Type 4b Research Articles

ChemInform Abstract: Abenquines A—D: Aminoquinone Derivatives Produced by Streptomyces sp. Strain DB634.

AbstractAbenquines A, B1, B2, C and D (Ia)—(Ie), resp., show inhibitory activity against bacteria, dermatophytic fungi and phosphodiesterase type 4b.

Simple holographic duals to boundary CFTs

By relaxing the regularity conditions imposed in arXiv:1107.1722 on half-BPS solutions to six-dimensional Type 4b supergravity, we enlarge the space of solutions to include two new half-BPS configurations, which we refer to as the AdS2-cap and the AdS2-funnel. We give evidence that the AdS2-cap and AdS2-funnel can be interpreted as fully back-reacted brane solutions with respectively AdS2 and AdS2 × S 2 world volumes. AdS2-cap and AdS2-funnel solutions with a single asymptotic AdS3 × S 3 region are constructed analytically. We argue that AdS2-cap solutions provide simple examples of holographic duals to boundary CFTs in two dimensions and present calculations of their holographic boundary entropy to support the BCFT dual picture.

Association of osteonecrosis and peripheral neuropathy in HIV-1-infected patients

Atraumatic osteonecrosis affects about 1% of HIV-infected persons when asymptomatic and about 5% when symptomatic [1]. Two clinical circumstances suggest that nerve growth factor (NGF) might be involved in the excessive prevalence. First, patients with hereditary sensory and autonomic neuropathy (HSAN) have a remarkable (5–23%) prevalence of osteonecrosis [2–5]; the genetic basis of HSAN type 4B is missense mutations in the trkA receptor for NGF [6,7]. Second, 16 patients who received a monoclonal antibody that blocks interaction of NGF with its receptor, developed osteonecrosis [8]. Moreover, NGF is both osteogenic [9] and angiogenic through upregulation of vascular endothelial growth factor (VEGF) [10]. The above circumstances suggested the hypothesis that HIV-infected persons with osteonecrosis might have more peripheral neuropathy than those without osteonecrosis and that impaired actions of NGF and, probably, of VEGF might contribute to the excess of osteonecrosis. We identified 106 patients with osteonecrosis among 11 506 HIV-infected persons; characteristics of these 106 individuals have been presented [11]. The diagnosis of peripheral neuropathy was taken from the electronic medical record (EMR). This was the only basis for that diagnosis in the 11 400 patients without osteonecrosis. For the 106 patients with osteonecrosis, we also required written documentation of symptoms and signs confirming the diagnosis of peripheral neuropathy. Unilateral symptoms or symptoms confined to the upper limbs were not accepted. Symptoms were generally recorded as burning, pain or numbness, or a combination of these, in the feet. Signs typically included impairment of pin-prick, light touch or vibratory, sensations in the toes or feet, and impairment or loss of tendo-Achilles reflexes. The diagnosis of diabetes mellitus required the use of antidiabetic medication, fasting blood glucose of more than 125 mg/dl on two separate occasions or glycated hemoglobin more than 6.4%. The diagnosis of alcohol abuse was taken from the EMR. Pharmacy records were reviewed for the use, before the diagnosis of peripheral neuropathy, of zalcitabine (ddC), didanosine (ddI) or stavudine (d4T). Statistical analyses used χ2 or Fisher's exact tests. Significance was two-tailed. Among the 106 patients with osteonecrosis, there were 44 diagnosed with peripheral neuropathy involving the lower limbs. We excluded 13 of these for various reasons. Peripheral neuropathy in the remaining 31 (29.2%) of the 106 osteonecrotic patients was 1.8-fold more frequent than in the 1856 (16.2%) of the 11 400 without osteonecrosis (odds ratio 2.1, 95% confidence interval 1.4–3.2, P < 0.0003). We did not seek written documentation confirming the diagnoses of peripheral neuropathy for the 1856 without osteonecrosis; were that number reduced, by a factor of 13/44, in order to provide the same proportion of excluded patients as in those with osteonecrosis, then the 31 (29.2%) of 106 would be compared with 1308 (11.5%) of 11 400 (P < 0.0001), a 2.5-fold difference. In the following analyses, group 1 comprises the 31 patients with peripheral neuropathy before osteonecrosis and group 2 excludes four with unobtainable records and comprises the 71 with osteonecrosis either without peripheral neuropathy or with peripheral neuropathy diagnosed after osteonecrosis. ddC, ddI or d4T were used by 90.3% of group 1 and by 69.0% of group 2 (P = 0.02). Diabetes mellitus was present before the diagnoses of peripheral neuropathy in 9.7% of group 1 and in 15.5% of group 2 (P = 0.54). Alcohol abuse was present before the diagnoses of osteonecrosis in 16.1% of group 1 and in 11.3% of group 2 (P = 0.53). The above data confirm that HIV-infected persons with osteonecrosis have between 1.8-fold and 2.6-fold more peripheral neuropathy than those without osteonecrosis and support the inference that low levels of NGF could be among the biological underpinnings of osteonecrosis. Antibodies against NGF impair nerve function and, in a clinical trial, resulted in osteonecrosis [8]. Low levels of NGF were seen in a group of 131 HIV-infected patients [12], and have been described in patients with diabetic peripheral neuropathy [13]. NGF recognizes a variety of ligands relevant to bone regeneration, including VEGF receptors and receptors on osteoblasts. The role of reduced levels of VEGF in the pathogenesis of osteonecrosis is shown by the observation of osteonecrosis in some patients given a monoclonal antibody against VEGF [14]. Corticosteroids and alcohol abuse, which together are associated with 90% of cases of atraumatic osteonecrosis of the femoral head [15], are both associated with low levels of VEGF [16–20]. In summary, excessive peripheral neuropathy in patients with osteonecrosis not only suggests that NGF and VEGF contribute to the pathogenesis, but also supports the hypothesis that impaired regenerative capacity of osteoblasts, imposed by these cytokines, is responsible for the excess of osteonecrosis in HIV-infected patients. Acknowledgements Conflicts of interest There are no conflicts of interest.

