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Biomedical subjects

R Hare

Publications and source records attributed to R Hare.

36 records · Page 2Linked to original sources
PubMed2000

Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection.

The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-gamma)-mediated resolution of replicative Legionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-gamma mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior to L. pneumophila infection inhibited induction of intrapulmonary IFN-gamma production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-gamma and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.

Animals↗
PubMed1997

A brain imaging (single photon emission computerized tomography) study of semantic and affective processing in psychopaths.

Psychopaths have been described as human predators who use charm, intimidation, and violence to control others and to satisfy their own needs. Underlying their propensity to violate social norms and expectations is a profound lack of empathy, guilt, or remorse, affective processes that have long resisted scientific investigation. Using brain imaging technology we found that psychopaths differed from nonpsychopaths in the pattern of relative cerebral blood flow during processing of emotional words. The results were consistent with the hypothesis that there are anomalies in the way psychopaths process semantic and affective information.

Adult↗
PubMed1996

DSM-IV antisocial personality disorder field trial.

The development of the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) included 12 field trials to assess proposed revisions. This article provides results from the antisocial personality disorder (APD) field trial that was conducted to obtain data of relevance to the proposals for simplification and for the inclusion of more traditional traits of psychopathy. Provided herein are the results from 4 sites that had sampled from populations of particular relevance to the diagnosis of APD (i.e., prison inmates, psychiatric inpatients, outpatients with substance use disorders, and homeless persons). The results indicated that some items from the 3rd revised Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987) could be deleted without affecting the diagnosis. The field trial provided mixed support for the proposal to include more traditional traits of psychopathy.

Adolescent↗
PubMed1996

Characterization of IMI-1 beta-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae.

In 1984, a year prior to the U.S. approval of imipenem for clinical use, a wound isolate and a bile isolate of Enterobacter cloacae were obtained from two patients in a California hospital. These isolates were resistant to imipenem, penicillins, and inhibitor combinations; early cephalosporins such as cephalothin, cefamandole, and cefoxitin; and cefoperazone. However, they were susceptible (MICs, < 4 micrograms/ml) to cefotaxime, ceftriaxone, ceftazidime, and moxalactam. Both strains produced an apparent TEM-1 beta-lactamase; an inducible NmcA-type imipenem-hydrolyzing beta-lactamase, IMI-1, with a pl of 7.05; and an inducible beta-lactamase with a pI of 8.1, typical of an E. cloacae AmpC beta-lactamase. Purified IMI-1 hydrolyzed imipenem and benzylpenicillin at modest rates, but more slowly than cephaloridine. The enzyme was inhibited by clavulanic acid and tazobactam. EDTA did not inhibit the cephaloridine-hydrolyzing activity. The beta-lactamase gene encoding IMI-1, imiA1, was cloned from E. cloacae 1413B. Sequence analysis identified the imiA1 gene as encoding a class A serine beta-lactamase. Both the imiA1 DNA and encoded amino acid sequences shared greater than 95% identity with the NmcA gene and its encoded protein. DNA sequence analysis also identified a gene upstream of imiA1 that shares > 95% identity with nmcR and that may encode a regulatory protein. In conclusion, IMI-1, a carbapenem-hydrolyzing beta-lactamase inhibited by clavulanic acid, was identified as a group 2f, class A, carbapenem-hydrolyzing cephalosporinase.

Amino Acid Sequence↗
PubMed1993

Characterization and transcriptional regulation of the 2'-N-acetyltransferase gene from Providencia stuartii.

We have cloned the chromosomally encoded 2'-N-acetyltransferase gene [aac(2')-Ia] from Providencia stuartii. DNA sequence analysis of the cloned insert identified a single open reading frame, which is capable of encoding a protein with a predicted molecular mass of 20,073 Da. The deduced AAC(2')-Ia protein showed no significant homology to other proteins, including all of the AAC(3) and AAC(6') proteins. Primer extension analysis was used to identify the aac(2')-Ia promoter, which contained an unusual sequence (CTTTTT) at the -35 region. Expression of the aac(2')-Ia gene occurs at low levels in wild-type P. stuartii strains; therefore, they are aminoglycoside susceptible. We have isolated mutants with high-level AAC(2')-Ia expression at a frequency of 4.8 x 10(-6). Detailed analysis of one mutant demonstrated a 12.2-fold increase in the accumulation of aac(2')-Ia mRNA. In addition, the levels of beta-galactosidase expression from a plasmid-encoded aac(2')-lacZ transcriptional fusion were increased 11.5-fold in this mutant relative to those in an isogenic wild-type strain. These results suggested that a trans-acting factor, designated aar (for aminoglycoside acetyltransferase regulator), controls AAC(2')-Ia expression in P. stuartii.

