Search PubMed⌕ Search

Biomedical subjects

S Greenberg

Publications and source records attributed to S Greenberg.

At least 55 records · Page 3Linked to original sources
PubMed1997

Human immunodeficiency virus-1 env impairs Fc receptor-mediated phagocytosis via a cyclic adenosine monophosphate-dependent mechanism.

Human immunodeficiency virus (HIV)-1 expression in mononuclear phagocytes is associated with multiple functional defects, including phagocytosis. To assess Fcgamma receptor (FcgammaR) function in cells expressing HIV-1, human promonocytic cells (U937) acutely or chronically infected with HIV-1, or stably transfected with a noninfectious reverse transcriptase (RT) defective HIV-1 provirus (Deltapol), were treated with phorbol 12-myristate 13-acetate for 48 hours and tested for their ability to ingest sheep erythrocytes coated with IgG (E-IgG). HIV-1-infected or transfected U937 cells ingested 50% to 65% fewer E-IgG than controls despite normal surface expression of FcgammaRs. HIV-1 specifically impaired FcgammaR-mediated phagocytosis, as ingestion of complement-coated erythrocytes was unaffected. U937 cells transfected with an env deficient mutant of HIV-1 ingested E-IgG normally, suggesting that the expression of HIV-1 env was required for HIV-1 to inhibit FcgammaR-mediated phagocytosis. Expression of HIV-1 in U937 cells was associated with an increased accumulation of intracellular cyclic adenosine monophosphate (cAMP); addition of the adenylate cyclase inhibitor 2',5'-dideoxyadenosine to these cells decreased intracellular cAMP levels to that of controls and restored FcgammaR-mediated phagocytosis. Addition of either interferon (IFN)-gamma or an inhibitor of cAMP-dependent protein kinase A (KT 5720) to HIV-1-transfected U937 cells also restored FcgammaR-mediated phagocytosis. Expression of HIV-1 induces a specific defect of FcgammaR function in mononuclear phagocytes that correlates with increased levels of cAMP, and can be corrected by pharmacologic manipulation.

Cyclic AMP↗
PubMed1997

Stimulus responses and amyloid precursor protein processing in DAMI megakaryocytes.

Platelets, when released as anuclear cells by their precursor megakaryocytes, already carry soluble proteolytic fragments of the amyloid precursor protein (APP) within their alpha-granules and intact APP in the alpha-granule membranes. In response to activation signals elicited by physiologic stimuli such as thrombin, platelets release their granules' soluble contents and translocate granule membrane-bound proteins to the plasma membrane. Because platelets carry >90% of the circulation's APP, activated platelets have been implicated as origins of the beta-amyloid peptide fragment of APP (A beta), whose deposition in the cerebrovasculature is characteristic of Alzheimer's disease. We have therefore studied the APP contents and proteolytic processing in resting DAMI human megakaryocytic cells, along with the consequences of the activation of these cells by thrombin, comparing the results in each case to those with human platelets. Resting and PMA-differentiated DAMI cell contents were examined by Western blotting, immunoprecipitation, or metabolic labeling with sulfur 35-labeled methionine during culture, while plasma membrane-bound APP was evaluated by flow cytometry. Activation was followed by changes in cytoplasmic calcium concentration ((Ca++)in) and in membrane potential. Like platelets, DAMI cells exhibited a thrombin dose-dependent delta(Ca++)in, and membrane potential change; in contrast to the surface of a platelet, the surface of an agranular resting DAMI cell expresses granule-membrane proteins (APP and CD63) that appear on platelets only after activation. DAMI cell culture with 35S-labeled methionine confirmed that megakaryocytes synthesize large amounts of APP, of slightly higher molecular weight, and degrade their APP extensively before platelets are formed.

Amyloid beta-Protein Precursor↗
PubMed1997

Superficial nasalis aponeurotic system (SNAS) flap reconstruction of nasal defects.

