Biomedical subjects

M D Lieberman

Publications and source records attributed to M D Lieberman.

At least 19 recordsLinked to original sources

PubMed2001

Why introverts can't always tell who likes them: multitasking and nonverbal decoding.

Despite personality theories suggesting that extraversion correlates with social skill, most studies have not found a positive correlation between extraversion and nonverbal decoding. The authors propose that introverts are less able to multitask and thus are poorer at nonverbal decoding, but only when it is a secondary task. Prior research has uniformly extracted the nonverbal decoding from its multitasking context and, consequently, never tested this hypothesis. In Studies 1-3, introverts exhibited a nonverbal decoding deficit, relative to extraverts, but only when decoding was a secondary rather than a primary task within a multitasking context. In Study 4, extraversion was found to correlate with central executive efficiency (r = .42) but not with storage capacity (r = .04). These results are discussed in terms of arousal theories of extraversion and the role of catecholamines (dopamine and norepinephrine) in prefrontal function.

Arousal↗

PubMed2001

Do amnesics exhibit cognitive dissonance reduction? The role of explicit memory and attention in attitude change.

In two studies, we investigated the roles of explicit memory and attentional resources in the process of behavior-induced attitude change. Although most theories of attitude change (cognitive dissonance and self-perception theories) assume an important role for both mechanisms, we propose that behavior-induced attitude change can be a relatively automatic process that does not require explicit memory for, or consciously controlled processing of, the discrepancy between attitude and behavior. Using a free-choice paradigm, we found that both amnesics and normal participants under cognitive load showed as much attitude change as did control participants.

Adolescent↗

PubMed2001

The emergence of social cognitive neuroscience.

Social cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand phenomena in terms of interactions between 3 levels of analysis: the social level, which is concerned with the motivational and social factors that influence behavior and experience; the cognitive level, which is concerned with the information-processing mechanisms that give rise to social-level phenomena; and the neural level, which is concerned with the brain mechanisms that instantiate cognitive-level processes. The social cognitive neuroscience approach entails conducting studies and constructing theories that make reference to all 3 levels and contrasts with traditional social psychological and cognitive neuroscientific research that primarily makes reference to 2 levels. The authors present an introduction to and analysis of the field by reviewing current research and providing guidelines and suggested directions for future work.

Forecasting↗

PubMed2000

Pancreatic anastomotic failure after pancreaticoduodenectomy.

BACKGROUND: Pancreatic anastomotic failure has historically been regarded as one of the most feared complications after pancreaticoduodenectomy. METHODS: We reviewed our recent experience (59 cases), March 1994 to December 1998, with pancreaticoduodenectomy and compared preoperative and intraoperative characteristics as well as outcomes in those patients who experienced (n = 10) versus those who did not experience a postoperative pancreatic leak (n = 49). Information was retrospectively collected from hospital records, office records, and interviews with patients. RESULTS: The clinical leak rate in this series was 8.5%. There were no significant differences in preoperative or intraoperative characteristics comparing those with versus those without a postoperative pancreatic leak. Only 1 of 10 patients with a postoperative pancreatic leak required reoperation to manage the leak. Those with a pancreatic leak had more other postoperative complications (median 2 versus 0 complications per patient, P = 0.01) and longer hospital duration compared with those without a leak (median 13 versus 23 days, P<0.01). Overall mortality in the series was 3.4%; no mortalities occurred as a result of a pancreatic leak. CONCLUSIONS: In the 1990s pancreatic anastomotic leak remains a potentially lethal problem after pancreaticoduodenectomy. Pancreatic leakage after pancreaticoduodenectomy is associated with other postoperative complications and a longer hospital stay.

Aged↗

PubMed2000

Intuition: a social cognitive neuroscience approach.

This review proposes that implicit learning processes are the cognitive substrate of social intuition. This hypothesis is supported by (a) the conceptual correspondence between implicit learning and social intuition (nonverbal communication) and (b) a review of relevant neuropsychological (Huntington's and Parkinson's disease), neuroimaging, neurophysiological, and neuroanatomical data. It is concluded that the caudate and putamen, in the basal ganglia, are central components of both intuition and implicit learning, supporting the proposed relationship. Parallel, but distinct, processes of judgment and action are demonstrated at each of the social, cognitive, and neural levels of analysis. Additionally, explicit attempts to learn a sequence can interfere with implicit learning. The possible relevance of the computations of the basal ganglia to emotional appraisal, automatic evaluation, script processing, and decision making are discussed.

