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Biomedical subjects

S David

Publications and source records attributed to S David.

At least 19 recordsLinked to original sources
PubMed2001

Synergic activity of D-cycloserine and beta-chloro-D-alanine against Mycobacterium tuberculosis.

D-Cycloserine (DCS) is a peptidoglycan inhibitor. Although very effective against Mycobacterium tuberculosis, it is seldom employed in the management of this infection due to its high toxicity. beta-Chloro-D-alanine (another peptidoglycan inhibitor) reduces the MIC of DCS from 50 to 2.5 mg/L at a concentration significantly below its MIC for this organism. A reduction in bacterial viability and significant growth inhibition (as quantified by the X/Y quotient for the Bactec radiometric procedure) were observed with subinhibitory concentrations of both drugs. It is suggested that this powerful synergic effect should be the object of in vivo and eventually clinical trials.

Cycloserine↗
PubMed2000

Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens.

In the present study, protection against Bordetella pertussis infection and humoral immunological responses in mice has been assessed upon immunization with custom-made acellular pertussis vaccines (ACVs) and whole-cell pertussis vaccine (WCV). Mice were immunized, next intranasally infected with B. pertussis and during 14 days the number of bacteria in the trachea and lungs and the level of serum antibodies were determined. ACV contained five immunogens, filamentous hemagglutinin, pertactin, fimbriae serotypes 2 and 3, and chemically detoxified pertussis toxin (PMC-5), or three immunogens, filamentous hemagglutinin, pertactin, and genetically detoxified (BC-3) or chemically detoxified pertussis toxin (SKB-3). Immunization with a high or low dose of ACV or WCV resulted in significant protection against B. pertussis, with differences in the degree of protection between the vaccines. The lowest protection was found with a low dose of SKB-3 and WCV. The pattern of cytokine production by spleen cells of immunized, non-infected, mice indicated that T-helper 1 cells are activated by vaccination with WCV, and T-helper 1 and T-helper 2 cells are involved in the immune response upon vaccination with ACVs. Each vaccine stimulated the production of IgG, but not IgA, antibodies. In mice immunized with ACV, elimination of B. pertussis from trachea and lungs correlated significantly with the titre of IgG1, but not IgG2a, antibodies.

Animals↗
PubMed2000

The intermolecular migration of polyol stannylenes as a reaction contributing to the regioselectivity of substitution.

Pairs of the partially protected glycosides benzyl 4,6-O-benzylidene-beta-D-galactopyranoside, benzyl 2,3-di-O-benzyl-beta-D-galactopyranoside, benzyl 2,6-di-O-benzyl-alpha-D-galactopyranoside, and benzyl 2,3-di-O-benzyl-alpha-D-glucopyranoside were treated with equimolar proportions of Bu2SnO in benzene in the conditions of stannylene formation, and the resulting mixture was benzoylated in situ with benzoyl chloride. Estimation of the product of benzoylation led to the following order of reactivity in the stannylenation reaction: 2,3-diol > 4,6-diol, and 2,3-diol > 3,4-diol. An intermolecular migration of dibutyltin between sugars was demonstrated. It is considered that these migrations contribute efficiently to the regiospecificity of the stannylene reaction.

Benzoates↗
PubMed2000

Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain.

Ceruloplasmin is a copper-containing ferroxidase that is essential for normal iron homeostasis. Whereas ceruloplasmin in plasma is produced and secreted by hepatocytes, in the brain a glycosylphosphatidylinositol (GPI)-anchored form of ceruloplasmin is expressed on the surface of astrocytes. By using a cDNA cloning approach, we have now determined that the GPI-anchored form of ceruloplasmin is generated by alternative RNA splicing. The splicing occurs downstream of exon 18 and replaces the C-terminal 5 amino acids of the secreted form with an alternative 30 amino acids that signal GPI anchor addition. RNase protection analysis demonstrates that the GPI-anchored form is the major form in the brain, whereas the secreted form predominates in the liver. Individuals with aceruloplasminemia, a hereditary deficiency of ceruloplasmin, have severe iron deposition in a number of organs, including the brain where it results in neurodegeneration. Therefore, this novel GPI-anchored form of ceruloplasmin is likely to play an important role in iron metabolism in the central nervous system.

