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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Total cellular calcium and magnesium content of cultured human peripheral blood mononuclear cells following exposure to antidiabetic drugs.

Drugs modulating the ATP-sensitive potassium (K(ATP)) channel activity are widely used for the treatment of diabetes mellitus, the target being pancreatic beta-cells. However, any cell type possessing K(ATP) channels might be concomitantly affected. We investigated the metabolic effect of glibenclamide, a K(ATP) channel closer, and/or diazoxide, a K(ATP) channel opener, on total intracellular content of calcium (Ca) and magnesium (Mg) of cultured peripheral blood mononuclear cells (PBMC). Metformin and rosiglitazone, acting via cellular mechanisms other than K(ATP) channels, were also tested. Ca and Mg were assessed in PBMC from healthy subjects following 72 h in vitro treatment with the respective drugs. Ca content increased significantly in PBMC treated with glibenclamide or rosiglitazone, however apparently via different intracellular pathways. Mg increased only following treatment with rosiglitazone. Metformin had no effect on intracellular Ca or Mg. Pretreatment with diazoxide resulted in a significant intracellular Ca and Mg loss in each experimental situation. If verified clinically, rosiglitazone-induced increase in Mg content of PBMC might prove beneficial beyond hypoglycaemic control. On the other hand, loss of intracellular Ca/Mg content following K(ATP) channel opening by diazoxide might eventually result in significant intracellular Ca and/or Mg depletion.

Adult↗
PubMed2006

Use of repetitive DNA sequences to determine the persistence of enteropathogenic Escherichia coli in vegetables and in soil grown in fields treated with contaminated irrigation water.

AIMS: Fresh fruits and vegetables are increasingly recognized as vectors for food-borne illness. On farm contamination through contaminated irrigation water is considered likely source of the pathogen for several outbreaks. The purpose of this study is to investigate the possible similarity of strains of Escherichia coli isolated from the soil and vegetables irrigated by treated wastewater. METHODS AND RESULTS: Seventy-five strains of enteropathogenic Escherichia coli isolated from vegetables, soil and irrigation water were tested for sensitivity to antibiotics and shown to be sensitive. The result of enterobacterial repetitive intergenic consensus (ERIC)-PCR shows similarities between analysed strains isolated from the three different samples. Moreover strains of E. coli isolated from vegetables over different periods of time have the same ERIC-PCR profile. CONCLUSIONS: The isolated strains of enteropathogenic E. coli can persist in soil and in vegetables growing in fields treated with contaminated irrigation water for an extended period of time. SIGNIFICANCE AND IMPACT OF THE STUDY: Contaminated irrigation water can transport pathogenic bacteria, which persists in the soil for a long period of time and contaminates the vegetables growing in the field irrigated by this contaminated water.

DNA, Bacterial↗
PubMed2005

Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning.

We characterize the infiltration of interstitial cells into tissue engineering scaffolds prepared with electrospun collagen, electrospun gelatin, electrospun poly(glycolic) acid (PGA), electrospun poly(lactic) acid (PLA), and an electrospun PGA/PLA co-polymer. Electrospinning conditions were optimized to produce non-woven tissue engineering scaffolds composed of individual fibrils less than 1000 nm in diameter. Each of these materials was then electrospun into a cylindrical construct with a 2 mm inside diameter with a wall thickness of 200-250 microm. Electrospun scaffolds of collagen were rapidly, and densely, infiltrated by interstitial and endothelial cells when implanted into the interstitial space of the rat vastus lateralis muscle. Functional blood vessels were evident within 7 days. In contrast, implants composed of electrospun gelatin or the bio-resorbable synthetic polymers were not infiltrated to any great extent and induced fibrosis. Our data suggests that topographical features, unique to the electrospun collagen fibril, promote cell migration and capillary formation.

Animals↗
PubMed2004

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--Part I.

