PubMed Health⌕ Search

Biomedical subjects

M McCord

Publications and source records attributed to M McCord.

16 recordsLinked to original sources
PubMed2001

Antisocial personality, substance abuse, and exposure to parental violence in males referred for domestic violence.

This study investigated whether childhood disruptive behavior (hyperactivity, oppositional-defiance, conduct problems) plus adult psychopathic adjustment are associated with domestic violence. Adult males (n = 66) in diversion programs completed the Wender Utah Rating Scale (WURS), MMPI Psychopathic Deviate scale (PD), Conflict Tactics Scales representing themselves and their parents, and substance use measures. Substance use and lifespan antisocial personality (measured by high WURS and PD scores) were robust predictors of verbal and moderate physical domestic abuse. Violence in the family of origin was associated with abuse when tested alone, but failed to exhibit unique association with abuse when other predictors were taken into account. The possibility that antisocial batterers respond to contingencies by moderating physical harm, while persisting at psychological harm, is discussed.

Adolescent↗
PubMed1999

Retrovirus DNA termini bound by integrase communicate in trans for full-site integration in vitro.

Integration of linear retrovirus DNA involves the concerted insertion of the viral termini (full-site integration) into the host chromosome. We investigated the interactions that occur between long terminal repeat (LTR) termini bound by avian retrovirus integrase (IN) for full-site integration in vitro. Wild-type (wt) or mutant LTR donors that possess gain-of-function ("G") or loss-of-function ("L") for full-site integration activity were used. G LTR termini are characterized as having significantly higher strand transfer activity than the wt and the L LTR termini. L LTR mutations are classified as partially or extremely defective for strand transfer activity. The L mutations were further classified by their ability to either permit or block the assembly of G or wt LTR termini into nucleoprotein complexes capable of full-site strand transfer. We demonstrated that avian myeloblastosis virus IN bound to G LTR termini increased the incorporation of partially defective L LTR termini into nucleoprotein complexes that were capable of full-site integration. The observed full-site integration activity of these assembled nucleoprotein complexes appeared to be influenced by each individual IN-LTR complex in trans. In contrast, extremely defective L LTR termini exhibited the ability to effectively block the assembly of wt LTR termini into nucleoprotein complexes capable of full-site strand transfer. Data from nonspecific DNA competition experiments suggested that IN had an apparent higher affinity for G LTR donor termini than for partially defective L LTR donor termini as measured by full-site integration activity. However, assembled nucleoprotein complexes containing either two G or two L LTR donors were stable, having a similar half-life of approximately 2 h on ice. The results suggest that LTR termini bound by IN exhibit an allosteric effect to modulate full-site integration in vitro. Similar regulatory controls also appear to exist in vivo between the wt U3 and wt U5 LTR termini in retroviruses as well as purified retrovirus preintegration complexes that promoted full-site integration in vitro.

Animals↗
PubMed1999

Respiratory failure. After the intensive care unit.

RF is a unique situation. It is specific in diagnosis and yet, at the same time, broad in concept. It can be acutely life threatening or chronic in presentation and need for intervention. Patients are cared for in ICUs, medical-surgical floors, and nursing homes as well as at home. When RF is a complicating condition of an already hospitalized patient, the road to recovery may be long and complicated. It is important that the health care team provides education and counseling so that the patient and family can cope with the changing events and the potentially long road to recovery. Outcome data from all the sites of care are currently lacking for a comparative analysis of the most effective site. All the sites of care discussed in this article are cost-effective alternatives to the ICU, but there is a lack of standards and evidence of measurable outcomes such as the quality and cost relationship. Outcome data are needed to document the cost of care and the relationship of that cost to specific outcomes such as final discharge disposition, survival, complications, and quality of life. Health care provides have a much clearer image of the care that can be provided in the multiple sites available. Unfortunately, patients and families do not have that same level of understanding. For many patients and families, regardless of what the facility is called, it is not the acute hospital, and that is where they wish to remain until discharge home. Clarification and standardization are needed regarding the terminology used to describe the various sites of care. It is important that integrated health care institutions provide education and counseling to patients and families regarding the continuum of care and the many alternatives along that path.

Acute Disease↗
PubMed1998

Hydroxamate-based inhibitors of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloprotease inhibitor Batimastat is described, which inhibits the proteolytic cleavage of the low affinity IgE receptor from cell membrane preparations. Limited SAR studies suggest that the structural requirements for effective inhibition are distinct from those required for the inhibition of collagenase.

Humans↗
PubMed1998

Selective inhibition of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloproteinase inhibitor Batimastat has been prepared, some members of which are potent inhibitors of the processing of the low affinity IgE receptor (CD 23). Increased activity is obtained by appropriate substitution at the alpha-position, whilst selectivity is gained by use of a P1' benzyl group in conjunction with a C-terminal primary amide.

