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Biomedical subjects

M Gottlieb

Publications and source records attributed to M Gottlieb.

At least 19 recordsLinked to original sources

Estimation of polymer-surface interfacial interaction strength by a contact AFM technique.

Atomic force microscopy (AFM) measurements were employed to assess polymer-surface interfacial interaction strength. The main feature of the measurement is the use of contact-mode AFM as a tool to scratch off the polymer monolayer adsorbed on the solid surface. Tapping-mode AFM was used to determine the depth of the scraped recess. Independent determination of the layer thickness obtained from optical phase interference microscopy (OPIM) confirmed the depth of the AFM scratch. The force required for the complete removal of the polymer layer with no apparent damage to the substrate surface was determined. Polypropylene (PP), low-density polyethylene (PE), and PP-grafted-maleic anhydride (PP-g-ma) were scraped off silane-treated glass slabs, and the strength of surface interaction of the polymer layer was determined. In all cases it was determined that the magnitude of surface interaction force is of the order of van der Waals (VDW) interactions. The interaction strength is influenced either by polymer ability to wet the surface (hydrophobic or hydrophilic interactions) or by hydrogen bonding between the polymer and the surface treatment.

Adsorption↗

Overexpression of genes in the CA1 hippocampus region of adult rat following episodes of global ischemia.

Ischemic stress is associated with marked changes in gene expression in the hippocampus--albeit little information exists on the activation of nonabundant genes. We have examined the expression of several known genes and identified novel ones in the adult rat hippocampus after a mild, transient, hypovolemic and hypotensive, global ischemic stress. An initial differential screening using a prototype array to assess gene expression after stress followed by a suppression subtractive hybridization protocol and cDNA microarray revealed 124 nonoverlapped transcripts predominantly expressed in the CA1 rat hippocampus region in response to ischemic stress. About 78% of these genes were not detected with nonsubtracted probes. Reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization on these 124 transcripts confirmed the differential expression of at least 83. Most robustly expressed were gene sequences NFI-B, ATP1B1, RHOGAP, PLA2G4A, BAX, CASP3, P53, MAO-A, FRA1, HSP70.2, and NR4A1 (NUR77), as well as sequence tags of unknown function. New stress-related genes of similar functional motifs were identified, reemphasizing the importance of functional grouping in the analysis of multiple gene expression profiles. These data indicate that ischemia elicits expression of an array of functional gene clusters that may be used as an index for stress severity and a template for target therapy design.

Animals↗

The effect of preconditioning on the iron deposition after transient forebrain ischemia in rat brain.

In this study we investigated iron deposition in the hippocampus CA1 area and the corpus striatum pars dorsolateralis in a rat model of cerebral ischemia and ischemic tolerance. Forebrain ischemia was induced by four-vessel occlusion for 5-min as ischemic preconditioning. Two days after the preconditioning or the sham operation, a second ischemia was induced for 20-min. With the use of iron histochemistry, regional changes were examined after 2 to 8 weeks of recirculation following the 20-min ischemia with or without preconditioning. Perl's reaction with DAB intensification demonstrated iron deposits in the CA1 area and in the corpus striatum pars dorsolateralis after 2 weeks of recirculation. These iron deposits gradually increased in density and formed clusters by the 8th week. When the rats were exposed to 5-min ischemia 2 days before lethal 20-min ischemia, the deposition of iron in the CA1 region of the hippocampus and also in the corpus striatum pars dorsolateralis was decreased and produced a minimal number of iron-containing cells between the second and the 8th week of recirculation. Preconditioning with sublethal 5-min ischemia followed by 2 days of reperfusion also prevented the neuronal destruction of the hippocampal CA1 region induced by 20-min ischemia.

Animals↗

A qualitative study of physicians' own wellness-promotion practices.

OBJECTIVE: To delineate the specific practices that physicians use to promote their own well-being. DESIGN, SETTING, AND PARTICIPANTS: 304 members of a primary care practice-based research group responded by mail to a survey on physician well-being. From the original survey, 130 subjects responded to an open-ended survey item regarding their own wellness-promotion practices. METHODS: Qualitative content analysis was used to identify the common themes in the physicians' responses to the open-ended question. A validated 18-item instrument, the Scales of Psychological Well-Being (SPWB), was used for measurement. MAIN OUTCOME MEASURES: Similarities and differences between the various wellness-promotion practices that respondents reported using and associations between the use of these practices and SPWB scores. RESULTS: The 5 primary wellness-promotion practices that evolved from thematic analysis of the survey responses included "relationships," "religion or spirituality," "self-care," "work," and "approaches to life." The use of the last type of practice was significantly associated with increased psychological well-being (SPWB) scores compared with the use of any of the other wellness-promotion practice categories (P<0.01), and there was a trend toward increased well-being among users of any category of wellness-promotion practices. Comments by our respondents provide specific descriptions of how physicians attend to their emotional, spiritual, and psychological well-being. CONCLUSION: Physicians use a variety of approaches to promote their own well-being, which sort themselves into 5 main categories and appear to correlate with improved levels of psychological well-being among users.