This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, ...) and other documents of normative character (ISO, ICH, FDA, ...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

Chemistry Techniques, Analytical↗
PubMed2004

Legionella in two splenectomized patients. Coincidence or causal relationship?

We describe two splenectomized patients admitted with pneumonia. The course in one was complicated by overwhelming multiorgan failure when the only indicative laboratory result was seropositivity for Legionella hackeliae and Legionella longbeachae. He was initially treated with ceftriaxone and roxithromycin, followed by levofloxacin as well as intensive supportive treatment, and survived. The second patient was seroreactive for Legionella micdadei. In some cases of pneumonia in splenectomized patients tentatively considered to be caused by Streptococcus pneumoniae, the causative agent might have, in fact, been Legionella. We suggest that splenectomy be considered a possible predisposing factor for Legionella pneumonia. Since prompt diagnosis of Legionella infection, especially the non- pneumophila species, is extremely difficult, alertness to this diagnostic option and early empirical initiation of appropriate aggressive antibiotic treatment may be of critical importance.

Adult↗
PubMed2004

Multiple pathogenetic mechanisms in X linked dilated cardiomyopathy.

X linked dilated cardiomyopathy is a familial disease that is allelic to Duchenne and Becker muscular dystrophies and caused by mutations in the dystrophin gene. In several families with X linked dilated cardiomyopathy, the pattern of expression of dystrophin mutations in cardiac muscle differs from that in skeletal muscle. A number of these mutations affect transcription and splicing of the dystrophin gene in a tissue specific manner; others may affect regions of dystrophin that are presumed to have a more important role in cardiac than in skeletal muscle. These mutations are important because they highlight the fundamental differences in processing of the dystrophin gene between skeletal and cardiac tissues, as well as differences in the functional domains more relevant for one tissue or the other. This review focuses on the major mechanisms that have been proposed to explain this disorder.

Cardiomyopathy, Dilated↗
PubMed2004

Use of immunohistochemical marker calretinin in the diagnosis of a diffuse malignant metastatic mesothelioma in an equine.

Mesotheliomas are rarely reported in animal species. In this report, the occurrence of a diffuse, metastatic mesothelioma in a 6-year-old gray Arabian mare is described. The mare was presented on clinical examination with ascites, bilateral pleural effusion, and pleural roughening. Necropsy revealed abundant fluid in the abdominal and thoracic cavities. The surface of all organs was thick and fibrosed with multiple raised nodules and hemorrhages. Histology was characteristic of a generalized, biphasic mesothelioma with vascular and lymph nodes metastases. It is believed that the primary tumor developed in the pericardium and spread through lymphatics. In this report, calretinin was used as an immunohistochemical marker in the diagnosis of mesothelioma in an equine species for the first time.

Animals↗
PubMed2004

Induction of tolerance by Porphyromonas gingivalis on APCS: a mechanism implicated in periodontal infection.

The periodontal pathogen Porphyromonas gingivalis (Pg) is a potent inducer of the production of pro-inflammatory cytokines by neutrophils, monocytes, and macrophages, and can desensitize immune cells in vitro and in vivo. We analyzed the ability of Pg lipopolysaccharide (LPS) to induce endotoxin tolerance. Treatment of dendritic cells (DC), the human macrophage cell line THP-1, and monocytes (antigen-presenting cells, APC) with Pg.LPS inhibited APC maturation assessed by CD80 and CD86 expression, and inhibited chemokine (CCL3 and CCL5) production. Pre-treatment with glucocorticoids (GC) and interleukin-10 (IL-10) abolished the effect of Pg.LPS on CD80, CD83, and CD86, and on CCL3 and CCL5 production. We also showed that Pg.LPS enhanced the tolerogenic properties of APCs and up-regulated ILT-3 and B7-H1 expression.

Antigen-Presenting Cells↗
PubMed2004

Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance.

