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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 19 recordsLinked to original sources
PubMed2007

Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic Friulimicin in Actinoplanes friuliensis.

Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. friuliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli, we provide biochemical evidence for the stereoselective synthesis of L-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.

Aminobutyrates↗
PubMed2006

Influx of extended-spectrum beta-lactamase-producing enterobacteriaceae into the hospital.

BACKGROUND: The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterobacteriaceae is increasing worldwide. The influx of these bacteria into hospitals has major implications for infection-control and empirical treatment strategies. METHODS: Isolates from 2 patient cohorts--patients with gram-negative bacteremia within 2 days after admission and patients screened for fecal colonization at admission--were assessed for ESBL production. ESBL phenotype was confirmed according to Clinical and Laboratory Standards Institute guidelines. Predictors of ESBL phenotype were examined by univariate and multivariate analyses. RESULTS: Of 80 Enterobacteriaceae isolates from blood samples obtained at admission to the hospital, 13.7% produced ESBL. Thirty-eight patients with ESBL-positive isolates and 72 with ESBL-negative isolates were included in a case-control study. Predictors of ESBL production were male sex and nursing home residence (area under receiver operator characteristic curve, 0.7). Of 241 persons screened at admission, 26 (10.8%) had fecal carriage of ESBL-producing Enterobacteriaceae. Predictors of fecal carriage were poor functional status, antibiotic use, chronic renal insufficiency, liver disease, and use of histamine2 blockers (area under receiver operator characteristic curve, 0.8). Four (15.4%) of the 26 individuals with fecal carriage had subsequent bacteremia with ceftazidime-resistant Enterobacteriaceae, compared with 1 (0.5%) noncarrier (odds ratio, 38.9; P<.001). Of 80 ESBL-producing Enterobacteriaceae isolates obtained at admission, 65 were health care associated, and 15 were community acquired. The 15 community-acquired ESBL-producing Enterobacteriaceae belonged to diverse clones. The most prevalent ESBL gene among these isolates was CTX-M-2 (found in 53.3% of the isolates). CONCLUSIONS: We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.

Aged↗
PubMed2006

"All-in-one-plate" E-test and disk diffusion susceptibility co-testing for multiresistant Acinetobacter baumannii.

Multiresistant Acinetobacter baumannii requires ancillary manual susceptibility testing with the E-test and disk diffusion when tested with the VITEK-2 system (bioMérieux, Marcy l'Etoile, France). In the study presented here, the E-test and disk diffusion were combined in a single plate, and the method was verified by comparing categorical agreement of combined and control plates. There were no very major, major or minor errors, and similar results were obtained for all ten representative bacterial strains used as controls. Co-testing is thus feasible, accurate and reproducible, and it merits evaluation with other bacterial species.

Acinetobacter baumannii↗
PubMed2006

Arginine uptake is attenuated through modulation of cationic amino-acid transporter-1, in uremic rats.

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial NO synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is the sole precursor for NO biosynthesis. Among several transporters that mediate L-arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major determinant of eNOS activity in CRF. We studied glomerular and aortic arginine uptake, CAT-1, and CAT-2 messenger ribonucleic acid (mRNA) expression, and CAT-1 protein in: (a) rats 6 weeks following 5/6 nephrectomy (CRF), (b) sham-operated animals, and (c) rats with CRF treated orally with either atorvastatin or arginine in drinking water (modalities which have been shown to enhance eNOS activity and improve endothelial function). Both glomerular and aortic arginine transport were significantly decreased in CRF. Treatment with either arginine or atorvastatin abolished the decrease in arginine uptake in CRF rats. Using reverse transcriptase-polymerase chain reaction and Northern blotting, we found a significant increase in glomerular and aortic CAT-1 mRNA expression in CRF. Western blotting revealed that CAT-1 protein was decreased in CRF, but remained intact following arginine and atorvastatin administration. Renal and systemic arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These findings provide a possible novel mechanism to eNOS inactivation and endothelial dysfunction in uremia.

