutant also formed aggregated microcolonies and showed increased cell-surface associated hydrophobicity as compared to the parent strain. Moreover, biochemical characterization of the wecC mutant indicated that glycosylation of surface glycoproteins was reduced. Therefore, our results suggest that the wecC operon is associated with glycosylation of surface-glycoprotein expression and likely plays an inhibitory role in T. forsythia biofilm formation.

OBJECTIVE

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD). The aim of this study was to investigate whether dialysate levels of cancer antigen-125 (CA125), K(+), interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are early diagnostic markers of EPS. Therefore, we analyzed the time courses of the above described dialysate markers in EPS patients and controls.

METHODS

Dialysate and serum samples of 11 EPS patients and 31 control patients, all treated with PD for at least 57 months, were longitudinally collected during standard peritoneal permeability analyses. CA125 and IL-6 were measured in dialysate only, K(+) and VEGF were measured in both dialysate and serum. CA125 and IL-6 are expressed as appearance rates (AR). The linear mixed model was used to analyze the time courses. Sensitivity and specificity were calculated based on the results of the last 2 time points.

RESULTS

No differences in the time courses of the different markers were present between the groups. For K(+) and VEGF attributed to local production, no differences between the groups were found. However, AR-CA125 was lower during the last 3 years prior to EPS (p < 0.05) and AR-IL-6 tended to be higher 2 years prior to EPS (p = 0.09). The combination of AR-CA125 < 33 U/min and AR-IL-6>> 350 pg/min had a sensitivity of 70% and a specificity of 89% for the development of EPS.

CONCLUSIONS

Compared to controls, AR-CA125 showed lower values and AR-IL-6 tended to be higher during the last years prior to the diagnosis of EPS. The sensitivity and specificity of the combination of CA125 and IL-6 indicate their potential use for an early diagnosis of EPS.

OBJECTIVE

Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with a multifactorial pathophysiology and possible increasing incidence. The aim of the present study was to evaluate the independent associations of PD duration, age, dialysis fluids, and kidney transplantation with EPS.

METHODS

A multicenter case-control study was performed in the Netherlands from 1 January 1996 until 1 July 2007. The population comprised 63 patients with EPS and 126 control patients. Control patients were selected from the national registry and were matched for date of PD start. Associations were analyzed using a log linear regression model. Primary outcome was appearance of EPS.

RESULTS

Compared with control patients, patients with EPS were younger at the start of PD (34.7 ± 15.4 years vs. 51.5 ± 14.7 years, p < 0.0001). The cumulative period on PD was longer in EPS patients than in control patients (78.7 ± 37.8 months vs. 32.8 ± 24 months, p < 0.0001), and the cumulative period on icodextrin was also longer in EPS patients (32.7 ± 23.3 months vs. 18.1 ± 15.7 months, p = 0.006). Compared with control patients, more EPS patients underwent kidney transplantation (47 vs. 59, p < 0.0001). With regard to the period after transplantation, the yearly probability of EPS increased in the year after transplantation to 7.5% from 1.75%. In multivariate regression analysis, cumulative PD duration, age at PD start, transplantation, time from last transplantation to EPS, calendar time, time on icodextrin, and ultrafiltration failure were independently associated with EPS. Transfer from PD to hemodialysis for reasons other than suspected EPS could not be identified as a risk factor for EPS.

CONCLUSIONS

Duration of PD, age at PD start, kidney transplantation, time since last transplantation, ultrafiltration failure, and time on icodextrin were associated with a higher risk of EPS.

OBJECTIVE

To determine whether a lack of symptoms in diabetic patients with gastrointestinal motility disorders is associated with visceral afferent neuropathy.