AIMS: Many congestive heart failure (CHF) patients suffer from various comorbidities, which may aggravate CHF or independently increase mortality risk. Renal failure (RF) is one of them. We defined bedside clinical, laboratory and electrocardiographic parameters characterizing CHF patients with and without concomitant RF, and analyzed their impact on mortality. METHODS: We studied symptomatic unselected consecutive furosemide-treated CHF patients hospitalized for various acute conditions. On admission, history taking, physical examination, chest x-ray, ECG and routine laboratory tests were performed. Subsequently, patients were divided into 2 subgroups, those with serum creatinine > or = 1.5 mg/dl (RF) and those with lower values. Following discharge, information concerning mortality and circumstance of death was obtained from hospital records and outpatient death certificates. RESULTS: Included were 398 patients, 163 (40.9%) with RF and 235 free of RF. Prevailing in the RF subgroup were older age (mean age 75.5 vs 70.8, p < 0.001), male gender (p < 0.001), admission pulmonary edema (p = 0.007), cardiac arrhythmias (p = 0.05), cardiac conduction disturbances (p = 0.002), severe CHF (p = 0.005), lower ejection fraction (p = 0.03), anemia (p = 0.009), higher furosemide maintenance dosages (p < 0.001), insulin treatment (p = 0.03) and receiving less ACE inhibitors (p = 0.006). On median follow-up of 43 months, mortality was 54.9% in the RF vs 31.9% in the non-RF subgroup (p < 0.001), RF being the parameter most significantly associated with low survival (OR 1.97, p < 0.001). In the RF subgroup older age (p < 0.02), female gender (p < 0.003) and not using ACE inhibitors (p = 0.04) or drugs with antiarrhythmic effects (p < 0.005), emerged significantly associated with low survival, while diabetes mellitus (DM) and admission pulmonary edema tended to be so associated (p < 0.2). Using multivariate analysis in the RF subgroup, older age, female gender and DM proved most significantly associated with poorer survival (p = 0.004, OR 1.5, p = 0.03, OR 1.72, p = 0.04, OR 1.28, respectively). In the non-RF subgroup, only older age (p = 0.005) and DM (p = 0.05) were significantly associated with low survival. Sudden death occurred in 21 patients, 14 (8.6%) in the RF and 7 (3%) in the non-RF subgroup (p < 0.001). CONCLUSIONS: RF is a marker of severity in CHF. Its full-blown deleterious prognostic effect is already manifested at serum creatinine 1.5 mg/dl. Older age, DM and female gender most significantly heralded a shorter survival. Such patients require special care.

Aged↗
PubMed2003

Isolated bone marrow non-Hodgkin's lymphoma. Report of two cases and literature review.

We report two patients with isolated bone marrow non-Hodgkin's lymphoma and we review the additional 23 cases thus far described. Bicytopenia or pancytopenia and an elevated erythrocyte sedimentation rate were universally present. Some 84% of the patients manifested fever of unknown origin (FUO), 64% constitutional symptoms, 48% hepatomegaly, and 52% splenomegaly. Of the variety of therapeutic protocols used, corticosteroids, alone or in combination, appeared to be the most effective. Survival ranged from 1 week to 4.5 years. Early diagnosis would avoid unnecessary work-up in patients with FUO and enable optimization of therapy.

Journal Article↗
PubMed2003

Serum magnesium aberrations in furosemide (frusemide) treated patients with congestive heart failure: pathophysiological correlates and prognostic evaluation.

