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Biomedical subjects

H Bernard

Publications and source records attributed to H Bernard.

At least 19 recordsLinked to original sources

Close amino acid sequence relationship between the new plasmid-mediated extended-spectrum beta-lactamase MEN-1 and chromosomally encoded enzymes of Klebsiella oxytoca.

Isolated from an Escherichia coli strain MEN-1 is a plasmid-mediated beta-lactamase that confers resistance to methoxy imino third-generation cephalosporins. The protein purified to homogeneity was digested by trypsin, chymotrypsin and endoproteinase Asp-N. Amino acid sequence determinations of the resulting peptides gave rise to the alignment of the 263 residues of the beta-lactamase. From amino acid sequence comparison MEN-1 was found to share more than 72% identity with the chromosomally mediated beta-lactamases of Klebsiella oxytoca. Therefore, MEN-1 is the first transferable extended-spectrum beta-lactamase which is not directly derived from the widespread TEMs or SHV-1 penicillinases with which it presents less than 39% identity.

Amino Acid Sequence

Thieno[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2-dihydrogenated homologues: synthesis, enhanced in vitro antiaggregant activity for reduced compounds.

Some derivatives of thieno[2,3-d]pyrimidin-4(3 H)-one A and their 1,2-dihydrogenated homologues B were synthesized. The study of their in vitro antiaggregating activity showed that the first compounds exhibited significant inhibiting power when aggregation was induced with ADP. Their reduction to derivatives of 1,2-dihydrothieno[2,3-d]pyrimidin-4(3 H)-one led to a new series of molecules possessing a large antiaggregant activity. When compared to that of acetylsalicylic acid under the same conditions, this activity was the same with collagen or arachidonic acid-induced aggregation, but greater when aggregation was induced by ADP. Serotonin release was also inhibited.

Adenosine Diphosphate

Synthesis and in vitro study of platelet antiaggregant activity of some 4-quinazolinone derivatives.

Some new 4-quinazolinones were prepared. Their antiplatelet activity was evaluated in vitro with respect to aggregation induced by ADP, collagen, arachidonic acid and the platelet serotonin release reaction. Most molecules showed an inhibiting power similar to that of acetylsalicylic acid under the same conditions, and even greater when aggregation was induced by ADP. Reduction of the 4-quinazolinone derivatives to their 1,2,3,4-tetrahydroquinazoline homologues produced an increase in platelet inhibitory action except when ADP is the inductor.

Blood Platelets

Action of some salicylate derivatives on in vitro platelet aggregation. Inhibitory and inhibition antagonistic effects.

Twenty salicylate derivatives were tested for their antagonistic activity on the inhibitory effect of aspirin on platelet aggregation. The blocking effect was not limited to the salicylate but also characterised some of its substituted compounds. The substituant influence did not seem to be related to electronic or size parameters. This antagonistic activity of these derivatives decreased as concentrations increased, owing to the emergence of their own inhibitory activity: several salicylate derivatives showed dual inhibitory and inhibition antagonistic activity, with both properties present at the same concentration. A mechanism involving dissociated activities on the two enzymatic sites of cyclooxygenase is proposed.

Arachidonic Acid

Coronary artery bypass surgery: the relationship between inhospital mortality rate and surgical volume after controlling for clinical risk factors.

This study uses a new database containing clinical risk factors for cardiac surgery to investigate the relationship between surgical volume (hospital and surgeon) and inhospital mortality rate for all patients receiving coronary artery bypass surgery in New York State in 1989. Also, hospitals with significantly higher and lower mortality rates than expected on the basis of patient preoperative risk factors are identified. The results demonstrate that both annual surgeon volume and annual hospital volume are significantly (inversely) related to mortality rate. The 36% of all coronary bypass operations performed in hospitals with annual bypass volumes of 700 or more by surgeons with annual bypass volumes of 180 or more had a risk-adjusted mortality rate of 2.67% in comparison to a risk-adjusted mortality rate of 4.29% for other bypass operations. Furthermore, low surgical volumes were a major contributor to the outlier status of four of the five hospitals with significantly higher mortality rates than expected.

Adult

In vitro antiaggregant activity of paracetamol and derivatives.

The in vitro antiaggregating action of paracetamol and ten of its derivatives was studied by observing their action on collagen, adenosine-5 diphosphate (ADP) and arachidonic acid-induced platelet aggregation. It is established that in vitro activity appears not only with paracetamol but also with its positional isomers and its isosteric derivatives; this involves the replacement of oxygen by sulfur and that of the NH group of oxygen. Paracetamol and its derivatives also have an inhibiting effect on the serotonin release and the thromboxane synthesis of collagen-stimulated platelets.

Acetaminophen

Relationship between structure and activity of aspirin-related compounds on the inhibition of in vitro platelet aggregation.

Thirteen aspirin-related compounds were tested for inhibitory activity on platelet aggregation in human platelet rich plasma (PRP) induced with ADP, collagen and arachidonic acid. The following structure-activity relationships were found: none of the functional groups used to replace the acetyl group retained the significant antiaggregant activity of aspirin; anti-aggregant activity was enhanced when the carboxylic group was replaced with a hydroxyl or an acetylated hydroxyl group. The activity of these mono and diacetylated pyrocatechol derivatives was unaffected by incubation of PRP with sodium salicylate.

Adenosine Diphosphate

Acetoxy benzene derivatives: in vitro antiaggregant activity.