Hydroxamic Acids↗
PubMed1998

Purification of recombinant Rous sarcoma virus integrase possessing physical and catalytic properties similar to virion-derived integrase.

Recombinant Rous sarcoma virus integrase cloned from the Prague A (PrA) virus strain was expressed in Escherichia coli. Here we report the detailed purification procedure resulting in an apparently homogeneous integrase. Recombinant PrA integrase was compared at both the protein structural and the catalytic levels to avian myeloblastosis virus integrase purified from virions. Both proteins exist minimally in a dimeric state at low nanomolar concentrations as analyzed by glycerol gradient sedimentation and protein crosslinking studies. Likewise, both proteins have similar specific activities for full-site (concerted integration reaction) and half-site strand transfer activities using linear 480-bp retrovirus-like donor substrates that contain wild-type or mutant termini. They respond similarly to high NaCl concentrations ( approximately 350 mM) as well as aprotic solvents for efficient full-site strand transfer. The data suggest that recombinant integrase proteins with physical and catalytic properties similar to the virion counterpart can be purified using these techniques and will faithfully and efficiently promote the full-site integration reaction in vitro.

Avian Sarcoma Viruses↗
PubMed1997

Cytosolic 85-kDa phospholipase A2-mediated release of arachidonic acid is critical for proliferation of vascular smooth muscle cells.

Recent evidence suggests that arachidonic acid (AA) may be involved in regulating cellular proliferation. The predominant mechanism of AA release from cellular phospholipids is via phospholipase A2 (PLA2) hydrolysis. The purpose of this study was to examine the roles of the distinct 14-kDa and 85-kDa PLA2 enzymes in human coronary artery vascular smooth muscle cell (hCAVSMC) proliferation. Cultured hCAVSMCs proliferate in the presence of growth medium with a typical doubling time of 30-40 h, grow at a slower proliferative rate upon reaching confluency (day 8), and eventually undergo contact inhibition of growth (day 10). Neither Type II 14-kDa PLA2 activity nor mass changed over a 10-day culture period. In contrast, 85-kDa PLA2 protein activity and mRNA decreased as time in culture progressed. This reduction in 85-kDa PLA2 correlated with reductions in DNA synthesis and suggested a possible association between 85-kDa PLA2 and proliferation. To directly evaluate the role of the 85-kDa PLA2 in proliferation we examined the effects of an 85-kDa PLA2 inhibitor (AACOCF3) and 85-kDa PLA2 antisense oligonucleotides on proliferation. Both reagents dose dependently inhibited proliferation, whereas a 14-kDa PLA2 inhibitor (SB203347), a calcium-independent PLA2 inhibitor (HELSS), an 85-kDa sense oligonucleotide, and a nonrelevant scrambled control oligonucleotide had no effect. The mechanism by which 85-kDa PLA2 influences cellular proliferation remains unclear. Inhibition of 85-kDa PLA2 activity produced neither phase-specific cell cycle arrest nor apoptosis (fluorescence-activated cell sorter analysis). Addition of AA (20 mu M) attenuated the effects of both AACOCF3 and 85-kDa antisense oligonucleotides implicating AA as a key mediator in cellular proliferation. However, although prostaglandin E2 (PGE2) was present in the culture medium, it peaked early (day 3) in culture, and indomethacin had no effect on cellular proliferation indicating that hCAVSMC proliferation was not mediated through PGE2. These data provide the first direct evidence that PLA2 is involved in control of VSMC proliferation and indicate that 85-kDa PLA2-mediated liberation of AA is critical for cellular proliferation.

Arachidonic Acid↗
PubMed1997

Avian retrovirus U3 and U5 DNA inverted repeats. Role Of nonsymmetrical nucleotides in promoting full-site integration by purified virion and bacterial recombinant integrases.

The U3 and U5 termini of linear retrovirus DNA contain imperfect inverted repeats that are necessary for the concerted insertion of the termini into the host chromosome by viral integrase. Avian myeloblastosis virus integrase can efficiently insert the termini of retrovirus-like DNA donor substrates (480 base pairs) by a concerted mechanism (full-site reaction) into circular target DNA in vitro. The specific activities of virion-derived avian myeloblastosis virus integrase and bacterial recombinant Rous sarcoma virus (Prague A strain) integrase (approximately 50 nM or less) appear similar upon catalyzing the full-site reaction with 3'-OH recessed wild type or mutant donor substrates. We examined the role of the three nonsymmetrical nucleotides located at the 5th, 8th, and 12th positions in the U3 and U5 15-base pair inverted repeats for their ability to modify the full-site and simultaneously, the half-site strand transfer reactions. Our data suggest that the nucleotide at the 5th position appears to be responsible for the 3-5-fold preference for wild type U3 ends over wild type U5 ends by integrase for concerted integration. Additional mutations at the 5th or 6th position, or both, of U3 or U5 termini significantly increased (approximately 3 fold) the full-site reactions of mutant donors over wild type donors.