Reconstruction of full-thickness tissue loss of the nose, particularly in the nasal tip and supratip areas, remains a technical and aesthetic challenge. Exposure of the alar cartilage can complicate an already difficult reconstruction. Many method of reconstruction have been described. We offer an alternative to previously described techniques, utilizing the nasalis aponeurosis to provide alar coverage and bulk, in conjunction with full-thickness skin grafting to minimize contour deformity. The authors describe the technique and anatomy based on cadaveric dissection and its use in 4 patients. We have performed the superficial nasalis aponeurotic system (SNAS) flap on 4 patients with satisfactory aesthetic results. Use of the SNAS for coverage obviates the need for resection of a dog-ear, as may be the case with cutaneous or musculocutaneous flaps. Alar contour deformity is minimal. The SNAS flap is a useful technique to provide soft-tissue coverage of full-thickness soft tissue loss of the nose.

Adult↗
PubMed1997

A prospective study of neonatal sepsis and meningitis in southern Israel.

OBJECTIVE: To study the epidemiology of neonatal sepsis and meningitis in the Negev area of southern Israel. DESIGN: A prospective 8-year study conducted at the neonatal intensive care unit and pediatric wards of the Soroka University Medical Center. RESULTS: Two hundred twenty-nine cases of hospital and community-acquired neonatal sepsis occurred during the study period. Thirty-two patients (14%) were meningitis. During this period 70,709 births (59% Jews and 41% Bedouins) were recorded; thus the rates of neonatal sepsis and meningitis were 3.2 and 0.5/1000 live births, respectively. One hundred seventeen (4/1000 live births) cases were recorded in Bedouins and 112 (2.6/1000 live births) in Jewish neonates (P < 0.001). Twenty-six percent of all sepsis cases occurred within < 24 h from birth, 25% from Days 2 to 7 of life and 49% between Days 8 and 28. A total of 251 organisms that were considered true pathogens were isolated. Fifty-seven of all isolates were Gram-negative organisms (mainly Klebsiella pneumoniae (20%) and Escherichia coli (16%)). Gram-positive organisms were isolated in 41% of cases. Although E. coli was the most frequently recovered Gram-negative pathogen in community-acquired late onset sepsis, Klebsiella and Enterobacter spp. represented the most commonly isolated Gram-negative organisms in nosocomial late onset sepsis. All Staphylococcus aureus isolates recovered in late onset sepsis were nosocomial. The incidence of Streptococcus agalactiae was 3 times higher in early onset sepsis than in late onset sepsis. All cases of Streptococcus pneumoniae sepsis occurred in Bedouins. CONCLUSIONS: Neonatal sepsis and meningitis rates in southern Israel are similar to those reported in Western Europe and the United States. The incidence of neonatal sepsis is significantly higher for Bedouins than for Jewish neonates. The distribution of the main pathogens is different in southern Israel and although Gram-negative enteric organisms are predominant, S. agalactiae plays a relatively minor role in the etiology of sepsis during the first month of life. In southern Israel the etiology of community-acquired late onset sepsis is different from that of nosocomial late onset sepsis.

Female↗
PubMed1997

Genetic stroke risk factors.

The development of modern molecular genetic techniques has opened up the study of how individual genes affect the risk of stroke. As the multiple genetic influences on stroke are slowly unravelled, the epidemiological basis of our understanding of the hereditary aspects of stroke will be complemented by a knowledge of the underlying molecular genetic risk factors.

Cerebrovascular Disorders↗
PubMed1996

Epidemiological, clinical, and neuropathological study of apolipoprotein E genotype in Alzheimer's disease.

Our studies of the APOE genotype in AD confirm a strong association of the epsilon 4 allele with development of AD and a decreased risk associated with epsilon 2. From a clinical/neuropathological perspective, the major effects of APOE epsilon 4 are to lower the age of onset and to increase the amount of A beta deposit in the brain. Neither rate of progression nor number of neurofibrillary tangles were affected. We also carried out a longitudinal population-based assessment of the APOE genotype to determine the risk for developing cognitive impairment of someone in the general population based on APOE genotype. APOE epsilon 4 carried about 1.4-fold increased risk, and APOE epsilon 2 about 1.7-fold decreased risk. Thus, inheritance of APOE epsilon 4 is a major biological risk factor for AD, but it has limited utility as a prognostic indicator for development of dementia in an individual.