OBJECTIVES: To determine the prevalence of hypomagnesaemia and hypermagnesaemia, to discern various factors associated with abnormal serum magnesium, and to estimate prognostic significance of serum magnesium aberrations in patients with congestive heart failure. DESIGN: Observational study. SETTING: Medical department of a university hospital (tertiary referral centre). PATIENTS: 404 consecutive patients admitted with congestive heart failure as one of the diagnoses and previously treated with furosemide (frusemide) for at least three months. MAIN OUTCOME MEASURES: Clinical, biochemical, and electrocardiographic variables were analysed with respect to serum magnesium aberrations. Following discharge, mortality rates, including sudden death, were registered. RESULTS: Hypomagnesaemia was found in 50 patients (12.3%) and 20 (4.9%) were hypermagnesaemic. Female sex (p < 0.04), diabetes mellitus (p < 0.006), hypocalcaemia (p = 0.03), hyponatraemia (p < 0.05), malignant disease (p = 0.05), and high fever (p = 0.05) were statistically associated with hypomagnesaemia. Renal failure, severe congestive heart failure, and high dose furosemide treatment (> 80 mg/day) were associated with hypermagnesaemia (p < 0.001, p = 0.05, and p < 0.03, respectively). Hypermagnesaemic patients were older and weighed less. On follow up (median duration 43 months), 169 (41.8%) died, with 22 (13%) sudden deaths. Mortality was highest with hypermagnesaemia, lowest with normomagnesaemia, and intermediate with hypomagnesaemia. After adjustment for renal failure, old age, and severity of congestive heart failure, hypomagnesaemia but not hypermagnesaemia emerged as being significantly associated with shorter survival (p = 0.009). No statistical association was found between sudden death and magnesium concentrations. CONCLUSIONS: While hypermagnesaemia seems to represent a prognostic marker only, hypomagnesaemia appears to have an adverse pathophysiological effect. The subgroup of patients at risk for hypomagnesaemia requires frequent serum magnesium determinations and magnesium replacement for as long as hypomagnesaemia persists.

Aged↗
PubMed2003

Evolution of the immunomodulatory role of the heat shock protein gp96.

In mammals, certain heat shock proteins (hsps) participate in specialized responses to stressors associated with pathogens or tumors, and as such, act as agents of immune surveillance interacting with both innate and adaptive immunity. We are investigating the conservation of this role throughout the class of vertebrates. We have shown that in Xenopus as in mammals, gp96, the major resident of the endoplasmic reticulum, generates MHC-restricted thymus-dependent immunity in vivo and CR in vitro against minor histocompatibility (H) antigens. By as yet unclear mechanisms that may involve classical MHC-unrestricted cytotoxic CD8+ T cells, gp96 also elicits peptide-specific responses against MHC-class I-negative tumors in adult frogs that may involve cytotoxic NK, MHC-unrestricted CD8+ T and NK/T cells. In naturally MHC class I-deficient but immunocompetent Xenopus larvae, gp96 also generates an innate type of anti-tumor response that is independent of chaperoned peptides. Finally, in a subset of Xenopus sIgM+ B cells, a substantial fraction of gp96 is directed to the cell surface by an active process that is upregulated by bacterial stimulation. This may allow gp96 to access the extracellular compartment without necrosis. Given the dual abilities of gp96 to chaperone antigenic peptides and to modulate innate immune responses, we propose that stimulated B cells that are up-regulating surface gp96 can directly interact with antigen presenting cells (APC) and/or T helper (Th) cells to trigger or amplify immune responses.

Adjuvants, Immunologic↗
PubMed2002

Intraspecific variability and pharmacokinetic characteristics of Androctonus mauretanicus mauretanicus scorpion venom.