Alternative Splicing↗
PubMed2000

Impaired culprit vessel flow in acute coronary syndromes ineligible for thrombolysis.

The majority of patients with acute myocardial infarction and other acute coronary syndromes (ACS) are considered ineligible for thrombolysis and do not routinely receive reperfusion therapy. We hypothesized that predictors and outcomes of angiographically impaired culprit vessel flow can be identified and compared. This trial evaluated the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with<24 hours of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy. This analysis was performed in 165 patients, from experimental and control arms, in whom angiography was performed on the index hospitalization with the outcome of interest being target vessel flow (Thrombolysis In Myocardial Infarction [TIMI] grades 0 to 2) on initial angiography. Patients with and without impaired culprit lesion flow were similar with respect to age, gender, diabetes, and prior coronary disease. A family history of premature coronary disease was more common in those with impaired flow, 50.0 versus 28.5% (p=0.02). Abnormal culprit vessel flow was found in 19.2% of patients who underwent angiography within 6 hours of symptom onset; however, after 24 hours this rate was reduced to 11.7%. Impaired culprit lesion flow can be expected in approximately 20% of patients presenting with ACS who are ineligible for reperfusion therapy by conventional guidelines and therefore represents an opportunity for early intervention within 6 hours of the onset of symptoms in these patients.

Actuarial Analysis↗
PubMed2000

Proteolysis of microtubule associated protein 2 and sensitivity of pancreatic tumours to docetaxel.

We have studied the state of microtubule associated protein 2 (MAP2) in the pancreatic ductal adenocarcinomas P03 and P02 (sensitive and refractory to docetaxel respectively) since they express the corresponding mRNA and MAP2-related peptides. Immunohistochemical localization showed that in tumour P03 the MAP2-related peptides are highly expressed and confined to the epithelial malignant cells while in P02 the Intensity of the immunostaining is lower. However, anti alpha-tubulin staining followed a similar pattern suggesting that the net amount of macromolecular structures in the sensitive tumour is higher than in the refractory one. This may explain its higher sensitivity to docetaxel, because tubulin assembled into microtubules is the target of the drug. We found that protein extracts from both tumours differed in their proteolytic activity on rat brain MAP2. Since the proteolysis pattern obtained was similar to the one produced by Cathepsin D, we studied the effect of MAP2 proteolysed by this enzyme on microtubule formation in vitro. Proteolysis was found to increase the tendency of tubulin to assemble into macromolecular structures (microtubules and aggregates) in the presence of docetaxel. This suggests that in vivo proteolysis of MAP2 might increase microtubule alterations and potentiate the antitumour effect of docetaxel.

Amino Acid Sequence↗
PubMed2000

Towards the charge-density study of proteins: a room-temperature scorpion-toxin structure at 0.96 A resolution as a first test case.

The number of protein structures refined at a resolution higher than 1.0 A is continuously increasing. Subatomic structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 A) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The structure of the scorpion Androctonus australis Hector toxin II has been refined at 0.96 A resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.

Crystallography, X-Ray↗
PubMed2000

In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors.

The susceptibilities of 43 pharyngeal isolates of Capnocytophaga to beta-lactam antibiotics, alone or in combination with beta-lactamase inhibitors, were tested by an agar dilution method. The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against Capnocytophaga, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection.

Anti-Bacterial Agents↗
PubMed2000

Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord.