Age of Onset↗
PubMed1996

Syk tyrosine kinase is required for immunoreceptor tyrosine activation motif-dependent actin assembly.

Clustering of several multisubunit receptors on hematopoetic cells results in a signaling cascade involving the phosphorylation of immunoreceptor tyrosine activation motifs, or "ITAMs," and actin polymerization. Recent experiments indicate that direct clustering of the ITAM-binding protein, p72(syk) (Syk), is capable of transmitting a phagocytic signal in COS cells (Greenberg, S., Chang, P., Wang, D., Xavier, R., and Seed, B.(1996) Proc. Natl. Acad. Sci. U. S. A. 93, 1103-1107). However, the possibility of redundant signaling pathways makes it difficult to test the requirement for Syk in ITAM-dependent actin polymerization in hematopoetic cells. We developed a model system to study ITAM-dependent actin assembly. DT40 lymphocytes were transfected with fusion proteins encoding the transmembrane and cytosolic domains of the ITAM-containing gamma subunit of Fc receptors. Clustering the gamma-containing fusion proteins with IgG-coated erythrocytes triggered submembranous actin assembly. This response depended on an intact ITAM, was absent in cell lines that had been engineered to lack Syk, and was augmented in cell lines that stably overexpressed Syk. These experiments demonstrate an absolute requirement for Syk tyrosine kinase in ITAM-dependent actin assembly in transfected lymphocytes.

Actins↗
PubMed1996

Clustered syk tyrosine kinase domains trigger phagocytosis.

Phagocytosis is a phylogenetically primitive mechanism adapted by specialized cells of the immune system to ingest particulate pathogens. Recent evidence suggests that the program of specific cytoskeletal rearrangements that underlies phagocytosis may share elements with the antigen receptor signaling pathway in lymphocytes. Tyrosine phosphorylation, necessary for both lymphocyte effector function and phagocytosis, is thought to allow cytoskeletal elements to couple to the intracellular domains of antigen and Fc receptor subunits. We show here that the intracellular domains of the receptors are not inherently required for cytoskeletal coupling. Chimeric transmembrane proteins bearing syk but not src family tyrosine kinase domains are capable of autonomously triggering phagocytosis and redistribution of filamentous actin in COS cells. These responses cannot be initiated by a receptor chimera bearing a point mutation in the syk catalytic domain, and the kinase domain alone is sufficient for initiating cytoskeletal coupling.

Actins↗
PubMed1996

Cellular signaling pathways and cytoskeletal organization.

We describe a possible mechanism by which the amyloid precursor protein (APP) may be linked to the intraneuronal pathology of Alzheimer's disease (AD). Extracellular proteolytic products of APP may directly or indirectly transduce signals to cells under normal as well as pathological conditions. This activity appears to reside in the cysteine-rich amino terminus of APP. How APP or its metabolic products may affect the phosphorylation of tau is considered.

Amino Acid Sequence↗
PubMed1996

Lack of association of trinucleotide repeat polymorphisms in very-low-density lipoprotein receptor gene with Alzheimer's disease.

Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD.

Alleles↗
PubMed1996

Natural beta-carotene and whole body irradiation in rats.

beta-carotene and other carotenoids are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body irradiation is known to cause an immunosuppression effect in mammals through the possible initiation and production of reactive oxygen species. We decided to test the possible antioxidative effect against whole-body irradiation of a natural beta-carotene, composed of equal amounts of the all-trans and 9-cis isomers, obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground commercial food enriched with natural beta-carotene (50 mg/kg diet). On completion of 1 week with beta-carotene, the rats were exposed to a single dose of 4 Gy whole-body irradiation, after which their livers and blood were removed for beta-carotene and retinol analysis in comparison with control livers of animals irradiated or not, or supplemented with beta-carotene after irradiation. A normal increase in body weight with no ill effects was noted in the groups of rats whose diet was supplemented by beta-carotene before and after irradiation, compared with the reduction in the specific growth rate in the group of rats irradiated without beta-carotene. Liver beta-carotene and retinol decreased significantly after irradiation compared with the rats which were not irradiated. This decrease was not shown in rats fed beta-carotene prior to irradiation, and the effect of irradiation was partially cured by supplementation with beta-carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis of the irradiated animals showed a selective decline in 9-cis beta-carotene and in retinol over all-trans beta-carotene and retinyl-esters. These results suggest that 9-cis beta-carotene and retinol protect in vivo against the cellular damage by free radicals induced after whole-body irradiation.