Basal Ganglia↗

PubMed1999

Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs.

Administration of adenovirus (Ad) vectors to immunologically naive experimental animals almost invariably results in the induction of systemic anti-Ad neutralizing antibodies. To determine if the human systemic humoral host responses to Ad vectors follow a similar pattern, we evaluated the systemic (serum) anti-Ad serotype 5 (Ad5) neutralizing antibodies in humans after administration of first generation (E1(-) E3(-)) Ad5-based gene transfer vectors to different hosts. AdGVCFTR.10 (carrying the normal human cystic fibrosis [CF] transmembrane regulator cDNA) was sprayed (8 x 10(7) to 2 x 10(10) particle units [PU]) repetitively (every 3 months or every 2 weeks) to the airway epithelium of 15 individuals with CF. AdGVCD.10 (carrying the Escherichia coli cytosine deaminase gene) was administered (8 x 10(8) to 8 x 10(9) PU; once a week, twice) directly to liver metastasis of five individuals with colon cancer and by the intradermal route (8 x 10(7) to 8 x 10(9) PU, single administration) to six healthy individuals. AdGVVEGF121.10 (carrying the human vascular endothelial growth factor 121 cDNA) was administered (4 x 10(8) to 4 x 10(9.5) PU, single administration) directly to the myocardium of 11 individuals with ischemic heart disease. Ad vector administration to the airways of individuals with CF evoked no or minimal serum neutralizing antibodies, even with repetitive administration. In contrast, intratumor administration of an Ad vector to individuals with metastatic colon cancer resulted in a robust antibody response, with anti-Ad neutralizing antibody titers of 10(2) to >10(4). Healthy individuals responded to single intradermal Ad vector variably, from induction of no neutralizing anti-Ad antibodies to titers of 5 x 10(3). Likewise, individuals with ischemic heart disease had a variable response to single intramyocardial vector administration, ranging from minimal neutralizing antibody levels to titers of 10(4). Evaluation of the data from all trials showed no correlation between the peak serum neutralizing anti-Ad response and the dose of Ad vector administered (P > 0.1, all comparisons). In contrast, there was a striking correlation between the peak anti-Ad5 neutralizing antibody levels evoked by vector administration and the level of preexisting anti-Ad5 antibodies (P = 0.0001). Thus, unlike the case for experimental animals, administration of Ad vectors to humans does not invariably evoke a systemic anti-Ad neutralizing antibody response. In humans, the extent of the response is dictated by preexisting antibody titers and modified by route of administration but is not dose dependent. Since the extent of anti-Ad neutralizing antibodies will likely modify the efficacy of administration of Ad vectors, these observations are of fundamental importance in designing human gene therapy trials and in interpreting the efficacy of Ad vector-mediated gene transfer.

Adenoviruses, Human↗

PubMed1997

In vivo adenoviral-mediated gene transfer in the treatment of pancreatic cancer.

Gene therapy may allow targeted delivery of tumoricidal drugs to treat pancreatic cancer. Cytosine deaminase (CD) is a bacterial enzyme that converts the nontoxic agent 5-fluorocytosine (5FC) to the active chemotherapeutic agent 5-fluorouracil (5FU). Neoplastic cells induced to express the CD gene treated with 5FC may generate locally high concentrations of 5FU while minimising systemic toxicity. Replication deficient adenovirus vector carrying the CD gene (AdCMV.CD) was tested for therapeutic efficacy against the murine pancreatic carcinoma cell line Pan02. Pan02 cells were infected in vitro with AdCMV.CD or null vector (Ad.-Null) and were examined for expression of CD messenger RNA (mRNA) (Northern blot) and CD enzymatic function (spectrophotometry). mRNA transcripts of the CD gene increased in a dose-dependent manner after infection with AdCMV.CD. Conversion of 5FC to 5FU at a multiplicity of infection (MOI) of 20 was measured to be 51% after a 48-hr incubation. Growth inhibition was measured by MTT assay and thymidine uptake. Pan02 growth in vitro treated with AdCMV.CD and 5FC was inhibited by 80% as compared to cells treated with Ad.Null and 5FC. An in vivo model of pancreatic cancer was established by injecting 2.5 x 10(5) PAN02 cells subcutaneously into the flanks of C57BL/ 6 mice. Seven days later AdCMV.CD was injected into each tumor and 5FC was administered for 10 days. Treatment of mice with AdCMV.CD and 5FC inhibited tumor growth compared to mice who received AdCMV.CD only or 5FC only. These data demonstrate the therapeutic efficacy of an enzyme prodrug strategy in experimental pancreatic cancer.

