Biomedical subjects

J D Conley

Publications and source records attributed to J D Conley.

8 recordsLinked to original sources

PubMed2001

A comparison of the effects of sarin and succinylcholine on respiratory parameters in anesthetized domestic swine.

Differences in the "respiratory paralysis" caused by sarin (GB) and succinylcholine (SDC) were observed in a domestic swine model using a bedside pulmonary dynamics monitor. GB was administered intravenously (9 micrograms/kg/30 min) and compared with SDC administered intravenously (20 mg/30 min). All animals developed respiratory insufficiency indicated by decreased respiratory frequency. Minute ventilation was relatively maintained in animals that received GB by increasing tidal volume, whereas both of these parameters decreased in animals that received SDC. GB animals showed an increase in airway resistance and work of breathing. The former was unchanged and the latter was decreased in animals that received SDC. Mouth occlusion pressure at 100 milliseconds and tidal volume were relatively maintained in GB animals but decreased in SDC animals, suggesting a central mechanism for respiratory paralysis with GB and a peripheral mechanism for respiratory paralysis with SDC.

Acetylcholinesterase↗

PubMed2001

Volatile anesthetics give a false-positive reading in chemical agent monitors in the "H" mode.

Chemical agent monitors (CAMs) are routinely used by the armed forces and emergency response teams of many countries for the detection of the vesicant sulfur mustard (HD) and the G series of organophosphate nerve agents. Ambient operating room isoflurane levels were found to produce strong positive signals in the "H" mode when the CAM was used to monitor the efficacy of decontamination procedures during routine surgical procedures on HD-poisoned animals requiring up to 8 hours of general anesthesia. Subsequent testing showed that isoflurane, as well as desflurane, sevoflurane, halothane and methoxyflurane, produce two ionization peaks in the CAM response. One of these peaks is interpreted by the CAM processing software as HD, resulting in a CAM "H" mode bar response. No interference was encountered with isoflurane, desflurane, and sevoflurane when the CAM was set to the "G" mode, although extremely high (nonclinical) concentrations of halothane and methoxyflurane yielded a weakly positive bar response. These findings have potentially serious ramifications for the medical management of patients resulting from terrorist, military, or chemical agent decommissioning activity when concomitant chemical injuries are also possible.

Anesthetics↗

PubMed2000

Construction and characterization of monoclonal antibodies against western equine encephalitis virus.

A repertoire of mouse monoclonal antibodies (MAbs) against western equine encephalitis virus (WEE) was constructed and characterized. Anti-WEE antibodies were expressed from hybridomas and purified by protein G chromatography. Each of the antibodies was functionally assessed by indirect enzyme-linked immunosorbent assays (ELISAs), Western blotting, and immunoprecipitations. All antibodies bound to WEE antigen in ELISAs, whereas only a subgroup of antibodies was found to be active in Western blotting and immunoprecipitations. A subset of antibodies was found to cross-react with other alphaviruses, such as Sindbis virus (SIN), Venezuelan equine encephalitis (VEE), and eastern equine encephalitis (EEE). Because many of the antibodies were highly reactive to WEE antigen in one or more of the assays, these antibodies are excellent candidates for immunodetection and immunotherapy studies.

Animals↗

PubMed1990

Preparation and anticonvulsant activity of a series of functionalized alpha-aromatic and alpha-heteroaromatic amino acids.

We recently reported the potent anticonvulsant activity of (R,S)-alpha-acetamido-N-benzyl-alpha-phenylacetamide (2b). Selectively substituted derivatives of this compound have now been prepared (23 examples) and evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. In several key cases, replacement of the alpha-phenyl substituent in 2b by a relatively small, electron-rich, heteroaromatic moiety led to a substantial improvement in the anticonvulsant potency of the drug candidate. The most active compounds were (R,S)-alpha-acetamido-N-benzyl-2-furanacetamide (2g) and (R,S)-alpha-acetamido-N-benzyl-2-pyrroleacetamide (2i). After ip administration, the MES ED50 values for 2g (10.3 mg/kg) and 2i (16.1 mg/kg) compared well with phenytoin (9.50 mg/kg). Evaluation of the two individual enantiomers of 2g demonstrated that the anticonvulsant activity resided in the R stereoisomer. The low ED50 value (3.3 mg/kg) for (R)-2g contributed to the large protective index (TD50/ED50) observed for this drug candidate, which approached that of phenytoin.

Amino Acids↗

PubMed1988

L-aspartase from Escherichia coli: substrate specificity and role of divalent metal ions.

The enzyme L-aspartase from Escherichia coli has an absolute specificity for its amino acid substrate. An examination of a wide range of structural analogues of L-aspartic acid did not uncover any alternate substrates for this enzyme. A large number of competitive inhibitors of the enzyme have been characterized, with inhibition constants ranging over 2 orders of magnitude. A divalent metal ion is required for enzyme activity above pH 7, and this requirement is met by many transition and alkali earth metals. The binding stoichiometry has been established to be one metal ion bound per subunit. Paramagnetic relaxation studies have shown that the divalent metal ion binds at the recently discovered activator site on L-aspartase and not at the enzyme active site. Enzyme activators are bound within 5 A of the enzyme-bound divalent metal ion. The activator site is remote from the active site of the enzyme, since the relaxation of inhibitors that bind at the active site is not affected by paramagnetic metal ions bound at the activator site.

Ammonia-Lyases↗

PubMed1988

Marked stereospecificity in a new class of anticonvulsants.

N-Acetyl-D,L-alanine-N-benzylamide and N-acetyl-D,L-phenylglycine-N-benzylamide are two novel anticonvulsants that selectively blocked maximal electric shock-induced tonic extensor seizures in mice. For both compounds, the anticonvulsant activity is due to the D-stereoisomer, and the L-stereoisomer is virtually inactive as an anticonvulsant. The marked stereoselectivity of these anticonvulsants may make them very useful pharmacological tools for the study of the mechanism(s) of anticonvulsants that selectively inhibit maximal electric shock-induced seizures.

Animals↗

PubMed1987

Functionalized DL-amino acid derivatives. Potent new agents for the treatment of epilepsy.

Structural analogues of the potent known anticonvulsant agent N-acetyl-DL-alanine N-benzylamide (1a) have been prepared (16 examples). The pharmacological activities of these products were evaluated in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole seizure threshold (sc Met), and the rotorod (Tox) tests. The median effective doses (ED50) and the median toxic doses (TD50) for the most active compounds by both intraperitoneal and oral administration are reported. The most active compounds were N-acetyl-DL-phenylglycine N-benzylamide (1d) and N-acetyl-DL-alanine N-m-fluorobenzylamide (1m) along with the parent compound 1a. The ED50 values in the MES test for these three compounds compared well with phenobarbital, while their high TD50 values contributed to their large protective indexes, which approached that of phenytoin. When tested against four convulsant agents, compounds 1a and 1d displayed activity profiles significantly different from those reported for conventionally used antiepileptic drugs.

Amino Acids↗

PubMedDate not supplied

Method for respiratory sound analysis.

A system is described for the analysis of respiratory sounds by means of a dual-channel sound envelope detector and a real-time spectrum analyzer. A three-dimensional spectral analyzer display for frequency, amplitude, and time has been utilized. Respiratory sounds have been observed with intensities up to 0.5 N/m2 and with normal frequencies in the range of 0 to 1.5 kHz. This system can extract useful information from the sounds of respiration, information which is not available by conventional auscultation.

Auscultation↗