METHODS

We investigated cerebral evoked potentials (EPs) after esophageal stimulation in 10 patients with motor dysfunction of the gastrointestinal tract and in 10 healthy control subjects. All patients had insulin-dependent diabetes mellitus (5 men, 5 women, age range 31-60 yr, diabetes duration 8-36 yr, 10 of 10 with polyneuropathy, 6 of 10 with cardiac autonomic neuropathy). Their esophageal and gastric motor disorders had been diagnosed by scintigraphy, and gastrointestinal stenosis had been excluded by gastroscopy. Only 2 patients had severe symptoms, whereas 6 patients complained of minor discomfort (distension, bloating), and 2 patients were symptom free.

RESULTS

EPs were recorded after electrical stimulation of the esophagus (32 cm from the incisors) at intensity just above the perception threshold. All control subjects exhibited regular EPs at 0.1 ms/30 mA stimulation intensity. In 6 diabetic patients, no EPs were detected at 0.1 and 0.3 ms/30 mA, and the perception thresholds were significantly elevated. In 4 patients with normal perception threshold, EPs of regular shape but decreased amplitude were recorded. These patients had mild or severe gastroparetic complaints.

CONCLUSIONS

These data show for the first time an association between a lack of symptoms in diabetic gastrointestinal motility disorders and visceral afferent neuropathy.

BACKGROUND

Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents.

OBJECTIVE

To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children.

METHODS

Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries.

RESULTS

In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P<0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels.

CONCLUSIONS

Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.

Renal cyclooxygenase-1 and cyclooxygenase-2 actively metabolize arachidonate to metabolism five primary prostanoids: prostaglandin E2, prostaglandin F2a, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G-protein-coupled prostanoid receptors designated <em>EP</em>, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped and the consequences their activation are being characterized. The FP, TP, and <em>EP</em>1 receptors preferentially couple to increased cell Ca2+. <em>EP</em>2, <em>EP</em>4, DP, and IP receptors stimulate cyclic adenosine monophosphate, whereas the <em>EP</em>3 receptor preferentially couples to Gi, inhibiting cyclic adenosine monophosphate generation. <em>EP</em>1 and <em>EP</em>3 messenger RNA expression predominate in the collecting duct and thick limb, respectively, where their stimulation reduces sodium chloride and water absorption, promoting natriuresis and diuresis. Interestingly, only a mild change in renal water handling is seen in the <em>EP</em>3 receptor knockout mouse. Although only low levels <em>EP</em>2 receptor messenger RNA are detected in kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the <em>EP</em>2 receptor display salt-sensitive hypertension, suggesting it also plays an important role in salt excretion. In contrast, <em>EP</em>4 messenger RNA is readily detected in the glomerulus where it may contribute to the regulation of renin release and decrease glomerular resistance. TP receptors are also highly expressed in the glomerulus, where they may increase glomerular vascular resistance. The IP receptor messenger RNA is most highly expressed in the afferent arteriole and it may also modulate renal arterial resistance and renin release. At present there is little evidence for DP receptor expression in the kidney. Together these receptors act as physiologic buffers that protect the kidney from excessive functional changes during periods of physiologic stress. Loss of the combined effects of these receptors contributes to the side effects seen in the setting of nonsteroidal anti-inflammatory drug administration, whereas selective antagonists for these receptors may provide new therapeutic approaches in disease.