Adenoviridae↗

PubMed1996

Elevation of intracellular cyclic adenosine monophosphate inhibits the epidermal growth factor signal transduction pathway and cellular growth in pancreatic adenocarcinoma cell lines.

BACKGROUND: The epidermal growth factor (EGF) signal transduction pathway, frequently activated in pancreatic cancer, is an important regulator of cellular growth and transformation. This study examined whether activation of the cyclic adenosine monophosphate protein kinase A pathway may inhibit the EGF signal transduction pathway in pancreatic cancer cell lines. METHODS: Human pancreatic cancer lines BxPC-3 and AsPC-1 were stimulated with EGF, forskolin, or both. Forskolin is a compound that increases cyclic adenosine monophosphate levels. Assays of cell lines were then obtained for cellular growth (MTT assay), anchorage-independent growth (soft agar), and EGF-induced mitogen-activated protein kinase activation as measured by an in-gel kinase assay. RESULTS: Treatment with forskolin resulted in inhibition of EGF-induced activation of mitogen-activated protein kinase activity (BxPC-3 78% inhibition and AsPC-1 70% inhibition, p < 0.005), diminished cellular proliferation (BxPC-3 92% inhibition and AsPC-1 86% inhibition, p < 0.001), and formation of colonies in soft agar (BxPC-3 98% inhibition and AsPC-1 76% inhibition, p < 0.001). Forskolin did not inhibit EGF receptor autophosphorylation or tyrosine kinase signaling in response to EGF. CONCLUSIONS: Forskolin-induced inhibition of mitogen-activated protein kinase is associated with diminished pancreatic cancer cell proliferation in vitro. Use of strategies to increase cyclic adenosine monophosphate levels may have therapeutic application in pancreatic cancer.

Adenocarcinoma↗

PubMed1995

Carcinoma of the esophagus. Prognostic significance of histologic type.

Previous investigators have reported that in patients with esophageal carcinoma tumor cell type affects prognosis. A retrospective analysis of 258 patients, from 1985 to 1991, undergoing curative esophagogastrectomy for adenocarcinoma (n = 134) or squamous cell carcinoma (n = 124) was performed to test the hypothesis that histologic cell type is an independent prognostic factor and to identify other predictors of survival after resection. The actuarial overall survival (p = 0.16) and disease-specific survival (p = 0.68) were similar for adenocarcinoma (median overall survival = 27 months) and squamous cell carcinoma (median overall survival = 22 months). Univariate analysis identified T stage, N stage, number of diseased nodes, tumor differentiation, tumor site, and blood transfusions as significant (p < 0.05) variables in predicting overall survival. The presence of Barrett's esophagus was not predictive of survival. Multivariate analysis demonstrated that T stage (p = 0.006), N stage (p = 0.01), and number of diseased lymph nodes (p = 0.03) were independent predictors of overall survival. This analysis demonstrated that histologic type is not an independent variable for overall survival in patients undergoing curative esophagogastrectomy for carcinoma of the esophagus and gastroesophageal junction. Outcome is most strongly influenced by extent of disease defined by T and N stage.

Actuarial Analysis↗

PubMed1995

Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancy.

OBJECTIVE: The authors examined the effect of hospital and surgeon volume on perioperative mortality rates after pancreatic resection for the treatment of pancreatic cancer. METHODS: Discharge abstracts from 1972 patients who had undergone pancreaticoduodenectomy or total pancreatectomy for malignancy in New York State between 1984 and 1991 were obtained from the Statewide Planning and Research Cooperative System. Logistic regression analysis was used to determine the relationship between hospital and surgeon experience to perioperative outcome. RESULTS: More than 75% of patients underwent resection at minimal-volume (fewer than 10 cases) or low-volume (10-50 cases) centers (defined as hospitals in which a minimal number of resections were performed in a given year), and these hospitals represented 98% of the institutions treating peripancreatic cancer. The two high-volume hospitals (more than 81 cases) demonstrated a significantly lower perioperative mortality rate (4.0%) compared with the minimal- (21.8%) and low-volume (12.3%) hospitals (p < 0.001). The perioperative mortality rate was 15.5% for low-volume (fewer than 9 cases) surgeons (defined as surgeons who had performed a minimal number of resections in any hospital in a given year) (n = 687) compared with 4.7% for high-volume (more than 41 cases) pancreatic surgeons (n = 4) (p < 0.001). Logistic regression analysis demonstrated that perioperative death is significantly (p < 0.05) related to hospital volume, but the surgeon's experience is not significantly related to perioperative deaths when hospital volume is controlled. CONCLUSIONS: These data support a defined minimum hospital experience for elective pancreatectomy for malignancy to minimize perioperative deaths.