Lysophosphatidylcholine (LPC) can induce rapid breakdown and removal of myelin from the adult mammalian CNS. In this paper we report the detailed characterization of the immune cell response as well as changes in the expression of cell adhesion molecules and the permeability of the blood-brain barrier after microinjection of LPC into the adult mouse spinal cord. T cells and neutrophils were seen in the spinal cord 6-12 h after LPC injection, but not in PBS-injected mice. Mac-1+ monocytes were also seen at 6 h and 12 h in the white and gray matter of mice injected with LPC and PBS but were significantly greater in the white matter after LPC injections. At later time points LPC induced an increase in the number of activated Mac-1+ macrophages that displayed a variety of morphologies in the white and gray matter. These cells were not present in PBS-injected control mice. LPC also induced widespread microglial activation in the white and gray matter. The number of these Mac-1+ microglia reduced drastically at 96 h after LPC injection suggesting that they may have transformed into Mac-1+ phagocytic cells with a different morphology. These LPC-induced changes in immune cells were accompanied by significant increases in VCAM-1+ and ICAM-1+ blood vessels in the spinal cord. In addition, LPC induced a rapid and widespread disruption of the blood-brain barrier, as compared to PBS injected mice. Therefore, LPC can induce an early and transient T cell and neutrophil response in the CNS. These cells likely promote the rapid influx of monocytes followed by widespread and effective activation of macrophages that mediate rapid phagocytosis of myelin debris.

Animals↗
PubMed2000

[Who delivers where? Who is born where? Analysis of the 1997-1998 AUDIPOG Sentinel Network].

OBJECTIVE: The purpose of this study was to describe the care level, legal status and size of the maternity units where deliveries take place in France according to risk level for mother and infant. We analyzed the 1997-1998 data to better implement the network's perinatal policy. MATERIAL: and methods. Our standardized sample included 4200 single births in 1997 and 3650 in 1998 collected by the French Sentinel Network after applying a sample rectification technique to offset the methodological problems created by the volunteer nature of the sample population. Distribution of care level, legal status and size of the maternity unit where deliveries took place were recorded according to the risk level of the patients. RESULTS: In 1997-1998, 22% of pregnant women delivered in level III maternity units and 33% in level II units. Twenty percent of the deliveries took place in level II maternity units with less than 1500 deliveries per year. During this period, women with diabetes or hypertension delivered more often in level III units (31% and 27% respectively) than women in the general population. This was not true for women with a previous perinatal death (23%). Inversely, births of infants before 33 weeks gestation or weighing less than 1500 g occurred more often in level III maternity units (55% and 59% respectively) than in the general population. Twenty-seven percent of the infants requiring neonatal transportation were born in level I maternity units. For 'low risk' mothers, delivery occurred more often in level I maternity units (more than 50%) or in small maternity units with less than 1000 deliveries per year (45%) than for the general population (45% and 36% respectively). CONCLUSION: These data obtained from the Sentinel Network provide precise information on where deliveries occur in France. These data will be useful for implementing the network's perinatal policy. They will also provide a means of following referral practices in the future.

Birth Rate↗
PubMed2000

Profile of hospital admissions following acute poisoning--experiences from a major teaching hospital in south India.

This study was conducted to determine the incidence of hospital admissions following acute poisoning, nature of agents involved and change in pattern of poisoning over a 5-year period. Data from hospital records of all admissions to emergency department following acute poisoning collected prospectively were analysed for the period January 1993 to January 1998. A steady increase in deliberate poisoning using pesticides, particularly among young adults, was noted. Kerosene (paraffin) was the commonest poison in children and plant poisons were also common. There were 52 deaths (3.3%) among the 1584 admissions. The majority of deaths were due to pesticides. Poisoning and mortality followed ingestion of readily-available and commonly used agents. Measures to increase public education, counselling and awareness could prevent a number of these admissions.

Adolescent↗
PubMed1999

Interleukin-12 is synthesized by mesangial cells and stimulates platelet-activating factor synthesis, cytoskeletal reorganization, and cell shape change.

