Biomedical subjects

M D Schwartz

Publications and source records attributed to M D Schwartz.

At least 19 recordsLinked to original sources

PubMed1997

The HIV-1 matrix domain of Gag is required for Vpu responsiveness during particle release.

HIV-1 viral protein U (Vpu) facilitates virus particle release. To determine whether Gag is sufficient for generation of a target for Vpu-mediated particle release, we expressed HIV-1 Gag protein in the absence of the other viral genes. The resulting particles were still Vpu responsive. Mutational analysis of Gag indicated that the matrix domain (MA) is required for Vpu responsiveness. However, additional mutations in other domains of Gag, which affect the formation of stable virus particles, also abrogate Vpu responsiveness on total Gag release. Coexpression of the wild-type gag gene and a gag mutant lacking the MA domain renders the MA- mutant Vpu responsive. This indicates that Gag molecules lacking MA are still incorporated into particles through association with wild-type Gag molecules and that the resulting composite particles are sufficient for Vpu-mediated exit.

Binding Sites↗

PubMed1997

The influence of psychological distress on use of genetic testing for cancer risk.

The recent identification of BRCA1, a breast cancer susceptibility gene, offers an unprecedented opportunity for high-risk individuals to learn whether they are genetically predisposed to develop breast or ovarian cancer. This study examined the relationships between psychological distress and use of BRCA1 testing by 149 high-risk individuals from hereditary cancer families. After a baseline assessment of demographics, objective risk, cancer-specific distress, and global distress (depressive symptoms), study participants were offered the opportunity to receive genetic counseling and to learn whether they carry a mutation in the BRCA1 gene. Overall, 58% of study participants requested BRCA1 test results, and 42% declined to learn their genetic status. After controlling for demographic factors and risk status, cancer-specific distress was significantly and positively related to BRCA1 test use, whereas global distress was unrelated to test use.

Adult↗

PubMed1997

Distinct functions and requirements for the Cys-His boxes of the human immunodeficiency virus type 1 nucleocapsid protein during RNA encapsidation and replication.

The process of retroviral RNA encapsidation involves interaction between trans-acting viral proteins and cis-acting RNA elements. The encapsidation signal on human immunodeficiency virus type 1 (HIV-1) RNA is a multipartite structure composed of functional stem-loop structures. The nucleocapsid (NC) domain of the Gag polyprotein precursor contains two copies of a Cys-His box motif that have been demonstrated to be important in RNA encapsidation. To further characterize the role of the Cys-His boxes of the HIV-1 NC protein in RNA encapsidation, the relative efficiency of RNA encapsidation for virus particles that contained mutations within the Cys-His boxes was measured. Mutations that disrupted the first Cys-His box of the NC protein resulted in virus particles that encapsidated genomic RNA less efficiently and subgenomic RNA more efficiently than did wild-type virus. Mutations within the second Cys-His box did not significantly affect RNA encapsidation. In addition, a full complement of wild-type NC protein in virus particles is not required for efficient RNA encapsidation or virus replication. Finally, both Cys-His boxes of the NC protein play additional roles in virus replication.

Amino Acid Sequence↗

PubMed1997

Efficient encapsidation of human immunodeficiency virus type 1 vectors and further characterization of cis elements required for encapsidation.

To determine whether there is a cis-acting effect of translational expression of gag on RNA encapsidation, we compared the encapsidation of wild-type RNA with that of a mutant in which the translation of gag was ablated. This comparison indicated that there is not such a cis effect. To determine what is necessary and sufficient for encapsidation, we measured the relative encapsidation efficiencies of human immunodeficiency virus type 1 vector RNAs containing mutations in domains proximal to the canonical encapsidation signal or containing large deletions in the remainder of the genome. These data indicate that TAR and two additional regions are required for encapsidation and that the 5' end of the genome is sufficient for encapsidation. The Rev-responsive element is required mainly for efficient RNA transport from the nucleus to the cytoplasm. A foreign sequence was found to have a negative effect on encapsidation upon placement within the parental vector. Interestingly, this negative effect was compounded by multiple copies of the sequence.

