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Biomedical subjects

L Simon

Publications and source records attributed to L Simon.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sakacin g, a new type of antilisterial bacteriocin.

Sakacin G is a 37-amino-acid-residue-long class IIa bacteriocin produced by Lactobacillus sake 2512, which is encoded by the duplicated structural genes skgA1 and skgA2. Sakacin G appears to be unique and seems to be an intermediate between pediocin-like bacteriocins, according to its double-disulfide bridges required for antimicrobial activity, and mesentericin-like bacteriocins in terms of sequence homologies, inhibition spectrum, and specific activity.

Amino Acid Sequence↗
PubMed2001

(-)-D-Deprenyl attenuates apoptosis in experimental brain ischaemia.

(-)-D-Deprenyl protects neurons from oxidative damage and helps to maintain the mitochondrial membrane potential by influencing intracellular anti-apoptotic oncoproteins, such as Bcl-2. The cellular rescue in the penumbra region by (-)-D-deprenyl administration was examined after permanent middle cerebral artery occlusion in rats. (-)-D-Deprenyl was given continuously following permanent middle cerebral artery occlusion. Two days later, the rats were killed and their infarct volumes were determined. Coronal brain sections were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate deoxyribonucleic acid (DNA) nick-end labelling (TUNEL) and caspase-3, TUNEL and anti-neuronal nuclei (NeuN) double labelling. Neural plasticity was characterized by growth-associated protein-43 (GAP-43) immunohistochemistry. A 1000 x 1000-microm region was sampled at both cortical margins of the TUNEL-positive area at its borders. The numbers of TUNEL-labelled and TUNEL-caspase-3-labelled cells decreased significantly. (-)-D-Deprenyl treatment increased the number of GAP-43-positive cells. We conclude that (-)-D-deprenyl reduced the number of affected cells and induced neuronal plasticity.

Animals↗
PubMed2001

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

Animals↗
PubMed2001

Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy.

The main impediment to effective ex vivo liver gene therapy of metabolic diseases is the lack of experimental work on large animals to resolve such important issues as effective gene delivery, cell-processing techniques, and the development of appropriate vectors. We have used a nonhuman primate, as a preclinical model, to analyze the limiting steps of this approach using recombinant retroviruses. Seven monkeys (Macaca fascicularis) underwent the complete protocol: their left liver lobe was resected, a catheter was placed in the inferior mesenteric vein and connected to an infusion chamber, and the hepatocytes were isolated, cultured, and transduced with a retroviral vector containing the beta-galactosidase gene. The hepatocytes were harvested and returned to the host via the infusion chamber. Biopsies were taken 4-40 days later. No animal was killed in the course of the experiments. They all tolerated the procedure well. We have developed and defined conditions that permit the proliferation and transduction of up to 90% of the plated hepatocytes. A significant proportion of genetically modified cells, representing up to 3% of the liver mass, were safely delivered to the liver via the chamber. Polymerase chain reaction analysis detected integrated viral DNA sequences and quantitative analysis of the in situ beta-Gal-expressing hepatocytes indicated that a significant amount of transduced hepatocytes, up to 2%, had become integrated into the liver and were functional. These results represent substantial advances in the development of the ex vivo approach and suggest that this approach is of clinical relevance for liver-directed gene therapy.

Animals↗
PubMed2001

Luminescent method for the detection of antibacterial activities.

A new rapid and sensitive method for the detection of antibacterial activities was based on luminescent indicator strains. Listeria innocua 8811 and Enterococcus faecalis 32 were transformed with plasmid carrying bacterial luciferase genes. Subsequent strains became capable to emit light during the exponential growth phase. The addition of bacteriocin containing culture supernatants to such cultures induced a drop of their light emission which was correlated to the combined antibacterial activity of acid stress and bacteriocin. The detection of antagonistic activity is independent of its mode of action, i.e. bactericidal or bacteriostatic. This method allowed to directly visualize the antagonistic activity of bacteriocin producer strains toward target strains in coculture experiments. However, a control co-culture with non-producing bacteriocin mutant was necessary in order to distinguish between nutrients competition and bacteriocin activity. Finally, five class IIa bacteriocins were purified from culture supernatants of eight strains detected in 3 days from a 120 lactic acid bacteria collection.