Animals↗
PubMed2006

The possible significance of Clostridium spp. in blood cultures.

The significance of Clostridium spp. in blood cultures was evaluated by two methods. In the first part of the study, a group of 80 patients with Clostridium spp. bacteraemia was compared with a group of 100 patients with Bacillus spp. in blood cultures, making the assumption that Bacillus almost invariably represents contamination (pseudobacteraemia). Significant differences were found between the two groups, suggesting that growth of Clostridium did not represent pseudobacteraemia. Patients with Clostridium bacteraemia were older, had a higher frequency of gastrointestinal disease (especially colorectal tumours), were associated more frequently with polymicrobial bacteraemia, and had a higher mortality rate. In the second part of the study, each of the 80 cases of Clostridium bacteraemia was evaluated individually for clinical relevance by an infectious diseases expert. In two-thirds of the cases, isolates of Clostridium from blood were considered to be of clinical relevance, whereas in one-third of cases, the clinical significance of this finding was doubtful. It was concluded that growth of Clostridium spp. in blood cultures, even in the absence of one of the histotoxic syndromes, is often of clinical significance, and that such findings should be properly evaluated and not ignored.

Aged↗
PubMed2005

Unexpected hospital-acquired bacteraemia in patients at low risk of bloodstream infection: the role of a heparin drip.

Following a cluster of cases of unexpected hospital-acquired bacteraemia suspected to be related to an intravenous (iv) heparin drip, all cases of hospital-acquired primary bloodstream infection (BSI) in patients at low risk of bacteraemia were analysed over a four-year period. Ninety-six bacteraemic patients (6%) from 1618 episodes of hospital-acquired bacteraemia had a peripheral iv line as the only risk factor. These patients were divided into two groups: 60 patients with phlebitis and 36 without local signs of inflammation. Baseline features of the two groups were comparable, but in univariate and multivariate analysis, a significant association was found between iv heparin use, predominance of Gram-negative organisms (especially Klebsiella, Serratia and Enterobacter species), and absence of phlebitis. In spite of clear statistical association, however, the means by which the heparin solution became contaminated with Gram-negative organisms remained unknown. Following implementation of infection control methods concerning heparin handling, no more cases occurred. Unexpected hospital-acquired Gram-negative bacteraemia in patients with peripheral iv lines should prompt investigation of potential infusate-related infection, especially in patients without phlebitis and those receiving iv heparin.

Aged↗
PubMed2005

Ischaemia or reperfusion: which is a main trigger for changes in nitric oxide mRNA synthases expression?

OBJECTIVE: To investigate alterations in endothelial nitric oxide synthase and inducible nitric oxide synthase mRNA expressions and nitric oxide release in the myocardium during ischaemia/reperfusion and determine whether these changes are ischaemic and/or reperfusion dependent. MATERIALS AND METHODS: Isolated rat hearts were perfused by a modified Langendorff system. Following 1 h of global cardioplegic ischaemia, left ventricle haemodynamic parameters were recorded at baseline and during 30 min of reperfusion. Levels of endothelial, inducible nitric oxide synthases mRNA expression and nitric oxide release were measured at baseline, after ischaemia and at 30 min of reperfusion. RESULTS: Global cardioplegic ischaemia caused a significant depression of left ventricular function and a decrease of coronary flow. Postischaemic intensities of the endothelial nitric oxide synthase mRNA bands were significantly lower than at baseline (P < 0.01). There were no significant differences in endothelial nitric oxide synthase mRNA band intensities immediately after ischaemia compared to the end of reperfusion, nor between the intensities of inducible nitric oxide synthase mRNA bands at baseline, at end of ischaemia and at end of reperfusion. Nitric oxide in the myocardial effluent was below detectable levels at all measured points. CONCLUSION: Ischaemic injury causes down-regulation of endothelial nitric oxide synthase mRNA expression, which is then associated with reduction of coronary flow during reperfusion, representing one possible mechanism of ischaemia/reperfusion injury. We did not find expected elevations of inducible nitric oxide synthase mRNA expression during ischaemia or reperfusion and we suggest that ischaemia/reperfusion injury is not associated with nitric oxide overproduction.