Base Sequence↗

PubMed1997

Physician job satisfaction: developing a model using qualitative data. SGIM Career Satisfaction Study Group.

The purpose of this study was to develop a current and comprehensive model of physician job satisfaction. Information was gathered by (1) analysis of open-ended responses from a large group practice physician survey in 1988, and (2) analysis of focus group data of diverse physician subgroups from 1995. Participants were 302 physicians from large-group practices and 26 participants in six focus groups of HMO, women, minority, and inner-city physicians. Data were used to develop a comprehensive model of physician job satisfaction. The large group practice survey data supported the key importance of day-to-day practice environment and relationships with patients and physician peers. Future concerns focused on the effect of managed care on the physician-patient relationship and the ability of physicians to provide quality care. Focus groups provided contemporary data on physician job satisfaction, reinforcing the centrality of relationships as well as special issues for diverse physician subgroups of practicing physicians. New variables that relate to physician job satisfaction have emerged from economic and organizational changes in medicine and from increasing heterogeneity of physicians with respect to gender, ethnicity, and type of practice. A more comprehensive model of physician job satisfaction may enable individual physicians and health care organizations to better understand and improve physician work life.

Adult↗

PubMed1996

HIV-1 particle release mediated by Vpu is distinct from that mediated by p6.

Vpu and the C-terminal peptide of Gag (p6) are both HIV-1-encoded proteins that augment the release of virus particles from cells. We examined the functional relationship between these proteins and their activities during particle release. Our results indicate that efficient HIV-1 particle release from HeLa and Jurkat cells depends on the presence of Vpu. However, Vpu is dispensable for efficient release from Cos cells. In contrast, p6 is required for efficient release from Cos cells but not from Jurkat or HeLa cells. These data suggest that Vpu and p6 have distinct activities in virus exit from different cell lines. Intracellular proteolytic processing of Gag precursor protein is more complete in Cos cells than in HeLa cells. However, this processing has little or no effect on Vpu- or p6-mediated particle release. p6 is required for incorporation of yet another virus protein (Vpr) into cells but our data suggest that Vpr plays no role in p6-dependent particle release. Vpu also facilitates the degradation of CD4 in virus producing cells but, in contrast to particle release, the ability of Vpu to facilitate the degradation of CD4 is not cell line-dependent.

Animals↗

PubMed1996

Gail model breast cancer risk components are poor predictors of risk perception and screening behavior.

The Gail model is being used increasingly to determine individual breast cancer risk and to tailor preventive health recommendations accordingly. Although widely known to the medical and biostatistical communities, the risk factors included in the model may not be salient to the women to whom the model is being applied. This study explored the relationship of the individual Gail model risk factors to perceived risk of breast cancer and prior breast cancer screening among women with a family history of breast cancer. Data from baseline interviews with 969 women found a striking disparity between the objective risk factors included in the model and the accuracy of perceived risk and screening behaviors of this population, particularly among women over the age of 50 years. Risk perception accuracy was unrelated to all of the Gail model risk factors for all age groups. Reported mammography adherence was only associated with having had a breast biopsy in both age groups. Breast self examination (BSE) practice was independent of all measured factors for both age groups. These findings support the need for further research to identify additional determinants of risk perception and motivators of screening behavior.

Adult↗

PubMed1996

A randomized trial of breast cancer risk counseling: interacting effects of counseling, educational level, and coping style.

The authors evaluated the impact of individualized breast cancer risk counseling (BCRC) on breast-cancer-specific distress and general distress in 239 women with a family history of breast cancer. Following a baseline assessment of demographics, risk factors, coping styles, and distress, participants were assigned randomly to receive either BCRC or general health education (GHE; i.e., control group). After controlling for education level, women who received BCRC had significantly less breast-cancer-specific distress at 3-month follow-up compared with women who received GHE. A significant Education Level x Treatment Group interaction indicated that the psychological benefits of BCRC were greater for women with less formal education. In both the BCRC and GHE groups, participants who had monitoring coping styles exhibited increases in general distress from baseline to follow-up.