Adolescent↗

PubMed1994

Esophageal carcinoma. The unusual variants.

The clinical behavior and response to therapy of rare histologic variants of esophageal carcinoma are unclear. To evaluate the results of therapy in this group the records of 29 patients treated between 1949 and 1991 with primary rare histologic variants of esophageal carcinoma were retrospectively reviewed. This group represented 1.2% of 2454 cases of esophageal carcinoma treated between 1949 and 1991 and included mucoepidermoid (n = 14), small-cell (n = 12), adenoid cystic (n = 2), and carcinosarcoma (n = 1) carcinomas. Treatment for localized disease consisted of esophagectomy in five of seven patients with mucoepidermoid carcinoma, two of six patients with small-cell carcinoma, two of two patients with adenoid cystic carcinoma, and one of one patient with carcinosarcoma. Patients with stage IV mucoepidermoid carcinoma were treated predominately with radiation therapy (5/7). The majority of small cell carcinomas were treated with multiagent chemotherapy (10/12). The 1- and 3-year disease-specific survivals were 54% and 9% for mucoepidermoid carcinoma (median survival, 5 months) and 16% and 0% for small-cell carcinoma (median survival, 7 months), respectively. Patients with stage III mucoepidermoid carcinoma (median survival, 20.5 months) compared with those with stage III small-cell carcinoma (median survival, 6.2 months) had a significantly longer duration of survival (p < 0.05). Distant disease was present in 86% of patients in whom recurrence developed after esophagectomy Esophagectomy is standard therapy for localized carcinomas of the esophagus. Small-cell carcinoma appears to be a more aggressive variant of carcinoma and is most commonly treated with chemotherapy.

Adult↗

PubMed1993

Infrageniculate bypass graft entrapment.

When failure of vein grafts is due to technical error it is usually observed in the early postoperative period. In this review we describe late failure of five bypass grafts as a result of entrapment of the vein graft caused by an improperly placed tunnel from the femoral to the popliteal artery. Vein graft entrapment may either produce no symptoms or eventually lead to limb ischemia. Pulses and pressures that vary with flexion and extension maneuvers should alert the clinician to the possibility of an entrapment syndrome. The characteristic arteriographic findings observed in these patients include an aberrant course of the vein graft outside the anatomic course of the popliteal artery and position-dependent compression of the graft. The ability of magnetic resonance angiography to demonstrate the arteriographic appearance of the graft as well as the precise location of the compression and to identify structures involved in the entrapment, make it a valuable noninvasive tool in the preoperative assessment of these patients. Treatment options include division of the gastrocnemius muscle, division of the vein graft, or replacement of the vein graft. Familiarity with vein graft entrapment should facilitate its recognition. Careful placement of bypass grafts along the anatomic course of the popliteal artery within the popliteal space will prevent this complication.

Aged↗

PubMed1992

Enhancement of interleukin-2 immunotherapy with L-arginine.

Nutrient substrates have been shown to enhance cell-mediated immunity, but their role as adjuvants to immunotherapy has not been previously determined. This study evaluated L-arginine as an essential substrate for optimal generation of lymphokine-activated killer (LAK) cells. This experiment also assessed supplemental dietary L-arginine as a means to potentiate the host antitumor response to interleukin-2 (IL-2) in a murine neuroblastoma (NRB) model. A/J mice received 1% arginine or isonitrogenous 1.7% glycine in addition to a regular diet 14 days before subcutaneous inoculation with C1300 NRB cells. Twenty-four hours later, animals received low (1 x 10(6) U/kg three times a day) or high (3 x 10(6) U/kg three times a day) doses of IL-2 or saline intraperitoneally for 4 days. On days 4 and 10 post-C1300 NRB inoculation, mice were killed for assessment of natural killer cell and tumor specific cytotoxicity. Remaining animals were followed for tumor incidence, tumor growth, and duration of host survival. Interleukin-2 therapy in mice receiving dietary arginine compared with those receiving glycine resulted in significantly augmented natural killer cell cytotoxicity (day 4) and generation of specific tumoricidal mechanisms (day 10). The addition of dietary arginine to low-dose IL-2 therapy significantly diminished C1300 NRB engraftment (p less than 0.05) and growth (p less than 0.001) and prolonged the duration of host survival (p less than 0.05) compared with the glycine treatment group. In vitro studies demonstrated that L-arginine is an essential substrate for optimal generation of LAK cells. Thus, supplemental dietary L-arginine enhances lymphocyte cytotoxic mechanisms and potentiates IL-2 immunotherapy.