Data Collection↗

Altered expression of the glutamate transporter EAAC1 in neurons and immature oligodendrocytes after transient forebrain ischemia.

Glutamate uptake is reduced during ischemia because of perturbations of ionic gradients across neuronal and glial membranes. Using immunohistochemical and Western blot analyses, the authors examined the expression of the glutamate transporters EAAC1, GLAST, and GLT-1 in the rat hippocampus and cerebral cortex 8 hours and 1 to 28 days after transient forebrain ischemia. Densitometric analysis of immunoblots of CA1 homogenates showed a moderate increase in EAAC1 protein levels early after the insult. Consistently, it was observed that EAAC1 immunostaining in CA1 pyramidal neurons was more intense after 8 hours and 1 day of reperfusion and reduced at later postischemia stages. A similar transient increase of EAAC1 immunolabeling was detected in layer V pyramidal neurons of the cerebral cortex. In addition, the authors observed that EAAC1 also was located in oligodendroglial progenitor cells in subcortical white matter. The number of EAAC1-labeled cells in this region was increased after 3 and 28 days of reperfusion. Finally, changes in GLAST and GLT-1 expression were not observed in the CA1 region after ischemia using immunohistochemical study or immunoblotting. Enhanced expression of EAAC1 may be an adaptive response to increased levels of extracellular glutamate during ischemia.

ATP-Binding Cassette Transporters↗

Predictors of treatment dropout from a spouse abuse abatement program.

This study evaluated predictors of dropout among men who began and attended at least 1 session of a cognitive-behavioral, skills training oriented spouse abuse abatement counseling program. Based on prior research, a number of demographic, criminal justice, partner violence pattern, and personality characteristics were studied. Dropout prediction was assessed at 2 phases of program participation, during assessment (early drop) and during intervention (late drop). Overall, few of the variables studied predicted dropout. Early dropout was predicted by high rates of police contact for violent crimes, failure to self-report an alcohol problem, and paranoid personality characteristics. Late dropout was predicted by both high and moderate levels of police contact for violent crimes, and borderline personality characteristics. An Age x Violent Crime interaction suggested that young violent offenders are more likely to complete treatment. The overall model accounted for only 7.15% of the variance. Clinical and research implications are discussed.

Adult↗

Expression of nerve growth factor in astrocytes of the hippocampal CA1 area following transient forebrain ischemia.

We have examined by immunoassay and immunohistochemistry, the expression of nerve growth factor in the rat hippocampus, one to 28 days after transient forebrain ischemia. In the CA1 area, the overall level of nerve growth factor expression remained constant over the first three days of reperfusion while it increased by about 45% of control levels after longer postischemic periods. In contrast, a slight decrease in nerve growth factor levels, which was most prominent at three days postlesion, was observed in the other hippocampal regions. Immunohistochemical analysis of the distribution of nerve growth factor showed that its expression was up-regulated in astrocytes but not in microglia of the postischemic CA1 region and that the intensity and temporal profile of the changes in nerve growth factor immunostaining in these cells, was consistent with that observed in the immunoassay. Interestingly, the regulation of the nerve growth factor expression in reactive astrocytes of the postischemic CA1 area closely parallels that of kainate receptor subunits GluR5-7, raising the possibility of a cause-effect relationship. These results indicate that after ischemia nerve growth factor expression is up-regulated in reactive astrocytes suggesting that these cells may contribute to rescuing damaged neurons by means of increasing nerve growth factor production.

Animals↗

What students value: learning outcomes in a required third-year ambulatory primary care clerkship.

PURPOSE: To determine learning outcomes from the students' perspective on the clinical portion of a third-year primary care ambulatory clerkship. METHOD: Over 18 months (December 1994 to June 1996), students at the Medical College of Wisconsin identified what they had learned during the clerkship in each of seven learning settings. Responses were transcribed and a coding dictionary developed. Response frequencies were compared by logistic regression analysis over time and between rural and urban sites. Course goals set by faculty were compared to learning outcomes reported by students. RESULTS: The authors coded 3,030 student outcomes into 48 categories. The top ten learning outcomes by frequency are reported. Logistic regression analysis revealed no significant difference by time of year or by rural versus urban clerkship experiences. Twenty-six of 29 original course goals were congruent with the student-generated outcomes. CONCLUSION: Basic professional knowledge, skills, and attitudes were the learning outcomes most valued throughout the year. Being alone with patients and working with their preceptors were the students' most valued learning settings.