Adaptation, Psychological↗

PubMed1996

Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome.

OBJECTIVE: The expression of proinflammatory cytokines is rapidly increased in experimental models of the acute respiratory distress syndrome (ARDS), in patients at risk for ARDS, and in patients with established ARDS. Because multiple cytokines are present in bronchoalveolar lavage fluid, a common, proximal activation mechanism may operate in these settings. The proinflammatory cytokines whose expression is increased in the lungs of patients with ARDS have binding sequences in their enhancer/promoter regions for transcriptional regulatory proteins, such as nuclear factor-kappa B (NF-kappa B), nuclear factor-IL6 (NF-IL6), cyclic adenosine monophosphate responsive element binding protein, serum protein-1, and activating protein-1. To test the hypothesis that activation of one or more of these nuclear transcriptional regulatory factors might provide a common mechanism for the simultaneous expression of multiple cytokine genes in the setting of ARDS, we measured activation of these factors in alveolar macrophages from patients with ARDS and from controls. DESIGN: Prospective, clinical study. SETTING: Medical and surgical intensive care units at a university hospital and a county hospital. PATIENTS: Twelve patients, six with established ARDS and six control patients without lung injury. INTERVENTIONS: Patients with ARDS and controls underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated from lavage fluid and the nuclear proteins were extracted. Activation of transcriptional factors NF-kappa B, NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, and serum protein-1 was determined using an electrophoretic mobility shift assay, followed by densitometry of the autoradiographed gels. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in gender, age, tobacco smoking, Acute Physiology and Chronic Health Evaluation II score, quantity of lavage fluid, or number of alveolar macrophages in lavage specimens in the patient groups. Acute Lung Injury score and the Pao2/Fio2 ratio differed significantly between controls and ARDS patients: 0.46 +/- 0.17 vs. 2.74 +/- 0.14 (p < .0001) and 310 +/- 45 torr (41.3 +/- 6.0 kPa) vs. 150 +/- 11 torr (21.3 +/- 1.5 kPa) (p < .006), respectively. The mean Fio2 of the control patients was not significantly different from the mean Fio2 of ARDS patients: 0.47 +/- 0.11 vs. 0.55 +/- 0.6 (p = .53). Patients with ARDS had significantly (p < .02) increased activation of NF-kappa B in alveolar macrophages compared with patients without the syndrome. There was no evidence of increased activation of the transcriptional factors activating protein-1, serum protein-1, NF-IL6, or cyclic adenosine monophosphate responsive element binding protein in alveolar macrophages from ARDS vs. control patients. CONCLUSIONS: These experiments demonstrated increased in vivo activation of the nuclear transcriptional regulatory factor NF-kappa B (but not NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, or serum protein-1) in alveolar macrophages from patients with ARDS. Because binding sequences for NF-kappa B are present in the enhancer/promoter sequences of multiple proinflammatory cytokines, activation of NF-kappa B may contribute to the increased expression of multiple cytokines in the lung in the setting of established ARDS.

Adult↗

PubMed1996

Hemorrhage activates NF-kappa B in murine lung mononuclear cells in vivo.

Hemorrhage rapidly increases the expression of proinflammatory and immunoregulatory cytokines in the lungs. Binding elements for the nuclear transcriptional regulatory factors (NF)-kappa B and NF-IL6 (C/EBP beta) are present in the promoter regions of multiple cytokine genes, including those whose expression is increased after blood loss. In the present experiments, we found increased activation in vivo of NF-kappa B in lung mononuclear cells, but not in splenocytes, taken from mice 1 h after hemorrhage. In contrast, hemorrhage did not activate NF-IL6 in lung cells or splenocytes. Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-kappa B. Incubating splenocytes in vitro with xanthine oxidase activated NF-kappa B but not NF-IL6. Xanthine oxidase-induced activation of NF-kappa B was inhibited by manganese superoxide dismutase, but not by catalase. These results suggest that xanthine oxidase-mediated superoxide anion-dependent activation of NF-kappa B occurs in vivo and in vitro. This mechanism may contribute to increased lung cytokine responses after hemorrhage.