A dozen acetoxy benzene derivatives (mono- or diacetylated diphenols) were tested for inhibitory activity on platelet aggregation in human platelet rich plasma induced with collagen, ADP and arachidonic acid. All the compounds tested showed an activity, and the results emphasize the antiaggregant properties of diacetylated derivatives which are more potent than aspirin. Unlike aspirin, their action is not prevented by salicylate. However, the large inhibition of serotonin release and thromboxane synthesis localizes their activity in arachidonic acid metabolism.

Benzene Derivatives

[Frequencies of HLA-A, C and Bf antigens in schizophrenic patients originated from Alsace (author's transl)].

A comparison of the frequency of HLA-A, B, C and Bf antigens observed in a group of 75 chronic schizophrenics and in a control group of 184, all strictly from Alsace, does not carry any argument in favour of a strong genetic association between schizophrenia and the antigens studied. In effect, the modifications observed in the schizophrenic sample--decrease in the frequency of A10 and B5 antigens, and increase of A29 and BfF--are not statistically significant when the probabilities are multiplied by the number of tested antigens. These preliminary results however do not permit to exclude the possibility of an association between schizophrenia and the tested antigens.

Adolescent

Enuresis, firesetting, and cruelty to animals: the significance of two thirds of this triad.

The full childhood triad of enuresis, firesetting, and cruelty to animals is seldom reported by patients in acute care psychiatric facilities. Two of the three elements have been reported with greater frequency and constitute useful diagnostic information. Literature on the triad has been reviewed and data from three studies have been presented. The authors concluded that a history of two thirds of the triad is significantly associated with aggressive behaviours directed against people.

Adolescent

Cryoprecipitate reversal of opsonic alpha2-surface binding glycoprotein deficiency in septic surgical and trauma patients.

Human opsonic alpha2-surface binding glyoprotein (alphs2SB-glycoprotein), a molecule having immunologic identity with an amino acid composition similar to cold-insoluble globulin, is concentrated in a cryoprecipitate of plasma. Septic surgical and trauma patients manifesting opsonic alpha2SB-glycoprotein deficiency and associated reticuloendothelial system dysfunction were treated by intravenous infusion of cryoprecipitate. This therapy restored circulating bioreactive and immunoreactive opsonin and improved their septicemia, pulmonary insufficiency, and duration of recovery. Cryoprecipitate infusion may offer a new approach to the treatment of septic injured patients in preventing multiple organ failure; measurement of immuno-reactive serum opsonic alpha2SB-glycoprotein may provide a noninvasive index of reticuloendothelial system function and patient status during servere sepsis that follows trauma.

Cryoglobulins

Opsonic alpha2 surface binding glycoprotein therapy during sepsis.

A pronounced depletion of an opsonic protein for hepatic reticuloendothelial (RE) phagocytosis has been demonstrated in critically ill trauma patients. This opsonic alpha(2) surface binding (SB) glycoprotein has immunologic identity and a similar amino acid composition to cold insoluble globulin (CIg). Since CIg can be concentrated in cryoprecipitate, it was utilized as a readily available source of opsonic alpha(2)SB glycoprotein for replacement therapy after injury with documented hypoopsonemia. Six septic patients (2 multiple trauma, 2 thermal burn, and 2 intra-abdominal abscess) were studied to test whether cryoprecipitate infusion would restore this humoral component. Pre- and posttherapy opsonin levels were determined by bioassay and electroimmunoassay. In all patients, severe opsonin depletion was reversed following cryoprecipitate infusion. All patients had a rapid improvement in febrile state, normalization of leukocyte levels, and improvement in pulmonary function as evidenced by decreasing requirements for end expiratory pressure at lowered levels of inspired oxygen. One patient was studied more extensively and demonstrated an increase in cardiac output, limb blood flow, total body and limb oxygen delivery, total body and limb oxygen consumption and a progressive decrease in pulmonary shunt fraction. Thus, opsonic alpha(2)SB glycoprotein deficiency can be reversed by cryoprecipitate infusion in critically ill septic injured patients. Replacement of this humoral factor may be an important therapeutic modality in prevention of multiple organ failure, but it should be administered only after documentation of hypoopsonemia in traumatized patients.

Adult

Reticuloendothelial phagocytic response to bacterial challenge after traumatic shock.

Resistance to intravenous (IV) and intraperitoneal (IP) bacterial challenge during periods of reticuloendothelial (RE) depression following trauma as well as the influence of bacteremia on RE phagocytosis were studied. The experimental shock model utilized was the anesthetized (2 mg/100 g sodium pentobarbital) male rat subjected to nonlethal Noble-Collip drum trauma. During post-traumatic RE depression (60 min after injury) rats were challenged IV or IP with Escherichia coli (1.02 X 10(10)). The clearance half-time of the bacterial load injected intravenously in controls was 1.23 +/- 0.10 min. In contrast, the half-time was 3.62 +/- 0.69 min after sublethal trauma (p less than 0.005) and associated with prolonged blood bacterial retention. Pulmonary localization of E. coli administered either IV or IP was elevated in traumatized rats. Comparison of routes of bacterial challenge with respect to blood levels of viable bacteria suggested lower host bacterial resistance to the IP injection as opposed to the IV route of administration. Production of experimental bacteremia in normal rats resulted in a 39% depression (p less than 0.01) of RE test colloid clearance rate accompanied by a 49% increase (p less than 0.01) in pulmonary colloid localization. The data suggest that depressed systemic RE clearance capacity following trauma may decrease systemic resistance to septicemia, and that severe bacteremia may further undermine the functional state of the reticuloendothelial system.

Animals