Preliminary studies indicate the involvement of interleukin (IL)-12 in experimental renal pathology. In the present study, we evaluated whether cultured glomerular mesangial cells are able to produce IL-12 and whether IL-12 may regulate some of their functions, including the cytoskeletal reorganization, the change in cell shape, and the production of platelet-activating factor (PAF). The results obtained indicate that pro-inflammatory stimuli, such as tumor necrosis factor-alpha and bacterial polysaccharides, induce the expression of IL-12 mRNA and the synthesis of the protein by cultured mesangial cells. Moreover, cultured mesangial cells were shown to bind IL-12 and to express the human low-affinity IL-12 beta1-chain receptor. When challenged with IL-12, mesangial cells produced PAF in a dose- and time-dependent manner and superoxide anions. No production of tumor necrosis factor-alpha and IL-8 was observed. Moreover, we demonstrate that IL-12 induced a delayed and sustained shape change of mesangial cells that reached its maximum between 90 and 120 minutes of incubation. The changes in cell shape occurred concomitantly with cytoskeletal rearrangements and may be consistent with cell contraction. As IL-12-dependent shape change of mesangial cells was concomitant with the synthesis of PAF, which is known to promote mesangial cell contraction, we investigated the role of PAF using two chemically different PAF receptor antagonists. Both antagonists inhibited almost completely the cell shape change induced by IL-12, whereas they were ineffective on angiotensin-II-induced cell shape change. In conclusion, our results suggest that mesangial cells can either produce IL-12 or be stimulated by this cytokine to synthesize PAF and to undergo shape changes compatible with cell contraction.

Angiotensin II↗
PubMed1999

A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord.

Axon growth inhibitors associated with myelin play an important role in the failure of axon regeneration in the adult mammalian central nervous system (CNS). Several inhibitors are present in the mature CNS. We now present a novel therapeutic vaccine approach in which the animals' own immune system is stimulated to produce polyclonal antibodies that block myelin-associated inhibitors without producing any detrimental cellular inflammatory responses. Adult mice immunized in this manner showed extensive regeneration of large numbers of axons of the corticospinal tracts after dorsal hemisection of the spinal cord. The anatomical regeneration led to recovery of certain hind limb motor functions. Furthermore, antisera from immunized mice were able to block myelin-derived inhibitors and promote neurite growth on myelin in vitro.

Animals↗
PubMed1999

No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study.

Schizophrenia is clinically and neuropsychologically characterized by severe cognitive and functional impairment suggesting the presence of a neurodegenerative process in the brains of affected individuals. A variety of neuroanatomical changes have been described such as loss and disorientation of neurons in grey and white matter and cortical atrophy. However, the neuropathological basis for schizophrenia is still unclear. In the present study we monitored the density of GFAP-positive astrocytes in brains of 33 schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal cortex and subiculum) and white matter (premotor cortex, subventricular zone of the third ventricle and next to inferior horn) structures were measured bilaterally. The overall finding was that there is no evidence for increased astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore, degeneration is unlikely to be the main neuropathological mechanism in schizophrenic brains.

Astrocytes↗
PubMed1999

Occlusal outcome in patients undergoing orthognathic surgery with internal fixation.

Fifty consecutive patients undergoing orthognathic surgery with internal fixation (IF) were studied retrospectively with a weighted Peer Assessment Rating (PAR) Index to assess occlusal outcome at the end of all active treatment, and compared with 50 patients who had undergone treatment for malocclusion by orthodontic means alone. In the surgically treated patients, the mean percentage reduction in the weighted PAR Index was 83% and 31 out of 38 patients (82%) were 'greatly improved'. This implies a high standard of treatment in terms of the occlusal outcome. There was no difference in the proportion of patients having a final weighted PAR Index of less than 10 and no significant difference in the final weighted PAR Index between the two groups. This suggests that the occlusal outcome is no different whether patients undergo orthognathic surgery or orthodontic treatment alone, and that excellent occlusal results can be achieved in patients undergoing orthognathic surgery with internal fixation.

Humans↗
PubMed1999

An overview of haemodialysis and oxidant stress.

Today's patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented.

Cardiovascular Diseases↗