Animals↗

PubMed1995

Learners as teachers: the conflicting roles of medical residents.

OBJECTIVE: To explore the impact of internal medicine residents' roles as learners, teachers, and physicians on their performance in teaching and supervising interns; to generate insights for educational policy and research. DESIGN: Qualitative analysis of in-depth, semistructured, recorded interviews with a cohort of second-postgraduate-year (PGY-2) residents. Questions elicited their accounts of differences in the learning process between the first and second residency years, their responses to situations in which they lacked sufficient clinical knowledge, their views of their supervisory relationship with interns, and their assessments of changes in their role in patient care since their internships. Transcripts were independently analyzed by the interdisciplinary team of authors. SETTING: New York University/Bellevue Hospital Center's internal medicine residency (New York City), a highly competitive program in a major public hospital and a university medical center, emphasizing housestaff autonomy and self-reliance. PARTICIPANTS: A cohort of 18 of 21 medical residents at Bellevue Hospital Center during the last rotation of PGY-2. RESULTS: Intense conflicts confound residents' roles as teachers. These conflicts fall into three categories: 1) as learners, residents' own needs frequently coincide with those of interns in ways that may undermine their teaching--they are expected to nurture others despite their own considerable needs for emotional support, teach material that they barely grasp, and exert authority while feeling ignorant; 2) as team leaders, residents must ensure that interns get the hospital's work done, sometimes at the expense of teaching them; and 3) as clinicians, residents' first priority is to address the medical needs of patients--the learning needs of interns are secondary. CONCLUSION: Second-year internal medicine residents experience conflicts inherent in their simultaneous commitment to learning, teaching, and service that may undermine both their effectiveness in supervising interns and their own professional development. Potential remedies are to restructure residency programs so as to equip residents with training and support for their role as teachers, reduce the tension between training and service by delegating tasks to nonphysician personnel, and provide graded responsibility to housestaff as physicians and teachers.

Attitude of Health Personnel↗

PubMed1995

The impact of an ambulatory rotation on medical student interest in internal medicine. The Society of General Internal Medicine Task Force on Career Choice in Internal Medicine.

OBJECTIVE: To determine whether students who take ambulatory rotations in internal medicine are more likely to choose internal medicine careers. DESIGN: National survey. SETTING AND PARTICIPANTS: The intended sample was 1,650 senior U.S. medical students from 16 medical schools, of whom 1,244 (76%) responded. Representative schools nationwide were selected using a stratified, random-sampling method. MEASUREMENTS: The questionnaire asked about characteristics of the ambulatory rotation, perceptions of internal medicine, and factors influencing students toward or away from an internal medicine career. RESULTS: Ambulatory rotations were taken by 543 students (43%). Of these rotations, 73% were required, 74% were during the fourth year, 77% were in general internal medicine, 73% provided continuity of care, and 19% were during the medicine clerkship. Overall, 24% of the students chose careers in general (9%) or subspecialty internal medicine (15%). Thirty percent of the students who did ambulatory rotations planned internal medicine careers, compared with 19% of the students who had no rotation [odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.3 to 2.4, p = 0.0001]. This association was of similar magnitudes for students completing required rotations (OR = 1.6, 95% CI 1.2 to 2.2, p = 0.002) and for students completing rotations before or in proximity to when they chose careers (OR = 1.7, 95% CI 1.1 to 2.4, p = 0.01). Ninety percent of the 543 students who had ambulatory rotations were satisfied with the experience. Thirty-eight percent of the highly satisfied students chose internal medicine careers, compared with 21% of the students who had low or moderate satisfaction (p = 0.0001). CONCLUSIONS: An ambulatory rotation is strongly associated with positive perceptions of, attraction to, and choice of a career in internal medicine. Research is needed to determine specific components of an effective rotation. Further development of ambulatory rotations could help attract more students to internal medicine.