Abenquines A–D: aminoquinone derivatives produced by Streptomyces sp. strain DB634

New bioactive secondary metabolites, called abenquines, were found in the fermentation broth of Streptomyces sp. strain DB634, which was isolated from the soils of the Chilean highland of the Atacama Desert. They are composed of an amino acid linked to an N-acetyl-aminobenzoquinone. Isolation of the abenquines (1-4), their structure elucidation by NMR analysis and MS, as well as the kinetics of their production are presented. The abenquines show inhibitory activity against bacteria, dermatophytic fungi and phosphodiesterase type 4b. The amino acid attached to the quinone is relevant to the enzyme inhibitory activity.

Endosomal Targeting of the Phosphoinositide 3-Phosphatase MTMR2 Is Regulated by an N-terminal Phosphorylation Site

MTMR2 is a member of the myotubularin family of inositol lipid phosphatases, a large protein-tyrosine phosphatase subgroup that is conserved from yeast to humans. Furthermore, the peripheral neuromuscular disease Charcot-Marie Tooth disease type 4B has been attributed to mutations in the mtmr2 gene. Because the molecular mechanisms regulating MTMR2 have been poorly defined, we investigated whether reversible phosphorylation might regulate MTMR2 function. We used mass spectrometry-based methods to identify a high stoichiometry phosphorylation site on serine 58 of MTMR2. Phosphorylation at Ser(58), or a phosphomimetic S58E mutation, markedly decreased MTMR2 localization to endocytic vesicular structures. In contrast, a phosphorylation-deficient MTMR2 mutant (S58A) displayed constitutive localization to early endocytic structures. This localization pattern was accompanied by displacement of a PI(3)P-specific sensor protein and an increase in signal transduction pathways. Thus, MTMR2 phosphorylation is likely to be a critical mechanism by which MTMR2 access to its lipid substrate(s) is temporally and spatially regulated, thereby contributing to the control of downstream endosome maturation events.