Ambulatory Care↗

Depression of acetylcholinesterase synthesis following transient cerebral ischemia in rat: pharmacohistochemical and biochemical investigation.

The effect of transient cerebral ischemia on acetylcholinesterase (AChE) synthesis was studied in rats by a modified pharmacohistochemical method. The procedure involved in vivo irreversible inhibition of AChE by administration of the inhibitor diisopropyl fluorophosphate (DFP; 1.2 mg/kg b.w., i.m.) 1 h before 30 min forebrain ischemia (the four-vessel occlusion model). At the onset of ischemia, 70-75% of AChE was inhibited in the brain. Recirculation was followed by histochemical and biochemical investigations of newly synthesized AChE in the striatum, septum, cortex and hippocampus. Control sham-operated animals were treated with the same dose of DFP. For correlation, rats not treated with DFP were subjected to the same ischemic procedures and investigated simultaneously. In these rats, significant decrease in AChE activity was found in the striatum, septum and hippocampus during 24 h recirculation. In DFP treated rats, ischemia markedly depressed resynthesis of AChE; after 4 h recirculation, AChE activity was decreased by 45-60% in all investigated areas in comparison with controls and the AChE histochemistry showed only slightly stained neurons in the striatum and septum. Twenty-four hours after ischemia, these neurons were densely stained and the increase in AChE activity indicated a partial recovery of the enzyme synthesis. These results suggest that the depression of AChE synthesis after forebrain ischemia is probably transient, not accompanied by cholinergic neuron degeneration.

Acetylcholinesterase↗

The intraischemic and early reperfusion changes of protein synthesis in the rat brain. eIF-2 alpha kinase activity and role of initiation factors eIF-2 alpha and eIF-4E.

Rats were subjected to the standard four-vessel occlusion model of transient cerebral ischemia (vertebral and carotid arteries). The effects of normothermic ischemia (37 degrees C) followed or not by 30-minute reperfusion, as well as 30-minute postdecapitative ischemia, on translational rates were examined. Protein synthesis rate, as measured in a cell-free system, was significantly inhibited in ischemic rats, and the extent of inhibition strongly depended on duration and temperature, and less on the model of ischemia used. The ability of reinitiation in vitro (by using aurintricarboxylic acid) decreased after ischemia, suggesting a failure in the synthetic machinery at the initiation level. Eukaryotic initiation factor 2 (eIF-2) presented almost basal activity and levels after 30-minute normothermic ischemia, and the amount of phosphorylated eIF-2 alpha in these samples, as well as in sham-control samples, was undetectable. The decrease in the levels of phosphorylated initiation factor 4E (eIF-4E) after 30-minute ischemia (from 32% to 16%) could explain, at least partially, the impairment of initiation during transient cerebral ischemia. After reperfusion, eIF-4E phosphorylation was almost completely restored to basal levels (29%), whereas the level of phosphorylated eIF-2 alpha was higher (13%) than in controls and ischemic samples (both less than 2%). eIF-2 alpha kinase activity in vitro as measured by phosphorylation of endogenous eIF-2 in the presence of ATP/Mg2+, was higher in ischemic samples (8%) than in controls (4%). It seems probable that the failure of the kinase in phosphorylating eIF-2 in vivo during ischemia is due to the depletion of ATP stores. The levels of the double-stranded activated eIF-2 alpha kinase were slightly higher in ischemic animals than in controls. Our results suggest that the modulation of eIF-4E phosphorylation could be implicated in the regulation of translation during ischemia. On the contrary, phosphorylation of eIF-2 alpha, by an eIF-2 alpha kinase already activated during ischemia, represents a plausible mechanism for explaining the inhibition of translation during reperfusion.

Animals↗

Predicting resident confidence to lead family meetings.

BACKGROUND AND OBJECTIVES: Family physicians frequently encounter patients' family members in family meetings regarding health care. Although residents are expected to learn how to interview families, no quantitative studies have examined variables associated with building residents' confidence in their ability to lead family meetings. The current study sought to clarify the relationship between a number of training, participant, and situational components and resident confidence. METHODS: All family practice residents (n = 90) in a five-residency program system were sent a survey that examined their experience in and perceived competence to conduct family meetings. Responses were analyzed with a hierarchical regression analysis and an ex post facto univariate analysis. RESULTS: Residents with higher perceived confidence in their ability to run a family meeting were male, had specific training for leading family meetings, had participated in and initiated more family meetings, perceived stronger family physician faculty support, and had more family systems training than lower-confidence residents. CONCLUSIONS: The results highlight the experiential, curricular, and environmental variables that are associated with building resident confidence to lead family meetings. Residents may benefit from early exposure to the skills needed for family meetings and from reinforcement of these skills through observations of skilled practitioners, the expectation that they will initiate meetings, and the opportunity to debrief meetings with supportive faculty. Family meeting curricula should include conflict management skills and incorporate input from other specialists and hospital personnel who meet with families.