Avian Myeloblastosis Virus↗
PubMed1995

Differential regulation of elicited-peritoneal macrophage 14 kDa and 85 kDa phospholipase A2(s) by transforming growth factor-beta.

Elicited guinea pig macrophages collected from inflammatory peritoneal exudate release soluble 14 kDa phospholipase A2 (PLA2) and prostaglandin E2 (PGE2) into surrounding media during culture (Marshall et al. (1994) J. Lipid Med. 10, 295-313). The effect of transformation growth factor beta 1 (TGF beta), an immunoregulatory growth factor, was examined in this system. Exposure of cultured macrophages to TGF beta reduced both the activity and protein levels of 14 kDa PLA2 measured in conditioned media. This inhibition occurred within the first 6-8 h, was prevalent through 72 h of exposure and was dependent on TGF beta concentration. The reduction, however, never reached more than 40-60%. Evaluation of the cellular PLA2 activity confirmed the existence of an immunologically-related 14 kDa PLA2 (ELISA) in the particulate fraction and an 85 kDa PLA2 (Western analysis) in the cytosol. Exposure to TGF beta halved the particulate activity and protein levels of 14 kDa PLA2 which was consistent with the reduction in the secreted form. Alternatively, TGF beta induced an increase in cytosolic 85 kDa PLA2 (activity and protein) which was not apparent until 12 h and significant at 20-24 h of exposure. This demonstrates that TGF beta differentially regulates the production of these two enzymes. Despite this, neither PGE2 synthesis nor the up-regulated cyclooxygenase -II were altered by TGF beta treatment suggesting that maximal prostanoid synthesis had been reached.

Animals↗
PubMed1995

Prostaglandin E2 requirement for transforming growth factor beta 1 inhibition of elicited macrophage 14 kDa phospholipase A2 release.

1. Cultured elicited-peritoneal macrophages release a soluble type II 14 kDa phospholipase A2 (PLA2) over time, reaching a plateau by 20-24 h of incubation and maintaining these levels over 72 h. Prostaglandin E2 (PGE2) is also produced but does not plateau until 48-72 h. 2. Transforming growth factor beta 1 (TGF beta 1) reduces cellular 14 kDa PLA2 and its subsequent release by approximately half, but does not alter PGE2 production. Co-incubation of TGF beta 1 with indomethacin interfered, in a concentration-dependent manner, with the ability of TGF beta 1 to reduce cellular 14 kDa PLA2 and its subsequent release over 24 h. The regulation of TGF beta 1 was not specific to indomethacin since other non-steroidal anti-inflammatory drugs had the same effect. This suggested that cyclooxygenase activity was essential for TGF beta 1 to exert its effect and indeed, the addition of exogenous PGE2 restored the TGF beta 1 action. 3. PGE2 alone exerted a concentration-dependent negative feedback action on elicited-macrophage 14 kDa PLA2 release. The inhibitory concentration (IC50 = approximately 180 ng PGE2 ml-1) approximated the PGE2 levels measured in the 24 h macrophage conditioned media (85-140 ng PGE2 ml-1) where PLA2 release began to plateau. Further, incubation of cells with indomethacin over 48 h resulted in the enhancement of 14 kDa PLA2 activity compared to that released from untreated cells. Forskolin failed to inhibit 14 kDa PLA2 release, suggesting PGE2 was not acting through an increase in adenylate cyclase. 4. Taken together, the data are consistent with the immunosuppressive aspects reported for both mediators during inflammation and demonstrates the requirement of PGE2 for TGF beta 1 action on the elicited macrophage.

Animals↗
PubMed1994

Efficient concerted integration of retrovirus-like DNA in vitro by avian myeloblastosis virus integrase.