222 EXPRESSION AND DISTRIBUTION OF PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN URETHRA

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology1 Apr 2011222 EXPRESSION AND DISTRIBUTION OF PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN URETHRA George Kedia, Markus Kuczyk, Petter Hedlund, and Stefan Ückert George KediaGeorge Kedia Hannover, Germany More articles by this author , Markus KuczykMarkus Kuczyk Hannover, Germany More articles by this author , Petter HedlundPetter Hedlund Lund, Sweden More articles by this author , and Stefan ÜckertStefan Ückert Hannover, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.332AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up untill today, only a very few studies have addressed the physiology/pharmacology of the human urethra (Hassouna M. et al., J. Urol. 129: 1262–1264, 1983; Abdel-Hakim A. et al., J. Urol. 130: 988–991, 1983; Werkström V. et al., BJU Int. 98: 414–423, 2006). An involvement of the nitric oxide (NO)/cyclic GMP pathway in mediating the relaxation of the bladder outlet and urethra during the micturition phase has been supposed. The present study aimed to evaluate in the human male urethra by means of immunohistochemistry the expression and distribution of cyclic AMP and cyclic GMP phosphodiesterase (PDE) isoenzymes in relation to key mediators/proteins of the cyclic GMP and cyclic AMP pathways. METHODS Using conventional immunohistochemistry (double-labelling technique, laser fluorescence microscopy), thin sections (8 μm – 10 μm) of the human male urethra were exposed to anti-PDE1A, -PDE2A, -PDE3A, -PDE4A, -PDE4B, -PDE5A, anti-nNOS (neuronal nitric oxide synthase), -VIP (vasoactive intestinal polypeptide) and -CGRP (calcitonin gene-related peptide) antibodies followed by the application of fluorochrome-labelled secondary antibodies. RESULTS In the smooth muscle (SM) portion of the urethra, immunosignals specific for PDE1A (cyclic AMP/cyclic GMP PDE, calcium/calmodulin-dependent), PDE4A, PDE4B (cyclic AMP PDEs) and PDE5A (cyclic GMP PDE) were registered. SM bundles were seen innervated by varicose nerve fibers characterized by the expression of nNOS. Some of these nerves also presented staining related to VIP or CGRP. No immunoreactivities specific for PDE2A or PDE3A were detected. CONCLUSIONS PDE isoenzymes type 1A, 4A, 4B and 5A are expressed in human urethral smooth muscle. The findings implicate that the cyclic AMP and cyclic GMP pathways work synergistically together in the control of urethral smooth muscle function. This might be of importance with regard to the identification of new pharmacological avenues to facilitate the contraction and relaxation of the human outflow region. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e91 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information George Kedia Hannover, Germany More articles by this author Markus Kuczyk Hannover, Germany More articles by this author Petter Hedlund Lund, Sweden More articles by this author Stefan Ückert Hannover, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling

Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding either the lipid phosphatase myotubularin-related protein-2 (MTMR2) or its regulatory binding partner MTMR13/SBF2. Mtmr2 dephosphorylates PI-3-P and PI-3,5-P2 to form phosphatidylinositol and PI-5-P, respectively, while Mtmr13/Sbf2 is an enzymatically inactive member of the myotubularin protein family. We have found altered levels of the critical signalling protein AKT in mouse mutants for Mtmr2 and Mtmr13/Sbf2. Thus, we analysed the influence of Mtmr2 and Mtmr13/Sbf2 on signalling processes. We found that overexpression of Mtmr2 prevents the degradation of the epidermal growth factor receptor (EGFR) and leads to sustained Akt activation whereas Erk activation is not affected. Mtmr13/Sbf2 counteracts the blockage of EGFR degradation without affecting prolonged Akt activation. Our data indicate that Mtmr2 and Mtmr13/Sbf2 play critical roles in the sorting and modulation of cellular signalling which are likely to be disturbed in CMT4B.

Reliability using the universal classification of acute myocardial infarction compared to ST-segment classification

To study the inter-physician reliability using the universal classification (UC) of acute myocardial infarction (AMI) compared to the ST-segment classification (STC). The UC is based on clinical, electrocardiographic (ECG), and pathophysiologic characteristics compared to the STC, which is mainly ECG based. In this registry of consecutive patients with AMI presenting to a tertiary hospital, we studied the inter-physician reliability [weighted kappa (wK)] using the UC and the STC. Two physician investigators independently classified each patient with AMI according to the UC and STC, and a third senior physician investigator resolved any disagreement. The study included Type 1=226 (89.7%), Type 2=16 (6.3%), Type 3=3 (1.2%), Type 4a=1 (0.4%), Type 4b=4 (1.6%), Type 5=2 (0.8%), ST-segment-elevation AMI (STEMI)=140 (55.6%), and non-ST-segment-elevation AMI (NSTEMI)=112 (44.4%). Inter-physician reliability using the UC was very good (wK=0.84, 95% CI 0.68-0.99) and using the STC was good (wK=0.78, 95% CI 0.70-0.86). Of patients with Type 1 AMI, 57.1% were STEMI and 42.9% were NSTEMI. In contrast, of patients with Type 2 AMI, 18.8% were STEMI and 81.2% were NSTEMI. The UC is a reliable method to classify patients with AMI and performs better than the STC in this study. Validation of the two classifications should be performed in large prospective studies.