Animals↗
PubMed1996

Implantable cardioverter defibrillator: use in patients with no symptoms and at high risk.

Twenty-seven patients with asymptomatic, nonsustained ventricular tachycardia whose evaluation suggested they were at high risk for sustained ventricular arrhythmias were treated with implantable cardioverter defibrillators. The option of conventional therapy (including the option of no therapy) was presented to each patient and rejected in favor of defibrillator implantation on an experimental basis. Eighteen patients had coronary artery disease and inducible sustained ventricular tachycardia, 8 had idiopathic dilated cardiomyopathy, and 1 had hypertrophic cardiomyopathy and a strong family history of sudden cardiac death. The mean ejection fraction was 27% +/- 10%. Operative morbidity (3%) and mortality (3%) were low. Mean overall survival was 92% and 88% at 1 and 2 years, respectively. Sixteen (59%) of the 27 patients had appropriate defibrillator discharges during a mean follow-up of 35 +/- 15 months. The mean time to first appropriate discharge was 18 +/- 17 months, and mean follow-up after first discharge was 17 +/- 20 months. In conclusion, implantable cardioverter defibrillator placement in high-risk patients without symptoms is a feasible approach that may have resulted in benefit in selected patients. Large-scale randomized trials currently under way will determine the risk/benefit ratio of this management approach.

Actuarial Analysis↗
PubMed1996

Twenty-four-hour ambulatory electrocardiography in elderly subjects: prevalence of various arrhythmias and prognostic implications (report from the Bronx Longitudinal Aging Study).

Functional, ambulatory, community-dwelling subjects (n = 423, aged 75 to 85 years) underwent baseline 24-hour ambulatory electrocardiography (ECG) examinations as part of the Bronx Aging Study, a 10-year prospective cohort study designed to identify risk factors and disease markers for cardiovascular, cerebrovascular, and dementia illnesses in old people. Premature ventricular contractions were the most commonly observed arrhythmia noted (93% of subjects), with a low prevalence of nonsustained ventricular tachycardia (5%), paroxysmal atrial tachycardia (13%), atrial fibrillation (4%), and atrioventricular blocks (4%). A 24-hour sinus rate of < 60 beats/min was noted in 13% of subjects, and 11% of subjects were noted to have transient episodes of severe bradycardia (< 40 beats/min). In a multivariate analysis, nonsustained ventricular tachycardia was an independent predictor of death (p = 0.015; relative risk [RR] 2.8; 95% confidence interval [CI] 1.4 to 5.8) and myocardial infarction (p = 0.031; RR 3.2; CI 1.2 to 9.4). Transient atrioventricular block was an independent predictor of stroke (p - 0.0006; RR 9.7; CI 3.3 to 28.9), as was sinus bradycardia over a 24-hour period (p = 0.033; RR 2.7; CI 1.2 to 6.4). Ventricular tachycardia approached significance as an independent predictor of multiinfarct dementia (p = 0.052; RR 6.3; CI 1.4 to 28.7). Episodes of paroxysmal atrial fibrillation, a trial tachycardia, and severe bradycardia were not associated with adverse outcomes. Some arrhythmias found on the ambulatory ECG in very old subjects can predict an increased risk for subsequent death, myocardial infarction, stroke, and multiinfarct dementia.

Aged↗
PubMed1996

Hemodynamic effects of peritoneovenous shunts in hemodialysis patients with ascites.