Experimental intravenous challenge of 8-week-old kittens with the feline immunodeficiency virus Maryland isolate (FIV-MD) was investigated for its ability to infect the central nervous system (CNS) and induce neurologic abnormalities. Six cats were inoculated with 1,000 TCID50 units of FIV-MD isolate, with six age-matched cats serving as uninfected controls. Clinical and immunological evaluation documented that challenged cats developed immunodeficiency and growth delay. Neurologic examination revealed an abnormal stereotypic motor behavior consisting of repetitive, compulsive roaming that developed as early as 4 weeks postinfection (PI) and persisted throughout the 16-month study in three cats. Serial neuroelectrodiagnostic evaluation revealed persistent abnormal electroencephalographic recordings in three infected cats. Serial evoked potential (EP) recordings at 3, 8, and 12 months PI demonstrated significantly prolonged interpeak latencies III-V at 3 months PI and I-III at 12 months PI for brainstem EP recordings. Alterations of visual EPs were detected only at the 3-month time period. Retinocortical time, however, was significantly different from that in control cats at 3 and 12 months PI. Magnetic resonance imaging evaluation of FIV-MD-infected cats at 12 months PI revealed cortical atrophy, mild ventricular enlargement, and discrete white matter lesions. At 16 months PI, however, histopathological examination of brain tissue indicated only mild lesions limited to satellitosis and perivascular lymphocytic infiltrates. Virus was detected in the CNS by reverse transcriptase, immunofluorescence, and antigen capture. Evaluation of the cerebrospinal fluid revealed intrathecal anti-FIV-MD antibody despite lack of detectable viremia in five challenged cats. Collectively, these findings demonstrate the induction of virus-associated neurologic disease following parenteral FIV challenge in conjunction with an immunodeficiency state. The nature of the nervous system infection is analogous to HIV-1 pediatric encephalopathy.

We reported previously that Muc1 on the surface of epithelial cells was a receptor for Pseudomonas aeruginosa (Lillehoj EP, Kim BT, and Kim KC. Am J Physiol Lung Cell Mol Physiol 282: L751-L756, 2002). Other studies showed that the Muc1 cytoplasmic tail (CT) contains multiple phosphorylation sites, some of which are phosphorylated constitutively and associated with signaling proteins. However, the relationship between extracellular P. aeruginosa binding and intracellular signaling is unknown. To investigate the signaling mechanism of Muc1, this study examined phosphorylation of its CT and activation of the extracellular signal-regulated kinase (ERK) in response to stimulation by P. aeruginosa or purified flagellin. Our results showed 1) the Muc1 CT was phosphorylated constitutively on serine and tyrosine, 2) serine phosphorylation was stimulated by bacterial cells or flagellin, and 3) binding of P. aeruginosa or flagellin to Muc1 induced phosphorylation of ERK. These results are the first to demonstrate Muc1 CT phosphorylation and ERK activation in response to a clinically important airway pathogen.

OBJECTIVE

To examine the clinical characteristics of individuals with schizophrenia that develop tardive dyskinesia (TD) associated with antipsychotic treatment.

METHODS

Baseline data on 1460 patients with schizophrenia were collected as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study. Subjects who met Schooler-Kane criteria for probable TD were compared to those without TD. Multiple regression analyses were used to examine the relationship between TD and clinical variables.

RESULTS

212 subjects met the Schooler-Kane criteria for probable TD and 1098 had no history or current evidence of TD. Subjects with TD were older, had a longer duration of receiving antipsychotic medication, and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent. After controlling for important baseline covariates, diabetes mellitus (DM) and hypertension did not predict TD, whereas substance abuse significantly predicted TD. Differences in cognitive functioning were not significantly different after controlling for baseline covariates. The TD subjects also had higher ratings of psychopathology, EPSE, and akathisia.

CONCLUSIONS

Our results confirm the established relationships between the presence of TD and age, duration of treatment with antipsychotics, treatment with a conventional antipsychotic, treatment with anticholinergics, the presence of EPS and akathisia, and substance abuse. Subjects with TD had higher ratings of psychopathology as measured by the PANSS. We found no support for DM or hypertension increasing the risk of TD, or for TD being associated with cognitive impairment.