The universal classification is an independent predictor of long-term outcomes in acute myocardial infarction

The long-term outcomes of patients with acute myocardial infarction (AMI) according to the universal classification (UC) are unknown. We investigated whether the outcome of these patients is better predicted by the UC than the ST-segment classification (STC). We conducted a retrospective study of 348 consecutive patients with AMI with mean follow-up of 30.6 months. The primary outcome was major adverse cardiovascular events (MACE) [composite of all causes of death and AMI]. The study included ST-segment elevation (STEMI) = 168 (48%), non-ST-segment elevation (NSTEMI) = 180 (52%), Type 1 = 278 (80%), Type 2 = 55 (15.8%), Type 3 = 5 (1.4%), Type 4a = 2 (0.6%), Type 4b = 5 (1.4%), and Type 5 = 3 (0.9%). During follow-up, 102 (29.3%) patients had MACE, 80 (23%) patients died, and 31 (8.9%) had an AMI. The adjusted risk of MACE was similar for NSTEMI and STEMI (HR 1.26, 95% CI 0.77-2.03, P = .35) but was significantly lower for patients with Type 2 AMI as compared to Type 1 (HR 0.44, 95% CI 0.21-0.90, P= .02). The UC, peak troponin levels, discharge glomerular filtration rate <60 ml/min per 1.73 m(2), and thrombolysis in myocardial infarction risk score were independent predictors of MACE (all, P<.05). The UC is an independent predictor of long-term outcomes in AMI patients compared to the STC. Type 2 AMI has less than half the risk of MACE as Type 1 AMI. Future studies should report outcomes of AMI patients according to the UC types.

Laparoscopic choledochal cyst excision, hepaticojejunostomy, and extracorporeal Roux-en-Y anastomosis: a technical skill and intermediate-term report in 62 cases

This study aimed to present the authors' technique and the intermediate-term outcome for laparoscopic choledochal cyst excision with Roux-en-Y hepatoenterostomy. This retrospective study investigated 62 children (39 girls and 23 boys) who had undergone laparoscopic resection of choledochal cyst. The average age of the children was 2.3 years. The retrospective data and the following investigations about type of choledochal cyst, surgical technique, conversion rate, morbidity, and mortality were analyzed. Of the 62 patients, 43 (69.4%) showed type 1a choledochal cysts, 16 (25.8%) showed type 1c, 2 (3.2%) showed type 4a, and 1 (1.6%) showed type 4b. Total cyst excision could be performed for 51 of the patients (82.3%). The large cysts were opened on the front wall, then divided circumferentially in 29 cases. The small cysts did not need to be opened before excision in 22 cases. For 11 patients (17.7%), Lilly's (Surg Gynecol Obstet 146:254-256, 1978) technique was adopted, and for 5 patients with a huge cyst, the duodenum together with the head of the pancreas had to be mobilized for visualization of the cyst's lower limit. The hepatic duct was excised, and plastic operation of bile duct was performed for two patients. The mean operative time was 226±41.2 min. Eight patients needed blood transfusion, and conversion was required for one patient. The mean hospital stay was 8±1.5 days, and the mean follow-up period was 38 months. The overall morbidity rate was 8.2% (5/61) including bile leakage (n=1), adhesive small bowel obstruction (n=1), intestinal necrosis (n=1), and cholangitis (n=1). Inflammatory edema anastomotic narrowing occurred in one patient. None of the patients needed surgery due to anastomotic stricture. Laparoscopic choledochal cyst excision, hepaticojejunostomy, and extracorporeal Roux-en-Y anastomosis can be safely and quickly performed for children, with satisfactory intermediate-term results. Extracorporeal Roux-en-Y anastomosis could shorten the operative time.

Can obstructive sleep apnea be a cause of in-stent thrombosis?

We present the case of a 45-year-old patient readmitted to Central University Hospital at 3 a.m. for acute retrosternal chest pain associated with ST-segment elevation in lead I, aVL, V1-V6 in standard 12-lead ECG performed on admission in emergency department. Coronary angiography revealed late in-stent thrombosis in left anterior descending artery. According to the new universal definition of myocardial infarction patient was finally recognized acute ST-segment elevation myocardial infarction type 4b with additional diagnosis of severe obstructive sleep apnea and overweight.