Acetyltransferases↗
PubMed1989

Sch 38519, a novel platelet aggregation inhibitor produced by a Thermomonospora sp. Taxonomy, fermentation, isolation, physico-chemical properties, structure and biological properties.

The complex containing a new platelet aggregation inhibitor, Sch 38519, was recovered from the fermentation filtrate of Thermomonospora sp. SCC 1793. A chemically defined medium was developed which favored the production of Sch 38519. The antibiotic was isolated from the fermentation filtrate by absorption on macroreticular resin and further purified by ion exchange chromatography and reverse phase HPLC. Sch 38519 is an isochromanequinone structurally related to medermycin, lactoquinomycin and granaticin. It inhibits thrombin-induced aggregation of human platelets with an IC50 of 68 micrograms/ml. Sch 38519 is also active against Gram-positive and Gram-negative bacteria.

Actinomycetales↗
PubMed1985

Gram-negative bacilli resistant to third-generation cephalosporins: beta-lactamase characterization and susceptibility to Sch 34343.

We studied 192 recent clinical isolates, comprising six species of Gram-negative bacilli resistant either to cefotaxime or latamoxef (Moxalactam), from several hospitals. All isolates were resistant to several other third-generation cephalosporins or a monobactam. Two to five types of chromosomal beta-lactamases, as defined by isoelectric focusing, were readily identified in each species. Isolates of Citrobacter, Enterobacter and Serratia produced higher levels of chromosomal beta-lactamase than corresponding cefotaxime-susceptible strains. In addition, 20 of 57 produced one or two plasmid-determined beta-lactamases, TEM-1, OXA-2, or a novel enzyme, OHIO-1. The penem and carbapenem antibiotics, Sch 34343 and imipenem, were more active than cefotaxime, ceftazidime, ceftriaxone, latamoxef and aztreonam against isolates of Acinetobacter, Citrobacter, Ent. aerogenes, Ent. cloacae and Morganella, whereas imipenem, ceftazidime, and aztreonam were more active against Serratia isolates. The addition of plasmid-determined beta-lactamase increased resistance to piperacillin, cefoperazone and cefamandole but not to cefotaxime, ceftazidime, ceftriaxone, latamoxef, aztreonam, Sch 34343, or imipenem. Of 24 strains susceptible to aminoglycosides, none produced a plasmid-determined beta-lactamase, whereas 20 were found among the 33 strains resistant to aminoglycosides. Resistance of clinical isolates to newer beta-lactams appears to be due primarily to a high level of chromosomal cephalosporinase present without inducing agents. The plasmid-determined beta-lactamases, TEM-1 and OHIO-1, contributed little to resistance to most of the newer beta-lactams but were strongly associated with aminoglycoside resistance in these selected isolates. The greater in-vitro efficacy of the penem and carbapenem antibiotics, Sch 34343 and imipenem, against most of these isolates makes them promising candidates as first line agents against these pathogens.

Acinetobacter↗
PubMed1985

Evaluation of the in-vitro antibacterial activity of Sch 34343.

The in-vitro activity (as measured by geometric mean MICs, mg/l) of Sch 34343 against aerobic and anaerobic bacteria was compared with that of 14 other selected beta-lactam antibiotics including aztreonam, latamoxef (moxalactam), ceftazidime and imipenem. Sch 34343 had good activity (less than 2 mg/l) against most Gram-negative aerobic bacteria whether or not they contained high levels of plasmid-mediated or chromosomally-mediated beta-lactamases. It was slightly less potent against strains of Morganella and Serratia (less than 4 mg/l) and inactive against Pseudomonas (greater than 64 mg/l). A very small inoculum effect was observed against strains containing beta-lactamases indicating stability. Unlike the third-generation cephalosporins, Sch 34343 had excellent activity (less than or equal to 0.18 mg/l) against staphylococci, comparable to that of imipenem and ampicillin. While Sch 34343 had equally good potency (0.17 mg/l) against penicillinase-positive staphylococci, it was inactive against methicillin-resistant staphylococci (greater than or equal to 35 mg/l). Sch 34343 also had good activity against streptococci. The most unusual aspect of the in-vitro activity was its activity against Bacteroides (including Bact. fragilis) and other anaerobes. Sch 34343 had mean MICs less than or equal to mg/l for all Bacteroides and Clostridium spp. tested except CI. difficile (3.4 mg/l).

Anti-Bacterial Agents↗