Transmission of Trypanosoma brucei by the tsetse fly entails several rounds of differentiation as the parasite migrates through the digestive tract to the salivary glands of its vector. Differentiation of the bloodstream to the procyclic form in the fly midgut is accompanied by the synthesis of a new coat consisting of <em>EP</em> and GPEET procyclins. There are three closely related <em>EP</em> isoforms, two of which (<em>EP</em>1 and <em>EP</em>3) contain N-glycans. To identify the individual <em>EP</em> isoforms that are expressed early during synchronous differentiation in vitro, we exploited the selective extraction of GPI-anchored proteins and mass spectrometry. Unexpectedly, we found that GPEET and all isoforms of <em>EP</em> were coexpressed for a few hours at the onset of differentiation. At this time, the majority of <em>EP</em>1 and <em>EP</em>3 molecules were already glycosylated. Within 24 hours, GPEET became the major surface component, to be replaced in turn by glycosylated forms of <em>EP</em>, principally <em>EP</em>1, at a later phase of development. Transient transfection experiments using reporter genes revealed that each procyclin 3' untranslated region contributes to differential expression as the procyclic form develops. We postulate that programmed expression of other procyclin species will accompany further rounds of differentiation, enabling the parasite to progress through the fly.

Prostanoid receptor-mediated sensitization of sensory nerve fibres is a key contributor to the generation of hyperalgesia. It is generally thought that prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid. Consequently, prostanoid EP receptors on sensory neurones have been identified as potential therapeutic targets. However, IP prostanoid receptors are also present on sensory neurones, and recent data from transgenic mice lacking the IP receptor demonstrate its importance in the induction of oedema and pain behaviour. PGI2, the primary endogenous agonist for the IP receptor, is rapidly produced following tissue injury or inflammation; thus, it may be of equal, or greater, importance than PGE2 during episodes of inflammatory pain. In this review, Keith Bley, John Hunter, Richard Eglen and Jacqueline Smith compare the roles of EP and IP receptors in nociception and suggest that the IP receptor constitutes a novel target for anti-nociceptive agents.

The contribution of major bacterial groups to the assimilation of extracellular polymeric substances (EPS) and glucose in the Delaware Estuary was assessed using microautoradiography and fluorescence in situ hybridization. Bacterial groups contributed to EPS and glucose assimilation in part according to their distribution in the estuary. Abundance of the phylogenetic groups explained 35% and 55% of the variation in EPS and glucose assimilation, respectively. Actinobacteria contributed 70% to glucose assimilation in freshwater, while Alphaproteobacteria assimilated 60% of this compound in saline water. In contrast, various bacterial groups dominated the assimilation of EPS. Actinobacteria and Betaproteobacteria contributed the most in the freshwater section, whereas Cytophaga-like bacteria and Alpha- and Gammaproteobacteria participated in EPS assimilation in the lower part of the estuary. In addition, we examined the fraction of bacteria in each group that assimilated glucose or EPS. Overall, the fraction of bacteria in all groups that assimilated glucose was higher than the fraction that assimilated EPS (15 to 30% versus 5 to 20%, respectively). We found no correlation between the relative abundance of a group in the estuary and the fraction of bacteria actively assimilating glucose or EPS; the more active groups were often less abundant. Our results imply that the bacterial community in the Delaware Estuary is not controlled solely by "bottom-up" factors such as dissolved organic matter.

Ethyl pyruvate (EP), an effective scavenger of reactive oxygen species, is also an anti-inflammatory agent in a variety of in vivo and in vitro model systems. To gain a better understanding of the molecular basis for the anti-inflammatory effects of EP, we compared the pharmacological properties of EP andN-acetyl-l-cysteine (NAC), a well studied scavenger of reactive oxygen species and a precursor for the endogenous antioxidant glutathione (GSH). The studies were performed using RAW 264.7 murine macrophage-like cells that were stimulated with lipopolysaccharide (LPS). Although EP and NAC both inhibited LPS-induced nitric oxide and interleukin (IL)-6 secretion, the former compound was considerably more potent than the latter. EP markedly inhibited inducible nitric-oxide synthase, IL-6, and IL-10 mRNA induction, whereas the effects of NAC were minimal. EP inhibited LPS-induced nuclear factor-kappaB DNA binding to a much greater extent than did NAC. Both compounds inhibited LPS-induced lipid peroxidation, but the two compounds had qualitatively different effects on cellular levels of GSH. Although NAC increased GSH levels, EP had the opposite effect. The anti-inflammatory effects of EP were partially reversed when RAW 264.7 cells were treated with a cell-permeable GSH analog, glutathione ethyl ester. These data support the view that the anti-inflammatory effects of EP are mediated, at least in part, by the ability of EP to deplete cellular GSH stores. Moreover, the findings presented here suggest that an unusual combination of biochemical effects (inhibition of lipid peroxidation and GSH depletion) might account for the anti-inflammatory effects of EP.

Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients. Fluids that are proximal to the prostate, such as expressed prostatic secretions (EPS), are attractive sources of potential prostate cancer biomarkers as these fluids likely bathe the tumor. Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ-confined (n = 8) prostate cancer were used as a discovery cohort, and were analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass spectrometer. A total of 624 unique proteins were identified by at least two unique peptides with a 0.2% false discovery rate. A semiquantitative spectral counting algorithm identified 133 significantly differentially expressed proteins in the discovery cohort. Integrative data mining prioritized 14 candidates, including two known prostate cancer biomarkers: prostate-specific antigen and prostatic acid phosphatase, which were significantly elevated in the direct-EPS from the organ-confined cancer group. These and five other candidates (SFN, MME, PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set of direct-EPS from patients with biochemically recurrent disease (n = 5) versus patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we performed proof-of-concept SRM-MS-based relative quantification of the five candidates using unpurified heavy isotope-labeled synthetic peptides spiked into pools of EPS-urines from men with extracapsular and organ-confined prostate tumors. This study represents the first efforts to define the direct-EPS proteome from two major subclasses of prostate cancer using shotgun proteomics and verification in EPS-urine by SRM-MS.

The goal of this study was to evaluate electrical field interactions produced by the stimulation of different types of intracochlear electrodes in 12 adult subjects (three Ineraid, four Clarion S-Series, three S-Series with the electrode positioning system-EPS and two Clarion HiFocus-I with the EPS). Psychophysical measurements were conducted with biphasic stimuli (813 pulse per second, 153.8 micros/phase). "Perturbation" signals (300 ms) were applied to one electrode chosen at the middle of the array and their effects on detection thresholds of "probe" signals (30 ms) were measured on the neighbor basal electrode. Perturbation levels were set below the detection threshold of the perturbation electrode (-2 dB re threshold). Measurements were first conducted for simultaneous stimulation of the probe and of the perturbation electrodes, for monopolar for all subjects and for bipolar stimulus configurations for both Clarion HiFocus-I subjects. The tested Clarion electrodes did not present lower monopolar interactions than the Ineraid electrodes. Nevertheless, considering the shorter distance between electrodes for the Clarion than for the Ineraid, the tested Clarion electrodes might be more selective than the Ineraid. We did not find any significant monopolar electrical field-interaction differences between subjects who received the S-Series array with and without the EPS. We did not find lower interactions for both subjects who received the HiFocus-I array than for subjects who received the S-Series. Electrical field interactions were lower for bipolar than for monopolar configurations for both HiFocus-I subjects. A second set of measurements was conducted for nonsimultaneous stimulation similar to the one used in continuous interleaved sampling sound strategy. These measurements showed that interactions evaluated for simultaneous biphasic stimuli were larger than for nonsimultaneous stimulation.

Group 1 capsular polysaccharides (CPSs) of Escherichia coli and some loosely cell-associated exopolysaccharides (EPSs), such as colanic acid, are assembled by a Wzy-dependent polymerization system. In this biosynthesis pathway, Wza, Wzb, and Wzc homologues are required for surface expression of wild-type CPS or EPS. Multimeric complexes of Wza in the outer membrane are believed to provide a channel for polymer export; Wzc is an inner membrane tyrosine autokinase and Wzb is its cognate phosphatase. This study was performed to determine whether the Wza, Wzb, and Wzc proteins for colanic acid expression in E. coli K-12 could function in the E. coli K30 prototype group 1 capsule system. When expressed together, colanic acid Wza, Wzb, and Wzc could complement a wza-wzb-wzc defect in E. coli K30, suggesting conservation in their collective function in Wzy-dependent CPS and EPS systems. Expressed individually, colanic acid Wza and Wzb could also function in K30 CPS expression. In contrast, the structural requirements for Wzc function were more stringent because colanic acid Wzc could restore translocation of K30 CPS to the cell surface only when expressed with its cognate Wza protein. Chimeric colanic acid-K30 Wzc proteins were constructed to further study this interaction. These proteins could restore K30 biosynthesis but were unable to couple synthesis to export. The chimeric protein comprising the periplasmic domain of colanic acid Wzc was functional for effective K30 CPS surface expression only when coexpressed with colanic acid Wza. These data highlight the importance of Wza-Wzc interactions in group 1 CPS assembly.