Animals↗
PubMed2005

Erroneous reporting of coagulase-negative Staphylococci as Kocuria spp. by the Vitek 2 system.

Misidentification of coagulase-negative staphylococci (CoNS) may delay appropriate treatment. We investigated 20 clinical isolates identified as Kocuria spp. by the Vitek 2 system. All were identified as CoNS by 16S rRNA gene sequencing (18 Staphylococcus epidermidis, 1 Staphylococcus haemolyticus). Four Kocuria isolates were shown to be identical to CoNS from the same patient by pulsed-field gel electrophoresis. Isolates identified by Vitek 2 as Kocuria most likely represent misidentified CoNS, and if clinically indicated, should be investigated further by genomic methods.

Bacteriological Techniques↗
PubMed2004

Protocol for the accelerated detection of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae strains from blood cultures.

The study presented here was performed to evaluate an accelerated protocol for the early detection of organisms producing extended-spectrum beta-lactamase (ESBL). The procedure involved testing isolates directly from positive blood-culture bottles, and a total of 40 clinical isolates (10 ESBL-producing and 10 non-ESBL-producing isolates of both Escherichia coli and Klebsiella pneumoniae) were used. The isolates were inoculated into blood cultures bottles and, upon growth signal, fluid from the bottle was cultured directly onto plates with combination discs containing cefotaxime or ceftazidime with and without clavulanate. Results were compared with those of standard methods for the detection of ESBL. High concordance between the two methods was found, and the direct test showed high sensitivity (95%) and specificity (100%). Use of this accelerated protocol may speed detection of the ESBL phenotype and thereby facilitate the early administration of appropriate antimicrobial therapy.

Bacteriological Techniques↗
PubMed2004

Effect of stimulus frequency and stimulation site on the N1m response of the human auditory cortex.

The aim of the present study was to investigate the functional organization of the auditory cortex for pure tones of 1, 2, 4, 6, 8 and 12 kHz. Ten subjects were tested with a whole-head magnetometer (151 channels). The location, latency and amplitude of the generators of the N1m (the main component of the response, peaking approximately at 100 ms) were explored simultaneously in the right and left hemispheres under monaural stimulation. Our results revealed that tonotopy is a rather complex functional organization of the auditory cortex. From 1 to 12 kHz, tonotopic maps were found for contralateral as well as for ipsilateral stimulation: N1m generators were found to be tonotopically organized mainly in an anterior-posterior direction in both hemispheres, whatever the stimulated ear, but also in an inferior-superior direction in the right hemisphere. Furthermore, latencies were longer in the left than in the right hemisphere. Two different representations of spectral distribution were found in the right auditory cortex: one for ipsilateral and one for contralateral stimulation.

Acoustic Stimulation↗
PubMed2004

Toxic epidermal necrolysis-like reaction secondary to colchicine overdose.

Colchicine is a microtubule-inhibiting drug used to treat gout, familial Mediterranean fever and many other skin diseases. Intoxication with colchicine affects multiple organs, often fatally. Cutaneous sequelae of colchicine toxicity are rare. We describe the clinical and histological features of a toxic epidermal necrolysis-like exanthem in a patient who lethally overdosed on colchicine.

Apoptosis↗
PubMed2003

Prenatal diagnosis of portal vein thrombosis by ultrasound.

Neonatal portal vein thrombosis (PVT) is a rare condition seen in the setting of thrombophilia or after umbilical vein catheterization. We report a case of fetal PVT with abnormal antenatal ultrasound findings at 27 weeks of gestation. This presented initially as dilation of the intrahepatic umbilical vein. To our knowledge, this is the first reported case evaluated prenatally. Color Doppler ultrasound was valuable in detecting constriction of the vessel with a high-velocity jet seen past the obstruction site. A discussion of this condition and differential diagnosis is presented.