A new ethanolamine phosphate-containing variant of the O-antigen of Shigella flexneri type 4a

The O-specific polysaccharide (O-antigen) structure of a Shigella flexneri type 4a strain from the Dysentery Reference Laboratory (London, UK) was elucidated in 1978 and its characteristic feature was found to be α- d-glucosylation of GlcNAc at position 6, which defines O-factor IV. Our NMR spectroscopic studies of the O-specific polysaccharides of two other strains belonging to S. flexneri type 4a (G1668 from Adelaide, Australia, and 1359 from Moscow, Russia) confirmed the carbohydrate backbone structure but revealed in both strains an additional component, ethanolamine phosphate (EtnP), attached at position 3 of one of the rhamnose residues: [Display omitted] Phosphorylation has not been hitherto reported in any S. flexneri O-antigen. Reinvestigation of the O-specific polysaccharide of S. flexneri type 4b showed that it is not phosphorylated and confirmed its structure established earlier.

Rare [(NHC)2Ni-OH]-Type Terminal Nickel Hydroxo and [(NHC)2Ni]-Type Complexes ofN/O-Functionalized N-Heterocyclic Carbenes as Precatalysts for Highly Desirable Base-Free Michael Reactions in Air at Ambient Temperature

Highly convenient base-free Michael reaction of β-dicarbonyl, β-keto ester, and α-cyano ester compounds with activated ethylene compounds in air at ambient temperature catalyzed by a series of new nickel complexes, 1b−4b, of N/O-functionalized N-heterocyclic carbenes (NHC) are reported. Quite interestingly, of these nickel complexes, 1b and 2b were found to be of the [(NHC)2Ni-OH] type bearing a terminal [Ni-OH] moiety and are among the few known structurally characterized examples of monomeric terminal [Ni-OH] complexes. Compounds 3b and 4b, on the other hand, were found to be of the commonly encountered [(NHC)2Ni]-type complexes. More significantly, both the [(NHC)2Ni-OH]-type complexes 1b and 2b and the [(NHC)2Ni]-type complexes 3b and 4b were synthesized using same synthetic methodology by sheer modulation of the N-substituents on the N-heterocyclic carbene ring by the reaction of the imidazolium chloride salts with NiCl2·6H2O in the presence of K2CO3 as a base.

Deleterious Variants of FIG4, a Phosphoinositide Phosphatase, in Patients with ALS

Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.

Abstract 555: The Universal Clinical Classification of Acute Myocardial Infarction is a Better Predictor of Long Term Outcomes than ST Segment Classification

Introduction: The universal classification (UC) of AMI aims to facilitate cross-study analysis, yet the long-term outcomes using UC are largely unknown. Hypothesis: We tested the hypothesis that the long-term outcome of patients with AMI is better predicted by UC than ST segment classification. Methods: We conducted a prospective study of 348 consecutive patients with AMI with mean follow-up of 30.6 months. The primary outcome was the major adverse cardiovascular events (MACE) [composite of all causes of mortality, recurrent AMI, and stroke]. Multivariate and survival analysis of MACE was performed. Results: The study population was STEMI=168, NSTEMI=180, Type 1=278, Type 2=55, Type 3=5, Type 4a=2, Type 4b=5, and Type 5=3. During follow-up 80 patients died, 31 had an AMI, and 7 had a stroke. UC correlates with the ST segment classification (p&lt;0.005). MACE free survival was different for Type 1 and Type 2 (p=0.043), but not for STEMI and NSTEMI. There was a positive association between MACE and the quartile of peak Troponin, number of cardiovascular risk factors, and number of vascular beds affected, and an inverse relationship with the utilization of discharge cardiovascular protective medications (all p≤0.01). No such inverse relationship existed for Type 2. Conclusions: UC of AMI is a better long-term predictor of MACE. The quartile of peak Troponin levels, cardiovascular risk factors, and number of vascular beds affected are independent predictors of MACE, while cardiac medications protect against MACE, except in Type 2 patients.