Amino Acids↗

PubMed1992

Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome.

The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune function, but prospective trials have not demonstrated their effects on clinical outcome. Patients (n = 85) who underwent operation for upper gastrointestinal malignancies were randomized to receive the supplemental diet or a standard enteral diet after surgery. Clinical patient characteristics were similar between the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs -6.6 gm/day) measured in the first 20 patients were significantly greater in the supplemented group than in the standard group (p = 0.05). In vitro lymphocyte mitogenesis was measured in the first 31 patients and was decreased on postoperative day 1 in both groups, but normal levels were regained only in the supplemented group. In the cohort of 77 eligible patients, infectious and wound complications occurred significantly less often (11% vs 37%) in the supplemented group than in the standard group (p = 0.02). Linear logistic models for infectious/wound complications with control for the amount of nitrogen suggested (p = 0.10) dietary treatment as the major factor. Mean length of stay in the hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/- 5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids instead of a standard enteral diet significantly improved immunologic, metabolic, and clinical outcomes in patients with upper gastrointestinal malignancies who were undergoing major elective surgery.

Aged↗

PubMed1991

Impaired macrophage function in severe protein-energy malnutrition.

Protein-energy malnutrition induces immunosuppression that predisposes to sepsis, but the mechanisms are unclear. This study examines the role of the macrophage in host defense in the malnourished state. Swiss-Webster mice (N = 300) were randomly allocated to control (24% casein) or low-protein (2.5% casein) diets for 8 weeks. We studied the ability of two populations of macrophages, peritoneal macrophages, and Kupffer cells to produce superoxide anion after in vivo administration of endotoxin or mycobacterium (bacille Calmette-Guérin). Phorbol diester and Candida albicans were used as stimuli. In another group of mice, we evaluated the ability of interferon gamma to up-regulate superoxide anion release and Candida phagocytosis and killing. Mice under protein-energy malnutrition demonstrated decreased mean body weights, serum protein levels, and cell yields. Superoxide anion production in resident and activated (lipopolysaccharide, interferon gamma, bacille Calmette-Guérin infection) peritoneal macrophages was significantly reduced in the malnourished group. Candida phagocytosis and killing were also both depressed in malnourished mice. Kupffer cells failed to generate superoxide anion in all groups. We conclude that severe protein-energy malnutrition significantly impairs macrophage function, which could diminish response to acute and chronic septic challenges. Interferon gamma up regulated peritoneal macrophage and Kupffer cell microbicidal function, which suggests a therapeutic role for this lymphokine in the malnourished septic host.

Animals↗

PubMed1991

Low-dose interferon gamma renders neuroblastoma more susceptible to interleukin-2 immunotherapy.

Neuroblastoma remains a common and deadly childhood tumor, resistant to both surgical and chemo/radiotherapeutic intervention in its advanced stages. The role of immunotherapy in such cancers has yet to be defined. In previous work, we found that the addition of interferon gamma (IFN-gamma) to 3-day in vitro tissue cultures of the murine neuroblastoma C1300, led not only to the tumor's increased cell surface expression of the immunologically important major histocompatibility complex (MHC) class I antigen, but also to an increased susceptibility of such modified tumor to subsequent lymphokine activated killer (LAK) cell lysis. In this study, we sought to determine the in vivo applicability of these findings. Initial dose-response studies helped define a regimen of rIFN-gamma's administration that upregulated MHC class I without activating host natural killer (NK) activity. A/J mice bearing 7-day-old subcutaneous C1300 were randomized to receive daily morning injections of either 0, 25,000, 50,000, or 100,000 U of rIFN-gamma intraperitoneally for 6 days. Animals were killed at days 3, 6, and 9 after initiation of rIFN-gamma therapy, and tumors were excised, digested, and stained for both MHC class I and II expression. At the time of sacrifice, splenocytes from each animal were tested for NK cytotoxicity toward YAC (an NK-sensitive lymphoma) and C1300. These studies defined 3 days of therapy with 25,000 U as a "priming" dose that increased expression of class I with minimal impact on NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1991

Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines.

The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.

Animals↗

PubMed1991

Nutritional support of patients with cancer of the gastrointestinal tract.

Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established.

Cachexia↗