Adult↗

PubMed1995

Conditioned emotional distress in women receiving chemotherapy for breast cancer.

This study investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Women scheduled to begin chemotherapy were randomly assigned either to an experimental group (exposed to a distinctive stimulus before each chemotherapy infusion) or a control group. After repeated infusions of chemotherapy, patients' responses to the distinctive stimulus were assessed in a location not associated with chemotherapy administration. At the test trial, experimental group patients showed evidence of increased emotional distress (self-reported on a visual analog scale) after the presentation of the distinctive stimulus, whereas control group patients did not. Post hoc analyses indicated that these increases in distress were not secondary to other conditioned responses (e.g., nausea, taste aversion). Thus, results supported the hypothesis that the pairing of a distinctive stimulus with chemotherapy would result in the development of a conditioned emotional response.

Adolescent↗

PubMed1995

Coping disposition, perceived risk, and psychological distress among women at increased risk for ovarian cancer.

The authors examined predictors of psychological distress among women who were at increased risk for ovarian cancer. Participants were 103 women who had at least 1 first degree relative with ovarian cancer. Specifically, the authors tested the relationship between the dispositional attentional style of monitoring (the tendency to scan for threat-relevant information), perceptions of risk for ovarian cancer, intrusive thoughts regarding ovarian cancer, and psychological distress. Overall, this sample exhibited moderately high levels of psychological distress. High scores on monitoring were associated with high perceived risk for ovarian cancer and elevated levels of intrusive thoughts and psychological distress. Finally, the authors proposed and tested a path model describing the interrelationships between these variables. The results of this study are discussed in terms of their implications for treating the psychological distress associated with being at increased risk for ovarian cancer.

Adaptation, Psychological↗

PubMed1995

Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock.

Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

PubMed1994

General internal medicine.

Internists advanced toward a patient care model based on critical, qualitative, and quantitative assessment of clinical care processes and outcomes. The complete internist must consider social context as well as traditional risk factors in promoting the health of patients.

Internal Medicine↗

PubMed1994

Effect of a simple ambulatory experience on career choice and attitudes of medical students.

Students were allocated randomly to participate in a simple ambulatory experience during their third-year medicine clerkship. A convenience sample was surveyed by questionnaire in the fall of their fourth year, after decisions were made regarding future career plans. The questionnaire assessed medical student attitudes toward general internal medicine and career choice. Valuation of the effectiveness of the clerkship was associated with choosing a career in internal medicine (p = 0.007); having an ambulatory experience was not associated with subsequent career choice. Sixty-two percent of all students felt the clerkship affected their career choice a great deal or moderately; these students were likely to find a career in general internal medicine less attractive as a result of their clerkship (p = 0.008). When stratified, this association disappeared in those students who participated in the ambulatory experience (p = 0.39) but persisted in those who did not (p = 0.01). A simple experience in internal medicine clinics during a third-year clerkship was not associated with subsequent career choice, but had some positive effects on attitudes toward general internal medicine as a career.

Adult↗

PubMed1994

Effects of therapy with soluble tumour necrosis factor receptor fusion protein on pulmonary cytokine expression and lung injury following haemorrhage and resuscitation.

Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor-alpha (TNF-alpha) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNF-alpha in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post-haemorrhage increases in circulating and pulmonary TNF-alpha levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL-1 beta, IL-6, TNF-alpha and interferon-gamma (IFN-gamma) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post-haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast to the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF-alpha among peripheral blood mononuclear cells, as well as increased IFN-gamma titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post-haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting.

Animals↗