PGE(2) is an endogenously synthesized inflammatory mediator that is over-produced in chronic inflammatory disorders such as allergic asthma. In this study, we investigated the regulatory effects of PGE(2) on mast cell degranulation and the production of cytokines relevant to allergic disease. Murine bone marrow-derived mast cells (BMMC) were treated with PGE(2) alone or in the context of IgE-mediated activation. PGE(2) treatment alone specifically enhanced IL-6 production, and neither induced nor inhibited degranulation and the release of other mast cell cytokines, including IL-4, IL-10, IFN-gamma, and GM-CSF. IgE/Ag-mediated activation of BMMC induced the secretion of IL-4, IL-6, and GM-CSF, and concurrent PGE(2) stimulation synergistically increased mast cell degranulation and IL-6 and GM-CSF, but not IL-4, production. A similar potentiation of degranulation and IL-6 production by PGE(2), in the context of IgE-directed activation, was observed in the well-established IL-3-dependent murine mast cell line, MC/9. RT-PCR analysis of unstimulated MC/9 cells revealed the expression of EP(1), EP(3), and EP(4) PGE receptor subtypes, including a novel splice variant of the EP(1) receptor. Pharmacological studies using PGE receptor subtype-selective analogs showed that the potentiation of IgE/Ag-induced degranulation and IL-6 production by PGE(2) is mediated through EP(1) and/or EP(3) receptors. Our results suggest that PGE(2) may profoundly alter the nature of the mast cell degranulation and cytokine responses at sites of allergic inflammation through an EP(1)/EP(3)-dependent mechanism.

BACKGROUND

Rhythmic auditory stimulation (RAS) can influence movement during straight line walking and direction transition in individuals with Parkinson disease (PD).

OBJECTIVE

The authors studied whether multidirectional step training with RAS would generalize to functional gait conditions used in daily activities and balance.

METHODS

In a matched-pairs design, 8 patients practiced externally paced (EP) stepping (RAS group), and 8 patients practiced internally paced (IP) stepping (no RAS group) for 6 weeks. Participants were evaluated on the first and last days of practice, and 1 week, 4 weeks, and 8 weeks after practice termination. Evaluations included a primary measurement--the Dynamic Gait Index (DGI)--and secondary measurements--the Unified Parkinson's Disease Rating Scale (UPDRS), Tinetti-gait and balance tests, Timed-Up-and-Go (TUG), and Freezing of Gait Questionnaire (FOGQ).

RESULTS

The RAS group significantly improved performance on the DGI and several secondary measures, and they maintained improvements for the DGI, Tinetti, FOGQ, and balance and gait items of the UPDRS above pretraining values at least 4 weeks after practice termination. The no RAS group revealed several improvements with training but could not maintain these improvements for as long as the other group.

CONCLUSIONS

Individuals with PD can generalize motor improvements achieved during multidirectional step training to contexts of functional gait and balance. Training with RAS is advantageous for enhancing functional gait improvements and the maintenance of functional gait and balance improvements over 8 weeks.

Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a serious disease of rice. In the related bacterium Xanthomonas campestris pv. campestris, the rpfF gene is involved in production of a diffusible extracellular factor (DSF) that positively regulates synthesis of virulence-associated functions like extracellular polysaccharide (EPS) and extracellular enzymes. Transposon insertions in the rpfF homolog of X. oryzae pv. oryzae are deficient for virulence and production of a DSF but are proficient for EPS and extracellular enzyme production. The rpfF X. oryzae pv. oryzae mutants exhibit an unusual tetracycline susceptibility phenotype in which exogenous iron supplementation is required for phenotypic expression of a tetracycline resistance determinant that is encoded on an introduced plasmid. The rpfF X. oryzae pv. oryzae mutants also overproduce one or more siderophores and exhibit a growth deficiency under low iron conditions as well as in the presence of reducing agents that are expected to promote the conversion of Fe+3 to Fe+2. Exogenous iron supplementation promotes migration of rpfF X. oryzae pv. oryzae mutants in rice leaves. The results suggest that rpfF may be involved in controlling an iron-uptake system of X. oryzae pv. oryzae and that an inability to cope with the conditions of low iron availability in the host may be the reason for the virulence deficiency of the rpfF X. oryzae pv. oryzae mutants.

The EP(2) and EP(4) prostanoid receptor subtypes are G-protein-coupled receptors for prostaglandin E(2) (PGE(2)). Both receptor subtypes are known to couple to the stimulatory guanine nucleotide binding protein (Galpha(s)) and, after stimulation with PGE(2), can increase the formation of intracellular cAMP. In addition, PGE(2) stimulation of the EP(4) receptor can activate phosphatidylinositol 3-kinase (PI3K) leading to phosphorylation of the extracellular signal-regulated kinases (ERKs) and induction of early growth response factor-1 (EGR-1). We now report that the PGE(2)-mediated phosphorylation of the ERKs and induction of EGR-1 can be blocked by pretreatment of EP(4)-expressing cells with pertussis toxin (PTX). Furthermore, pretreatment with PTX increased the amount of PGE(2)-stimulated intracellular cAMP formation in EP(4)-expressing cells but not in EP(2)-expressing cells. These data indicate that the EP(4) prostanoid receptor subtype, but not the EP(2), couples to a PTX-sensitive inhibitory G-protein (Galpha(i)) that can inhibit cAMP-dependent signaling and activate PI3K/ERK-dependent signaling.

An earliness per se gene, designated Eps-A(m) 1, was mapped in diploid wheat in F(2) and single-seed descent mapping populations from the cross between cultivated (DV92) and wild (G3116) Triticum monococcum accessions. A QTL with a peak on RFLP loci Xcdo393 and Xwg241, the most distal markers on the long arm of chromosome 1A(m), explained 47% of the variation in heading date (LOD score 8.3). Progeny tests for the two F(2:3) families with critical recombination events between Xcdo393 and Xwg241 showed that the gene was distal to Xcdo393 and linked to Xwg241. Progeny tests and replicated experiments with line #3 suggested that Eps-A(m) 1 was distal to Xwg241. This gene showed a large effect on heading date in the controlled environment experiments, and a smaller, but significant, effect under natural conditions. Eps-A(m) 1 showed significant epistatic interactions with photoperiod and vernalization treatments, suggesting that the different classes of genes affecting heading date interact as part of a complex network that controls the timing of flowering induction. Besides its interactions with other genes affecting heading date, Eps-A(m) 1 showed a significant interaction with temperature. The effect of temperature was larger in plants carrying the DV92 allele for late flowering than in those carrying the G3116 allele for early flowering. Average differences in heading date between the experiments performed at 16 degrees C and 23 degrees C were approximately 11 days ( P < 0.001) for the lines carrying the Eps-A(m) 1 allele for early flowering but approximately 50 days ( P < 0.0001) for the lines carrying the allele for late flowering. The large differences in heading time (average 80 days) observed between plants carrying the G3116 and DV92 alleles when grown at 16 degrees C, suggest that it would be possible to produce very detailed maps for this gene to facilitate its future positional cloning.