Biomarker Release After Percutaneous Coronary Intervention

Cardiac biomarkers of necrosis provide clinicians with important “messages” from the heart. They are released into the interstitium of the myocardium after loss of the integrity of cardiac myocyte membranes. The pattern of the rise and fall of an individual biomarker (ie, its release kinetics) depends on its intracellular location in the myocyte, molecular weight, and clearance from the interstitium of the myocardium and ultimately the circulation.1 Cardiac biomarkers play an integral role in the clinical diagnosis of myocardial infarction (MI). Referring to the spontaneous occurrence of MI in patients, the World Health Organization required that at least 2 of the following be present to fulfill the criteria for MI: a history of ischemia-type chest discomfort, evolutionary changes on serially obtained ECG tracings, and a rise and fall in serum cardiac markers.2 Article see p 10 See Editorial Circulation . 2008;118:609–611 See Article Circulation . 2008;118:632–638 Several dramatic advances have occurred in the biomarker component of the diagnosis of MI. Analytes with greater specificity for the myocardium were introduced into clinical medicine, with creatine kinase-MB replacing total creatine kinase and subsequently cardiac-specific troponins replacing creatine kinase-MB as the biomarker of choice for diagnosing MI.3 Assay technology improved as clinical chemists moved from enzymatic activity assays for CK to highly specific immunoassays that can detect progressively smaller concentrations of cardiac troponins in the peripheral circulation.4 Although ST-elevation MI (STEMI) is easily identified on the 12-lead ECG, we now recognize that many patients previously diagnosed with unstable angina are more properly diagnosed as having non–ST-elevation MI (NSTEMI) on the basis of the detection of elevated levels of cardiac troponins in their blood.5 Cardiac biomarkers are used as a rough guide to the extent of myocardial necrosis. The higher the peak biomarker level after STEMI, the larger the …

Fatal meningitis due to Listeria monocytogenes in elderly patients with underlying malignancy

Adult patients with malignancies are considered to be at a high risk for Listeria monocytogenes meningitis. The Microbiology Laboratory's database of the University Hospital of Ioannina, Greece, was searched for cases of L. monocytogenes during the period from January 1990 to December 2002. Listerial meningitis occurred in three patients: one with brain tumour, one with chronic lymphocytic leukaemia, and one with non-Hodgkin's lymphoma. All the patients were older than 70 and they were actively receiving therapy for their malignancy. L. monocytogenes type 4b was isolated from blood and cerebrospinal fluid. All were treated with ampicillin and gentamicin, but they died shortly after the initiation of the treatment. Experience with the three present cases indicated the high mortality rate due to listerial meningitis in this immunosuppressed population. So, listeriosis should be suspected in patients with meningitis and underlying malignancy. Since meningitis due to L. monocytogenes is not distinguishable clinically from other types of bacterial meningitis, it is recommended to cover Listeria in the initial empirical therapy of bacterial meningitis in immunosuppressed patients.

New Soluble-Polymer Bound Ruthenium Carbene Catalysts: Synthesis, Characterization, and Application to Ring-Closing Metathesis

Exchange of benzylidene ligand of commercially available Grubbs catalysts 1a or 1b with an appropriate soluble-polymer supported ligand leads to new boomerang type catalysts either of the Grubbs (3) or the Hoveyda type (4a or 4b). These catalysts, supported on poly-(ethylene glycol) (PEG), were fully characterized by solution NMR and MALDI mass spectrometry. They were tested in ring-closing metathesis (RCM), and 1 H NMR analysis provided key information concerning the recovery of the catalyst at the end of the reaction. While in the case of 3 the active ruthenium did not hook back to the ligand, catalysts 4a and 4b can be recovered and recycled. 4b owning a N-heterocyclic carbene ligand is particularly active and was used in the parallel synthesis of cyclic amino esters.

Salmonella enterica serotype Enteritidis phage type 4b outbreak associated with bean sprouts.

In November 2000 in the Netherlands, an outbreak of Salmonella enterica serotype Enteritidis phage type 4b was investigated. Eating bean sprouts was the only exposure associated with S. Enteritidis pt 4b infection (matched odds ratio 13.0, 95% confidence interval 2.0-552.5). Contaminated seeds were the most likely cause of contamination of the sprouts. The sprout grower applied a concentration of hypochlorite solution that was too low for seed disinfection.

Diagnosis of X-linked myotubular myopathy by detection of myotubularin.

Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM; MIM310400). Myotubularin, the implicated protein, is a phosphoinositide phosphatase that belongs to a large protein family conserved through evolution that also includes the antiphosphatase Sbfl and the protein hMTMR2 mutated in Charcot-Marie-Tooth type 4B. Myotubularin is detectable in a variety of cell lines by immunoprecipitation followed by Western blotting. We screened 29 independant patients with XLMTM phenotype and four with centronuclear myopathy. 87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin levels, including some with missense mutations. Moreover, myotubularin was also undetectable in a patient for whom no mutation could be identified by SSCP screening. The centronuclear cases investigated have a normal level of protein, suggesting that the centronuclear form is not the result of a decrease in myotubularin level. Thus, immunoprecipitation of myotubularin from cultured cells represents a rapid and helpful method for classifying those cases where no mutation was found. On the other hand, the amount of expression may be of diagnostic value for disease course in patients with a mutation.