Bacteriocins↗
PubMed2001

[Evaluation of antibacterial filters for peridural obstetrical anesthesia].

OBJECTIVES: To assess the antibacterial efficiency of filters used in obstetrics when epidural top-ups are performed. STUDY DESIGN: Observational prospective study. PATIENTS AND METHODS: We aseptically collected 201 antibacterial filters that had been used for top-ups with ropivacaine +/- sufentanil for epidural analgesia during labour. We flushed them first with 2 mL of saline and then with 2 mL of a solution containing 1.5 x 10(6) Staphylococcus epidermidis/mL. The filtrates were incubated at 37 degrees C for 72 h. Number of top-ups and duration of epidural analgesia are expressed as median (extremes). RESULTS: 3 (1-10) top-ups were performed for labour analgesia over a period of 6.5 h (1.8-18). After filtering, all the solutions were found to be sterile. Especially, when using Staphylococcus epidermidis solutions, bacteria were not found beyond any filter. These results suggest the integrity of the filter membrane after several boluses. No infection related to epidural analgesia was reported. CONCLUSION: Antibacterial filters provide a good protection against a potentially contaminated procedure during epidural top-ups.

Adult↗
PubMed2001

[Acute severe pain in emergencies. The key for efficient analgesia].

OBJECTIVE: To measure severe acute pain (SAP) frequency, to describe SAP management and to bring to view the conditions of analgesia success in emergency medicine. DESIGN: Multicentre prospective survey: 7 days in Emergency Departments (ED), 30 days in Mobile Intensive Care Units (MICU). Multivariate analysis to measure the independent effect on pain relief of factors identified by Chi squared test. SETTING: All of 6 ED and 8 MICU of a French region. PATIENTS: Over 15 years of age. MAIN OUTCOME MEASURES: Pain intensity was assessed with Visual Analog Scale (VAS) before and after ED or MICU management. SAP group (defined by initial VAS score > 40 mm) was analyzed for pain relief (defined by final VAS score < or = 40 mm). Influence on pain relief through pain aetiology, initial pain intensity, treatment delay and opioid use was analyzed. RESULTS: 1,082 fulfilled medical forms for 3,419 eligible patients. SAP frequency was estimated 36% (CI95 = 34-38%) in ED and 29% (CI95 = 25-33%) in MICU. SAP (n = 368) was often persistent: 45% (CI95 = 43-47%) after discharge from ED and 26% (CI95 = 22-30%) after MICU intervention. The prognostic factors of pain control success revealed by Chi squared test were: MICU (vs ED), treatment delay < or = 3 hours (vs > 3 hours), opioid use (vs non opioid use) and VAS pain level < or = 70 mm (vs > 70 mm). The last 3 factors were confirmed by multivariate analysis. Treatment delay, opioid use, and pain level were found to be determinants of efficient analgesia for SAP. CONCLUSION: Despite the high frequency of SAP in ED and MICU, pain control is not satisfying. Opioid use and early treatment are determinant in analgesia efficiency for SAP and should be therefore encouraged to improve pain relief in emergency medicine.

Acute Disease↗
PubMed2001

Dose of prophylactic intravenous ephedrine during spinal anesthesia for cesarean section.