Adult↗
PubMed2003

The prevalence and cost of diabetes in metropolitan France: what trends between 1998 and 2000?*.

OBJECTIVES: Our aim was to update available data concerning the prevalence and cost of diabetes in metropolitan France. METHODS: We performed a retrospective study using patient reimbursement data from all the 128 local health offices (CPAM) in metropolitan France. We selected patients who received reimbursements for an oral hypoglycemic agent or insulin. Thus, 704,423 patients were studied by using 1998 data and 1,145,603 patients were studied by using data from 2000. The expenditures studied represented the total amount reimbursed by national health insurance to diabetic patients. The cost differential which could be attributed to diabetes was calculated by determining the difference between costs generated by diabetic patients to those generated by the rest of the population of the same age. RESULTS: Between 1998 and 2000, the prevalence of diabetes treated in the population of affiliates covered by the general scheme increased from 2.78% to 2.96%. The total amount paid by the general scheme for care to diabetic patients (related to diabetes or not) was 5.710 billion euros in 2000 compared to 4.862 billion euros in 1998. The amount which can be attributed to diabetes alone can be estimated to be 2.414 billion euros in 2000 compared to 2.021 billion euros in 1998. After considering the impact of the increase in the number of treated diabetics, a modification in the modalities of medical care probably accounts for 183 million euros of the cost increase. Medical equipment (self blood glucose monitoring devices, reagent strips, finger lancets...) accounts for 39.3% (72 million euros) of this cost differential, medications account for 34.4% (63 million euros) and nursing care 16.9% (31 million euros). There was no change in the cost of diabetes with relation to expenses for medical consultations.

Costs and Cost Analysis↗
PubMed2003

Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA expression in the lungs of antigen-challenged allergic mice.

BACKGROUND: Growing evidence suggests that inducible nitric oxide synthase (iNOS) is the main source of the high output of exhaled nitric oxide (NO) in asthma. Treatment of asthmatic patients with glucocorticoids reduces high levels of exhaled NO mainly by inhibiting the transcription of iNOS. A similar reduction in exhaled NO was recently observed in patients treated with the leukotriene receptor antagonists, but the exact interaction between these drugs and iNOS remains obscure. OBJECTIVE: The purpose of this study was to evaluate the effect of a leukotriene receptor antagonist, montelukast, on the expression and activity of iNOS in a murine model of allergic asthma. METHODS: Twenty-four BALB/c mice were sensitized to OVA and were equally divided into 3 groups (Groups 1-3). Eight additional mice were sham sensitized and served as a negative control group (Group 4). Group 1 received montelukast 1 mg/kg/day in their drinking water, Group 2 received dexamethasone 1 mg/kg/day in their drinking water and Groups 3 and 4 received plain tap water. After 1 week, the animals were challenged by inhalation of OVA and, 3 h later, they were killed and their lung cells were isolated by enzymatic tissue digestion. NO generation was measured by a Griess assay, and iNOS mRNA was studied by RT-PCR. RESULTS: A significant increase in iNOS mRNA expression and in NO generation was evident after allergen challenge compared with the controls. Pretreatment with montelukast mildly decreased NO production without producing a concomitant significant decrease in iNOS mRNA expression. CONCLUSION: Unlike pretreatment with glucocorticoids, we failed to find compelling evidence for a major role for montelukast treatment in the modulation of iNOS mRNA in a murine model of acute asthma.

Acetates↗
PubMed2003

A glutamate mutase is involved in the biosynthesis of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis.

Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin. This antibiotic is active against gram-positive bacteria such as multiresistant Enterococcus and Staphylococcus strains. It consists of 10 amino acids that form a ring structure and 1 exocyclic amino acid to which an acyl residue is attached. By a reverse genetic approach, biosynthetic genes were identified that are required for the nonribosomal synthesis of the antibiotic. In close proximity two genes (glmA and glmB) were found which are involved in the production of methylaspartate, one of the amino acids of the peptide core. Methylaspartate is synthesized by a glutamate mutase mechanism, which was up to now only described for glutamate fermentation in Clostridium sp. or members of the family ENTEROBACTERIACEAE: The active enzyme consists of two subunits, and the corresponding genes overlap each other. To demonstrate enzyme activity in a heterologous host, it was necessary to genetically fuse glmA and glmB. The resulting gene was overexpressed in Streptomyces lividans, and the fusion protein was purified in an active form. For gene disruption mutagenesis, a host-vector system was established which enables genetic manipulation of Actinoplanes spp. for the first time. Thus, targeted inactivation of biosynthetic genes was possible, and their involvement in friulimicin biosynthesis was demonstrated.

Amino Acid Sequence↗
PubMed2003

Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms.

BACKGROUND: There is a paucity of bronchial biopsy data in children. A major limitation is concern over the safety of the procedure. This paper reports the results of efforts to develop a method that is safe and provides adequate specimen for evaluation. METHODS: 170 children aged 2.5 to 16 years with chronic respiratory symptoms were studied under general anaesthesia in an outpatient surgery setting. Bronchoalveolar lavage and biopsies were obtained using a 4.9 mm flexible bronchoscope through a laryngeal mask airway. At least three bioipsies were taken. RESULTS: No patient required topical adrenaline to control bleeding, nor was there a change in the state of any of the patients. There were no episodes of pneumothorax, haemoptysis, pneumonia, or significant fever. All children less than four years old received a single dose of antibiotic intravenously after the procedure. The average length of time for the procedure was 12 minutes (range 6 to 27). Recovery time averaged 90 minutes. The limiting factor was the ability of the child's airway to accomodate the bronchoscope. CONCLUSIONS: This report should encourage clinicians to incorporate endobronchial biopsy into the evaluation of children with difficult respiratory problems.

Adolescent↗
PubMed2002

Nuclear distribution of porphobilinogen deaminase (PBGD) in glioma cells: a regulatory role in cancer transformation?

Recently, considerable interest has been directed to red-fluorescence photodiagnosis of brain and other tumours during surgery using the protoporphyrin IX natural precursor, 5-aminolaevulinic acid. In the present study we focused on the role of the rate-limiting enzyme porphobilinogen deaminase in glioma C6 cell activity, differentiation and sub-cellular distribution. Over-expression of the human housekeeping porphobilinogen deaminase in the glioma cells, using the housekeeping-porphobilinogen deaminase plasmid, induced a G1 cell cycle attenuation accompanied by increases in enzyme activity and c6 differentiation toward astrocytes. Visualisation of subcellular localisation of the porphobilinogen deaminase using the independent techniques of fluorescence immuno-staining with specific anti-human porphobilinogen deaminase antibodies and cellular expression of porphobilinogen deaminase fused to green fluorescent protein, revealed (unexpectedly) a major fraction of porphobilinogen deaminase in the nucleus and only a minor fraction in the cytoplasm. Both C and N terminals of porphobilinogen deaminase fused to green fluorescent protein revealed a major fraction of the newly synthesized fused porphobilinogen deaminase in the nucleus. Furthermore, newborn rat brain cells grown in a primary culture showed the same localisation pattern of porphobilinogen deaminase in the nuclei. Stimulation of C6 glioma cell differentiation by butyrate induced a marked decrease in porphobilinogen deaminase both in the nucleus and in the cytoplasm as determined by Western blotting and fluorescence immuno-localisation. These findings suggest a possible dual role for housekeeping porphobilinogen deaminase in fast dividing glioma cells, one related to the porphyrin synthesis pathway and another coupled to nuclear function, which might be linked to tumorigenesis.

Animals↗