We evaluated the degree of venom toxicity and protein content of several specimens of Androctonus mauretanicus mauretanicus. The quantity of protein of individual venom obtained after manual extraction from 31 different scorpions varied from a minimum of 0.15 mg to a maximum of 1.53 mg. We determined the venom toxicity, in mice, by estimating the number of LD(50)s of 20 scorpions chosen randomly among the 31 scorpions. It ranged from less than 40 LD(50)s to a maximum of 272 LD(50)s. The correlation between protein content and venom lethality is not systematic. We also determined the pharmacokinetics of the venom and its specific anti-venom in rabbits to compare their distribution and elimination properties. After a subcutaneous injection, high concentrations of venom were measured by ELISA in the vascular space rapidly after the injection (T(max) = 0.5 h). The terminal half-life was 2.8 h, close the one determined after intravenous injection (t(1/2beta) = 3.2 h). The total volume of distribution (Vd(ss) or Vd(beta)) was between 317 and 380 ml/kg. The total body clearance was 82 ml/kg/h. For scorpion anti-venom, the terminal half-life, after intravenous injection, was 20.25 h; the volume of distribution was 83 ml/kg and the total body clearance was 3 ml/kg/h. After intramuscular administration, T(max) was reached at 36 h. The results show that venom lethality varies from specimen to specimen and that pharmacokinetic parameters of venom and anti-venom are totally different. This must be taken under consideration in anti-venom production (anti-venom titre) as well as in therapeutic protocols (dose, injection route) to improve serotherapy.

Animals↗
PubMed2002

99mTc-MDP bone SPECT for the evaluation of sternal ischaemia following internal mammary artery dissection.

Coronary artery bypass grafting (CABG) is one of the most frequently performed operations in the United States. The use of internal mammary artery (IMA) grafting has been identified as increasing the risk of sternal wound infections and mediastinitis. The purpose of our study was to prospectively evaluate the effect of different techniques of left internal mammary artery (LIMA) harvesting on sternal vascularity. Thirty-three patients undergoing primary coronary artery bypass grafting were studied. The patients were divided into groups that received a skeletonized IMA (group I, n=11), a pedicled IMA (group II, n=12), or a semiskeletonized IMA (group III, n=10) graft. Each patient underwent a preoperative 99mTc-methylene diphosphonate bone scan using single photon emission computed tomography (SPECT). The ratio of the mean counts/pixel for each side of the sternum was obtained. Post-operatively, all patients had a repeat bone SPECT. Ratios of unilateral sternal uptakes were compared to the preoperative study. A univariable analysis of post-operative to pre-operative ratios revealed statistically significant reduction in vascularity to the left side of the sternum post-operatively in group II compared with groups I and III (0.68 0.12 vs 0.99 0.24 and 0.93 0.09; P<0.01). There was no difference between groups I and III (P=1). Multivariable analysis revealed only the type of harvesting to be associated with post-operative reduction in left to right sternal activity ratio (P<0.02). Pairwise comparisons revealed that differences are due to pedicled type of harvesting (group II vs group I, P=0.03; II vs III, P=0.001; and I vs III, P=0.115). A pedicled IMA graft causes acute post-operative sternal ischaemia. This does not occur when the IMA is skeletonized or semiskeletonized. Hence, it may be prudent to minimize dissection during mobilization of the IMA to decrease the likelihood of post-operative sternal complications.

Aged↗
PubMed2001

MHC-restricted and -unrestricted CD8 T cells: an evolutionary perspective.

BACKGROUND: In mammals, cytotoxic CD8 T cells are crucial effectors of a typical adaptive cellular immune response. They recognize and kill cells that express at their surface antigenic peptides complexed to major histocompatibility complex (MHC) class I molecules. Although T cells (undefined as to CD determinants) and associated in vitro cytotoxic activity have been described in a few amphibian and teleost species, their in vivo functions have yet to be characterized. METHODS AND RESULTS: CD8 function has been investigated in the frog Xenopus by antibody depletion, skin allografting, and tumor transplantation. Injection of adult frogs with anti-Xenopus CD8 monoclonal antibody effects transient CD8 T-cell depletion in vivo that correlates with delayed rejection of MHC-disparate skin allografts and an impaired immune response against transplanted syngeneic MHC class I-negative tumors. CONCLUSIONS: For the first time, CD8 T cells have been shown to be involved in acute skin allograft rejection in an ectothermic vertebrate. Our data also suggest that, at least in Xenopus, T cells that express a CD8 epitope may be effectors in MHC-unrestricted anti-tumor responses.

Animals↗