Ascites in hemodialysis patients has been reported in association with systemic diseases, such as cirrhosis or congestive heart failure, and as an idiopathic form. Regardless of the etiology, these patients often are refractory to treatment with intradialytic ultrafiltration because of recurrent hypotensive episodes. In this report we describe the hemodynamic effects of peritoneovenous shunts (PVSs) in three hemodialysis patients with ascites refractory to conventional treatment. One patient had idiopathic ascites and the other two had associated liver disease. Patients were monitored for lowest blood pressure, number of intradialytic hypotensive episodes, number of grams of albumin infused to treat hypotensive episodes, interdialytic weight gain, and hemodynamic stability (defined as the difference between the predialysis mean arterial pressure and the lowest intradialytic mean arterial pressure). In all three patients the hemodynamic parameters stabilized after PVS placement despite equal or greater ultrafiltration during dialysis (due to a significant increase in the lowest measured intradialytic blood pressure). The total number of hypotensive episodes decreased from 219 prior to PVS placement to zero after shunt placement. The need for albumin infusion during hemodialysis (for blood pressure support) decreased (significantly in two patients), as did the volume of ascites in all three patients. One patient required PVS replacement secondary to infection, which was the only complication. We believe that refractory ascites in end-stage renal disease patients can be successfully treated by placement of a PVS, which often results in relief of the ascites and significant improvement in intradialytic hemodynamic stability.

Aged↗
PubMed1996

Leukemic phase of mantle cell lymphoma two case reports and review of the literature.

Two cases of mantle cell lymphoma are presented. Both patients were women, aged 68 and 56 years, who presented with lymph node enlargement. Each case was initially interpreted as a follicular small cleaved cell lymphoma. Both patients later presented with splenomegaly and recurrent lymphadenopathy. Morphologic and immunologic studies on a parotid swelling in one case and a splenectomy specimen in the other indicated a diagnosis of mantle cell lymphoma. Both women subsequently presented in leukemic phase associated with a poor prognosis, and both patients succumbed soon after. The characteristics, differential diagnosis, and leukemic phase of mantle cell lymphoma are discussed. The importance of appropriate immunohistochemical and flow cytometry analysis in distinguishing mantle cell lymphoma from morphologically similar follicular center cell lymphomas is demonstrated.

Aged↗
PubMed1995

Soluble ligands of the alpha v beta 3 integrin mediate enhanced tyrosine phosphorylation of multiple proteins in adherent bovine pulmonary artery endothelial cells.

Binding of substrate-bound extracellular matrix proteins to cell surface integrins results in a variety of cellular responses including adhesion, cytoskeletal reorganization, and gene expression. We have previously shown that addition of soluble SC5b-9, the complement-vitronectin complex, resulted in an RGD-dependent increase in lung venular hydraulic conductivity (Ishikawa, S., Tsukada, H., and Bhattacharya, J. (1993) J. Clin. Invest. 91, 103-109). To identify specific integrin(s) and signal transduction pathways that are responsive to soluble vitronectin-containing ligands, we exposed confluent bovine pulmonary artery cells to purified soluble human mono- or multimeric vitronectin, or SC5b-9, and determined the extent of endothelial cell protein tyrosine phosphorylation. Monomeric vitronectin (Vn) did not induce enhanced protein tyrosine phosphorylation. However, multimeric Vn and SC5b-9 elicited time- and concentration-dependent increases in tyrosine phosphorylation of numerous proteins. Antiserum against vitronectin, RGD peptides, and monoclonal and polyclonal antibodies against the alpha v beta 3 integrin blocked the vitronectin- or SC5b-9-induced enhanced accumulation of tyrosine phosphoproteins, while antibodies against beta 1 integrins and the alpha v beta 5 integrin did not. Clustering of the alpha v beta 3 integrin using monoclonal antibody LM609 caused a pattern of enhanced tyrosine phosphorylation similar to that caused by multimeric Vn and SC5b-9, suggesting that aggregation of alpha v beta 3 was critical for signaling. Among the proteins that underwent enhanced tyrosine phosphorylation in response to vitronectin were the cytoskeletal proteins paxillin, cortactin, and ezrin, as well as the SH2 domain-containing protein Shc, and p125FAK. We conclude that ligation of the alpha v beta 3 integrin by soluble ligands promotes enhanced phosphorylation of several proteins implicated in tyrosine kinase signaling and suggest that this pathway may be important in inflammatory states which are accompanied by accumulation of SC5b-9.

Animals↗