STUDY OBJECTIVE: To compare the incidence of maternal hypotension associated with spinal anesthesia for cesarean section when 10-, 15-, or 20-mg prophylactic boluses of intravenous (IV) ephedrine are used. DESIGN: Prospective observational study. SETTING: Teaching hospital. PATIENTS: 108 women admitted for elective cesarean section. INTERVENTIONS: Spinal anesthesia was performed using hyperbaric bupivacaine 10 mg, sufentanil 2 microg, and morphine 0.2 mg (volume 4 mL). Ephedrine (10, 15, or 20 mg) was administered 2 minutes after the intrathecal injection. Maternal blood pressure was checked every 2 minutes. Hypotension was promptly treated with 5-mg ephedrine boluses. MAIN RESULTS: Incidence of hypotension was significantly higher in women receiving a 10-mg prophylactic dose of ephedrine than in those receiving either a 15-mg or a 20-mg prophylactic dose of ephedrine [23/36 in the 10-mg ephedrine group vs. 13/36 and 10/36 in the 15-mg and 20-mg ephedrine groups, respectively (p< 0.05)]. CONCLUSION: In the conditions of this study, a single bolus of IV ephedrine with doses of either 15 or 20 mg decreased significantly the incidence of maternal hypotension as compared to a single 10-mg bolus of ephedrine.

Adult↗
PubMed2001

Probabilistic neural networks using Bayesian decision strategies and a modified Gompertz model for growth phase classification in the batch culture of Bacillus subtilis.

Probabilistic neural networks (PNNs) were used in conjunction with the Gompertz model for bacterial growth to classify the lag, logarithmic, and stationary phases in a batch process. Using the fermentation time and the optical density of diluted cell suspensions, sampled from a culture of Bacillus subtilis, PNNs enabled a reliable determination of the growth phases. Based on a Bayesian decision strategy, the Gompertz based PNN used newly proposed definition of the lag and logarithmic phases to estimate the latent, logarithmic and stationary phases. This network topology has the potential for use with on-line turbidimeter for the automation and control of cultivation processes.

Journal Article↗
PubMed2001

Comparing sports injuries in men and women.

OBJECTIVE: To compare the pattern of injury between men and women in seven collegiate sports to determine if gender-specific factors exist which could be modified to reduce the risk of injury to female athletes. DESIGN: Retrospective cohort study of injury reports compiled by certified athletic trainers between Fall 1980 and Spring 1995. SETTING: An NCAA division III College. PARTICIPANTS: Eighteen to 22 year-old male and female college athletes competing in seven like sports (basketball, cross-country running, soccer, swimming, tennis, track and water polo) at the intercollegiate level, playing similar number of contests and using the same facilities. MAIN OUTCOME MEASURES: Analyses of injury patterns, classified by sport and anatomic location, for men and women in seven like sports. RESULTS: A total of 3,767 participants were included in the study, with 1874 sports-related injuries reported among the men and women's teams. Of these injuries, 856 (45.7%) were sustained by female and 1018 (54.3%) by male athletes. Overall, no statistically significant gender difference was found for injuries per 100 participant-years (52.5 for female athlete versus 47.7 for males). A statistically significant gender difference in injury incidence (p < 0.001) was seen for two sports: swimming and water polo. Female swimmers reported more back/neck, shoulder, hip, knee and foot injuries: and female water polo players reported more shoulder injuries. When evaluating all sports concurrently, female athletes reported a higher rate of hip, lower-leg and shoulder injuries, while male athletes reported a higher rate of thigh injuries. CONCLUSION: Except for some minor gender differences in total injuries for two sports and several differences in total injuries by anatomic location, our data suggest very little difference in the pattern of injury between men and women competing in comparable sports. The increased rate of shoulder injury among female swimmers probably resulted from the more rigorous training philosophy of their coach. Thus, no gender-specific recommendations can be suggested for decreasing the incidence of injury to female athletes competing in these sports.

Adolescent↗
PubMed2001

Minimal clinically important differences: review of methods.

Determining a minimal clinically important difference to be detected in a clinical trial is a critical methodological step in the design of a study. In this review, the different methods that have been used in detecting important changes or differences are considered and categorized according to a classification system consisting of which groups are contrasted, the setting of the results, and the type of change of difference being quantified. It was found that most methods and procedures for deriving minimal clinically important differences considered important changes from the viewpoint of a group of patients. Development of methods that focus on individuals should be a goal of the future.