We report the efficient concerted integration of a linear virus-like DNA donor into a 2.8 kbp circular DNA target by integrase (IN) purified from avian myeloblastosis virus. The donor was 528 bp, contained recessed 3' OH ends, was 5' end labeled, and had a unique restriction site not found in the target. Analysis of concerted (full-site) and half-site integration events was accomplished by restriction enzyme analysis and agarose gel electrophoresis. The donor also contained the SupF gene that was used for genetic selection of individual full-site recombinants to determine the host duplication size. Two different pathways, involving either one donor or two donor molecules, were used to produce full-site recombinants. About 90% of the full-site recombinants were the result of using two donor molecules per target. These results imply that juxtapositioning an end from each of two donors by IN was more efficient than the juxtapositioning of two ends of a single donor for the full-site reaction. The formation of preintegration complexes containing integrase and donor on ice prior to the addition of target enhanced the full-site reaction. After a 30 min reaction at 37 degrees C, approximately 20-25% of all donor/target recombinants were the result of concerted integration events. The efficient production of full-site recombinants required Mg2+; Mn2+ was only efficient for the production of half-site recombinants. We suggest that these preintegration complexes can be used to investigate the relationships between the 3' OH trimming and strand transfer reactions.

Avian Myeloblastosis Virus↗
PubMed1994

Human keratinocytes possess an sn-2 acylhydrolase that is biochemically similar to the U937-derived 85-kDa phospholipase A2.

The phospholipase A2 (PLA2) activities that are localized in the keratinocyte cytosolic and microsomal fractions were biochemically and pharmacologically characterized. The cytosol and to a lesser extent the microsome were sensitive to heat treatment and stable in the presence of sulfhydryl reducing agents. Both fractions were almost totally inactivated by reduction of pH to 2. The cytosolic activity demonstrated a sevenfold preference for arachidonic acid over oleic acid in the sn-2 position of substrate phospholipid and the microsome exhibited a fourfold preference. Neither the cytosol nor the microsome was inactivated by a neutralizing mouse monoclonal antibody 3F10 generated against recombinant human (rh) type II 14-kDa PLA2. Western immunoblot analysis of both fractions identified a high-molecular-mass protein in keratinocyte cytosol but not the microsome that migrated with rh 85-kDa PLA2. Neither the cytosol nor the microsome possessed immunoreactive bands that migrated with rh type II 14-kDa PLA2 when probed with monoclonal antibody 3F10. Further analysis of the cytosolic activity showed that it was activated by submicromolar concentrations of Ca2+, reduced by arachidonyl trifloromethylketone, a selective 85-kDa PLA2 inhibitor, but was unaffected by C-7 phosphonate phospholipid, a selective 14-kDa PLA2 transition state inhibitor. Taken together, the data supports the existence of a PLA2 activity in the cytosol that displays characteristics that are indistinguishable from those exhibited by the 85-kDa PLA2. Alternatively, both the cytosol and microsome were devoid of type II 14-kDa-like PLA2 activity. The failure of 12-epi scalaradial, a 14-kDa PLA2 inhibitor, to modify A23187-stimulated keratinocyte prostaglandin E2 release, was consistent with the biochemistry and suggests that the 85-kDa PLA2 may play an important role in keratinocyte prostaglandin E2 formation.

Antibodies, Monoclonal↗
PubMed1993

An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia.

In 1989, our medical center used continuous quality improvement concepts in the creation of a Nosocomial Pneumonia Prevention Team whose aim was to significantly reduce nosocomial ventilator-associated pneumonia. The team included representatives from nursing, respiratory therapy, pulmonary medicine, internal medicine, anesthesiology, education and training, and infection control. Because the majority of mechanically ventilated patients were located in the intensive care unit, this unit became the focus of the prevention efforts. Team meetings were held regularly, with all representatives brainstorming barriers, possible interventions, methods of outcome measurement, and frequency of evaluation. Policies and procedures were reviewed, surveillance was increased, handwashing practices were surveyed, periodic feedback to staff was begun, and an educational program was developed and presented. During 1990, we observed a 57% reduction in ventilator-associated pneumonia from the baseline years, 1987 and 1988. Statistical comparison of proportions by z test indicated a p value less than 0.05. Fifteen cases of nosocomial ventilator-associated pneumonia were prevented and a cost saving of $105,000 was realized. Performance of traditional surveillance for outliers, coupled with literature-based thresholds, can lead to tolerance of inordinately high endemic rates. Infection control programs can significantly reduce endemic rates of nosocomial ventilator-associated pneumonia through continuous quality improvement methods and multidisciplinary interventions, with standard infection control procedures used for improvement.

California↗
PubMed1992

Operationalizing dyspnea: focus on measurement.

Dyspnea is a multidimensional disorder that nurses and physicians deal with in a variety of settings. Because dyspnea can have major effects on the lives of patients, health care providers need to accurately assess the antecedents and reactions to dyspnea and to evaluate the efficacy of their individualized interventions. To help practitioners assess patients who experience dyspnea related to physiologic and psychogenic alterations, we critically appraised the current tools used to evaluate dyspnea and present an organizing framework to categorize these tools.

Dyspnea↗