Data Collection↗

Lipid peroxidation and phospholipid composition in rat brain regions after ischemia and in early perfusion periods.

Lipid peroxidation products (LPPs) and phospholipid composition were studied in a model of four-vessel occlusion in rats in homogenates of cortex, striatum and hippocampus after 30 min forebrain ischemia and following 1, 5, 10, 15, 30 and 180 min of recirculation. Major modification of LPPs was found after shorter reperfusion time, 5 min in hippocampus and 15 min in cortex and striatum when compared to control, while a slight decrease in the level of LPPs in the striatum and hippocampus was detected after longer (30 and 180 min) intervals. However, significant decrease was found in the homogenates of cortex. The results obtained from enhanced iron-dependent peroxidation in homogenates of frontal and occipital cortex indicated marked susceptibility to lipid peroxidation in the tissue subjected to 30 min ischemia and after 15 min of recirculation. The level of DG + PA was significantly higher during ischemia in the striatum, while increased hydrolysis of PI and DG + PA concentrations in the cortex, PI and PE levels in the striatum and PE and PS in the hippocampus after 30 min of ischemia were found. After 15 min of reperfusion considerably higher degradation of almost all phospholipids was found within all brain regions studied. The irreversibility of changes in PS, PE and SM was noted in the hippocampus after longer reperfusion periods. Our results indicate that the correlation between the lipid peroxidat ion product formation and phospholipid hydrolysis does exist, and, moreover, early reperfusion period seems to be highly critical in the development of ischemia-reperfusion induced neuronal damage.

Animals↗

The acquisition of purines by trypanosomatids.

Parasites of the family Trypanosomatidae have an absolute requirement for purines, yet lack the intracellular machinery to synthesize their own purine ring de novo. As a result, the enzymes devoted to the transport and metabolism of purines are extremely important to the parasite. Here, Claudia Cohn and Michael Gottlieb emphasize the value of understanding purine salvage for the development of trypanocidal drugs, and discuss the putative transporters devoted to purine uptake.

Journal Article↗

Increasing clinical prevention efforts in a family practice residency program through CQI methods.

BACKGROUND: As primary care physicians develop ongoing relationships with their patients, each contact provides another opportunity for primary, secondary, or tertiary prevention activities. In 1991 an interdisciplinary prevention project team using continuous quality improvement (CQI) principles was established to improve family practice residents' provision of such services. DIAGNOSTIC JOURNEY: For a random sample of 60 patient charts, abstractors looked for documentation of 23 clinical preventive services, including nursing screens, physician on-site and off-site implemented services, lifestyle education (diet, tobacco use), and self-screening education. After the chart review, the physicians, nurses, residents, and clinical staff used a fishbone analysis to identify physician-, clinic system-, and patient-centered factors contributing to the lack of conformance with clinical prevention guidelines. REMADIAL JOURNEY: The residency program began a series of didactic sessions on clinical prevention and instituted a procedures rotation to teach prevention procedure skills such as flexible sigmoidoscopy, stress testing, and colposcopy. On the CQI team's recommendation, a checklist developed by physicians and staff which itemized age- and gender-specific clinical prevention services was placed at the front of all patient charts. Clinic-system and patient factors were also addressed. HOLDING THE GAINS--MONITORING PERFORMANCE: The 1993 postintervention chart review showed significant improvements for 17 (81%) of the 21 targeted services. DISCUSSION: Providing educational sessions on prevention, permitting residents to select the areas of prevention on which to focus, and giving feedback on resident and staff performance through ongoing, nonpunitive monitoring resulted in increased provision of clinical prevention services in a family practice residency training center.

Family Practice↗

Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia.

We examined by immunohistochemistry the expression of ionotropic glutamate receptor subunits (GluRs) in glial cells of the rat dorsal hippocampus 3 to 28 days after transient forebrain ischemia. In general, the expression of GluRs at all time points studied underwent a drastic reduction that was primarily restricted to the CA1 region. In addition to the disappearance of GluRs as a result of neuronal cell death, we observed their expression in reactive glial cells. The time course of expression and the subunits involved were different for astrocytes and microglia. Reactive astrocytes exhibited kainate, GluR5-7, and N-methyl-D-aspartate (NMDA), NR2A/B, receptor subunits, both of which were maximally expressed approximately 4 weeks after ischemia. In contrast, reactive microglia expressed GluR4 and NR1 subunits, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and NMDA receptor subtypes, respectively, with maximal expression observed between 3 and 7 days after ischemia. These results demonstrate that specific types of GluRs are expressed in reactive glial cells after ischemia and that, overall, their expression levels peak around or after the periods of maximal astrogliosis and microgliosis. Thus, modulation of GluR expression may be one of the molecular components accompanying the gliotic process.

Animals↗