Clinical Trials as Topic↗
PubMed2001

Discrimination of changes in osteoporosis outcomes.

The purpose of this paper was to identify existing work related to discrimination, responsiveness, and minimal clinically important differences (MCID) for 4 key clinical outcomes in osteoporosis, to serve as a background to discussions about how to define MCID for both individuals and groups. The outcomes assessed were bone density, fractures, quality of life, and function. We conducted a systematic literature search in MEDLINE, EMBASE, and Current Contents for articles that discussed responsiveness, detectable difference, improvement criteria, and clinical importance. We used the Beaton cube to classify the studies depending on whether they compared differences between or changes within individuals or groups. Although a number of studies were identified that presented data on detectable differences beyond error and observed differences, few studies presented data on how to define clinically important differences. A key priority for future research is to define minimally clinical important differences for clinically important osteoporosis outcomes using a consensus based approach that will be accepted by the osteoporosis community at large. Furthermore, these MCID will likely be different for individual patients seen in clinical practice than for individuals in a clinical trial.

Clinical Trials as Topic↗
PubMed2001

[Reflex sympathetic dystrophy: psychological and psychopathologic features].

It has traditionally been accepted that a predisposing psychological field exists with the appearance of the reflex sympathetic dystrophy. Nevertheless, there is no unanimous agreement in this interpretation, since surveys exist unanimous are in favour the reactive character of the psychological effect on reflex sympathetic dystrophy. In this study, we revise literature already published on the subject, present arguments on the psychological evaluation tests carried out to date and propose the possibility of using other test unanimous are easier to manage and to interpret.

Humans↗
PubMed2000

(R)-tert-Butoxycarbonylamino-fluorenylmethoxycarbonyl-glycine from (S)-benzyloxycarbonyl-serine or from papain resolution of the corresponding amide or methyl ester.

The enantiospecific synthesis of (R)-Boc-(Fmoc)-aminoglycine 7 was achieved. (S)-Cbz-serine 1 was reacted with diphenylphosphoryl azide in the presence of triethylamine to yield cyclic (S) carbamate 2. The ring nitrogen of 2 was protected with a Boc group (3). The cyclic carbamate of 3 was hydrolyzed with benzyltrimethylammonium hydroxide to yield the (R)-enantiomer of alcohol 4. The oxidation of 4 with pyridinium dichromate yielded the enantiomerically pure (97% ee) (R)-Boc-(Cbz)-aminoglycine 5, which was converted to 7 with retention of optical purity. Similarly, starting from (S)-Boc-serine 9, cyclic (S) carbamate 10 was obtained. The ring nitrogen of 10 was protected with a Cbz group (11) with retention of configuration. The cyclic carbamate of 11 was base hydrolyzed to yield 12, the (S)-enantiomer alcohol. Independently, Boc-(Fmoc)-aminoglycine amide 13 and Boc-(Fmoc)-aminoglycine methyl ester 14 were resolved using papain. The stereochemistry of the isolated acid was determined to be (R) by coelution on HPLC of its derivative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.

Amides↗
PubMed2000

Red laser-induced fluorescence energy transfer in an immunosystem.

We describe two near-infrared fluorescent squaraine dyes (Sq635 and Sq660), their spectra, their covalent linkage to proteins, and their use as donor and acceptor, respectively, in a fluorescence resonance energy transfer (FRET) immunoassay based on the use of red lasers. The dyes show quantum yields of around 10% in the free form and up to 68% when bound to proteins. If converted into their N-hydroxysuccinimide esters, they can be linked to free amino groups of proteins. To improve water solubility, two sulfo groups were introduced. The emission spectrum of Sq635 overlaps the absorption spectrum of Sq660, a fact that makes them a useful pair of dyes for use in FRET immunoassay which is demonstrated for human serum albumin/anti-human serum albumin.

Antibodies↗